The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft in Treatment of Chronic Knee Osteoarthritis

*Sabah S. Moshref, Yasir S. Jamal, Amro M. Al-Hibshi and Abdullah M. Kaki*

### **Abstract**

The study started in 2010 to find the effect of autologous fat micrograft for osteoarthritis (OA); the result was published on normal animal's model, in 10 patients, then in 80 patients with knee osteoarthritis, and the current study in 205 patients. The study was conducted at King Abdulaziz University Hospital (January 2012–October 2015); 80 adult patients were suffering from moderate to severe knee osteoarthritis. About 10–20 mL fat micrograft was prepared with liposuction and injected intra-articularly into the affected knee/s. The results revealed that pain improvement after the fat injection during rest and with activity with the visual analogue scale. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) indicated improvement, both in the three domains (pain, stiffness, and physical function) and in total. The use of intra-articular autologous fat micrograft is simple, safe, and effective for degenerative knee osteoarthritis.

**Keywords:** autologous fat micrograft, intra-articular injection, knee osteoarthritis, cartilage degeneration, regenerative therapy repair

### **1. Introduction**

Fat grafting and its use in aesthetic and reconstructive surgeries are considered a state of art, but looking back at the history, it is just a revival in the techniques, which was described previously by others when **Gustav Neuber** on 1893 was the first to perform fat graft for orbital depression in human and Erich Lexer who is a skilled German orthopedic and plastic surgeon reported a variety of clinical uses of fat graft in management of knee ankylosis and fat graft wrapped around the tendon during tendon repair to prevent skin tendon adhesion and restore gliding [1, 2].

The revolution in surgical specialty directed toward minimally invasive therapeutic modalities where endoscopic surgery replaced the open surgical operations; similarly, the recent discovery of the regenerative effect of fat micrograft due to presence of adipose-derived stem cells (ADSCs), cytokines, growth factors, pre adipocytes, and mature adipocytes led to a growing interest for the

use fat graft as regenerative treatment replacing the major surgical rejuvenative operation, and Liu et al. [3] in his major review article, which includes over 265 clinical trials about therapeutic application of mesenchymal stem cells (MSCs) for common bone and joint diseases, indicated that the MSCs are considered as an ideal source of cell therapy for different types of diseases including bone and joint diseases [3–5].

In this chapter we present our experience over the current decade in management of osteoarthritis (OA) by intra-articular injection of fat micrograft (IAFMG), describing our approach, which was developed from the belief in the powerful reparative effect of autologous fat graft for damage tissue as well as natural lubricating effect on the joints. We started on animal model, and upon confirming its safety and positive regenerative effects, we applied this minimally invasive modality on patients with advanced and moderate chronic osteoarthritis with fulfillment of ethical approval requirement for the trials on human subjects. The satisfactory outcome of this minimally invasive modality indicates that intra-articular injection of fat micrograft can replace or delay considerably the need for the classical major joint replacement surgery (JRS), with its impact on the quality of life of patients and financial cost of JRS, and long hospitalization and absence of work when compared to our minimally invasive procedure [6, 7].

### **2. Disease characteristics**

Chronic osteoarthritis is a common complex disorder affecting middle-aged and elderly females more than males but all races. The main risk factors are constitutional, including sedentary lifestyle, obesity and aging, and genetic and local factors (biomechanical consequences of joint injury, joint laxity, or malalignment). Therefore, the stress from mechanical force plays an important critical role in the initiation and progression of the disease; it is also associated with chronic disease such as diabetes, gout, and poor diet [8–15].

Osteoarthritis is the disease of the whole joint, including the bone, cartilage, tendons, ligaments, synovium, and synovial fluid. Osteoarthritis mainly affects weight-bearing joints (i.e., knees, hips, or spine) due to chronic high stress, which leads to degradation of the cartilage; subchondral cysts; sclerosis, which stimulates new bone outgrowths (osteophytes); and synovitis leading to reduction of joint viscosity and lubrication with more friction, irritation, consequently more cartilage damage and effusion, ligament laxity and meniscal tears, and progressive narrowing of joint space. The usual patient presentation is joint pain, swelling, crepitus, morning joint stiffness, and, after prolonged rest, hyperthermia, progressively restricted movement, and major disability with deterioration in quality of life [9, 10, 16, 17].

### **3. Management**

Management included the diagnosis of the disease and its extent based on clinical presenting symptoms and signs of the patient, evaluating the degree of pain, mobility, and functions of the diseased joint, and then utilizing the radiological modalities to confirm the disease and its severity with plain X-ray, CT scan, MRI, and other available imaging modalities; following clinical and radiological diagnoses, the plan of treatment is established according to the extent of the disease, which is ranging from nonsurgical to minimally invasive or major surgical procedure.

**89**

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft...*

Currently there is no curative intervention; all treatment modalities are directed toward pain control, improvement of joint mobility and functions, and avoiding drugs with adverse effects. Non-pharmacological management should include a combination approach in the form of patient education, modification of lifestyle, selfmanagement, weight reduction, exercise, conventional physiotherapy, electrotherapy, hydrotherapy, and occupational therapy to prevent excessive stress on the joint.

The pharmacological symptomatic therapies for pain control are in the form of nonsteroidal anti-inflammatory medications such as acetaminophen and COX-2 specific inhibitors and topical nonsteroidal anti-inflammatory drugs. On the other hand, intra-articular injection of corticosteroids and viscous supplementation injections of hyaluronic acid improve pain and viscosity, but these pharmacological treatments have short-term improvement effect and are costly, and the intra-

Recently, the intra-articular injection of platelet-rich plasma to human osteoarthritic joints associated with significant clinical symptomatic improvements of

Surgical therapy included minor and major surgical operations, but the recent use of the minimally invasive surgical procedure of intra-articular injection fat micrograft with the contained adipose-derived stem cells, which we studied on animal model followed by human joints, showed very satisfactory outcome; this modality of

The minor surgical procedures include arthroscopic joint lavage debridement, which demonstrated short-term symptom relief with more improvement when combined with marrow-stimulating microfracture and drilling procedures of articular surface; this improvement in joint functions would postpone the need for

On the other hand, joint replacement as major surgical intervention is reserved for patients with failure of other modalities and in patients with joint end-stage disease, as joint implants have a finite life span (~10–15 years). After that a variety of complications might occur such as wear particle formation, which contribute to loosening which required revision surgery; therefore the use of artificial joints in young patients (e.g., <55 years) is associated with higher revision rates of this operation with its associated disadvantages as being a major procedure with complications, long hospitalization, absence from work, and high cost, which indicate the need to develop new treatment options. Therefore tissue engineering regeneration offers a long-term solution for repair of the affected tissue components of the joints

Osteoarthritis is an active disease process with an imbalance between the repair and destruction and degeneration of joint with poor intrinsic healing power and

treatment is the main theme of this chapter which will be discussed in details.

*DOI: http://dx.doi.org/10.5772/intechopen.88220*

articular injections have a risk of acute synovitis [18–23].

inflammation and pain and viscosity [24].

**5. Surgical therapy**

knee replacement [25].

**6. The major surgical procedures**

**7. The stem cell line therapy**

such as the bone, ligament, and knee meniscus [26–28].

**4. Nonsurgical therapy**

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft... DOI: http://dx.doi.org/10.5772/intechopen.88220*

### **4. Nonsurgical therapy**

*Tibia Pathology and Fractures*

invasive procedure [6, 7].

**2. Disease characteristics**

such as diabetes, gout, and poor diet [8–15].

diseases [3–5].

use fat graft as regenerative treatment replacing the major surgical rejuvenative operation, and Liu et al. [3] in his major review article, which includes over 265 clinical trials about therapeutic application of mesenchymal stem cells (MSCs) for common bone and joint diseases, indicated that the MSCs are considered as an ideal source of cell therapy for different types of diseases including bone and joint

In this chapter we present our experience over the current decade in management of osteoarthritis (OA) by intra-articular injection of fat micrograft (IAFMG), describing our approach, which was developed from the belief in the powerful reparative effect of autologous fat graft for damage tissue as well as natural lubricating effect on the joints. We started on animal model, and upon confirming its safety and positive regenerative effects, we applied this minimally invasive modality on patients with advanced and moderate chronic osteoarthritis with fulfillment of ethical approval requirement for the trials on human subjects. The satisfactory outcome of this minimally invasive modality indicates that intra-articular injection of fat micrograft can replace or delay considerably the need for the classical major joint replacement surgery (JRS), with its impact on the quality of life of patients and financial cost of JRS, and long hospitalization and absence of work when compared to our minimally

Chronic osteoarthritis is a common complex disorder affecting middle-aged and elderly females more than males but all races. The main risk factors are constitutional, including sedentary lifestyle, obesity and aging, and genetic and local factors (biomechanical consequences of joint injury, joint laxity, or malalignment). Therefore, the stress from mechanical force plays an important critical role in the initiation and progression of the disease; it is also associated with chronic disease

Osteoarthritis is the disease of the whole joint, including the bone, cartilage, tendons, ligaments, synovium, and synovial fluid. Osteoarthritis mainly affects weight-bearing joints (i.e., knees, hips, or spine) due to chronic high stress, which leads to degradation of the cartilage; subchondral cysts; sclerosis, which stimulates new bone outgrowths (osteophytes); and synovitis leading to reduction of joint viscosity and lubrication with more friction, irritation, consequently more cartilage damage and effusion, ligament laxity and meniscal tears, and progressive narrowing of joint space. The usual patient presentation is joint pain, swelling, crepitus, morning joint stiffness, and, after prolonged rest, hyperthermia, progressively restricted movement, and major disability with deterioration in quality of life [9, 10, 16, 17].

Management included the diagnosis of the disease and its extent based on clinical presenting symptoms and signs of the patient, evaluating the degree of pain, mobility, and functions of the diseased joint, and then utilizing the radiological modalities to confirm the disease and its severity with plain X-ray, CT scan, MRI, and other available imaging modalities; following clinical and radiological diagnoses, the plan of treatment is established according to the extent of the disease, which is ranging from nonsurgical to minimally invasive or

**88**

**3. Management**

major surgical procedure.

Currently there is no curative intervention; all treatment modalities are directed toward pain control, improvement of joint mobility and functions, and avoiding drugs with adverse effects. Non-pharmacological management should include a combination approach in the form of patient education, modification of lifestyle, selfmanagement, weight reduction, exercise, conventional physiotherapy, electrotherapy, hydrotherapy, and occupational therapy to prevent excessive stress on the joint.

The pharmacological symptomatic therapies for pain control are in the form of nonsteroidal anti-inflammatory medications such as acetaminophen and COX-2 specific inhibitors and topical nonsteroidal anti-inflammatory drugs. On the other hand, intra-articular injection of corticosteroids and viscous supplementation injections of hyaluronic acid improve pain and viscosity, but these pharmacological treatments have short-term improvement effect and are costly, and the intraarticular injections have a risk of acute synovitis [18–23].

Recently, the intra-articular injection of platelet-rich plasma to human osteoarthritic joints associated with significant clinical symptomatic improvements of inflammation and pain and viscosity [24].

### **5. Surgical therapy**

Surgical therapy included minor and major surgical operations, but the recent use of the minimally invasive surgical procedure of intra-articular injection fat micrograft with the contained adipose-derived stem cells, which we studied on animal model followed by human joints, showed very satisfactory outcome; this modality of treatment is the main theme of this chapter which will be discussed in details.

The minor surgical procedures include arthroscopic joint lavage debridement, which demonstrated short-term symptom relief with more improvement when combined with marrow-stimulating microfracture and drilling procedures of articular surface; this improvement in joint functions would postpone the need for knee replacement [25].

### **6. The major surgical procedures**

On the other hand, joint replacement as major surgical intervention is reserved for patients with failure of other modalities and in patients with joint end-stage disease, as joint implants have a finite life span (~10–15 years). After that a variety of complications might occur such as wear particle formation, which contribute to loosening which required revision surgery; therefore the use of artificial joints in young patients (e.g., <55 years) is associated with higher revision rates of this operation with its associated disadvantages as being a major procedure with complications, long hospitalization, absence from work, and high cost, which indicate the need to develop new treatment options. Therefore tissue engineering regeneration offers a long-term solution for repair of the affected tissue components of the joints such as the bone, ligament, and knee meniscus [26–28].

### **7. The stem cell line therapy**

Osteoarthritis is an active disease process with an imbalance between the repair and destruction and degeneration of joint with poor intrinsic healing power and

regeneration due to poor vascularization and absence of direct access to progenitor cells of bone marrow [29].

For many years, researchers have been seeking to understand the body's ability to repair and replace the damaged tissues; these researches led them to the discovery of the unique mesenchymal stem cell, which is partly responsible for maintenance and repairing of damaged connective tissues after injury. They can migrate toward injured tissues, where they display trophic effects of synthesis of proliferative, proangiogenic, and regenerative molecules. Mesenchymal stem cells undergo site-specific differentiation into a variety of connective tissues including cartilage, bone, fat, tendon, ligament, marrow stroma, and others, with its reparative and regenerative effects with anti-inflammatory and immunomodulatory actions via direct cell-cell interaction or secretion of bioactive factors, resulting in differentiation, stemness maintenance, self-renewal, prevention, and modification of progress of the disease [17, 30–38].

Mesenchymal stem cells can be isolated from several human sources other than the bone marrow and fetal tissues, including adipose tissue (ADSCs) with similar phenotypic characteristics but different propensities in proliferation and differentiation potentials, and provide an abundant and easily accessible source of stem cells [39–46].

With all these properties, MSCs are considered as an ideal source of cell therapy for different types of diseases including bone and joint diseases as reviewed by Liu et al. [3] as a review article about therapeutic application of MSCs for common bone and joint diseases, which include over 265 clinical trials of MSCs registered with clinical trial for knee osteoarthritis and other joint and bone diseases; they conclude that MSC is a promising prospect in clinical application for bone and joint diseases, without any reports of post application adverse immune side effects [5].

### **8. Animal and human researches on uses of MSCs in joints**

With the growing interest of using MSCs as biological treatment for cartilage repair in arthritic joint diseases on different animal models where stem cells grown on different media scaffolds include synthetic or natural extracellular matrix, implantation of stem cells into the joints is either as invasive via arthroscopy with possible increased risk of infection or noninvasive intra-articular injection MSCs. These trials are summarized in **Table 1** [6, 46–59].


**91**

**9. Our animal trial**

*The other animal model trial studies.*

**Table 1.**

Our study started as an idea on 2010, when we plan to use autologous fat micrograft for treatment of osteoarthritis and we started by injecting fat micrograft into normal hind joints of sheep to determine the safety and effects of intra-articular injection of autologous fat micrograft, followed by observing the animal's activities in using their injected joints, and by examining any macroscopic or microscopic changes in the articular cartilage of the fat-injected joints compared to other similar

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft...*

**Publication MSCs Description Intervention Outcome**

hyaluronic gel sponge by open arthrotomy

of polylactic acid by open

hyaluronan in injected mini

Intra-articular injection

of collagen gel by open

controlled clinical trial on the effect? IN dogs with chronic OA of the coxofemoral and humeroradial joints Intra-articular injection

dimensional biodegradable

Synovium MSCs in massive meniscal defect knee rat intra-articular injection

hyaluronan in Hartley strain

autologous fat micrograft **in normal** sheep hind joints, intra-articular injection

Intra-articular injection

Intra-articular injection

hyaluronan in donkey Intra-articular injection

arthrotomy

pig OA joint

arthrotomy

scaffolds

guinea pig

Invasive with risk of infection

Invasive with risk of infection

Minimally invasive

Invasive with risk of infection

Minimally invasive

Minimally invasive

Minimally invasive

Minimally invasive

Minimally invasive

Minimally invasive

Marked improvement

Marked improvement

+Cartilage regeneration

+Cartilage regeneration

Significant improvement

+Cartilage regeneration

Promoted meniscal regeneration

+Cartilage regeneration

+Cartilage regeneration

Increase of the articular hyaline cartilage thickness Significant chondrocyte proliferation

*DOI: http://dx.doi.org/10.5772/intechopen.88220*

Kayakabe et al. [50] BMC MSCs grow on scaffold of

Yan et al. [51] BMC MSCs grow on scaffolds

Lee et al. [52] BMC MSC and suspension of

Kuroda et al. [53] BMC MSCs grow on scaffolds

Black et al. [54, 55] ADMSCs Double-blinded, placebo-

Noth et al. [56] BMC MSCs seeded on three-

Mokbel et al. [58] BMC MSC and suspension of

Sato et al. [59] BMC MSC and suspension of

Moshref et al. [6] ADMSCs Intra-articular injection of

MSCs

Horie et al. [57] Synovium

**Animal model trial**

**Animal model trial Publication MSCs Description Intervention Outcome** Kayakabe et al. [50] BMC MSCs grow on scaffold of hyaluronic gel sponge by open arthrotomy Invasive with risk of infection Marked improvement Yan et al. [51] BMC MSCs grow on scaffolds of polylactic acid by open arthrotomy Invasive with risk of infection Marked improvement Lee et al. [52] BMC MSC and suspension of hyaluronan in injected mini pig OA joint Intra-articular injection Minimally invasive +Cartilage regeneration Kuroda et al. [53] BMC MSCs grow on scaffolds of collagen gel by open arthrotomy Invasive with risk of infection +Cartilage regeneration Black et al. [54, 55] ADMSCs Double-blinded, placebocontrolled clinical trial on the effect? IN dogs with chronic OA of the coxofemoral and humeroradial joints Intra-articular injection Minimally invasive Significant improvement Noth et al. [56] BMC MSCs seeded on threedimensional biodegradable scaffolds Intra-articular injection Minimally invasive +Cartilage regeneration Horie et al. [57] Synovium MSCs Synovium MSCs in massive meniscal defect knee rat intra-articular injection Minimally invasive Promoted meniscal regeneration Mokbel et al. [58] BMC MSC and suspension of hyaluronan in donkey Intra-articular injection Minimally invasive +Cartilage regeneration Sato et al. [59] BMC MSC and suspension of hyaluronan in Hartley strain guinea pig Intra-articular injection Minimally invasive +Cartilage regeneration Moshref et al. [6] ADMSCs Intra-articular injection of autologous fat micrograft **in normal** sheep hind joints, intra-articular injection Minimally invasive Increase of the articular hyaline cartilage thickness

**Table 1.**

*Tibia Pathology and Fractures*

cells of bone marrow [29].

modification of progress of the disease [17, 30–38].

regeneration due to poor vascularization and absence of direct access to progenitor

Mesenchymal stem cells can be isolated from several human sources other than the bone marrow and fetal tissues, including adipose tissue (ADSCs) with similar phenotypic characteristics but different propensities in proliferation and differentiation potentials, and provide an abundant and easily accessible source of stem cells [39–46]. With all these properties, MSCs are considered as an ideal source of cell therapy for different types of diseases including bone and joint diseases as reviewed by Liu et al. [3] as a review article about therapeutic application of MSCs for common bone and joint diseases, which include over 265 clinical trials of MSCs registered with clinical trial for knee osteoarthritis and other joint and bone diseases; they conclude that MSC is a promising prospect in clinical application for bone and joint diseases,

without any reports of post application adverse immune side effects [5].

With the growing interest of using MSCs as biological treatment for cartilage repair in arthritic joint diseases on different animal models where stem cells grown on different media scaffolds include synthetic or natural extracellular matrix, implantation of stem cells into the joints is either as invasive via arthroscopy with possible increased risk of infection or noninvasive intra-articular injection MSCs.

**Publication MSCs Description Intervention Outcome**

OA joint

hyaluronan injected in goat

bioceramic beta-tricalcium phosphate via open arthrotomy

Minimally invasive

Invasive with risk of infection

Invasive with risk of infection

Invasive risk of infection

+ Cartilage regeneration

Marked improvement

Marked improvement

Marked improvement

Intra-articular injection

of fibrin glue by open arthrotomy implantation

hyaluronic acid and gelatin by open arthrotomy

**8. Animal and human researches on uses of MSCs in joints**

These trials are summarized in **Table 1** [6, 46–59].

Murphy et al. [46] BMC MSC and suspension of

Guo et al. [47] BMC MSCs grow on scaffolds of

Hui et al. [48] BMC MSCs grow on scaffolds

Liu et al. [49] BMC MSCs grow on scaffolds of

**Animal model trial**

For many years, researchers have been seeking to understand the body's ability to repair and replace the damaged tissues; these researches led them to the discovery of the unique mesenchymal stem cell, which is partly responsible for maintenance and repairing of damaged connective tissues after injury. They can migrate toward injured tissues, where they display trophic effects of synthesis of proliferative, proangiogenic, and regenerative molecules. Mesenchymal stem cells undergo site-specific differentiation into a variety of connective tissues including cartilage, bone, fat, tendon, ligament, marrow stroma, and others, with its reparative and regenerative effects with anti-inflammatory and immunomodulatory actions via direct cell-cell interaction or secretion of bioactive factors, resulting in differentiation, stemness maintenance, self-renewal, prevention, and

**90**

*The other animal model trial studies.*

### **9. Our animal trial**

Our study started as an idea on 2010, when we plan to use autologous fat micrograft for treatment of osteoarthritis and we started by injecting fat micrograft into normal hind joints of sheep to determine the safety and effects of intra-articular injection of autologous fat micrograft, followed by observing the animal's activities in using their injected joints, and by examining any macroscopic or microscopic changes in the articular cartilage of the fat-injected joints compared to other similar

Significant chondrocyte proliferation

### **Figure 1.**

*(a–c) The control sheep H&E stain; longitudinal sections in femoral diarthrosis of left hind knee. (a) Normal histological structure of the articular hyaline cartilage (Hc) compact bone (Cb), spongy bone (head arrows), and bone marrow (\*), 100×. (b, c) Flattened chondrocytes (head arrows) of the surface layer of hyaline cartilage followed by internal globular chondrocytes arranged in rows (arrows), 400×; 1000×.*

### **Figure 2.**

*(a–c) The treated sheep right hind knee; longitudinal sections in femoral diarthrosis H&E stain. (a) Increasing the thickness of the articular hyaline cartilage (Hc) layer; compact bone (arrows), spongy bone (head arrows), and bone marrow (\*) were observed in normal view, 100×. (b) Increasing the number of chondrocytes (arrows), 400×. (c) Chondrocyte division, metaphase (head arrows), telophase (arrows) 1000×.*

**93**

summarized in **Table 3** [28, 70–73, 76].

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft...*

*Number of chondrocytes in control and treated articular cartilage of sheep knee joints.*

non-injected joint of the same animal; the study confirmed the safety, without any associated detrimental effects, on the joint tissues. Furthermore, it had positive microscopic findings as there was increase of the thickness of the articular hyaline cartilage layer with significant proliferation of chondrocytes including different mitosis stages (**Figures 1** and **2**, **Table 2**). Therefore, intra-articular injection of fat micrograft is an ideal minimally invasive choice for joint lubrication with high

**Knee Joints Femoral diarthrosis Tibial diarthrosis**

Left joints

Right joint

42.72 ± 0.700

49.10 ± 0.585\*

After the successful encouraging results of our previous animal study, which demonstrates the potential healing power and regenerative effect of autologous fat micrograft with its stem cells and all other study reports of clinical trials and publication by using mesenchymal stromal/stem cells for management of osteoarthritis, which offer a great hope for the treatment of osteoarthritic joints, we decided to evaluate the efficacy of fresh non-processed autologous fat micrograft with its ADSCs for management of osteoarthritic joints as prospective interventional clinical trial, which was conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, after obtaining the ethical approval from the local research and ethics committee, No. 822-12, according to latest vision of the Declaration of Helsinki. Over the period of 2012–2013, a preliminary clinical trial was conducted on 10 adult patients of both genders suffering from severe to moderate knee osteoarthritis with encouraging results as an effective and safe method for the treatment of knee osteoarthritis, then we expand the trial on 80 adult patients which confirm our previous finding, and then the clinical trial concluded with

the final reporting to ethical committee on December 2016 [2, 3, 6, 7, 66].

But our work in utilizing this modality of treatment continued, and we are currently presenting the outcome in 205 adult patients (392 knee joints) who were managed and completed the required period of follow-up [7, 60–75, 77, 78].

The other studies were mainly revolving around the use of bone marrow or expanded adipose tissues and non-expanded autologous MSCs although some trials use allogenic MSCs. Most researchers focus on the use of intra-articular injections without the use of scaffolds or major surgeries since injections are more cost-effective, have little morbidity, and are a desirable way of treatment. The satisfactory outcome of our study over 10 years indicated that MSC treatment appears to be a good option for treatment of moderate to severe OA in the elderly; other studies reported similar results to ours in demonstrating promising prospect of cell therapy in many refractory diseases, including bone and joint diseases, in great improvement of pain, mobility, and other joint functions; these have high potential for clinical use in tissue engineering and regenerative and reparative medicine. Other studies found MSCs effective in cartilage healing; these trials are

*DOI: http://dx.doi.org/10.5772/intechopen.88220*

Control 40.90 ± 0.432

Treated 55.31 ± 0.681\*\*

potential healing effects.

*\**

**Table 2.**

*Significant at p* ≤ *0.01. \*\*High significant at p* ≤ *0.001.*

**10. Our human trial**

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft... DOI: http://dx.doi.org/10.5772/intechopen.88220*


**Table 2.**

*Tibia Pathology and Fractures*

**92**

**Figure 2.**

**Figure 1.**

*(a–c) The control sheep H&E stain; longitudinal sections in femoral diarthrosis of left hind knee. (a) Normal histological structure of the articular hyaline cartilage (Hc) compact bone (Cb), spongy bone (head arrows), and bone marrow (\*), 100×. (b, c) Flattened chondrocytes (head arrows) of the surface layer of hyaline* 

*(a–c) The treated sheep right hind knee; longitudinal sections in femoral diarthrosis H&E stain. (a) Increasing the thickness of the articular hyaline cartilage (Hc) layer; compact bone (arrows), spongy bone (head arrows), and bone marrow (\*) were observed in normal view, 100×. (b) Increasing the number of chondrocytes (arrows), 400×. (c) Chondrocyte division, metaphase (head arrows), telophase (arrows) 1000×.*

*cartilage followed by internal globular chondrocytes arranged in rows (arrows), 400×; 1000×.*

*Number of chondrocytes in control and treated articular cartilage of sheep knee joints.*

non-injected joint of the same animal; the study confirmed the safety, without any associated detrimental effects, on the joint tissues. Furthermore, it had positive microscopic findings as there was increase of the thickness of the articular hyaline cartilage layer with significant proliferation of chondrocytes including different mitosis stages (**Figures 1** and **2**, **Table 2**). Therefore, intra-articular injection of fat micrograft is an ideal minimally invasive choice for joint lubrication with high potential healing effects.

### **10. Our human trial**

After the successful encouraging results of our previous animal study, which demonstrates the potential healing power and regenerative effect of autologous fat micrograft with its stem cells and all other study reports of clinical trials and publication by using mesenchymal stromal/stem cells for management of osteoarthritis, which offer a great hope for the treatment of osteoarthritic joints, we decided to evaluate the efficacy of fresh non-processed autologous fat micrograft with its ADSCs for management of osteoarthritic joints as prospective interventional clinical trial, which was conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, after obtaining the ethical approval from the local research and ethics committee, No. 822-12, according to latest vision of the Declaration of Helsinki. Over the period of 2012–2013, a preliminary clinical trial was conducted on 10 adult patients of both genders suffering from severe to moderate knee osteoarthritis with encouraging results as an effective and safe method for the treatment of knee osteoarthritis, then we expand the trial on 80 adult patients which confirm our previous finding, and then the clinical trial concluded with the final reporting to ethical committee on December 2016 [2, 3, 6, 7, 66].

But our work in utilizing this modality of treatment continued, and we are currently presenting the outcome in 205 adult patients (392 knee joints) who were managed and completed the required period of follow-up [7, 60–75, 77, 78].

The other studies were mainly revolving around the use of bone marrow or expanded adipose tissues and non-expanded autologous MSCs although some trials use allogenic MSCs. Most researchers focus on the use of intra-articular injections without the use of scaffolds or major surgeries since injections are more cost-effective, have little morbidity, and are a desirable way of treatment. The satisfactory outcome of our study over 10 years indicated that MSC treatment appears to be a good option for treatment of moderate to severe OA in the elderly; other studies reported similar results to ours in demonstrating promising prospect of cell therapy in many refractory diseases, including bone and joint diseases, in great improvement of pain, mobility, and other joint functions; these have high potential for clinical use in tissue engineering and regenerative and reparative medicine. Other studies found MSCs effective in cartilage healing; these trials are summarized in **Table 3** [28, 70–73, 76].


### **Table 3.**

*The other human clinical studies.*

### **11. Study guidelines and patient selection**

• **Patients**: all patients were adult patients from both genders and were screened for eligibility to participate in the study; each patient underwent a complete medical history, a physical examination, and a full assessment of the joint.

**95**

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft...*

supine radiographs involving one or both knees.

rest and during activity was obtained.

side effect that may arise post-procedure.

ture, and noninvasive blood pressure.

**12. Anesthesia**

**13. Procedures**

and refusal of the patient to be included in the study.

• **Informed written consent** was obtained from each patient before treatment after explaining to him all about the study and this modality of treatment.

• **Exclusion criteria**: recent knee surgery, chronic opioid intake, bleeding disorders, malignant disease, congenital or traumatic deformity of the knee joint,

• **For the evaluation of patient**, we used **the visual analogue scale** for pain assessment (on scale 0–10 cm line, 0 = no pain and 10 = worst imaginable pain) was explained to patients during the preoperative visit; visual analogue scale at

• **The Western Ontario and McMaster Universities Osteoarthritis Index**

(WOMAC) is a questionnaire widely used to assess the symptoms and physical disability associated with osteoarthritis; we used five-point Likert-type Western Ontario and McMaster Universities Osteoarthritis Index to collect information regarding the three subscales of Western Ontario and McMaster Universities Osteoarthritis Index. Pain (five items): while sitting or lying, walking, using stairs, standing, and in bed. Stiffness (two items): after first walking and later in the day. Physical function (17 items): standing, walking, sitting, rising from sitting, stair use, bending, putting on or taking off socks, lying in bed, rising from bed, getting in or out of the bath, sitting on or rising from the toilet, getting in or out of a car, shopping, light household duties, and heavy household duties

• **Anesthesia and surgical interventions** were explained to the patients. A list of adverse effects was reviewed with the patients to allow for reporting of any

The procedures were performed under controlled local anesthesia and sedation. Dexmedetomidine 0.7 mcg/kg/hour was administered intravenously as a sedative and pain reliever. Patients were monitored for heart rate, pulse oximetry, tempera-

The surgical site of liposuction was carefully chosen based on the availability of fat and the patients' wishes. Liposuction was performed under complete aseptic technique and antibiotic coverage of cefuroxime 1.5 g IV one dose, 1 hour preoperative followed by 500 mg orally every 12 hours for 7 days. Fat harvesting was obtained using 10-hole, Olivaire blunt cannula (Pouret Medical, Clichy, France) with 1 mm tip attached to a 10 mL Luer-Lok syringe (Terumo, Auburn, WA, USA). Fifty milliliters of fat micrograft was collected and then left for thirty minutes to settle and separate into various layers; the upper and lower layers were removed, while the middle layer of fat was kept for intra-articular injection (**Figure 1**).

• **Inclusion criteria**: all cases of severe to moderate knee osteoarthritis, the changes to be confirmed by bilateral anterior-posterior standing and lateral

*DOI: http://dx.doi.org/10.5772/intechopen.88220*

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft... DOI: http://dx.doi.org/10.5772/intechopen.88220*


### **12. Anesthesia**

*Tibia Pathology and Fractures*

**Human clinical studies**

Wakitani et al. [70] BMC

Buda et al. [73] BMC

Koh et al. [77] ADSCs

Koh et al. [78] ADSCs

**94**

the joint.

*The other human clinical studies.*

Moshref 2019 (under consideration)

**Table 3.**

**11. Study guidelines and patient selection**

• **Patients**: all patients were adult patients from both genders and were

ADSCs Intra-articular injection of

**Publication Type of MSCs Description Intervention Outcome**

patients

control

females)

BMSCs intra-articularly of four

MSC embedded in collagen gel injected into medial femoral condyle of 12 patients and 12 as

prosthesis and injected in the threesevere arthritic ankle for patients

for 46-A case report study year

MSC and hyaluronic acid for 20 patients (12 males and eight

calcium chloride, a nanogram dose of dexamethasone, and platelet-rich plasma injected intra-articularly for knee osteoarthritis or hip osteonecrosis

Autologous AMSCs from infrapatellar fat pad injected at intraarticular injection for 25 patients

AMSCs autologous injection intra-articular of 18 patients

autologous fat micrograft for the treatment of knee osteoarthritis Preliminary trail of 10 patients

autologous fat micrograft for the treatment of knee osteoarthritis. 80 patients and 148 joints

autologous fat micrograft for the treatment of knee osteoarthritis. 205 patients and 392 joints

Minimally invasive

Invasive with risk of infection

Invasive with risk of infection

Minimally invasive

Minimally invasive

Minimally invasive

Minimally invasive

Minimally invasive

Minimally invasive

Minimally invasive

Minimally invasive

Marked improvement

Marked improvement

Marked improvement

Marked improvement

Marked improvement

Marked clinical improvement and cartilage thickening

Significant regeneration of cartilage

Marked improvement

Significant clinical improvement

Significant clinical improvement

Significant clinical improvement

Davatchi et al. [76] BMC MSCs injected with autologous

Ohgushi et al. [71] BMC MSC seeded at ceramic ankle

Centeno et al. [72] BMC MSCs injected intra-articularly

Pak et al. [74, 75] ADSCs MSC and hyaluronic acid,

Infrapatellar fat pad

Infrapatellar fat pad

Moshref et al. [7] ADSCs Intra-articular injection of

Moshref et al. [66] ADSCs Intra-articular injection of

Human autologous culture expanded

Human autologous culture expanded

screened for eligibility to participate in the study; each patient underwent a complete medical history, a physical examination, and a full assessment of

The procedures were performed under controlled local anesthesia and sedation. Dexmedetomidine 0.7 mcg/kg/hour was administered intravenously as a sedative and pain reliever. Patients were monitored for heart rate, pulse oximetry, temperature, and noninvasive blood pressure.

### **13. Procedures**

The surgical site of liposuction was carefully chosen based on the availability of fat and the patients' wishes. Liposuction was performed under complete aseptic technique and antibiotic coverage of cefuroxime 1.5 g IV one dose, 1 hour preoperative followed by 500 mg orally every 12 hours for 7 days. Fat harvesting was obtained using 10-hole, Olivaire blunt cannula (Pouret Medical, Clichy, France) with 1 mm tip attached to a 10 mL Luer-Lok syringe (Terumo, Auburn, WA, USA). Fifty milliliters of fat micrograft was collected and then left for thirty minutes to settle and separate into various layers; the upper and lower layers were removed, while the middle layer of fat was kept for intra-articular injection (**Figure 1**).

The surgical site was prepared and injected with 100–200 mL of tumescent solution. Solution was prepared by mixing 30–50 mL of 1% lidocaine and 0.5 mg (0.5 mL) of epinephrine in 449.5 mL of lactated ringers. The osteoarthritic knee joint was injected with autologous intra-articular fat micrograft 15–20 mL through the lateral approach according to the case in an amount that did not produce high pressure inside the joint and did not produce pain to the patients due to tension of the joint capsule.

### **14. Postoperative advice and care**


### **15. Statistical analysis**

IBM SPSS Statistics for Windows, Version 20 (IBM Corp., Armonk, NY USA), was used for data analysis. Data were presented as mean ± SD and minimummaximum or number and percentage (*n*, %) as appropriate. Wilcoxon test for nonparametric variables was used to compare preinjection to postinjection values. A probability of ≤0.05 was considered significant.

### **16. The current study outcome of 205 patients**

In this current study, we used the same methodology and patient's selection that we applied in the preliminary trial and in the main study of 80 patients indicated in the requested ethical approval, but in this chapter, we are presenting our experience in the management of 205 patients.

**Table 4** showed the demographic data and the clinical characteristics of the patients. The median age of the patients was 61.59 years, and the body mass index was 35.10 kg/m2 . The female patients were more than male (74.10% versus 25.90%) with a ratio of 2.88:1. Only five patients (2.90%) were smoking. The associated comorbidities were obesity (74.60%), hypertension (34.60%), *diabetes mellitus* (21.50%), hypothyroidism (6.80%), rheumatoid arthritis (4.90%), low back pain (4.90%), hepatitis (2.00%), and lower limb edema (1.50%).

**97**

**Table 5.**

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft...*

**Parameters Data Age** (years) 61.59 ± 10.32 (33–92) **Weight** (kg) 87.25 ± 16.89 (48–164) **Height** (meter) 1.56 ± 0.10 (1.14–1.86)

Male 53 (25.90%) Female 152 (74.10%) **Smoking** 5 (2.90%)

Obesity 153 (74.60%) Hypertension 71 (34.60%) Type 2 *diabetes mellitus* 44 (21.50%) Hypothyroidism 14 (6.80%) Rheumatoid arthritis 10 (4.90%) Low back pain 10 (4.90%) Lower limb edema 3 (1.50%) Hepatitis 4 (2.00%)

*Data are expressed as mean ± SD (minimum-maximum) or number (%) as appropriate.*

**Parameters Data**

**Disease duration** (years) 8.00 ± 5.98 (1.00–33.00)

Right knee 13 (6.30%) Left knee 5 (2.40%) Bilateral knees 187 (91.20%)

Nonsteroidal anti-inflammatory 204 (99.50%) Glucosamine 18 (8.80%) Prednisone 10 (4.90%) Methotrexate 7 (3.40%) Relaxon 9 (4.40%)

Single injection 199 (97.10%) Two injections 5 (2.40%) Three injections 1 (0.50%)

*Data are expressed as mean ± SD (minimum-maximum) or number (%) as appropriate.*

*Disease duration and treatment of patients (*n *= 205).*

*Demographic and clinical characteristics of patients (*n *= 205).*

) 35.10 ± 5.77 (22.00–50.60)

*DOI: http://dx.doi.org/10.5772/intechopen.88220*

**Body mass index** (kg/m2

**Gender**

**Comorbidity**

**Table 4.**

**Knee affected**

**Medications**

**Fat injection**

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft... DOI: http://dx.doi.org/10.5772/intechopen.88220*


### **Table 4.**

*Tibia Pathology and Fractures*

**14. Postoperative advice and care**

recurrence of pain.

**15. Statistical analysis**

possible and increase activity as tolerated.

predisposing risk and comorbid factors.

A probability of ≤0.05 was considered significant.

**16. The current study outcome of 205 patients**

(4.90%), hepatitis (2.00%), and lower limb edema (1.50%).

in the management of 205 patients.

The surgical site was prepared and injected with 100–200 mL of tumescent solution. Solution was prepared by mixing 30–50 mL of 1% lidocaine and 0.5 mg (0.5 mL) of epinephrine in 449.5 mL of lactated ringers. The osteoarthritic knee joint was injected with autologous intra-articular fat micrograft 15–20 mL through the lateral approach according to the case in an amount that did not produce high pressure inside the joint

• After operation, the patient received antibiotics at home for 1 week and on regular pain killer for 2 weeks and is to start walking immediately as early as

• Stress the preoperative advice to reduce weight, improve diet regimen, and perform regular exercise especially aqua or hydrotherapy therapy to strengthen muscle with consequently more improvement of outcome of the procedure.

• All patients were followed up in the clinic on a regular basis every 1–2 weeks in the first month and then every 3 months to assess incidence of side effects, complications, pain evaluation, stiffness and knee function problems, and

• The patient was informed that the improvement will start during the first month and increase with time, and the maximum appreciated improvement at 6 months, provided he will follow the given instructions and improve the

IBM SPSS Statistics for Windows, Version 20 (IBM Corp., Armonk, NY USA),

In this current study, we used the same methodology and patient's selection that we applied in the preliminary trial and in the main study of 80 patients indicated in the requested ethical approval, but in this chapter, we are presenting our experience

**Table 4** showed the demographic data and the clinical characteristics of the patients. The median age of the patients was 61.59 years, and the body mass index

with a ratio of 2.88:1. Only five patients (2.90%) were smoking. The associated comorbidities were obesity (74.60%), hypertension (34.60%), *diabetes mellitus* (21.50%), hypothyroidism (6.80%), rheumatoid arthritis (4.90%), low back pain

. The female patients were more than male (74.10% versus 25.90%)

was used for data analysis. Data were presented as mean ± SD and minimummaximum or number and percentage (*n*, %) as appropriate. Wilcoxon test for nonparametric variables was used to compare preinjection to postinjection values.

and did not produce pain to the patients due to tension of the joint capsule.

**96**

was 35.10 kg/m2

*Demographic and clinical characteristics of patients (*n *= 205).*


### **Table 5.**

*Disease duration and treatment of patients (*n *= 205).*

The duration of OA ranged from 1 to 33 years. The right knee was affected in 6.30% of patients and left knee in 2.40%, while both knees were affected in 91.20% of the cases. 99.50% of patients used NSAID, while glucosamine was used by 8.80%, prednisone by 4.90%, methotrexate by 3.40%, and relaxon by 4.40%. The number of fat injection was single in 97.10%, twice in 2.4%, or triple in 0.50% of cases (**Table 5**).

VAS values were significantly higher in preinjection versus postinjection both during rest (8.02 ± 1.81 versus 0.69 ± 0.64, *p* < 0.0001) and with activity (9.53 ± 0.88 versus 1.46 ± 0.80, *p* < 0.0001) which reflected a highly significant improvement in OA pain (**Table 6** and **Figure 3**).

**Table 7** presented the Western Ontario and McMaster Universities Osteoarthritis Index before and after intra-articular fat micrograft injection. The three domains of WOMAC index, pain, stiffness, and physical function, were significantly lower in the post intra-articular fat injection period than the preinjection values. The total score of WOMAC test and its percentage were significantly lower in the post intra-articular fat injection period than the preinjection values (77.65 ± 11.84 versus 5.69 ± 4.60, *p* < 0.0001; 80.89 ± 12.34 versus 5.93 ± 4.79, *p* < 0.0001) (**Table 7** and **Figures 4**–**7**).


### **Table 6.**

*Visual analogue scale values at rest and with activity before and after intra-articular fat micrograft injection.*

### **Figure 3.**

*Visual analogue scale values at rest and with activity before and after intra-articular fat micrograft injection.*


**99**

**Figure 4.**

*micrograft injection.*

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft...*

7. Stiffness occurring later in the day 2.04 ± 1.17 (0.00–4.00) 0.14 ± 0.35 (0.00–1.00) **0.0001**

8.Descending stairs 3.90 ± 0.34 (2.00–4.00) 0.93 ± 0.36 (0.00–2.00) **0.0001** 9.Ascending stairs 3.92 ± 0.32 (2.00–4.00) 0.94 ± 0.45 (0.00–4.00) **0.0001** 10. Rising from sitting 3.28 ± 0.76 (1.00–4.00) 0.20 ± 0.47 (0.00–4.00) **0.0001** 11. Standing 3.52 ± 0.69 (1.00–4.00) 0.47 ± 0.58 (0.00–4.00) **0.0001** 12. Bending to floor 3.09 ± 0.86 (0.00–4.00) 0.22 ± 0.43 (0.00–2.00) **0.0001** 13. Walking on flat surface 3.20 ± 0.75 (1.00–4.00) 0.21 ± 0.41 (0.00–1.00) **0.0001** 14. Getting in/out of car 3.40 ± 0.80 (1.00–4.00) 0.64 ± 0.54 (0.00–2.00) **0.0001** 15. Going shopping 3.87 ± 0.41 (2.00–4.00) 1.02 ± 0.52 (0.00–2.00) **0.0001** 16. Putting on socks 2.62 ± 0.84 (0.00–4.00) 0.22 ± 0.41 (0.00–1.00) **0.0001** 17. Lying in bed 2.80 ± 0.91 (0.00–4.00) 0.12 ± 0.32 (0.00–1.00) **0.0001** 18. Taking off socks 2.16 ± 0.86 (0.00–4.00) 0.05 ± 0.22 (0.00–1.00) **0.0001** 19. Rising from bed 2.86 ± 0.86 (0.00–4.00) 0.14 ± 0.34 (0.00–1.00) **0.0001** 20. Getting in/out of bath 3.84 ± 0.60 (0.00–4.00) 1.17 ± 0.60 (0.00–2.00) **0.0001** 21. Sitting 2.95 ± 0.78 (0.00–4.00) 0.14 ± 0.40 (0.00–3.00) **0.0001** 22. Getting on/off toilet 2.65 ± 0.79 (1.00–4.00) 0.14 ± 0.36 (0.00–2.00) **0.0001** 23. Heavy domestic duties 3.91 ± 0.40 (1.00–4.00) 1.15 ± 0.53 (0.00–4.00) **0.0001** 24. Light domestic duties 2.35 ± 0.76 (0.00–4.00) 0.04 ± 0.22 (0.00–2.00) **0.0001**

(32.00–96.00)

(33.33–100.00)

*The activities in each category are rated according to the following scale of difficulty: 0 = none; 1 = slight; 2 = moderate; 3 = very; 4 = extremely. Data are expressed as mean ± SD (minimum-maximum). Wilcoxon test for nonparametric* 

*The Western Ontario and McMaster Universities Osteoarthritis Index before and after intra-articular fat* 

*The Western Ontario and McMaster Universities Osteoarthritis Index Pain before and after intra-articular fat* 

**Preinjection Postinjection Significance** 

5.69 ± 4.60 (0.00–24.00) **0.0001**

5.93 ± 4.79 (0.00–25.25) **0.0001**

**(***P***-value)**

*DOI: http://dx.doi.org/10.5772/intechopen.88220*

**Western Ontario and McMaster Universities Osteoarthritis Index**

**Physical function**

**Total score**

**Table 7.**

*micrograft injection.*

Out of 96 77.65 ± 11.84

Percentage (%) 80.89 ± 12.34

*variables was used to compare pre- to postinjection values.*


*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft... DOI: http://dx.doi.org/10.5772/intechopen.88220*

*The activities in each category are rated according to the following scale of difficulty: 0 = none; 1 = slight; 2 = moderate; 3 = very; 4 = extremely. Data are expressed as mean ± SD (minimum-maximum). Wilcoxon test for nonparametric variables was used to compare pre- to postinjection values.*

### **Table 7.**

*Tibia Pathology and Fractures*

**Visual analogue** 

**scale**

**Table 6.**

**Figure 3.**

**Pain**

**Stiffness**

**Western Ontario and McMaster Universities Osteoarthritis Index**

improvement in OA pain (**Table 6** and **Figure 3**).

The duration of OA ranged from 1 to 33 years. The right knee was affected in 6.30% of patients and left knee in 2.40%, while both knees were affected in 91.20% of the cases. 99.50% of patients used NSAID, while glucosamine was used by 8.80%, prednisone by 4.90%, methotrexate by 3.40%, and relaxon by 4.40%. The number of fat injection was single in 97.10%, twice in 2.4%, or triple in 0.50% of cases (**Table 5**). VAS values were significantly higher in preinjection versus postinjection both during rest (8.02 ± 1.81 versus 0.69 ± 0.64, *p* < 0.0001) and with activity (9.53 ± 0.88 versus 1.46 ± 0.80, *p* < 0.0001) which reflected a highly significant

**Table 7** presented the Western Ontario and McMaster Universities Osteoarthritis Index before and after intra-articular fat micrograft injection. The three domains of WOMAC index, pain, stiffness, and physical function, were significantly lower in the post intra-articular fat injection period than the preinjection values. The total score of WOMAC test and its percentage were significantly lower in the post intra-articular fat injection period than the preinjection values (77.65 ± 11.84 versus 5.69 ± 4.60, *p* < 0.0001; 80.89 ± 12.34 versus 5.93 ± 4.79, *p* < 0.0001) (**Table 7** and **Figures 4**–**7**).

Rest 8.02 ± 1.81 (2.00–10.00) 0.69 ± 0.64 (0.00–4.00) **0.0001** Exercise 9.53 ± 0.88 (6.00–10.00) 1.46 ± 0.80 (0.00–5.00) **0.0001**

*Visual analogue scale values at rest and with activity before and after intra-articular fat micrograft injection.*

*Visual analogue scale values at rest and with activity before and after intra-articular fat micrograft injection.*

1.Walking 3.85 ± 0.401 (2.00–4.00) 0.65 ± 0.52 (0.00–2.00) **0.0001** 2.Stair climbing 3.95 ± 0.24 (2.00–4.00) 0.98 ± 0.40 (0.00–2.00) **0.0001** 3.Nocturnal 3.36 ± 0.76 (0.00–4.00) 0.25 ± 0.50 (0.00–4.00) **0.0001** 4.Rest 3.15 ± 0.79 (0.00–4.00) 0.11 ± 0.32 (0.00–1.00) **0.0001** 5.Weight-bearing 3.94 ± 0.29 (2.00–5.00) 0.96 ± 0.45 (0.00–2.00) **0.0001**

6.Morning stiffness 3.103 ± 0.89 (0.00–4.00) 0.20 ± 0.40 (0.00–1.00) **0.0001**

**Preinjection Postinjection Significance** 

**Preinjection Postinjection Significance** 

**(***P***-value)**

**(***P***-value)**

**98**

*The Western Ontario and McMaster Universities Osteoarthritis Index before and after intra-articular fat micrograft injection.*

### **Figure 4.**

*The Western Ontario and McMaster Universities Osteoarthritis Index Pain before and after intra-articular fat micrograft injection.*

### **Figure 5.**

*The Western Ontario and McMaster Universities Osteoarthritis Index Stiffness before and after intra-articular fat micrograft injection.*

*The Western Ontario and McMaster Universities Osteoarthritis Index Physical activity before and after intraarticular fat micrograft injection.*

### **Figure 7.**

*The Western Ontario and McMaster Universities Osteoarthritis Index Total Score before and after intraarticular fat micrograft injection.*

**101**

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft...*

Wilcoxon test for nonparametric variables was used to compare pre- to postin-

We did have complication like infection or graft rejection; it was well tolerated

Over 10 years our clinical study of treatment of chronic osteoarthritis using intra-articular injection of autologous fat micrograft offers an effective and safe treatment as a nonantigenic, lubricating, regenerative, and reparative modality which helps to restore the damaged cartilages and in turn improve joint pain, mobility, and other functions of the osteoarthritic joints; it is minimally invasive, without scars, and with lower cost than other lines of therapy, improves the quality of life, and is mostly effective with single injection, but reinjection is needed in some patients according to disease severity and chronicity. We found a selection of patients and preoperative correction of risk factors, e.g., obesity muscle weakness

The authors did not receive any type of commercial support either in forms of compensation or financial support for this study. The authors have no financial interest in any of the products or devices or drugs mentioned in this article.

The study design was reviewed and approved by the Unit of Biomedical Ethics

*DOI: http://dx.doi.org/10.5772/intechopen.88220*

led to better outcome of the procedure.

The authors have no conflict of interest.

Research Committee at King Abdulaziz University.

**Conflict of interest**

**Disclosure**

**Ethical approval**

jection values.

**17. Complications**

**18. Conclusion**

because it is autologous.

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft... DOI: http://dx.doi.org/10.5772/intechopen.88220*

Wilcoxon test for nonparametric variables was used to compare pre- to postinjection values.

### **17. Complications**

*Tibia Pathology and Fractures*

**Figure 5.**

**Figure 6.**

*articular fat micrograft injection.*

*fat micrograft injection.*

*The Western Ontario and McMaster Universities Osteoarthritis Index Stiffness before and after intra-articular* 

*The Western Ontario and McMaster Universities Osteoarthritis Index Physical activity before and after intra-*

*The Western Ontario and McMaster Universities Osteoarthritis Index Total Score before and after intra-*

**100**

**Figure 7.**

*articular fat micrograft injection.*

We did have complication like infection or graft rejection; it was well tolerated because it is autologous.

### **18. Conclusion**

Over 10 years our clinical study of treatment of chronic osteoarthritis using intra-articular injection of autologous fat micrograft offers an effective and safe treatment as a nonantigenic, lubricating, regenerative, and reparative modality which helps to restore the damaged cartilages and in turn improve joint pain, mobility, and other functions of the osteoarthritic joints; it is minimally invasive, without scars, and with lower cost than other lines of therapy, improves the quality of life, and is mostly effective with single injection, but reinjection is needed in some patients according to disease severity and chronicity. We found a selection of patients and preoperative correction of risk factors, e.g., obesity muscle weakness led to better outcome of the procedure.

### **Conflict of interest**

The authors have no conflict of interest.

### **Disclosure**

The authors did not receive any type of commercial support either in forms of compensation or financial support for this study. The authors have no financial interest in any of the products or devices or drugs mentioned in this article.

### **Ethical approval**

The study design was reviewed and approved by the Unit of Biomedical Ethics Research Committee at King Abdulaziz University.

*Tibia Pathology and Fractures*

### **Author details**

Sabah S. Moshref1 \*, Yasir S. Jamal1 , Amro M. Al-Hibshi2 and Abdullah M. Kaki3

1 Department of Surgery, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia

2 Department of Orthopedics, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia

3 Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia

\*Address all correspondence to: dr.sabahmoshref@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**103**

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft...*

[9] The National Collaborating Centre for Chronic Conditions: Osteoarthritis. National clinical guideline for care and management in adults. Available from: www.nice.org.uk/nicemedia/pdf/

[10] Goldring SR, Goldring MB. Bone and cartilage in osteoarthritis: Is what's best for one good or bad for the other? Arthritis Research and Therapy.

Buckwalter J. Aging theories of primary osteoarthritis: From epidemiology to molecular biology. Rejuvenation

musculoskeletal disease characterized by aging. Frontiers in Physiology. 2011;**2**:108

[13] Gharbi M, Deberg M, Henrotin Y. Application for proteomic techniques in studying osteoarthritis: A review. Frontiers in Physiology. 2011;**2**:90

[14] Hunter DJ. Lower extremity osteoarthritis management needs a paradigm shift. British Journal of Sports

Medicine. 2011;**45**:283-288

10.1016/j.rdc.2012.11.002

[16] Schroeppel JP, Crist JD, Anderson HC, Wang J. Molecular regulation of articular chondrocyte function and its significance in osteoarthritis. Histology and Histopathology. 2011;**26**(3):377-394

[17] Chen FH, Tuan RS. Mesenchymal stem cells in arthritic diseases. Arthritis Research and Therapy. 2008;**10**(5):223

[15] Wilson DR, Mc Walter EJ, Johnston JD. The measurement of joint mechanics and their role in osteoarthritis genesis and progression. Rheumatic Diseases Clinics of North America. 2013;**39**(1):21-44. DOI:

[11] Aigner T, Rose J, Martin J,

[12] Mobasheri A. Applications of proteomics to osteoarthritis, a

Research. 2004;**7**:134-145

CG59NICEguideline.pdf

2011;**12**:143

*DOI: http://dx.doi.org/10.5772/intechopen.88220*

[1] Neuber G. Gustav Adolf Neuber (24 June 1850-13 April 1932) was a German surgeon born in Tondern (today-Tønder.

[2] Lexer E. Fettegewebe verpflanzung. In: Lexer E. Die freien Transplantation en. I Teil. Stuttgart: Enke; 1919.

[3] Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: Implications for cellbased therapies. Tissue Engineering. 2001;**7**:211-228

[4] Rigotti G, Marchi A, Galie M, Baroni G, Benati D, Krampera M, et al. Clinical treatment of radiotherapy tissue damage by lipoaspirate

2007;**119**:1409-1422

transplant: A healing process mediated by adipose-derived adult stem cells. Plastic and Reconstructive Surgery.

[5] Liu Y, Wu J, Zhu Y, Han J. Therapeutic application of mesenchymal stem cells in bone and joint diseases. Clinical and Experimental Medicine. 2014;**14**(1): 13-24. DOI: 10.1007/s10238-012-0218-1. Epub: 3 November 2012 (Review)

[6] Moshref S, Jamal Y, Hummdi L, Kaki A, Al-Hibshi A. Intra-articular injection of autologous fat micro graft in sheep hind knee joints. Life Science Journal. 2013;**10**(4):2115-2120. (ISSN: 1545-1003). Available from: http:// www.lifesciencesite.org. 281

[7] Moshref S, Kaki A, Al-Hibshi A, Jamal YS. Intra-articular injection of autologous fat micro-graft for the treatment of knee osteoarthritis: Preliminary experience. Life Science

Journal. 2014;**11**(2):55-60

Sciences. 2010;**1211**:37-50

[8] Sun HB. Mechanical loading, cartilage degradation, and arthritis. Annals of the New York Academy of

**References**

Wir Kieler)

pp. 264-547

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft... DOI: http://dx.doi.org/10.5772/intechopen.88220*

### **References**

*Tibia Pathology and Fractures*

**102**

**Author details**

Sabah S. Moshref1

Jeddah, Saudi Arabia

Hospital, Jeddah, Saudi Arabia

University Hospital, Jeddah, Saudi Arabia

provided the original work is properly cited.

\*Address all correspondence to: dr.sabahmoshref@gmail.com

\*, Yasir S. Jamal1

, Amro M. Al-Hibshi2

1 Department of Surgery, Faculty of Medicine, King Abdulaziz University Hospital,

3 Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

2 Department of Orthopedics, Faculty of Medicine, King Abdulaziz University

and Abdullah M. Kaki3

[1] Neuber G. Gustav Adolf Neuber (24 June 1850-13 April 1932) was a German surgeon born in Tondern (today-Tønder. Wir Kieler)

[2] Lexer E. Fettegewebe verpflanzung. In: Lexer E. Die freien Transplantation en. I Teil. Stuttgart: Enke; 1919. pp. 264-547

[3] Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: Implications for cellbased therapies. Tissue Engineering. 2001;**7**:211-228

[4] Rigotti G, Marchi A, Galie M, Baroni G, Benati D, Krampera M, et al. Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: A healing process mediated by adipose-derived adult stem cells. Plastic and Reconstructive Surgery. 2007;**119**:1409-1422

[5] Liu Y, Wu J, Zhu Y, Han J. Therapeutic application of mesenchymal stem cells in bone and joint diseases. Clinical and Experimental Medicine. 2014;**14**(1): 13-24. DOI: 10.1007/s10238-012-0218-1. Epub: 3 November 2012 (Review)

[6] Moshref S, Jamal Y, Hummdi L, Kaki A, Al-Hibshi A. Intra-articular injection of autologous fat micro graft in sheep hind knee joints. Life Science Journal. 2013;**10**(4):2115-2120. (ISSN: 1545-1003). Available from: http:// www.lifesciencesite.org. 281

[7] Moshref S, Kaki A, Al-Hibshi A, Jamal YS. Intra-articular injection of autologous fat micro-graft for the treatment of knee osteoarthritis: Preliminary experience. Life Science Journal. 2014;**11**(2):55-60

[8] Sun HB. Mechanical loading, cartilage degradation, and arthritis. Annals of the New York Academy of Sciences. 2010;**1211**:37-50

[9] The National Collaborating Centre for Chronic Conditions: Osteoarthritis. National clinical guideline for care and management in adults. Available from: www.nice.org.uk/nicemedia/pdf/ CG59NICEguideline.pdf

[10] Goldring SR, Goldring MB. Bone and cartilage in osteoarthritis: Is what's best for one good or bad for the other? Arthritis Research and Therapy. 2011;**12**:143

[11] Aigner T, Rose J, Martin J, Buckwalter J. Aging theories of primary osteoarthritis: From epidemiology to molecular biology. Rejuvenation Research. 2004;**7**:134-145

[12] Mobasheri A. Applications of proteomics to osteoarthritis, a musculoskeletal disease characterized by aging. Frontiers in Physiology. 2011;**2**:108

[13] Gharbi M, Deberg M, Henrotin Y. Application for proteomic techniques in studying osteoarthritis: A review. Frontiers in Physiology. 2011;**2**:90

[14] Hunter DJ. Lower extremity osteoarthritis management needs a paradigm shift. British Journal of Sports Medicine. 2011;**45**:283-288

[15] Wilson DR, Mc Walter EJ, Johnston JD. The measurement of joint mechanics and their role in osteoarthritis genesis and progression. Rheumatic Diseases Clinics of North America. 2013;**39**(1):21-44. DOI: 10.1016/j.rdc.2012.11.002

[16] Schroeppel JP, Crist JD, Anderson HC, Wang J. Molecular regulation of articular chondrocyte function and its significance in osteoarthritis. Histology and Histopathology. 2011;**26**(3):377-394

[17] Chen FH, Tuan RS. Mesenchymal stem cells in arthritic diseases. Arthritis Research and Therapy. 2008;**10**(5):223

[18] Pendleton A, Arden N, Dougados M, et al. EULAR recommendations for the management of knee osteoarthritis: Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Annals of the Rheumatic Diseases. 2000;**59**(12):936-944

[19] Hernández-Díaz S, García-Rodríguez LA. Epidemiologic assessment of the safety of conventional nonsteroidal anti-inflammatory drugs. The American Journal of Medicine. 2001;**110**(Suppl 3):20S-27S

[20] Flood J. The role of acetaminophen in the treatment of osteoarthritis. The American Journal of Managed Care. 2010;**16**(Suppl Management):S48-S54

[21] Hameed F, Ihm J. Injectable medications for osteoarthritis. PM and R: The Journal of Injury, Function, and Rehabilitation. 2012;**4**(5 Suppl):S75-S81

[22] Miller LE, Block JE. US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee osteoarthritis: Systematic review and meta-analysis of randomized, saline-controlled trials. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. 2013;**6**:57-63

[23] Rudzinski M. What Are Optimal Strategies in the Management of Osteoarthritis? Medscape Family Medicine. May 2001. Available at: http:// www.medscape.com/viewarticle/413591 [Accessed: February 2016]

[24] Spaková T, Rosocha J, Lacko M, Harvanová D, Gharaibeh A. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. American Journal of Physical Medicine & Rehabilitation. 2012;**91**(5):411-417

[25] Douleh D, Frank RM. Marrow stimulation: Microfracture, drilling, and abrasion. Operative Techniques in Sports Medicine. 2018;**26**(3):170-174

[26] Malchau H, Herberts P, Garellick G, Soderman P, Eisler T. Prognosis of total hip replacement: Update of results and risk-ratio analysis for revision and re-revision from the Swedish National Hip Arthoplasty Register 1979-2000. In: Scientific Exhibition. Presented at: 69th Annual Meeting of the American Academy of Orthopaedic Surgeons; 11-15 June 2002; Dallas, TX, USA

[27] Santaguida PL, Hawker GA, Hudak PL, et al. Patient characteristics affecting the prognosis of total hip and knee joint arthroplasty: A systematic review. Canadian Journal of Surgery. 2008;**51**(6):428-436

[28] Roberts S, Genever P, McCaskie A. Prospects of stem cell therapy in osteoarthritis. Regenerative Medicine. 2011;**6**(3):351-366. DOI: 10.2217/ RME.11.21

[29] Vinatier C, Bouffi C, Merceron C, Gordeladze J, Brondello JM, Jorgensen C, et al. Cartilage tissue engineering: Towards a biomaterial-assisted mesenchymal stem cell therapy. Current Stem Cell Research & Therapy. 2009;**4**(4):318-329

[30] Oh W, Kim DS, Yang YS, Lee JK. Immunological properties of umbilical cord blood-derived mesenchymal stromal cells. Cellular Immunology. 2008;**251**:116-123

[31] Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;**99**:3838-3843

[32] Ren G, Su J, Zhang L, Zhao X, Ling W, L'huillie A, et al. Species variation in the mechanisms of mesenchymall stem cell-mediated immunosuppression. Stem Cells. 2009;**27**:1954-1962

**105**

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft...*

human umbilical cord blood-derived mesenchymal stem cells in disease models. World Journal of Stem Cells.

[42] Rodriguez AM, Elabd C, Amri EZ, Aihaud G, Dani C. The human adipose tissue is a source of multipotent stem cells. Biochimie. 2005;**87**:125-128

membranes: A source of stem cells for tissue regeneration and repair? Placenta.

[44] Vishnubalaji R, Al-Nbaheen M, Kadalmani B, Aldahmash A, Ramesh T. Comparative investigation of the differentiation capability of bonemarrow-and adipose-derived

mesenchymal stem cells by qualitative and quantitative analysis. Cell and Tissue Research. 2012;**347**:419-427

[45] Guilak F, Awad HA, Fermor B, Leddy HA, Gimble JM. Adiposederived adult stem cells for cartilage tissue engineering. Biorheology.

[46] Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis and Rheumatism. 2003;**48**:3464-3474

[47] Guo X, Wang X, Zhang Y, Xia R, Hu M, Duan C. Repair of large articular cartilage defects with implants of autologous mesenchymal stem cells seeded into beta-tricalcium phosphate in a sheep model. Tissue Engineering.

[48] JHP H, Chen F, Thambyah A, Lee EH. Treatment of chondral lesions in advanced osteochondritis dissecans: a comparative study of the efficacy of chondrocytes, mesenchymal stem cells, periosteal graft, and

mosaicplasty (osteochondral autograft) in animal models. Journal of Pediatric

Orthopedics. 2004;**24**:427-433

[43] Ilancheran S, Moodley Y, Manuelpillai U. Human fetal

2010;**2**:34-38

2009;**30**:2-10

2004;**41**:389-399

2004;**10**:1818-1829

*DOI: http://dx.doi.org/10.5772/intechopen.88220*

[33] Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, et al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induced T-cell unresponsiveness. Blood.

[34] Salibian AA, Widgerow AD, Abrouk M, Evans GRD. Stem cells in plastic surgery: A review of current clinical and translational applications.

2013;**40**:666-675. Available from: http:// dx.doi.org/10.5999/aps.2013.40.6.666 [Accepted: 25 September 2013] pISSN:

[36] Caplan AI, Dennis JE. Mesenchymal

[37] Lodi D, Iannitti T, Palmieri B. Stem cells in clinical practice: Applications and warnings. Journal of Experimental & Clinical Cancer Research. 2011;**30**:9

[38] Caplan AI. Review: Mesenchymal stem cells: Cell-based reconstructive therapy in orthopedics. Tissue Engineering. 2005;**11**(7-8):1198-1211

[39] da Silva ML, Chagatelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. Journal of Cell Science.

[40] Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stem/ progenitor cells in human first-trimester fetal blood, liver, and bone marrow.

2006;**119**:2204-2213

Blood. 2001;**98**:2396-2402

[41] Kim JY, Jeon HB, Yang YS, Oh W, Chang JW. Application of

stem cells as trophic mediators. Journal of Cellular Biochemistry.

2006;**98**(5):1076-1084

Archives of Plastic Surgery.

2234-6163, eISSN: 2234-6171

[35] Walia B, Satija N, Tripathi RP, et al. Induced pluripotent stem cells: Fundamentals and applications of the reprogramming process and its ramifications on regenerative medicine. Stem Cell Reviews. 2012;**8**:100-115

2005;**105**:2214-2219

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft... DOI: http://dx.doi.org/10.5772/intechopen.88220*

[33] Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, et al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induced T-cell unresponsiveness. Blood. 2005;**105**:2214-2219

*Tibia Pathology and Fractures*

[19] Hernández-Díaz S, García-Rodríguez LA. Epidemiologic

2001;**110**(Suppl 3):20S-27S

[21] Hameed F, Ihm J. Injectable medications for osteoarthritis. PM and R: The Journal of Injury, Function, and Rehabilitation. 2012;**4**(5 Suppl):S75-S81

[22] Miller LE, Block JE. US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee osteoarthritis: Systematic review and meta-analysis of randomized, saline-controlled trials. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. 2013;**6**:57-63

[23] Rudzinski M. What Are Optimal Strategies in the Management of Osteoarthritis? Medscape Family Medicine. May 2001. Available at: http:// www.medscape.com/viewarticle/413591

[24] Spaková T, Rosocha J, Lacko M, Harvanová D, Gharaibeh A. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. American Journal of Physical Medicine & Rehabilitation. 2012;**91**(5):411-417

[25] Douleh D, Frank RM. Marrow stimulation: Microfracture, drilling, and abrasion. Operative Techniques in Sports Medicine. 2018;**26**(3):170-174

[Accessed: February 2016]

assessment of the safety of conventional nonsteroidal anti-inflammatory drugs. The American Journal of Medicine.

[20] Flood J. The role of acetaminophen in the treatment of osteoarthritis. The American Journal of Managed Care. 2010;**16**(Suppl Management):S48-S54

[18] Pendleton A, Arden N, Dougados M, et al. EULAR recommendations for the management of knee osteoarthritis: Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Annals of the Rheumatic Diseases. 2000;**59**(12):936-944

[26] Malchau H, Herberts P, Garellick G, Soderman P, Eisler T. Prognosis of total hip replacement: Update of results and risk-ratio analysis for revision and re-revision from the Swedish National Hip Arthoplasty Register 1979-2000. In: Scientific Exhibition. Presented at: 69th Annual Meeting of the American Academy of Orthopaedic Surgeons; 11-15 June 2002; Dallas, TX, USA

[27] Santaguida PL, Hawker GA, Hudak PL, et al. Patient characteristics affecting the prognosis of total hip and knee joint arthroplasty: A systematic review. Canadian Journal of Surgery.

[28] Roberts S, Genever P, McCaskie A. Prospects of stem cell therapy in osteoarthritis. Regenerative Medicine. 2011;**6**(3):351-366. DOI: 10.2217/

[29] Vinatier C, Bouffi C, Merceron C, Gordeladze J, Brondello JM, Jorgensen C, et al. Cartilage tissue engineering: Towards a biomaterial-assisted mesenchymal stem cell therapy.

Current Stem Cell Research & Therapy.

[30] Oh W, Kim DS, Yang YS, Lee JK. Immunological properties of umbilical cord blood-derived mesenchymal stromal cells. Cellular Immunology.

[31] Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood.

[32] Ren G, Su J, Zhang L, Zhao X, Ling W, L'huillie A, et al. Species variation in the mechanisms of mesenchymall stem cell-mediated immunosuppression. Stem Cells.

2008;**51**(6):428-436

RME.11.21

2009;**4**(4):318-329

2008;**251**:116-123

2002;**99**:3838-3843

2009;**27**:1954-1962

**104**

[34] Salibian AA, Widgerow AD, Abrouk M, Evans GRD. Stem cells in plastic surgery: A review of current clinical and translational applications. Archives of Plastic Surgery. 2013;**40**:666-675. Available from: http:// dx.doi.org/10.5999/aps.2013.40.6.666 [Accepted: 25 September 2013] pISSN: 2234-6163, eISSN: 2234-6171

[35] Walia B, Satija N, Tripathi RP, et al. Induced pluripotent stem cells: Fundamentals and applications of the reprogramming process and its ramifications on regenerative medicine. Stem Cell Reviews. 2012;**8**:100-115

[36] Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. Journal of Cellular Biochemistry. 2006;**98**(5):1076-1084

[37] Lodi D, Iannitti T, Palmieri B. Stem cells in clinical practice: Applications and warnings. Journal of Experimental & Clinical Cancer Research. 2011;**30**:9

[38] Caplan AI. Review: Mesenchymal stem cells: Cell-based reconstructive therapy in orthopedics. Tissue Engineering. 2005;**11**(7-8):1198-1211

[39] da Silva ML, Chagatelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. Journal of Cell Science. 2006;**119**:2204-2213

[40] Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stem/ progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 2001;**98**:2396-2402

[41] Kim JY, Jeon HB, Yang YS, Oh W, Chang JW. Application of human umbilical cord blood-derived mesenchymal stem cells in disease models. World Journal of Stem Cells. 2010;**2**:34-38

[42] Rodriguez AM, Elabd C, Amri EZ, Aihaud G, Dani C. The human adipose tissue is a source of multipotent stem cells. Biochimie. 2005;**87**:125-128

[43] Ilancheran S, Moodley Y, Manuelpillai U. Human fetal membranes: A source of stem cells for tissue regeneration and repair? Placenta. 2009;**30**:2-10

[44] Vishnubalaji R, Al-Nbaheen M, Kadalmani B, Aldahmash A, Ramesh T. Comparative investigation of the differentiation capability of bonemarrow-and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis. Cell and Tissue Research. 2012;**347**:419-427

[45] Guilak F, Awad HA, Fermor B, Leddy HA, Gimble JM. Adiposederived adult stem cells for cartilage tissue engineering. Biorheology. 2004;**41**:389-399

[46] Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis and Rheumatism. 2003;**48**:3464-3474

[47] Guo X, Wang X, Zhang Y, Xia R, Hu M, Duan C. Repair of large articular cartilage defects with implants of autologous mesenchymal stem cells seeded into beta-tricalcium phosphate in a sheep model. Tissue Engineering. 2004;**10**:1818-1829

[48] JHP H, Chen F, Thambyah A, Lee EH. Treatment of chondral lesions in advanced osteochondritis dissecans: a comparative study of the efficacy of chondrocytes, mesenchymal stem cells, periosteal graft, and mosaicplasty (osteochondral autograft) in animal models. Journal of Pediatric Orthopedics. 2004;**24**:427-433

[49] Liu Y, Shu XZ, Prestwich GD. Osteochondral defect repair with autologous bone marrow-derived mesenchymal stem cells in an injectable, in situ, cross-linked synthetic extracellular matrix. Tissue Engineering. 2006;**12**:3405-3416

[50] Kayakabe M, Tsutsumi S, Watanabe H, Kato Y, Takagishi K. Transplantation of autologous rabbit BM-derived mesenchymal stromal cells embedded in hyaluronic acid gel sponge into osteochondral defects of the knee. Cytotherapy. 2006;**8**:343-353

[51] Yan H, Yu C. Repair of full-thickness cartilage defects with cells of different origin in a rabbit model. Arthroscopy. 2007;**23**:178-187

[52] Lee KBL, Hui JHP, Song IC, Ardany L, Lee EH. Injectable mesenchymal stem cell therapy for large cartilage defects—A porcine model. Stem Cells. 2007;**25**:2964-2971

[53] Kuroda R, Ishida K, Matsumoto T, Akisue T, Fujioka H, Mizuno K. Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone marrow stromal cells. Osteoarthritis and Cartilage. 2007;**15**:226-231

[54] Black LL, Gaynor J, Adams C, Dhupa S, Sams AE, Taylor R, et al. Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs. Veterinary Therapeutics. 2008;**9**:192-200

[55] Black LL, Gaynor J, Gahring D, Adams C, Aron D, Harman S, et al. Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: A randomized, double-blinded, multicenter, controlled trial. Veterinary Therapeutics. 2007;**8**:272-284

[56] Noth U, Steinert AF, Tuan RS. Technology insight: Adult mesenchymal stem cells for osteoarthritis therapy: Delivery modes for mesenchymal stem cells. Nature Clinical Practice. Rheumatology. 2008;**4**:371-380

[57] Horie M, Sekiya I, Muneta T, Ichinose S, Matsumoto K, Saito H, et al. Intra-articular injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization of distant organs in rat massive meniscal defect. Stem Cells. 2009;**27**:878-887

[58] Mokbel AN, El Tookhy OS, Shamaa AA, Rashed LA, Sabry D, El Sayed AM. Homing and reparative effect of intra-articular injection of autologous mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskeletal skeletal Disorders. 2011;**12**:259

[59] Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, et al. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Research and Therapy. 2012;**14**:R31

[60] Ameye LG, Young MF. Animal models of osteoarthritis: Lessons learned while seeking the 'Holy Grail'. Current Opinion in Rheumatology. 2006;**18**:537-547

[61] Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, et al. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Research and Therapy. 2013;**15**:R22. DOI: 10.1186/ar4156

[62] van Lent PLEM, van den Berg WB. Mesenchymal stem cell therapy in osteoarthritis: Advanced tissue repair or intervention with smouldering synovial activation? Arthritis Research and Therapy. 2013;**15**:112

**107**

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft...*

Arthroscopy. 2013;**21**:1717-1729. DOI:

[70] Wakitani S, Imoto K, Yamamoto T,

Human autologous culture expanded bone marrow mesenchymal cell transplantation

10.1007/s00167-012-2329-3

Saito M, Murata N, Yoneda M.

for repair of cartilage defects in osteoarthritic knee. Osteoarthritis and

[71] Ohgushi H, Kotobuki N, Funaoka H, Machida H, Hirose M, Tanaka Y, et al. Tissue engineered ceramic artificial joint—Ex vivo osteogenic differentiation of patient mesenchymal cells on total ankle joints for treatment of osteoarthritis. Biomaterials.

[72] Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician.

[73] Buda R, Vannini F, Cavallo M, Grigolo B, Cenacchi A, Giannini S. Osteochondral lesions of the knee: A new one-step repair technique with bone-marrow-derived cells. The Journal of Bone and Joint Surgery American Volume.

[74] Pak J. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: A case series. Journal of Medical

[75] Koh YG, Choi YJ. Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. The

Cartilage. 2002;**10**:199-206

2005;**26**:4654-4661

2008;**11**:343-353

2010;**92**(Suppl 2):2-11

Case Reports. 2011;**5**:296

Knee. 2012;**19**(6):902-907

[76] Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B. Mesenchymal stem cell therapy for knee

*DOI: http://dx.doi.org/10.5772/intechopen.88220*

[63] Hou T, Xu J, Wu X, Xie Z, Luo F, Zhang Z, et al. Umbilical cord Wharton's Jelly: A new potential cell source of mesenchymal stromal cells for bone tissue engineering. Tissue Engineering. Part A. 2009;**15**:2325-2334

[64] Fan CG, Zhang Q J, Zhou JR. Therapeutic potentials of mesenchymal

stem cells derived from human umbilical cord. Stem Cell Reviews.

[65] Fong CY, Subramanian A,

Reviews. 2012;**8**:195-209

lifesciencesite.com

[67] Kon E, Filardo G, Roffi A,

Medicine. 2012;**5**(3, 243):236

Andriolo L, Marcacci M. New trends for knee cartilage regeneration: From cellfree scaffolds to mesenchymal stem cells. Current Reviews in Musculoskeletal

[68] Madry H, Grun UW, Knutsen G. Cartilage repair and joint preservation:

[69] Filardo G, Madry H, Jelic M, Roffi A, Cucchiarini M, Kon E. Mesenchymal stem cells for the treatment of cartilage lesions: From preclinical findings to clinical application in orthopaedics. Knee Surgery, Sports Traumatology,

Medical and surgical treatment options. Deutsches Arzteblatt International Impact Factor. 2011;**108**(40):669-677

Gauthaman K, Venugopal J, Biswas A, Ramakrishna S, et al. Human umbilical cord Wharton's Jelly stem cells undergo enhanced chondrogenic differentiation when grown on nanofibrous scaffolds and in a sequential two-stage culture medium environment. Stem Cell

[66] Moshref S, Jamal S, Al-Hibshi A, Kaki A. Intra-articular injection of autologous fat graft for the treatment of knee osteoarthritis. Life Science Journal. 2017;**14**(4):30-35. DOI: 10.7537/marslsj140417.05. ISSN: 1097-8135 (Print)/ISSN: 2372-613X (Online). Available from: http://www.

2011;**7**:195-207

*The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft... DOI: http://dx.doi.org/10.5772/intechopen.88220*

[63] Hou T, Xu J, Wu X, Xie Z, Luo F, Zhang Z, et al. Umbilical cord Wharton's Jelly: A new potential cell source of mesenchymal stromal cells for bone tissue engineering. Tissue Engineering. Part A. 2009;**15**:2325-2334

*Tibia Pathology and Fractures*

[49] Liu Y, Shu XZ, Prestwich GD. Osteochondral defect repair with autologous bone marrow-derived mesenchymal stem cells in an injectable, in situ, cross-linked synthetic extracellular matrix. Tissue Engineering. 2006;**12**:3405-3416

[56] Noth U, Steinert AF, Tuan RS. Technology insight: Adult mesenchymal stem cells for osteoarthritis therapy: Delivery modes for mesenchymal stem cells. Nature Clinical Practice. Rheumatology. 2008;**4**:371-380

[57] Horie M, Sekiya I, Muneta T, Ichinose S, Matsumoto K, Saito H, et al. Intra-articular injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization of distant organs in rat massive meniscal defect. Stem Cells. 2009;**27**:878-887

[58] Mokbel AN, El Tookhy OS, Shamaa AA, Rashed LA, Sabry D, El Sayed AM. Homing and reparative effect of intra-articular injection of autologous mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskeletal skeletal Disorders. 2011;**12**:259

[59] Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S,

[60] Ameye LG, Young MF. Animal models of osteoarthritis: Lessons learned while seeking the 'Holy Grail'. Current Opinion in Rheumatology.

[61] Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, et al. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Research and Therapy. 2013;**15**:R22.

[62] van Lent PLEM, van den Berg WB. Mesenchymal stem cell therapy in osteoarthritis: Advanced tissue repair or intervention with smouldering synovial activation? Arthritis Research and

2006;**18**:537-547

DOI: 10.1186/ar4156

Therapy. 2013;**15**:112

et al. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Research and Therapy. 2012;**14**:R31

[50] Kayakabe M, Tsutsumi S, Watanabe H, Kato Y, Takagishi K. Transplantation of autologous rabbit BM-derived mesenchymal stromal cells embedded in hyaluronic acid gel sponge into osteochondral defects of the knee.

Cytotherapy. 2006;**8**:343-353

[52] Lee KBL, Hui JHP, Song IC, Ardany L, Lee EH. Injectable

2007;**23**:178-187

[51] Yan H, Yu C. Repair of full-thickness cartilage defects with cells of different origin in a rabbit model. Arthroscopy.

mesenchymal stem cell therapy for large cartilage defects—A porcine model. Stem Cells. 2007;**25**:2964-2971

[53] Kuroda R, Ishida K, Matsumoto T, Akisue T, Fujioka H, Mizuno K. Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone marrow stromal cells. Osteoarthritis and

Cartilage. 2007;**15**:226-231

2008;**9**:192-200

[54] Black LL, Gaynor J, Adams C, Dhupa S, Sams AE, Taylor R, et al. Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs. Veterinary Therapeutics.

[55] Black LL, Gaynor J, Gahring D, Adams C, Aron D, Harman S, et al. Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: A randomized, double-blinded, multicenter, controlled trial. Veterinary

Therapeutics. 2007;**8**:272-284

**106**

[64] Fan CG, Zhang Q J, Zhou JR. Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord. Stem Cell Reviews. 2011;**7**:195-207

[65] Fong CY, Subramanian A, Gauthaman K, Venugopal J, Biswas A, Ramakrishna S, et al. Human umbilical cord Wharton's Jelly stem cells undergo enhanced chondrogenic differentiation when grown on nanofibrous scaffolds and in a sequential two-stage culture medium environment. Stem Cell Reviews. 2012;**8**:195-209

[66] Moshref S, Jamal S, Al-Hibshi A, Kaki A. Intra-articular injection of autologous fat graft for the treatment of knee osteoarthritis. Life Science Journal. 2017;**14**(4):30-35. DOI: 10.7537/marslsj140417.05. ISSN: 1097-8135 (Print)/ISSN: 2372-613X (Online). Available from: http://www. lifesciencesite.com

[67] Kon E, Filardo G, Roffi A, Andriolo L, Marcacci M. New trends for knee cartilage regeneration: From cellfree scaffolds to mesenchymal stem cells. Current Reviews in Musculoskeletal Medicine. 2012;**5**(3, 243):236

[68] Madry H, Grun UW, Knutsen G. Cartilage repair and joint preservation: Medical and surgical treatment options. Deutsches Arzteblatt International Impact Factor. 2011;**108**(40):669-677

[69] Filardo G, Madry H, Jelic M, Roffi A, Cucchiarini M, Kon E. Mesenchymal stem cells for the treatment of cartilage lesions: From preclinical findings to clinical application in orthopaedics. Knee Surgery, Sports Traumatology,

Arthroscopy. 2013;**21**:1717-1729. DOI: 10.1007/s00167-012-2329-3

[70] Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knee. Osteoarthritis and Cartilage. 2002;**10**:199-206

[71] Ohgushi H, Kotobuki N, Funaoka H, Machida H, Hirose M, Tanaka Y, et al. Tissue engineered ceramic artificial joint—Ex vivo osteogenic differentiation of patient mesenchymal cells on total ankle joints for treatment of osteoarthritis. Biomaterials. 2005;**26**:4654-4661

[72] Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008;**11**:343-353

[73] Buda R, Vannini F, Cavallo M, Grigolo B, Cenacchi A, Giannini S. Osteochondral lesions of the knee: A new one-step repair technique with bone-marrow-derived cells. The Journal of Bone and Joint Surgery American Volume. 2010;**92**(Suppl 2):2-11

[74] Pak J. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: A case series. Journal of Medical Case Reports. 2011;**5**:296

[75] Koh YG, Choi YJ. Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. The Knee. 2012;**19**(6):902-907

[76] Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B. Mesenchymal stem cell therapy for knee

### *Tibia Pathology and Fractures*

osteoarthritis. Preliminary report of four patients. International Journal of Rheumatic Diseases. 2011;**14**:211-215

[77] Koh YG, Jo SB, Kwon OR, Suh DS, Lee SW, Park SH, et al. Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy: The Journal of Arthroscopic and Related Surgery: Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2013;**29**(4):748-755

[78] Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE. Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surgery, Sports Traumatology, Arthroscopy. 2015;**23**(5):1308-1313

**109**

outcomes.

re-alignment of the knee.

**Chapter 6**

**Abstract**

protocol are paramount.

**1. Introduction**

High Tibial Osteotomy

*Tuna Pehlivanoglu, Kerem Yildirim and Tahsin Beyzadeoglu*

To address lower limb malalignment with concomitant medial compartment osteoarthritis, meniscal deficiency, focal chondral defects, and ligamentous instability, high tibia osteotomy (HTO) is a reliable treatment option. In order to achieve a good long-term outcome with HTO, a comprehensive history and physical examination, together with a meticulous patient selection and careful pre-operative planning, and selection of the appropriate fixation technique and rehabilitation

**Keywords:** medial compartment osteoarthritis, chondral defect, high tibial

osteotomy, medial opening wedge, lateral closing wedge, survival rates, complications

Cartilage degeneration of a particular compartment of the knee joint is usually the result of overloading of medial compartment which is associated with the malalignment of the lower extremity. In other words, cartilage degeneration is an inevitable result of lower extremity malalignment and it is associated with clinical symptoms including pain and gait difficulty. In addition to arthritis, rickets, Blount disease, or tibial plateau fractures are other reasons for lower limb deformity, but we will not further mention them here because they are irrelevant to this chapter. In order to prevent the progressive cartilage degeneration followed by amelioration of the symptoms, re-alignment osteotomies, which have the potential to unload the compartment while preserving the native joint, are generally applied. Considering the relative young age of these patients with unicompartmental arthrosis, in order to delay the arthroplasty, re-alignment osteotomies, while being technically challenging constitute the most important treatment modality by providing earlier return to high-level activities in contrast to arthroplasty. Osteotomies might also be applied with procedures including meniscal repairs, ligamentous reconstructions, or cartilage regenerating procedures, because of augmenting the success rates of these co-applied procedures. Indications for re-alignment osteotomies have been expanded recently as a result of high activity levels of the relatively older patients. Meanwhile, an optimization of the re-alignment osteotomies occurred as a result of the modified surgical instruments and techniques, leading to more reliable

In young and active patients, it is important to preserve the medial compartment of the knee and provide adequate cartilage coverage to prevent a premature arthritis and to delay the arthroplasty as much as possible [1]. High tibial osteotomy (HTO) for varus deformity is one of the most common types of osteotomies for the

## **Chapter 6** High Tibial Osteotomy

*Tuna Pehlivanoglu, Kerem Yildirim and Tahsin Beyzadeoglu*

### **Abstract**

*Tibia Pathology and Fractures*

Arthroscopy Association. 2013;**29**(4):748-755

2015;**23**(5):1308-1313

osteoarthritis. Preliminary report of four patients. International Journal of Rheumatic Diseases. 2011;**14**:211-215

[77] Koh YG, Jo SB, Kwon OR, Suh DS, Lee SW, Park SH, et al. Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy: The Journal of Arthroscopic and Related Surgery: Official Publication of the Arthroscopy Association of North America and the International

[78] Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE. Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surgery, Sports Traumatology, Arthroscopy.

**108**

To address lower limb malalignment with concomitant medial compartment osteoarthritis, meniscal deficiency, focal chondral defects, and ligamentous instability, high tibia osteotomy (HTO) is a reliable treatment option. In order to achieve a good long-term outcome with HTO, a comprehensive history and physical examination, together with a meticulous patient selection and careful pre-operative planning, and selection of the appropriate fixation technique and rehabilitation protocol are paramount.

**Keywords:** medial compartment osteoarthritis, chondral defect, high tibial osteotomy, medial opening wedge, lateral closing wedge, survival rates, complications

### **1. Introduction**

Cartilage degeneration of a particular compartment of the knee joint is usually the result of overloading of medial compartment which is associated with the malalignment of the lower extremity. In other words, cartilage degeneration is an inevitable result of lower extremity malalignment and it is associated with clinical symptoms including pain and gait difficulty. In addition to arthritis, rickets, Blount disease, or tibial plateau fractures are other reasons for lower limb deformity, but we will not further mention them here because they are irrelevant to this chapter. In order to prevent the progressive cartilage degeneration followed by amelioration of the symptoms, re-alignment osteotomies, which have the potential to unload the compartment while preserving the native joint, are generally applied. Considering the relative young age of these patients with unicompartmental arthrosis, in order to delay the arthroplasty, re-alignment osteotomies, while being technically challenging constitute the most important treatment modality by providing earlier return to high-level activities in contrast to arthroplasty. Osteotomies might also be applied with procedures including meniscal repairs, ligamentous reconstructions, or cartilage regenerating procedures, because of augmenting the success rates of these co-applied procedures. Indications for re-alignment osteotomies have been expanded recently as a result of high activity levels of the relatively older patients. Meanwhile, an optimization of the re-alignment osteotomies occurred as a result of the modified surgical instruments and techniques, leading to more reliable outcomes.

In young and active patients, it is important to preserve the medial compartment of the knee and provide adequate cartilage coverage to prevent a premature arthritis and to delay the arthroplasty as much as possible [1]. High tibial osteotomy (HTO) for varus deformity is one of the most common types of osteotomies for the re-alignment of the knee.

First HTO was performed by Jackson and Waugh in 1958, while they defined the technique as a ball and socket osteotomy inferior to anterior tibial tuberosity and at the middle third portion of the fibula [2]. Modifications of the original technique were reported with a success rate of 85% [3]. In 1965, Coventry reported his results regarding long-term outcomes, which was not very promising and made several publications in the following years [4]. The introduction of the blade plate for maintaining correction and allowing early motion was undertaken by Koshino. Opening wedge technique was later introduced by Hernigou and Debeyre with medial approach, where bone grafts and plates were used in order to have a stable fixation, while they recognized the importance of maintaining the sagittal slope while the coronal plane was being corrected [5, 6]. In the beginning of 1980, Maquet described the tibial dome osteotomy. The modern HTO is actually a variation of the Coventry osteotomy. HTO's high popularity between 1960 and 1980, showed a slow decline afterwards as a result of many reported good outcomes of total-unicondylar knee arthroplasty that changed the surgeons' preferences.

HTO is regaining popularity, especially in young and active patients with high expectations for physical activities and increased life expectancy, in order to preserve the native joint together with bone stock, cartilage covering and proprioception, which are compromised with unicompartmental knee arthroplasty, in addition to its allowance to relatively limited physical activities [1, 7, 8]. The currently used plates are providing very stable osteosynthesis by preserving the periosteal blood supply; while there are also new biomaterials and bone substitutes that prevent many complications related to iliac crest graft harvest [9–11]. Meanwhile, HTO became a more popular option for young and active patients as a result of the improvements regarding the surgical technique, fixation devices, and fewer complications accompanied with a meticulous patient selection [12–15].

HTO, as a re-alignment osteotomy is applied to transfer the medially deviated mechanical axis to lateral toward the midline of the knee to unload the medial compartment and delay the process of osteoarthritis (OA) [11, 13, 14]. The first aim of HTO is to eliminate or reduce pain, by translating loads to the contralateral (femorotibial) compartment as a result of the deformity correction; while some studies has reported that the regenerative process was beginning after the accomplishment of re-alignment [16–18].

### **2. Indications**

Careful pre-operative planning and strict indication criteria are paramount in order to have a successful outcome in the long term [1, 11].

Indications of HTO can be categorized as physical and radiological. Physical indications include: *an age between 40 and 70 years; a well-localized pain at the medial joint line; an arc of flexion more than 90° and, a lack of extension less than 10°; normal or correctable ligamentous status, while anterior cruciate ligament [ACL] or posterior cruciate ligament [PCL] insufficiency is not a contraindication; non-reducible deformity; and an active lifestyle* [7, 11]*.*

Physical contraindications comprise: *any inflammatory disease, obesity, smoking, history of meniscectomy in the contralateral compartment, osteoarthritis in the contralateral compartment, and a tibial subluxation more than 1 cm.*

Radiological indications include: *no contralateral femorotibial joint space narrowing or patellofemoral joint space narrowing, partial or complete joint space narrowing in one compartment, significant symptomatic chondral injury to the patellofemoral or lateral compartments, tricompartmental arthritis and extra-articular deformity more than 5°* [1, 14]. To accurately assess the lateral compartment MRI could be very helpful.

**111**

*High Tibial Osteotomy*

appropriately.

indicated [1, 8].

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

Controversial contraindications regarding the HTO procedure include: *age > 60; obese females; flexion less than 120°, flexion contracture > 5°, or fixed flexion deformity; patellofemoral arthritis; accompanying severe extra-articular deformity* [11, 14]*.* HTO was recently suggested to be included in joint preservation surgery, to unload a cartilage restoration site (autologous chondrocyte implantation [ACI], osteochondral autograft or allograft, microfracture), and to correct the sagittal slope in cruciate ligament insufficiency [1, 8, 17]. When HTO is performed before medial compartment, arthritis has become severe and subchondral bone has been

We would like to underline some important scenarios that should be meticulously assessed. Patients with anterior knee pain may get worse after the HTO procedure providing a coronal plane correction that can worsen their symptoms. Patients should be carefully explained, that the recovery from an HTO is time consuming and requiring commitment of the patient. Patients should be explained, that HTO procedure's post-operative rehabilitation protocol typically requires a period of protected weight-bearing followed by extensive lower limb muscular training. Patients should understand that an average of 6 months is needed to have a total recovery to a pain-free state of full activity. It is also very important that, pre-operatively, patient expectations should be thoroughly discussed and managed

Indications of HTO might differ according to the geographical region. Patients older than 60 of age are typically offered total or unicompartmental knee arthroplasty over an HTO in the United States, while outside the United States, HTO is frequently performed in older patients, who are fit and active, and are explained

It should be noted that the ideal patient for the application of HTO is a relatively

A large-scale population-based study looking at 2671 patients who had undergone an HTO before conversion to a TKA found that certain factors lowered HTO survival rates, including accompanied ligament injuries, prior meniscectomy, older age, and female sex were reported to lower the HTO survival rates in 2761 patients, who

A thorough history and physical exam are paramount before proceeding with HTO. As a result of that, patients with a prior traumatic knee injury and patients with a new onset of medial compartment arthritis could be distinguished. Previous trauma may be associated with other concomitant ligamentous and cartilaginous injuries. In every patient, in order to meet the expectations, the levels of activity,

Physical exam starts with the observation of patient's gait and stance, especially to assess varus thrust, accompanied with the presence of lateral collateral ligament insufficiency. Patients with varus deformity at the knee joint can be identified by observing them standing and walking. However, in cases of large body habitus, observation alone might not be very reliable. Examination of gait is critical regarding the decision with HTO. In patients with varus deformity at the knee joint, medial compartment is overloaded which creates an increased knee adduction moment,

young, active, and non-smoking patient, for whom arthroplasty should be prevented or delayed. As described above, obesity was also reported as a contraindication in old patients, because of the increased stresses that the osteotomy site must support; while it is a relative indication in younger patients in whom arthroplasty is

underwent HTO before conversion to total knee arthroplasty [21].

exposed, superior clinical and outcomes can be achieved [19, 20].

that they may not obtain total symptom relief [1, 8].

**3. Patient history and physical exam**

and overall health should be precisely noted.

### *High Tibial Osteotomy DOI: http://dx.doi.org/10.5772/intechopen.92887*

*Tibia Pathology and Fractures*

of re-alignment [16–18].

**2. Indications**

First HTO was performed by Jackson and Waugh in 1958, while they defined the technique as a ball and socket osteotomy inferior to anterior tibial tuberosity and at the middle third portion of the fibula [2]. Modifications of the original technique were reported with a success rate of 85% [3]. In 1965, Coventry reported his results regarding long-term outcomes, which was not very promising and made several publications in the following years [4]. The introduction of the blade plate for maintaining correction and allowing early motion was undertaken by Koshino. Opening wedge technique was later introduced by Hernigou and Debeyre with medial approach, where bone grafts and plates were used in order to have a stable fixation, while they recognized the importance of maintaining the sagittal slope while the coronal plane was being corrected [5, 6]. In the beginning of 1980, Maquet described the tibial dome osteotomy. The modern HTO is actually a variation of the Coventry osteotomy. HTO's high popularity between 1960 and 1980, showed a slow decline afterwards as a result of many reported good outcomes of total-unicondylar

HTO is regaining popularity, especially in young and active patients with high expectations for physical activities and increased life expectancy, in order to preserve the native joint together with bone stock, cartilage covering and proprioception, which are compromised with unicompartmental knee arthroplasty, in addition to its allowance to relatively limited physical activities [1, 7, 8]. The currently used plates are providing very stable osteosynthesis by preserving the periosteal blood supply; while there are also new biomaterials and bone substitutes that prevent many complications related to iliac crest graft harvest [9–11]. Meanwhile, HTO became a more popular option for young and active patients as a result of the improvements regarding the surgical technique, fixation devices, and fewer complications accompanied with a meticulous patient selection [12–15]. HTO, as a re-alignment osteotomy is applied to transfer the medially deviated mechanical axis to lateral toward the midline of the knee to unload the medial compartment and delay the process of osteoarthritis (OA) [11, 13, 14]. The first aim of HTO is to eliminate or reduce pain, by translating loads to the contralateral (femorotibial) compartment as a result of the deformity correction; while some studies has reported that the regenerative process was beginning after the accomplishment

Careful pre-operative planning and strict indication criteria are paramount in

Indications of HTO can be categorized as physical and radiological. Physical indications include: *an age between 40 and 70 years; a well-localized pain at the medial joint line; an arc of flexion more than 90° and, a lack of extension less than 10°; normal or correctable ligamentous status, while anterior cruciate ligament [ACL] or posterior cruciate ligament [PCL] insufficiency is not a contraindication; non-reducible* 

Physical contraindications comprise: *any inflammatory disease, obesity, smoking, history of meniscectomy in the contralateral compartment, osteoarthritis in the contra-*

Radiological indications include: *no contralateral femorotibial joint space narrowing or patellofemoral joint space narrowing, partial or complete joint space narrowing in one compartment, significant symptomatic chondral injury to the patellofemoral or lateral compartments, tricompartmental arthritis and extra-articular deformity more than 5°* [1, 14]. To accurately assess the lateral compartment MRI could be very helpful.

order to have a successful outcome in the long term [1, 11].

*lateral compartment, and a tibial subluxation more than 1 cm.*

*deformity; and an active lifestyle* [7, 11]*.*

knee arthroplasty that changed the surgeons' preferences.

**110**

Controversial contraindications regarding the HTO procedure include: *age > 60; obese females; flexion less than 120°, flexion contracture > 5°, or fixed flexion deformity; patellofemoral arthritis; accompanying severe extra-articular deformity* [11, 14]*.*

HTO was recently suggested to be included in joint preservation surgery, to unload a cartilage restoration site (autologous chondrocyte implantation [ACI], osteochondral autograft or allograft, microfracture), and to correct the sagittal slope in cruciate ligament insufficiency [1, 8, 17]. When HTO is performed before medial compartment, arthritis has become severe and subchondral bone has been exposed, superior clinical and outcomes can be achieved [19, 20].

We would like to underline some important scenarios that should be meticulously assessed. Patients with anterior knee pain may get worse after the HTO procedure providing a coronal plane correction that can worsen their symptoms. Patients should be carefully explained, that the recovery from an HTO is time consuming and requiring commitment of the patient. Patients should be explained, that HTO procedure's post-operative rehabilitation protocol typically requires a period of protected weight-bearing followed by extensive lower limb muscular training. Patients should understand that an average of 6 months is needed to have a total recovery to a pain-free state of full activity. It is also very important that, pre-operatively, patient expectations should be thoroughly discussed and managed appropriately.

Indications of HTO might differ according to the geographical region. Patients older than 60 of age are typically offered total or unicompartmental knee arthroplasty over an HTO in the United States, while outside the United States, HTO is frequently performed in older patients, who are fit and active, and are explained that they may not obtain total symptom relief [1, 8].

It should be noted that the ideal patient for the application of HTO is a relatively young, active, and non-smoking patient, for whom arthroplasty should be prevented or delayed. As described above, obesity was also reported as a contraindication in old patients, because of the increased stresses that the osteotomy site must support; while it is a relative indication in younger patients in whom arthroplasty is indicated [1, 8].

A large-scale population-based study looking at 2671 patients who had undergone an HTO before conversion to a TKA found that certain factors lowered HTO survival rates, including accompanied ligament injuries, prior meniscectomy, older age, and female sex were reported to lower the HTO survival rates in 2761 patients, who underwent HTO before conversion to total knee arthroplasty [21].

### **3. Patient history and physical exam**

A thorough history and physical exam are paramount before proceeding with HTO. As a result of that, patients with a prior traumatic knee injury and patients with a new onset of medial compartment arthritis could be distinguished. Previous trauma may be associated with other concomitant ligamentous and cartilaginous injuries. In every patient, in order to meet the expectations, the levels of activity, and overall health should be precisely noted.

Physical exam starts with the observation of patient's gait and stance, especially to assess varus thrust, accompanied with the presence of lateral collateral ligament insufficiency. Patients with varus deformity at the knee joint can be identified by observing them standing and walking. However, in cases of large body habitus, observation alone might not be very reliable. Examination of gait is critical regarding the decision with HTO. In patients with varus deformity at the knee joint, medial compartment is overloaded which creates an increased knee adduction moment,

leading to increased stresses of the tensions of lateral ligamentous structures. In the presence of varus malalignment at knee joint, lateral ligamentous insufficiency may develop over time, and can even progress to varus recurvatum deformity associated with anterior cruciate ligament (ACL) insufficiency requiring ligament reconstruction in addition to HTO procedure [1, 11]. Joint instability including insufficiency of collateral and cruciate ligaments, any ankle deformity and limb length discrepancy should be considered for concomitant or staged surgery [22, 23].

### **4. Radiographic evaluation**

A complete radiographic evaluation comprises the following X-rays:


Indices regarding the pre-operative patellar height (Caton-Deschamps index, modified Insall-Salvati index, Blackburne-Peel index) should be calculated because both opening and closing wedge HTOs have had the potential to result in patella baja. Therefore, patients with pre-existing patella baja should be evaluated very carefully before performing the HTO procedure [24, 25].

To establish the posterior tibial slope baseline, a lateral radiograph should be obtained. Because of the anatomical-triangular shape of tibia, a medial opening wedge osteotomy comprises a bone cut from anteromedial to posterolateral aspect of the tibia. As the osteotomy site is opened, the tibial slope increases. For a lateral closing wedge osteotomy, the same principle can be used but in a reverse fashion. Considering this type of osteotomy, the bone cut is directed from anterolateral-to-posteromedial, decreasing the tibial slope [1, 23].

In knee joints with cruciate ligament deficiencies, tibial slope changes could directly affect the problem regarding the ligaments. Meanwhile, PCL insufficiency is accentuated by an increased tibial slope, while in an ACL-deficient knee as a result of the decreased tibial slope, the degree of instability is frequently progressed [1, 21, 24]. However, to improve the outcome of HTO procedure, tibial slope adjustments can be applied. To enhance stability in an ACL-deficient knee, tibial slope may be increased, whereas in PCL-deficient knees decreasing the slope can be helpful in establishing stability [1, 21, 24]. We recommend using magnetic resonance imaging (MRI) in order to evaluate the soft tissue problems, including meniscus tears, ligamentoıus injuries, osteochondral defects, or even for the detection of subchondral bone edema.

**113**

*High Tibial Osteotomy*

**5. Patient selection**

• Malalignment < 15°

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

• Metaphyseal varus (i.e., TBVA > 5°)

• No ligamentous instability

• Young (40–60 years of age)

• Some level of pain tolerance

• Tricompartmental OA

• Patellofemoral OA

• Knee ROM < 120°

• Heavy smokers

(>15 × 15 mm)

as the followings:

• Knee flexion contracture > 5°

• Diagnosis of inflammatory arthritis

• Ahlback grade 0 arthritis of medial plateau

• Age > 65

• Non-smoker

• Full range of motion (ROM) of the knee joint

• Moderately active high-demand patient

• Isolated medial joint line tenderness

In 2004, ISAKOS (International Society of Arthroscopy, Knee Surgery and Orthopedic Sports Medicine) developed a protocol for the HTO [23]. As a result of

that protocol, an ideal patient for HTO is defined by following criteria:

• Normal, near-normal lateral, and patellofemoral compartments

• BMI < 30 (in other words: obesity is a contraindication)

HTO is contraindicated in patients with followings:

• Severe OA of the medial compartment (Ahlback grade III or higher)

• large area of exposed bone on tibial and femoral articular surface

Good prognostic factors [26–28] regarding the HTO procedure can be summarized

### **5. Patient selection**

*Tibia Pathology and Fractures*

**4. Radiographic evaluation**

femorotibial compartment;

alignment;

(PFJ);

leading to increased stresses of the tensions of lateral ligamentous structures. In the presence of varus malalignment at knee joint, lateral ligamentous insufficiency may develop over time, and can even progress to varus recurvatum deformity associated with anterior cruciate ligament (ACL) insufficiency requiring ligament reconstruction in addition to HTO procedure [1, 11]. Joint instability including insufficiency of collateral and cruciate ligaments, any ankle deformity and limb length discrepancy

should be considered for concomitant or staged surgery [22, 23].

A complete radiographic evaluation comprises the following X-rays:

• A full-length, three-joint (bilateral hip to ankle on the same cassette) weightbearing view in full extension with the feet in a neutral position to evaluate the

• A 45° flexion posteroanterior view to evaluate any narrowing in the posterior

• A lateral view to measure patellar height and assess the patellofemoral joint

• Stress views are mandatory when physical exam reveals ligamentous laxity,

• A skyline view for detailed evaluation of the patellofemoral joint [1, 8, 11].

Indices regarding the pre-operative patellar height (Caton-Deschamps index, modified Insall-Salvati index, Blackburne-Peel index) should be calculated because both opening and closing wedge HTOs have had the potential to result in patella baja. Therefore, patients with pre-existing patella baja should be evaluated very

To establish the posterior tibial slope baseline, a lateral radiograph should be obtained. Because of the anatomical-triangular shape of tibia, a medial opening wedge osteotomy comprises a bone cut from anteromedial to posterolateral aspect of the tibia. As the osteotomy site is opened, the tibial slope increases. For a lateral closing wedge osteotomy, the same principle can be used but in a reverse fashion. Considering this type of osteotomy, the bone cut is directed from

In knee joints with cruciate ligament deficiencies, tibial slope changes could directly affect the problem regarding the ligaments. Meanwhile, PCL insufficiency is accentuated by an increased tibial slope, while in an ACL-deficient knee as a result of the decreased tibial slope, the degree of instability is frequently progressed [1, 21, 24]. However, to improve the outcome of HTO procedure, tibial slope adjustments can be applied. To enhance stability in an ACL-deficient knee, tibial slope may be increased, whereas in PCL-deficient knees decreasing the slope can be helpful in establishing stability [1, 21, 24]. We recommend using magnetic resonance imaging (MRI) in order to evaluate the soft tissue problems, including meniscus tears, ligamentoıus injuries, osteochondral defects, or even for the detection of

• The tibia bone varus angle (TBVA) is measured on AP radiograph and

TBVA ˃ 5° is a good prognostic factor after osteotomy

carefully before performing the HTO procedure [24, 25].

anterolateral-to-posteromedial, decreasing the tibial slope [1, 23].

**112**

subchondral bone edema.

In 2004, ISAKOS (International Society of Arthroscopy, Knee Surgery and Orthopedic Sports Medicine) developed a protocol for the HTO [23]. As a result of that protocol, an ideal patient for HTO is defined by following criteria:


HTO is contraindicated in patients with followings:


Good prognostic factors [26–28] regarding the HTO procedure can be summarized as the followings:

• Ahlback grade 0 arthritis of medial plateau


Poor prognostic factors [26–28] regarding the HTO procedure can be summarized as the followings:


Cartilage defect at the medial tibial plateau was shown not to affect the clinical results of HTO procedure by Niemeyer et al. [14] in their study with minimum of 36-month follow-up of 69 patients after medial open wedge high tibial osteotomy (MOWHTO). They also concluded that partial thickness defect in lateral tibial plateau was well-tolerated.

### **6. Pre-operative decision-making and planning**

Before starting with the decision-making process, some important terms regarding the alignment of the lower extremities should be explained [29–32].


**115**

**Figure 1.**

*The main axes of the lower extremity. AC: mechanical axis of femur, BC: anatomical axis of femur,* 

*CD: anatomical and mechanical axis of tibia, and AD: weight-bearing axis.*

*High Tibial Osteotomy*

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

Normal values of the aforementioned axis are [29–32]:


*Tibia Pathology and Fractures*

rized as the followings:

• Age > 56 years

plateau was well-tolerated.

center of the knee.

center of ankle joint.

• **Mechanical axis:** 1–3° varus

• **Anatomical axis:** 5–7° valgus

• Smoking

• Obesity

• Pre-operative TBVA > 5°

• Post-operative obliquity of tibiofemoral joint line in a narrow range close to 0°

Poor prognostic factors [26–28] regarding the HTO procedure can be summa-

Cartilage defect at the medial tibial plateau was shown not to affect the clinical results of HTO procedure by Niemeyer et al. [14] in their study with minimum of 36-month follow-up of 69 patients after medial open wedge high tibial osteotomy (MOWHTO). They also concluded that partial thickness defect in lateral tibial

Before starting with the decision-making process, some important terms regarding the alignment of the lower extremities should be explained [29–32].

• **Mechanical axis:** A line drawn from the center of the femoral head to the

• **Anatomical axis:** A line drawn from the piriformis fossa to the center of the

• **Weight-bearing axis:** A line drawn from the center of the femoral head to the

• Anatomical valgus alignment of ≥8° at 5 weeks post-op

• Excellent pre-operative Knee Society Score (KSS)

• Valgus alignment of ≤5° at 5 weeks post-op

**6. Pre-operative decision-making and planning**

knee joint and a line through the long axis of the tibia.

Normal values of the aforementioned axis are [29–32]:

• 6° of valgus between the mechanical and anatomical axes

• Post-operative flexion < 120°

• Age < 50

**114**

### **Figure 1.**

*The main axes of the lower extremity. AC: mechanical axis of femur, BC: anatomical axis of femur, CD: anatomical and mechanical axis of tibia, and AD: weight-bearing axis.*


These measurements are performed on the alignment view (**Figure 1**). As a result of that, the type, location, and most importantly the amount of corrective osteotomy is ascertained. The pre-operative mechanical axis deviation and the degree of medial compartment arthrosis determine the amount of correction needed. Unicompartmental OA was reported to yield clinical symptoms, when the lower extremity alignment was a more than 10° of normal range [33].

If a decision to perform the HTO procedure is established, a medial opening wedge osteotomy or a lateral closing wedge osteotomy can be chosen purely based on the surgeon's decision.

Lateral closing wedge osteotomy, which allow for immediate weight-bearing, possess lower rates of non-union/mal-union, and is theoretically associated with lower risks of increasing the posterior sagittal slope and leading to patella baja was widely used by Coventry in 1960s [34, 35]. However, an exposure violating the anterior compartment of the leg, loss of the present bone stock together with a narrow window for modification once the bone wedge is removed, a possible concomitant fibular osteotomy, and risks associated with peroneal nerve exposure are the disadvantages associated with lateral closing wedge osteotomy.

Recently, as a result of advancements regarding low-contact profile-plated and fixation techniques, bone grafting options and most importantly regarding the technical advantages of the exposure and approach, medial opening wedge osteotomy has gained popularity [10, 13, 14]. By performing the HTO from the medial side and avoiding the lateral side, certain risks associated with the anterior compartment dissection, peroneal nerve exploration and fibular osteotomies can be avoided [8, 13, 14]. HTO procedure, performed as medial opening wedge osteotomy, facilitates correction and allow for fine-tuning in both the coronal and the sagittal planes. However, the risk to increase the sagittal slope and historically higher rates of non-union are the associated disadvantages of this approach [36].

### **7. Pre-operative planning of correction**

The degree of correction is established according to the location of the mechanical axis line through the knee joint [1, 8]. The reference point on the tibial plateau is set at 62.5% of its width as measured from the medial cortex for most cases of genu varum resulting from OA [1, 14, 32]. In order to unload the medial compartment, the mechanical axis is planned to pass lateral to the center of the knee, aiming the lateral compartment [1, 14, 32] (**Figure 2**). A careful pre-operative planning should be undertaken in order to avoid the overloading of the lateral compartment, especially in cases with mild degenerative changes within the lateral compartment [14, 21, 36]. In these cases, massive corrections, or subtle corrections with a concomitant cartilage transplant, the mechanical axis can be moved to the midline of the knee joint to prevent overloading of the lateral side [14, 21, 36].

HTO procedure aims to reach a slight valgus axis to prevent any recurring of genu varum deformity. 3–5° of valgus in the mechanical axis or 8–10° of valgus in the anatomical axis are considered as the primary goals regarding correction after surgery [1, 5, 16, 34]. There is a fine balance between over- and under-correction; while slight varus correction can lead to recurrence of previous deformity, whereas overcorrection and over-deviation of the axis to the lateral compartment

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*High Tibial Osteotomy*

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

can cause cartilage degeneration at the lateral compartment, leading to lateral

*Pre-operative planning for MOWHTO. (A) The white dashed line represents the weight-bearing axis, whereas the red circle represents the desired point where the weight-bearing axis is planned to pass post-operatively. (B) α, the correction angle, is the angle formed by the mechanical axes of femur and tibia that are aimed to be provided post-operatively. The osteotomy line (the red dashed line) is planned to be started about 4 cm distal to* 

when measured from the medial edge point of the medial tibial plateau [32, 37]. The point where WBL intersects the tibial plateau is called as the Fujisawa point [32, 37] (**Figure 3**). Fujisawa point is located slightly lateral to the lateral tibial spine and matches over the mechanical axis with 3–5° of valgus [32, 37]. A line is drawn from this point to the center of the ankle joint and another line from this point to the center of the ipsilateral femoral head is drawn to determine the amount of required correction [32, 37]. The angle measured between these two lines indicates the amount of required correction to re-align the knee joint [11, 32, 37]. The line for the osteotomy is drawn approximately 4 cm below the medial joint line toward the fibular head. This line has to be transferred to the apex of triangle that is created just during planning. The width of the triangle's base corresponds to the amount of correction that is required during a medial open wedge osteotomy [11, 13, 14].

The weight-bearing line (WBL) should pass from 62% of the tibial plateau width

The correction angle for lateral closing wedge osteotomies is calculated using a similar technique. Perpendicular to the axis of tibia and approximately 2 cm below

compartment OA [1, 5, 16, 34].

*the medial joint line, aiming the tip of the head of fibula.*

**Figure 2.**

*Tibia Pathology and Fractures*

on the surgeon's decision.

• Weight-bearing line passing through the lateral 30–40% of the tibial plateau

• 60% of the total body weight force passes through the medial compartment.

These measurements are performed on the alignment view (**Figure 1**). As a result of that, the type, location, and most importantly the amount of corrective osteotomy is ascertained. The pre-operative mechanical axis deviation and the degree of medial compartment arthrosis determine the amount of correction needed. Unicompartmental OA was reported to yield clinical symptoms, when the

If a decision to perform the HTO procedure is established, a medial opening wedge osteotomy or a lateral closing wedge osteotomy can be chosen purely based

Lateral closing wedge osteotomy, which allow for immediate weight-bearing, possess lower rates of non-union/mal-union, and is theoretically associated with lower risks of increasing the posterior sagittal slope and leading to patella baja was widely used by Coventry in 1960s [34, 35]. However, an exposure violating the anterior compartment of the leg, loss of the present bone stock together with a narrow window for modification once the bone wedge is removed, a possible concomitant fibular osteotomy, and risks associated with peroneal nerve exposure are the disad-

Recently, as a result of advancements regarding low-contact profile-plated and fixation techniques, bone grafting options and most importantly regarding the technical advantages of the exposure and approach, medial opening wedge osteotomy has gained popularity [10, 13, 14]. By performing the HTO from the medial side and avoiding the lateral side, certain risks associated with the anterior compartment dissection, peroneal nerve exploration and fibular osteotomies can be avoided [8, 13, 14]. HTO procedure, performed as medial opening wedge osteotomy, facilitates correction and allow for fine-tuning in both the coronal and the sagittal planes. However, the risk to increase the sagittal slope and historically higher rates of non-union are the associated disadvantages of this approach [36].

The degree of correction is established according to the location of the mechanical axis line through the knee joint [1, 8]. The reference point on the tibial plateau is set at 62.5% of its width as measured from the medial cortex for most cases of genu varum resulting from OA [1, 14, 32]. In order to unload the medial compartment, the mechanical axis is planned to pass lateral to the center of the knee, aiming the lateral compartment [1, 14, 32] (**Figure 2**). A careful pre-operative planning should be undertaken in order to avoid the overloading of the lateral compartment, especially in cases with mild degenerative changes within the lateral compartment [14, 21, 36]. In these cases, massive corrections, or subtle corrections with a concomitant cartilage transplant, the mechanical axis can be moved to the midline of

HTO procedure aims to reach a slight valgus axis to prevent any recurring of genu varum deformity. 3–5° of valgus in the mechanical axis or 8–10° of valgus in the anatomical axis are considered as the primary goals regarding correction after surgery [1, 5, 16, 34]. There is a fine balance between over- and under-correction;

while slight varus correction can lead to recurrence of previous deformity, whereas overcorrection and over-deviation of the axis to the lateral compartment

the knee joint to prevent overloading of the lateral side [14, 21, 36].

lower extremity alignment was a more than 10° of normal range [33].

vantages associated with lateral closing wedge osteotomy.

**7. Pre-operative planning of correction**

**116**

### **Figure 2.**

*Pre-operative planning for MOWHTO. (A) The white dashed line represents the weight-bearing axis, whereas the red circle represents the desired point where the weight-bearing axis is planned to pass post-operatively. (B) α, the correction angle, is the angle formed by the mechanical axes of femur and tibia that are aimed to be provided post-operatively. The osteotomy line (the red dashed line) is planned to be started about 4 cm distal to the medial joint line, aiming the tip of the head of fibula.*

can cause cartilage degeneration at the lateral compartment, leading to lateral compartment OA [1, 5, 16, 34].

The weight-bearing line (WBL) should pass from 62% of the tibial plateau width when measured from the medial edge point of the medial tibial plateau [32, 37]. The point where WBL intersects the tibial plateau is called as the Fujisawa point [32, 37] (**Figure 3**). Fujisawa point is located slightly lateral to the lateral tibial spine and matches over the mechanical axis with 3–5° of valgus [32, 37]. A line is drawn from this point to the center of the ankle joint and another line from this point to the center of the ipsilateral femoral head is drawn to determine the amount of required correction [32, 37]. The angle measured between these two lines indicates the amount of required correction to re-align the knee joint [11, 32, 37]. The line for the osteotomy is drawn approximately 4 cm below the medial joint line toward the fibular head. This line has to be transferred to the apex of triangle that is created just during planning. The width of the triangle's base corresponds to the amount of correction that is required during a medial open wedge osteotomy [11, 13, 14].

The correction angle for lateral closing wedge osteotomies is calculated using a similar technique. Perpendicular to the axis of tibia and approximately 2 cm below

**Figure 3.** *Picture defining Fujisawa point.*

the joint line the first osteotomy line is drawn. Applying the 1° to 1-mm equivalence at the lateral cortex below the initial osteotomy, the second osteotomy line is drawn. The wedge that has been bordered by the two osteotomy lines should be removed. By performing lateral closing wedge osteotomies, the sagittal slope must be assessed repeatedly to avoid significant slope perturbations [5, 8, 12].

### **8. Surgical technique**

We usually start with arthroscopy to perform the debridement of the lateral compartment and to manage the concomitant pathologies regarding the menisci and chondral tissues before starting with the HTO, as recommended [38]. For the correction of genu varum deformity and re-alignment of the lower extremity, medial opening wedge, lateral closing wedge, and dome osteotomy can safely be applied. Our preference is the medial opening wedge osteotomy.

**119**

sagittal),

• no bone loss,

• no limb shortening,

*High Tibial Osteotomy*

structures.

medial cortex.

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

In the middle of the line drawn from the tibial tubercule to medial border of tibia, a 3–5 cm longitudinal skin incision is made carefully by beginning 1–2 cm inferior to the medial joint line and continuing caudally to the pes anserinus. After dividing the sartorial fascia, we usually distract the tendons of pes anserinus distally, but an inverted L-shaped flap can also be elevated. After subperiosteal dissection and sufficient exposure of the proximal-medial tibia and the joint line, the superficial medial collateral ligament (sMCL) fibers are elevated from their medial tibial attachment sides; otherwise, if the attachment of sMCL is left intact on the medial tibia, pressures of the medial compartment may inevitably increase as a result of the tensioning of sMCL fibers during the distraction phase of the osteotomy [1, 8]. Proximal to the tibial tubercule, patellar tendon should be identified and protected from the possible damage that might be caused by the blade of the saw by placing a broad retractor anteriorly. It is of high importance to conduct careful subperiosteal dissections in order to protect and secure the posterior neurovascular

After the subperiosteal dissection and exposure of the entire proximal-medial

An oscillating saw is used to make the first cut of the osteotomy on the antero-

This cut is advanced with osteotomes until to a distance of 1–1.5 cm to the lateral cortex of the tibia, in order not to cause any fracture on the tibial plateau. In addition to that, it is also recommended, that the vertical distance from the tip of the osteotome to the lateral tibial plateau should be 1.25 times of the horizontal distance to the lateral tibial cortex, to minimize the risk of any fracture on the lateral tibial plateau. Hereby, the osteotomy is ended, followed by the opening of the osteotomized bone and very gentle and careful application of valgus force on the tibia. Osteotomy side is opened sequentially with calibrated wedges. As a result of that, a new mechanical axis has been reconstructed (**Figure 4**). The new mechanical axis is confirmed by either placing a cord of electrocautery or a long alignment rod from the center of the hip to the center of the ankle and confirming its distance from the knee joint under image intensifier. It was also suggested to add a concomitant tibial tuberosity osteotomy, if more than 12.5 mm correction is required, in order to avoid the potentially adverse effects of patella baja and increased pressure

The advantages of the medial open wedge osteotomy can be summarized as:

• the ability to provide biplanar correction and biplanar alignment (coronal and

portion of the tibia, a guide wire is inserted, starting proximal to the tibial tubercule and aiming toward the tip of the fibular head with an anteromedial to posterolateral trajectory. After the insertion of the first guide wire, it is optional to place another wire posteriorly to determine the osteotomy's sagittal angle that can influence the amount of the sagittal slope. If a reduction of the posterior tibial slope is desired, the posterior guide wire should be placed more superiorly resulting in a flatter cut. If a rise of the sagittal slope is desired, then the posterior guidewire

**8.1 Medial open wedge osteotomy**

should be placed more inferiorly.

in patellofemoral compartment [8, 39].

• no need for fibular osteotomy,

### **8.1 Medial open wedge osteotomy**

*Tibia Pathology and Fractures*

**118**

**Figure 3.**

**8. Surgical technique**

*Picture defining Fujisawa point.*

the joint line the first osteotomy line is drawn. Applying the 1° to 1-mm equivalence at the lateral cortex below the initial osteotomy, the second osteotomy line is drawn. The wedge that has been bordered by the two osteotomy lines should be removed. By performing lateral closing wedge osteotomies, the sagittal slope must be assessed

We usually start with arthroscopy to perform the debridement of the lateral compartment and to manage the concomitant pathologies regarding the menisci and chondral tissues before starting with the HTO, as recommended [38]. For the correction of genu varum deformity and re-alignment of the lower extremity, medial opening wedge, lateral closing wedge, and dome osteotomy can safely be

repeatedly to avoid significant slope perturbations [5, 8, 12].

applied. Our preference is the medial opening wedge osteotomy.

In the middle of the line drawn from the tibial tubercule to medial border of tibia, a 3–5 cm longitudinal skin incision is made carefully by beginning 1–2 cm inferior to the medial joint line and continuing caudally to the pes anserinus. After dividing the sartorial fascia, we usually distract the tendons of pes anserinus distally, but an inverted L-shaped flap can also be elevated. After subperiosteal dissection and sufficient exposure of the proximal-medial tibia and the joint line, the superficial medial collateral ligament (sMCL) fibers are elevated from their medial tibial attachment sides; otherwise, if the attachment of sMCL is left intact on the medial tibia, pressures of the medial compartment may inevitably increase as a result of the tensioning of sMCL fibers during the distraction phase of the osteotomy [1, 8]. Proximal to the tibial tubercule, patellar tendon should be identified and protected from the possible damage that might be caused by the blade of the saw by placing a broad retractor anteriorly. It is of high importance to conduct careful subperiosteal dissections in order to protect and secure the posterior neurovascular structures.

After the subperiosteal dissection and exposure of the entire proximal-medial portion of the tibia, a guide wire is inserted, starting proximal to the tibial tubercule and aiming toward the tip of the fibular head with an anteromedial to posterolateral trajectory. After the insertion of the first guide wire, it is optional to place another wire posteriorly to determine the osteotomy's sagittal angle that can influence the amount of the sagittal slope. If a reduction of the posterior tibial slope is desired, the posterior guide wire should be placed more superiorly resulting in a flatter cut. If a rise of the sagittal slope is desired, then the posterior guidewire should be placed more inferiorly.

An oscillating saw is used to make the first cut of the osteotomy on the anteromedial cortex.

This cut is advanced with osteotomes until to a distance of 1–1.5 cm to the lateral cortex of the tibia, in order not to cause any fracture on the tibial plateau. In addition to that, it is also recommended, that the vertical distance from the tip of the osteotome to the lateral tibial plateau should be 1.25 times of the horizontal distance to the lateral tibial cortex, to minimize the risk of any fracture on the lateral tibial plateau. Hereby, the osteotomy is ended, followed by the opening of the osteotomized bone and very gentle and careful application of valgus force on the tibia. Osteotomy side is opened sequentially with calibrated wedges. As a result of that, a new mechanical axis has been reconstructed (**Figure 4**). The new mechanical axis is confirmed by either placing a cord of electrocautery or a long alignment rod from the center of the hip to the center of the ankle and confirming its distance from the knee joint under image intensifier. It was also suggested to add a concomitant tibial tuberosity osteotomy, if more than 12.5 mm correction is required, in order to avoid the potentially adverse effects of patella baja and increased pressure in patellofemoral compartment [8, 39].

The advantages of the medial open wedge osteotomy can be summarized as:


### **Figure 4.**

*Post-operative weight-bearing orthoroentgenogram of a patient after MOWHTO. β (7° in this case) is the angle formed by the anatomical axis of femur and the weight-bearing axis (white dashed line) or the mechanical and anatomical axes of tibia, where all three axes are overlapping each other in the tibia.*

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ceramic spacer [49].

*High Tibial Osteotomy*

rized as:

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

• the risk of delayed union or non-union.

*8.1.1 Fixation of the medial open wedge osteotomy*

*8.1.2 Bone healing after the medial open wedge osteotomy*

consolidation is visible at the end of the first post-operative year.

*8.1.3 Spacers and autografts for the medial open wedge osteotomy*

and incorporated into osteotomized tibia [47].

• the need for bone graft,

the osteotomy gap [43–45].

The disadvantages of the medial open wedge osteotomy can be summa-

Plate fixation was reported to be biomechanically superior as compared to external fixation [40, 41]. Plates without spacer wedges were shown to have higher rates of failure compared to those with wedges [11, 41]. Plate fixators (i.e., The TomoFix plate) are manufactured with the principles of the locking compression plate (LCP) concept; meanwhile offering the advantage of a rigid fixation, and providing early weight-bearing, and early start of motion while the normal pre-operative posterior tibial slope is maintained [13, 14, 42]. TomoFix plates (Synthes, West Chester, PA) and Puddu plates (Arthrex, Naples, FL) were detected to provide adequate biomechanical stability, whereas in case of lateral cortex fracture, TomoFix plates were detected to provide adequate stability without the need of any additional lateral fixation [8, 42]. The biomechanics of three spacer plates with different length was studied, while two were with locking bolts, and one was the TomoFix plate, which was shown to be superior at single load-to-failure and cyclical load-to-failure tests and also possessed the maximum residual stability after failure of the lateral cortex, in addition to least motion at

After medial open wedge HTO procedure, healing was shown to start from the lateral hinge and advancing toward the medial aspect, while 3 months after the procedure, callus formation, and ossification was visible [8, 11, 13]. In our clinical practice, 6 months post-operatively more than 80% of the gap is filled with newly formed bone (**Figure 5**), and more than 80% of patients X-ray and CT scan, a

To enhance stability and accelerate the healing, we like many other surgeons prefer to fill the gap of osteotomy with grafts or bone substitutes. Post-operative alignment and clinical outcome were reported to be comparable between betatricalcium phosphate (TCP) and hydroxyapatite (HAp), but TCP was noted to possess a significant superiority regarding osteoconductivity and bioabsorbability after 18 months [46]. After the TomoFix plate removal, it was observed, that TCP was completely absorbed and the newly forming bone was completely remodeled

Autogenous iliac bone graft as the bone filler is widely used at the end of the HTO procedure. It is also considered as a reliable bone filler in patients who are at risk of non-/delayed union such as smokers, obese patients, and those with [48]. Results with autograft were reported to be superior with lower rates of total complications as compared to allograft and bone substitutes such as the calcium-phosphate

The disadvantages of the medial open wedge osteotomy can be summarized as:

• the need for bone graft,

*Tibia Pathology and Fractures*

• use of a single cut with no need to detach the muscles,

• ability to adjust the amount of correction during surgery,

*Post-operative weight-bearing orthoroentgenogram of a patient after MOWHTO. β (7° in this case) is the angle formed by the anatomical axis of femur and the weight-bearing axis (white dashed line) or the mechanical and anatomical axes of tibia, where all three axes are overlapping each other in the tibia.*

• little risk of peroneal nerve injury,

• easier conversion to arthroplasty.

**120**

**Figure 4.**

• the risk of delayed union or non-union.

### *8.1.1 Fixation of the medial open wedge osteotomy*

Plate fixation was reported to be biomechanically superior as compared to external fixation [40, 41]. Plates without spacer wedges were shown to have higher rates of failure compared to those with wedges [11, 41]. Plate fixators (i.e., The TomoFix plate) are manufactured with the principles of the locking compression plate (LCP) concept; meanwhile offering the advantage of a rigid fixation, and providing early weight-bearing, and early start of motion while the normal pre-operative posterior tibial slope is maintained [13, 14, 42]. TomoFix plates (Synthes, West Chester, PA) and Puddu plates (Arthrex, Naples, FL) were detected to provide adequate biomechanical stability, whereas in case of lateral cortex fracture, TomoFix plates were detected to provide adequate stability without the need of any additional lateral fixation [8, 42]. The biomechanics of three spacer plates with different length was studied, while two were with locking bolts, and one was the TomoFix plate, which was shown to be superior at single load-to-failure and cyclical load-to-failure tests and also possessed the maximum residual stability after failure of the lateral cortex, in addition to least motion at the osteotomy gap [43–45].

### *8.1.2 Bone healing after the medial open wedge osteotomy*

After medial open wedge HTO procedure, healing was shown to start from the lateral hinge and advancing toward the medial aspect, while 3 months after the procedure, callus formation, and ossification was visible [8, 11, 13]. In our clinical practice, 6 months post-operatively more than 80% of the gap is filled with newly formed bone (**Figure 5**), and more than 80% of patients X-ray and CT scan, a consolidation is visible at the end of the first post-operative year.

### *8.1.3 Spacers and autografts for the medial open wedge osteotomy*

To enhance stability and accelerate the healing, we like many other surgeons prefer to fill the gap of osteotomy with grafts or bone substitutes. Post-operative alignment and clinical outcome were reported to be comparable between betatricalcium phosphate (TCP) and hydroxyapatite (HAp), but TCP was noted to possess a significant superiority regarding osteoconductivity and bioabsorbability after 18 months [46]. After the TomoFix plate removal, it was observed, that TCP was completely absorbed and the newly forming bone was completely remodeled and incorporated into osteotomized tibia [47].

Autogenous iliac bone graft as the bone filler is widely used at the end of the HTO procedure. It is also considered as a reliable bone filler in patients who are at risk of non-/delayed union such as smokers, obese patients, and those with [48]. Results with autograft were reported to be superior with lower rates of total complications as compared to allograft and bone substitutes such as the calcium-phosphate ceramic spacer [49].

**Figure 5.** *Anteroposterior and lateral X-rays of the patient after 6 weeks (A and B) and 6 months (C and D) post-operatively.*

### **8.2 Lateral closing wedge osteotomy**

Lateral closing wedge osteotomy (LCWO) starts with an inverted L-shaped incision directed anterolaterally, while the vertical part is placed on the lateral edge of the tibial tubercule and the horizontal part is placed 1–1.5 cm distally to lateral knee joint line. This osteotomy requires peroneal nerve exposure and dissection, which is

**123**

*lines.*

**Figure 6.**

*High Tibial Osteotomy*

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

found on the anatomical area located the 2–3 cm distally to fibular proximal styloid process and crossing the neck of the fibula. The nerve should be carefully dissected and protected. After the dissection and protection of the peroneal nerve, the anterior compartment muscles are elevated subperiosteally from the anterolateral aspect of tibia while the incision is advanced distally. Patellar tendon should be protected while placing a retractor between the tendon and the anterior tibia. Following this

*Pre-operative planning for LCWHTO. α, the correction angle, is the angle formed by the mechanical axes of femur and tibia that are aimed to be provided post-operatively. The osteotomy lines are drawn as red dashed* 

### *High Tibial Osteotomy DOI: http://dx.doi.org/10.5772/intechopen.92887*

*Tibia Pathology and Fractures*

**122**

**Figure 5.**

*post-operatively.*

**8.2 Lateral closing wedge osteotomy**

Lateral closing wedge osteotomy (LCWO) starts with an inverted L-shaped incision directed anterolaterally, while the vertical part is placed on the lateral edge of the tibial tubercule and the horizontal part is placed 1–1.5 cm distally to lateral knee joint line. This osteotomy requires peroneal nerve exposure and dissection, which is

*Anteroposterior and lateral X-rays of the patient after 6 weeks (A and B) and 6 months (C and D)* 

found on the anatomical area located the 2–3 cm distally to fibular proximal styloid process and crossing the neck of the fibula. The nerve should be carefully dissected and protected. After the dissection and protection of the peroneal nerve, the anterior compartment muscles are elevated subperiosteally from the anterolateral aspect of tibia while the incision is advanced distally. Patellar tendon should be protected while placing a retractor between the tendon and the anterior tibia. Following this

### **Figure 6.**

*Pre-operative planning for LCWHTO. α, the correction angle, is the angle formed by the mechanical axes of femur and tibia that are aimed to be provided post-operatively. The osteotomy lines are drawn as red dashed lines.*

step, the tibiofibular joint can be disrupted by using an osteotome, combined with the resection of the medial one-third of fibula or applying a fibular shaft osteotomy placed 10 cm distally to the fibular head. After that, we usually identify the joint by using two needles and placing the osteotomy guide parallel to the needles aiming 2–2.5 cm distal to the joint line. Following this step, the osteotomy guide is secured to the bone by using two smooth pins, over which the plate is also placed with high precision to the bone while directing it exactly parallel to the posterior slope of the tibial. Before starting to perform with the osteotomy by using an oscillating saw and osteotomes, posterior neurovascular structures, and patellar tendon should be ensured to be protected by the retractors. It is important to end the tip of the osteotome with a distance of 1 cm from the medial tibial cortex and 2–2.5 cm distal to the knee joint line (**Figure 6**). With the help of the osteotomy guide, the required amount of bone can be resected. This step is followed by the application of the plate over the previously placed pins that are replaced with screws. By using a large reduction clamp, the osteotomy is closed and compressed, followed by the insertion of the remaining screws.

### **8.3 Dome osteotomy**

A dome osteotomy is usually indicated when a correction more than 20° are needed. The osteotomy is performed by applying an inverted U-shaped (dome shaped) osteotomy proximal to tibial tubercule. Especially in cases with accompanying patellofemoral disease, by staying proximal to tibial tubercule, distal tibia is shifted anteriorly, yielding to anterior translation of the tibial tubercule, which maintains the patellar height. After the placement of a jig, anteroposterior drill holes are applied in a half barrel shaped configuration while staying proximal to tibial tubercule. During dome osteotomy a partial resection of the fibular shaft might be necessary. Before starting with the osteotomy, the amount of correction should be certainly indicated on the jig and marked with Steinmann pins located in the proximal and distal fragments. Removal of the jig is followed by careful osteotomizing of the posterior cortex, while the pre-determined amount of correction is achieved by anteriorization of the distal fragment together with the tibial tubercule. Dome osteotomy is usually fixed by using an external fixator. Increased operative time, patient discomfort caused by the external fixator, possible risks of pin tract infections, need for frequent follow-up visits for the fine-tuning of external fixator or assessment of the wound side are the disadvantages of dome osteotomy. In our clinical practice, we do not apply the dome osteotomy frequently as a result of the aforementioned disadvantages, while we spare this procedure for patients requiring high degrees of bony correction.

### **9. Survival rates of high tibial osteotomy**

A good surgical technique combined with rigid fixation together with meticulous patient selection and appropriate post-operative rehabilitation protocols are keys to long-term survival of HTO. Koshino et al. reported 93.2% as the 10-year survival rate for closed wedge osteotomy, related to some post operation factors including, valgus anatomical angle of 10°, no flexion contracture and concomitant patellofemoral decompression procedure if indicated [50]. In patients who underwent medial open wedge high tibial osteotomy a 10-year delay of arthroplasty in 63% of 73 patients [51], and in 85% of 203 patients was shown [52].

In a study of 54 patients with osteoarthritis limited to medial compartment, 24% rate of conversion to arthroplasty was reported after a median of 16.5 years with

**125**

possible.

**12. Results of high tibial osteotomy**

*High Tibial Osteotomy*

techniques [53].

**10. Complications**

complication [1, 7, 8].

decreased to 8–15% [1].

**procedures**

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

either medial opening or lateral closing wedge HTO, while no significant difference regarding the functional scores and survival rates was found between the two

HTO's complication rate was reported between 7 and 55%. It should be remembered that HTO requires a long learning curve leading to decreased rates of

displaced lateral hinge fractures, and patients with no compliance [59].

**11. High tibial osteotomy combined with concurrent cartilage** 

HTO with and without articular cartilage procedures or meniscus allograft transplantation was evaluated in a systematic review assessed and concluded that HTO combined with cartilage procedures led to excellent short-term and midterm survival and good clinical outcomes, while deterioration was detected after 10 years [60]. Another study of 43 patients with HTO and ACI showed long-term, improved cartilage survival, and a decreased rate of revision in patients with mild varus deformity (<5°) of knee joint [61]. HTO was intended to preserve the joint and chondral surfaces as much as possible to delay the time interval until total knee arthroplasty. In order to be successful and preserve the joint as much as possible, we also prefer to apply concurrent cartilage procedure to delay the TKA as much as

La Prade et al. reported about the modified Cincinnati Knee Scores (CKS) in patients younger than 55 years old who underwent HTO for medial OA and varus deformity in a single surgeon study from 2000 to 2007. They had strict inclusion and exclusion criteria which excluded patients undergoing additional

With more experience and over the course of years, rates of complications were

It is a fact that medial opening wedge HTO became more popular that the other techniques, because of the successful outcomes. Complications including hardware failure, hardware irritation (up to 40%), loss of correction, non-union, lateral tibial plateau fractures, medial collateral ligament injuries were reported for opening wedge HTO [1, 8, 57]. In addition to that, lateral cortex violation was reports as an important factor for fixation failure, resulting in a minimum 4° of loss of correction in the final follow-up as compared to immediate post-operative X-rays [49]. In a study comprising 100 consecutive MOWHTO patients with an average follow-up of 4 years, allograft combined with plasma-rich platelets and/or DBM was associated with the risk of non-union [58]. Severe adverse events were reported to be seen more common as a result of HTO in patients with diabetes, active smoking,

It was reported, that authors showed that the lateral closing wedge osteotomy was related to higher number of conversion to total joint replacement, whereas the medial opening wedge HTO was related to higher incidence of complications [54]. Results of HTO were noted to be good within the first 10 years following the surgery; whereas, a worsening of the results was also shown after 15 years [55, 56].

### *High Tibial Osteotomy DOI: http://dx.doi.org/10.5772/intechopen.92887*

either medial opening or lateral closing wedge HTO, while no significant difference regarding the functional scores and survival rates was found between the two techniques [53].

It was reported, that authors showed that the lateral closing wedge osteotomy was related to higher number of conversion to total joint replacement, whereas the medial opening wedge HTO was related to higher incidence of complications [54].

Results of HTO were noted to be good within the first 10 years following the surgery; whereas, a worsening of the results was also shown after 15 years [55, 56].

### **10. Complications**

*Tibia Pathology and Fractures*

of the remaining screws.

high degrees of bony correction.

**9. Survival rates of high tibial osteotomy**

**8.3 Dome osteotomy**

step, the tibiofibular joint can be disrupted by using an osteotome, combined with the resection of the medial one-third of fibula or applying a fibular shaft osteotomy placed 10 cm distally to the fibular head. After that, we usually identify the joint by using two needles and placing the osteotomy guide parallel to the needles aiming 2–2.5 cm distal to the joint line. Following this step, the osteotomy guide is secured to the bone by using two smooth pins, over which the plate is also placed with high precision to the bone while directing it exactly parallel to the posterior slope of the tibial. Before starting to perform with the osteotomy by using an oscillating saw and osteotomes, posterior neurovascular structures, and patellar tendon should be ensured to be protected by the retractors. It is important to end the tip of the osteotome with a distance of 1 cm from the medial tibial cortex and 2–2.5 cm distal to the knee joint line (**Figure 6**). With the help of the osteotomy guide, the required amount of bone can be resected. This step is followed by the application of the plate over the previously placed pins that are replaced with screws. By using a large reduction clamp, the osteotomy is closed and compressed, followed by the insertion

A dome osteotomy is usually indicated when a correction more than 20° are needed. The osteotomy is performed by applying an inverted U-shaped (dome shaped) osteotomy proximal to tibial tubercule. Especially in cases with accompanying patellofemoral disease, by staying proximal to tibial tubercule, distal tibia is shifted anteriorly, yielding to anterior translation of the tibial tubercule, which maintains the patellar height. After the placement of a jig, anteroposterior drill holes are applied in a half barrel shaped configuration while staying proximal to tibial tubercule. During dome osteotomy a partial resection of the fibular shaft might be necessary. Before starting with the osteotomy, the amount of correction should be certainly indicated on the jig and marked with Steinmann pins located in the proximal and distal fragments. Removal of the jig is followed by careful osteotomizing of the posterior cortex, while the pre-determined amount of correction is achieved by anteriorization of the distal fragment together with the tibial tubercule. Dome osteotomy is usually fixed by using an external fixator. Increased operative time, patient discomfort caused by the external fixator, possible risks of pin tract infections, need for frequent follow-up visits for the fine-tuning of external fixator or assessment of the wound side are the disadvantages of dome osteotomy. In our clinical practice, we do not apply the dome osteotomy frequently as a result of the aforementioned disadvantages, while we spare this procedure for patients requiring

A good surgical technique combined with rigid fixation together with meticulous patient selection and appropriate post-operative rehabilitation protocols are keys to long-term survival of HTO. Koshino et al. reported 93.2% as the 10-year survival rate for closed wedge osteotomy, related to some post operation factors including, valgus anatomical angle of 10°, no flexion contracture and concomitant patellofemoral decompression procedure if indicated [50]. In patients who underwent medial open wedge high tibial osteotomy a 10-year delay of arthroplasty in

In a study of 54 patients with osteoarthritis limited to medial compartment, 24% rate of conversion to arthroplasty was reported after a median of 16.5 years with

63% of 73 patients [51], and in 85% of 203 patients was shown [52].

**124**

HTO's complication rate was reported between 7 and 55%. It should be remembered that HTO requires a long learning curve leading to decreased rates of complication [1, 7, 8].

With more experience and over the course of years, rates of complications were decreased to 8–15% [1].

It is a fact that medial opening wedge HTO became more popular that the other techniques, because of the successful outcomes. Complications including hardware failure, hardware irritation (up to 40%), loss of correction, non-union, lateral tibial plateau fractures, medial collateral ligament injuries were reported for opening wedge HTO [1, 8, 57]. In addition to that, lateral cortex violation was reports as an important factor for fixation failure, resulting in a minimum 4° of loss of correction in the final follow-up as compared to immediate post-operative X-rays [49]. In a study comprising 100 consecutive MOWHTO patients with an average follow-up of 4 years, allograft combined with plasma-rich platelets and/or DBM was associated with the risk of non-union [58]. Severe adverse events were reported to be seen more common as a result of HTO in patients with diabetes, active smoking, displaced lateral hinge fractures, and patients with no compliance [59].

### **11. High tibial osteotomy combined with concurrent cartilage procedures**

HTO with and without articular cartilage procedures or meniscus allograft transplantation was evaluated in a systematic review assessed and concluded that HTO combined with cartilage procedures led to excellent short-term and midterm survival and good clinical outcomes, while deterioration was detected after 10 years [60]. Another study of 43 patients with HTO and ACI showed long-term, improved cartilage survival, and a decreased rate of revision in patients with mild varus deformity (<5°) of knee joint [61]. HTO was intended to preserve the joint and chondral surfaces as much as possible to delay the time interval until total knee arthroplasty. In order to be successful and preserve the joint as much as possible, we also prefer to apply concurrent cartilage procedure to delay the TKA as much as possible.

### **12. Results of high tibial osteotomy**

La Prade et al. reported about the modified Cincinnati Knee Scores (CKS) in patients younger than 55 years old who underwent HTO for medial OA and varus deformity in a single surgeon study from 2000 to 2007. They had strict inclusion and exclusion criteria which excluded patients undergoing additional procedures or treatments. Each patient was applied an offloading brace preoperatively. If the patient did not get symptom relief, they were not offered a HTO. Forty-seven patients were available for follow-up. The CKS improved from 42.9 to 65.1 (*P* < 0.0001). Function subscore improved from 24.2 to 34.2 (*P* < 0.001). Functional score improved significantly at 6 weeks, 1 and 2 years [62].

Howells et al. reviewed 164 consecutive patients that underwent lateral closing wedge HTO between 2000 and 2002. Among them, 100 patients met the inclusion criteria and had a follow-up duration of 5–10 years post-operatively. Data were collected prospectively; however, the study reviewed the data retrospectively. To assess outcome WOMAC and KSS were used. At 5 years, 87% of survival rate was reported with the remainder undergoing TKA. This rate dropped to 79% after 10 at 10 years. It was detected that those requiring revision to TKA had a significantly lower WOMAC score (47 vs. 65, *P* < 0.001), were older (54 years old vs. 49, *P* = 0.006) and had a higher BMI (30.2 vs. 27.9, *P* = 0.005). They concluded that a patient less than 55 years old, with a BMI less than 30 and a pre-operative WOMAC score of >45, were positive predictors regarding failure. The authors underlined the importance of using of pre- operative functional scores to use in the decision-making process [63].

### **Conflict of interest**

The authors declare no conflict of interest.

### **Author details**

Tuna Pehlivanoglu1,2, Kerem Yildirim3,4 and Tahsin Beyzadeoglu3,5\*

1 Department of Orthopedic Surgery and Traumatology, EMSEY Hospital, Istanbul, Turkey

2 Faculty of Health Sciences, Yeni Yuzyil University, Istanbul, Turkey

3 Beyzadeoglu Clinic, Istanbul, Turkey

4 Faculty of Health Sciences, Istanbul Gelisim University, Istanbul, Turkey

5 Faculty of Health Sciences, Halic University, Istanbul, Turkey

\*Address all correspondence to: tbeyzade@superonline.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**127**

*High Tibial Osteotomy*

2010;**34**:155-160

**References**

1961;**43-B**:746-751

1974;**56**:236-245

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

[1] Amendola A, Bonasia DE. Results of high tibial osteotomy: Review of the literature. International Orthopaedics.

knee: A systematic review. Arthroscopy.

[10] Saragaglia D, Blaysat M, Inman D, et al. Outcome of opening wedge high tibial osteotomy augmented with a biosorb(R) wedge and fixed with a plate and screws in 124 patients with a mean of ten years follow-up. International Orthopaedics. 2011;**35**:1151-1156

[11] Sabzevari S, Ebrahimpour A, Roudi MK, et al. High tibial osteotomy: A systematic review and current concept. Archives of Bone and Joint

[12] Lobenhoffer P, Agneskirchner JD. Improvements in surgical technique of valgus high tibial osteotomy. Knee Surgery, Sports Traumatology, Arthroscopy. 2003;**11**:132-138

[13] Staubli AE, De Simoni C, Babst R, et al. TomoFix: A new LCP-concept for open wedge osteotomy of the medial proximal tibia—Early results in 92 cases.

[14] Niemeyer P, Schmal H, Hauschild O, et al. Open-wedge osteotomy using an internal plate fixator in patients with medial-compartment gonarthritis and varus malalignment: 3-year results with regard to preoperative arthroscopic and radiographic findings. Arthroscopy.

[15] Sommer C, Gautier E, Muller M, et al. First clinical results of the locking compression plate (LCP). Injury. 2003;**34**(Suppl 2):B43-B54

[16] Akamatsu Y, Koshino T, Saito T, et al. Changes in osteosclerosis of the osteoarthritic knee after high tibial osteotomy. Clinical Orthopaedics and Related Research. 1997;**334**:207-214

[17] Takahashi S, Tomihisa K, Saito T. Decrease of osteosclerosis

Injury. 2003;**34**(Suppl 2):B55-B62

2010;**26**:1607-1616

Surgery. 2016;**4**:204-212

2015;**31**:720-730

[2] Jackson JP, Waugh W. Tibial osteotomy for osteoarthritis of the knee. Journal of Bone and Joint Surgery. British Volume (London).

[3] Jackson JP, Waugh W. The

technique and complications of upper tibial osteotomy. A review of 226 operations. Journal of Bone and Joint Surgery. British Volume (London).

[4] Coventry MB. Proximal tibial varus osteotomy for osteoarthritis of the lateral compartment of the knee. The Journal of Bone and Joint Surgery. American Volume. 1987;**69**:32-38

[5] Hernigou P, Medevielle D, Debeyre J, et al. Proximal tibial osteotomy for osteoarthritis with varus deformity. A ten to thirteen-year follow-up study. The Journal of Bone and Joint Surgery. American Volume. 1987;**69**:332-354

corrective osteotomies in the treatment of certain knee diseases with axial deviation. Revue du Rhumatisme et des Maladies Ostéo-Articulaires.

[7] Aglietti P, Buzzi R, Vena LM, et al. High tibial valgus osteotomy for medial gonarthrosis: A 10- to 21-year study. The Journal of Knee Surgery.

[8] Lee DC, Byun SJ. High tibial osteotomy. Knee Surgery & Related

[9] Lash NJ, Feller JA, Batty LM, et al. Bone grafts and bone substitutes for opening-wedge osteotomies of the

Research. 2012;**24**:61-69

[6] Debeyre J, Patte D. Value of

1962;**29**:722-729

2003;**16**:21-26

### **References**

*Tibia Pathology and Fractures*

**126**

**Author details**

process [63].

**Conflict of interest**

3 Beyzadeoglu Clinic, Istanbul, Turkey

provided the original work is properly cited.

The authors declare no conflict of interest.

Turkey

Tuna Pehlivanoglu1,2, Kerem Yildirim3,4 and Tahsin Beyzadeoglu3,5\*

procedures or treatments. Each patient was applied an offloading brace preoperatively. If the patient did not get symptom relief, they were not offered a HTO. Forty-seven patients were available for follow-up. The CKS improved from 42.9 to 65.1 (*P* < 0.0001). Function subscore improved from 24.2 to 34.2 (*P* < 0.001).

Howells et al. reviewed 164 consecutive patients that underwent lateral closing wedge HTO between 2000 and 2002. Among them, 100 patients met the inclusion criteria and had a follow-up duration of 5–10 years post-operatively. Data were collected prospectively; however, the study reviewed the data retrospectively. To assess outcome WOMAC and KSS were used. At 5 years, 87% of survival rate was reported with the remainder undergoing TKA. This rate dropped to 79% after 10 at 10 years. It was detected that those requiring revision to TKA had a significantly lower WOMAC score (47 vs. 65, *P* < 0.001), were older (54 years old vs. 49, *P* = 0.006) and had a higher BMI (30.2 vs. 27.9, *P* = 0.005). They concluded that a patient less than 55 years old, with a BMI less than 30 and a pre-operative WOMAC score of >45, were positive predictors regarding failure. The authors underlined the importance of using of pre- operative functional scores to use in the decision-making

Functional score improved significantly at 6 weeks, 1 and 2 years [62].

2 Faculty of Health Sciences, Yeni Yuzyil University, Istanbul, Turkey

5 Faculty of Health Sciences, Halic University, Istanbul, Turkey

\*Address all correspondence to: tbeyzade@superonline.com

4 Faculty of Health Sciences, Istanbul Gelisim University, Istanbul, Turkey

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

1 Department of Orthopedic Surgery and Traumatology, EMSEY Hospital, Istanbul,

[1] Amendola A, Bonasia DE. Results of high tibial osteotomy: Review of the literature. International Orthopaedics. 2010;**34**:155-160

[2] Jackson JP, Waugh W. Tibial osteotomy for osteoarthritis of the knee. Journal of Bone and Joint Surgery. British Volume (London). 1961;**43-B**:746-751

[3] Jackson JP, Waugh W. The technique and complications of upper tibial osteotomy. A review of 226 operations. Journal of Bone and Joint Surgery. British Volume (London). 1974;**56**:236-245

[4] Coventry MB. Proximal tibial varus osteotomy for osteoarthritis of the lateral compartment of the knee. The Journal of Bone and Joint Surgery. American Volume. 1987;**69**:32-38

[5] Hernigou P, Medevielle D, Debeyre J, et al. Proximal tibial osteotomy for osteoarthritis with varus deformity. A ten to thirteen-year follow-up study. The Journal of Bone and Joint Surgery. American Volume. 1987;**69**:332-354

[6] Debeyre J, Patte D. Value of corrective osteotomies in the treatment of certain knee diseases with axial deviation. Revue du Rhumatisme et des Maladies Ostéo-Articulaires. 1962;**29**:722-729

[7] Aglietti P, Buzzi R, Vena LM, et al. High tibial valgus osteotomy for medial gonarthrosis: A 10- to 21-year study. The Journal of Knee Surgery. 2003;**16**:21-26

[8] Lee DC, Byun SJ. High tibial osteotomy. Knee Surgery & Related Research. 2012;**24**:61-69

[9] Lash NJ, Feller JA, Batty LM, et al. Bone grafts and bone substitutes for opening-wedge osteotomies of the

knee: A systematic review. Arthroscopy. 2015;**31**:720-730

[10] Saragaglia D, Blaysat M, Inman D, et al. Outcome of opening wedge high tibial osteotomy augmented with a biosorb(R) wedge and fixed with a plate and screws in 124 patients with a mean of ten years follow-up. International Orthopaedics. 2011;**35**:1151-1156

[11] Sabzevari S, Ebrahimpour A, Roudi MK, et al. High tibial osteotomy: A systematic review and current concept. Archives of Bone and Joint Surgery. 2016;**4**:204-212

[12] Lobenhoffer P, Agneskirchner JD. Improvements in surgical technique of valgus high tibial osteotomy. Knee Surgery, Sports Traumatology, Arthroscopy. 2003;**11**:132-138

[13] Staubli AE, De Simoni C, Babst R, et al. TomoFix: A new LCP-concept for open wedge osteotomy of the medial proximal tibia—Early results in 92 cases. Injury. 2003;**34**(Suppl 2):B55-B62

[14] Niemeyer P, Schmal H, Hauschild O, et al. Open-wedge osteotomy using an internal plate fixator in patients with medial-compartment gonarthritis and varus malalignment: 3-year results with regard to preoperative arthroscopic and radiographic findings. Arthroscopy. 2010;**26**:1607-1616

[15] Sommer C, Gautier E, Muller M, et al. First clinical results of the locking compression plate (LCP). Injury. 2003;**34**(Suppl 2):B43-B54

[16] Akamatsu Y, Koshino T, Saito T, et al. Changes in osteosclerosis of the osteoarthritic knee after high tibial osteotomy. Clinical Orthopaedics and Related Research. 1997;**334**:207-214

[17] Takahashi S, Tomihisa K, Saito T. Decrease of osteosclerosis in subchondral bone of medial compartmental osteoarthritic knee seven to nineteen years after high tibial valgus osteotomy. Bulletin/Hospital for Joint Diseases. 2002-2003;**61**(1-2):58-62

[18] Jung W-H, Takeuchi R, Chun C-W, et al. Second-look arthroscopic assessment of cartilage regeneration after medial opening-wedge high tibial osteotomy. Arthroscopy. 2014;**30**:72-79

[19] Holden DL, James SL, Larson RL, et al. Proximal tibial osteotomy in patients who are fifty years old or less. A long-term follow-up study. The Journal of Bone and Joint Surgery. American Volume. 1988;**70**:977-982

[20] Odenbring S, Tjornstrand B, Egund N, et al. Function after tibial osteotomy for medial gonarthrosis below aged 50 years. Acta Orthopaedica Scandinavica. 1989;**60**:527-531

[21] Khoshbin A, Sheth U, Ogilvie-Harris D, et al. The effect of patient, provider and surgical factors on survivorship of high tibial osteotomy to total knee arthroplasty: A population-based study. Knee Surgery, Sports Traumatology, Arthroscopy. 2017;**25**:887-894

[22] Preston CF, Fulkerson EW, Meislin R, et al. Osteotomy about the knee: Applications, techniques, and results. The Journal of Knee Surgery. 2005;**18**:258-272

[23] Brinkman J-M, Lobenhoffer P, Agneskirchner JD, et al. Osteotomies around the knee: Patient selection, stability of fixation and bone healing in high tibial osteotomies. Journal of Bone and Joint Surgery. British Volume (London). 2008;**90**:1548-1557

[24] Rossi R, Bonasia DE, Amendola A. The role of high tibial osteotomy in the varus knee. The Journal of the American Academy of Orthopaedic Surgeons. 2011;**19**:590-599

[25] Phillips CL, Silver DAT, Schranz PJ, et al. The measurement of patellar height: A review of the methods of imaging. Journal of Bone and Joint Surgery. British Volume (London). 2010;**92**:1045-1053

[26] Babis GC, An K-N, Chao EYS, et al. Double level osteotomy of the knee: A method to retain joint-line obliquity. Clinical results. The Journal of Bone and Joint Surgery. American Volume. 2002;**84**:1380-1388

[27] Coventry MB, Ilstrup DM, Wallrichs SL. Proximal tibial osteotomy. A critical long-term study of eightyseven cases. The Journal of Bone and Joint Surgery. American Volume. 1993;**75**:196-201

[28] Bonasia DE, Dettoni F, Sito G, et al. Medial opening wedge high tibial osteotomy for medial compartment overload/arthritis in the varus knee: Prognostic factors. The American Journal of Sports Medicine. 2014;**42**:690-698

[29] Hsu RW, Himeno S, Coventry MB, et al. Normal axial alignment of the lower extremity and load-bearing distribution at the knee. Clinical Orthopaedics and Related Research. 1990;**255**:215-227

[30] Moreland JR, Bassett LW, Hanker GJ. Radiographic analysis of the axial alignment of the lower extremity. The Journal of Bone and Joint Surgery. American Volume. 1987;**69**:745-749

[31] Tetsworth K, Paley D. Malalignment and degenerative arthropathy. The Orthopedic Clinics of North America. 1994;**25**:367-377

[32] Fujisawa Y, Masuhara K, Shiomi S. The effect of high tibial osteotomy on osteoarthritis of the knee. An arthroscopic study of 54 knee joints. The Orthopedic Clinics of North America. 1979;**10**:585-608

**129**

*High Tibial Osteotomy*

1979;**10**:191-210

1982;**48**:139-156

Knee. 2011;**18**:361-368

1992;**274**:248-264

[33] Iorio R, Healy WL.

[34] Coventry MB. Upper tibial osteotomy for gonarthrosis. The evolution of the operation in the last 18 years and long term results. The Orthopedic Clinics of North America.

[35] Coventry MB, Bowman PW. Long-term results of upper tibial osteotomy for degenerative arthritis of the knee. Acta Orthopaedica Belgica.

[36] Smith TO, Sexton D, Mitchell P, et al. Opening- or closing-wedged high tibial osteotomy: A meta-analysis of clinical and radiological outcomes. The

[37] Dugdale TW, Noyes FR, Styer D. Preoperative planning for high tibial osteotomy. The effect of lateral tibiofemoral separation and tibiofemoral length. Clinical Orthopaedics and Related Research.

[38] Muller M, Strecker W. Arthroscopy prior to osteotomy around the knee? Archives of Orthopaedic and Trauma

Surgery. 2008;**128**:1217-1221

Arthroscopy. 2013;**21**:23-31

Avon). 2005;**20**:871-876

[39] McNamara I, Birmingham TB, Fowler PJ, et al. High tibial osteotomy: Evolution of research and clinical applications—A Canadian experience. Knee Surgery, Sports Traumatology,

[40] Zhim F, Laflamme GY, Viens H, et al. Biomechanical stability of high tibial opening wedge osteotomy: Internal fixation versus external

fixation. Clinical Biomechanics (Bristol,

[41] Spahn G, Muckley T, Kahl E, et al. Biomechanical investigation of

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

Unicompartmental arthritis of the knee. The Journal of Bone and Joint Surgery. American Volume. 2003;**85**:1351-1364

different internal fixations in medial opening-wedge high tibial osteotomy. Clinical Biomechanics (Bristol, Avon).

[42] Stoffel K, Stachowiak G, Kuster M. Open wedge high tibial osteotomy: biomechanical investigation of the modified Arthrex Osteotomy Plate (Puddu Plate) and the TomoFix Plate. Clinical Biomechanics (Bristol, Avon).

[43] Pape D, Kohn D, van Giffen N, et al. Differences in fixation stability between spacer plate and plate fixator following high tibial osteotomy. Knee Surgery, Sports Traumatology, Arthroscopy.

[44] Kyung H-S, Lee B-J, Kim J-W, et al. Biplanar open wedge high tibial osteotomy in the medial compartment osteoarthritis of the knee joint: Comparison between the Aescula and TomoFix plate. Clinics in Orthopedic

[45] Golovakhsmall A, Maxim LC, Orljanski W, Benedetto K-P, et al. Comparison of theoretical fixation stability of three devices employed in medial opening wedge high tibial osteotomy: A finite element analysis. BMC Musculoskeletal Disorders.

[46] Onodera J, Kondo E, Omizu N, et al. Beta-tricalcium phosphate shows superior absorption rate and osteoconductivity compared to hydroxyapatite in open-wedge high tibial osteotomy. Knee Surgery, Sports Traumatology, Arthroscopy.

[47] Gaasbeek RDA, Toonen HG, van Heerwaarden RJ, et al. Mechanism of bone incorporation of beta-TCP bone substitute in open wedge tibial osteotomy in patients. Biomaterials.

Surgery. 2015;**7**:185-190

2006;**21**:272-278

2004;**19**:944-950

2013;**21**:82-89

2014;**15**:230

2014;**22**:2763-2770

2005;**26**:6713-6719

*High Tibial Osteotomy DOI: http://dx.doi.org/10.5772/intechopen.92887*

*Tibia Pathology and Fractures*

in subchondral bone of medial compartmental osteoarthritic knee seven to nineteen years after high tibial valgus osteotomy. Bulletin/Hospital for Joint Diseases. 2002-2003;**61**(1-2):58-62 [25] Phillips CL, Silver DAT, Schranz PJ, et al. The measurement of patellar height: A review of the methods of imaging. Journal of Bone and Joint Surgery. British Volume (London).

[26] Babis GC, An K-N, Chao EYS, et al. Double level osteotomy of the knee: A method to retain joint-line obliquity. Clinical results. The Journal of Bone and Joint Surgery. American Volume.

Wallrichs SL. Proximal tibial osteotomy. A critical long-term study of eightyseven cases. The Journal of Bone and Joint Surgery. American Volume.

2010;**92**:1045-1053

2002;**84**:1380-1388

1993;**75**:196-201

2014;**42**:690-698

1990;**255**:215-227

1994;**25**:367-377

1979;**10**:585-608

[30] Moreland JR, Bassett LW,

[27] Coventry MB, Ilstrup DM,

[28] Bonasia DE, Dettoni F, Sito G, et al. Medial opening wedge high tibial osteotomy for medial compartment overload/arthritis in the varus knee: Prognostic factors. The American Journal of Sports Medicine.

[29] Hsu RW, Himeno S, Coventry MB, et al. Normal axial alignment of the lower extremity and load-bearing distribution at the knee. Clinical Orthopaedics and Related Research.

Hanker GJ. Radiographic analysis of the axial alignment of the lower extremity. The Journal of Bone and Joint Surgery. American Volume. 1987;**69**:745-749

[31] Tetsworth K, Paley D. Malalignment and degenerative arthropathy. The Orthopedic Clinics of North America.

[32] Fujisawa Y, Masuhara K, Shiomi S. The effect of high tibial osteotomy on osteoarthritis of the knee. An

arthroscopic study of 54 knee joints. The Orthopedic Clinics of North America.

[18] Jung W-H, Takeuchi R, Chun C-W, et al. Second-look arthroscopic assessment of cartilage regeneration after medial opening-wedge high tibial osteotomy. Arthroscopy. 2014;**30**:72-79

[19] Holden DL, James SL, Larson RL, et al. Proximal tibial osteotomy in patients who are fifty years old or less. A long-term follow-up study. The Journal of Bone and Joint Surgery. American

Volume. 1988;**70**:977-982

[20] Odenbring S, Tjornstrand B, Egund N, et al. Function after tibial osteotomy for medial gonarthrosis below aged 50 years. Acta Orthopaedica

Scandinavica. 1989;**60**:527-531

to total knee arthroplasty: A

[22] Preston CF, Fulkerson EW, Meislin R, et al. Osteotomy about the knee: Applications, techniques, and results. The Journal of Knee Surgery.

[23] Brinkman J-M, Lobenhoffer P, Agneskirchner JD, et al. Osteotomies around the knee: Patient selection, stability of fixation and bone healing in high tibial osteotomies. Journal of Bone and Joint Surgery. British Volume

(London). 2008;**90**:1548-1557

[24] Rossi R, Bonasia DE, Amendola A. The role of high tibial osteotomy in the varus knee. The Journal of the American Academy of Orthopaedic Surgeons.

2017;**25**:887-894

2005;**18**:258-272

2011;**19**:590-599

[21] Khoshbin A, Sheth U, Ogilvie-Harris D, et al. The effect of patient, provider and surgical factors on survivorship of high tibial osteotomy

population-based study. Knee Surgery, Sports Traumatology, Arthroscopy.

**128**

[33] Iorio R, Healy WL. Unicompartmental arthritis of the knee. The Journal of Bone and Joint Surgery. American Volume. 2003;**85**:1351-1364

[34] Coventry MB. Upper tibial osteotomy for gonarthrosis. The evolution of the operation in the last 18 years and long term results. The Orthopedic Clinics of North America. 1979;**10**:191-210

[35] Coventry MB, Bowman PW. Long-term results of upper tibial osteotomy for degenerative arthritis of the knee. Acta Orthopaedica Belgica. 1982;**48**:139-156

[36] Smith TO, Sexton D, Mitchell P, et al. Opening- or closing-wedged high tibial osteotomy: A meta-analysis of clinical and radiological outcomes. The Knee. 2011;**18**:361-368

[37] Dugdale TW, Noyes FR, Styer D. Preoperative planning for high tibial osteotomy. The effect of lateral tibiofemoral separation and tibiofemoral length. Clinical Orthopaedics and Related Research. 1992;**274**:248-264

[38] Muller M, Strecker W. Arthroscopy prior to osteotomy around the knee? Archives of Orthopaedic and Trauma Surgery. 2008;**128**:1217-1221

[39] McNamara I, Birmingham TB, Fowler PJ, et al. High tibial osteotomy: Evolution of research and clinical applications—A Canadian experience. Knee Surgery, Sports Traumatology, Arthroscopy. 2013;**21**:23-31

[40] Zhim F, Laflamme GY, Viens H, et al. Biomechanical stability of high tibial opening wedge osteotomy: Internal fixation versus external fixation. Clinical Biomechanics (Bristol, Avon). 2005;**20**:871-876

[41] Spahn G, Muckley T, Kahl E, et al. Biomechanical investigation of different internal fixations in medial opening-wedge high tibial osteotomy. Clinical Biomechanics (Bristol, Avon). 2006;**21**:272-278

[42] Stoffel K, Stachowiak G, Kuster M. Open wedge high tibial osteotomy: biomechanical investigation of the modified Arthrex Osteotomy Plate (Puddu Plate) and the TomoFix Plate. Clinical Biomechanics (Bristol, Avon). 2004;**19**:944-950

[43] Pape D, Kohn D, van Giffen N, et al. Differences in fixation stability between spacer plate and plate fixator following high tibial osteotomy. Knee Surgery, Sports Traumatology, Arthroscopy. 2013;**21**:82-89

[44] Kyung H-S, Lee B-J, Kim J-W, et al. Biplanar open wedge high tibial osteotomy in the medial compartment osteoarthritis of the knee joint: Comparison between the Aescula and TomoFix plate. Clinics in Orthopedic Surgery. 2015;**7**:185-190

[45] Golovakhsmall A, Maxim LC, Orljanski W, Benedetto K-P, et al. Comparison of theoretical fixation stability of three devices employed in medial opening wedge high tibial osteotomy: A finite element analysis. BMC Musculoskeletal Disorders. 2014;**15**:230

[46] Onodera J, Kondo E, Omizu N, et al. Beta-tricalcium phosphate shows superior absorption rate and osteoconductivity compared to hydroxyapatite in open-wedge high tibial osteotomy. Knee Surgery, Sports Traumatology, Arthroscopy. 2014;**22**:2763-2770

[47] Gaasbeek RDA, Toonen HG, van Heerwaarden RJ, et al. Mechanism of bone incorporation of beta-TCP bone substitute in open wedge tibial osteotomy in patients. Biomaterials. 2005;**26**:6713-6719

[48] Meidinger G, Imhoff AB, Paul J, et al. May smokers and overweight patients be treated with a medial openwedge HTO? Risk factors for non-union. Knee Surgery, Sports Traumatology, Arthroscopy. 2011;**19**:333-339

[49] Kuremsky MA, Schaller TM, Hall CC, et al. Comparison of autograft vs allograft in opening-wedge high tibial osteotomy. The Journal of Arthroplasty. 2010;**25**:951-957

[50] Koshino T, Yoshida T, Ara Y, et al. Fifteen to twenty-eight years' follow-up results of high tibial valgus osteotomy for osteoarthritic knee. The Knee. 2004;**11**:439-444

[51] Weale AE, Lee AS, MacEachern AG. High tibial osteotomy using a dynamic axial external fixator. Clinical Orthopaedics and Related Research. 2001;**382**:154-167

[52] Hernigou P, Ma W. Open wedge tibial osteotomy with acrylic bone cement as bone substitute. The Knee. 2001;**8**:103-110

[53] Schallberger A, Jacobi M, Wahl P, et al. High tibial valgus osteotomy in unicompartmental medial osteoarthritis of the knee: A retrospective follow-up study over 13-21 years. Knee Surgery, Sports Traumatology, Arthroscopy. 2011;**19**:122-127

[54] Duivenvoorden T, Brouwer RW, Baan A, et al. Comparison of closingwedge and opening-wedge high tibial osteotomy for medial compartment osteoarthritis of the knee: A randomized controlled trial with a six-year follow-up. The Journal of Bone and Joint Surgery. American Volume. 2014;**96**:1425-1432

[55] Akizuki S, Shibakawa A, Takizawa T, et al. The long-term outcome of high tibial osteotomy: A ten- to 20-year follow-up. Journal of Bone and Joint Surgery. British Volume (London). 2008;**90**:592-596

[56] Billings A, Scott DF, Camargo MP, et al. High tibial osteotomy with a calibrated osteotomy guide, rigid internal fixation, and early motion. Long-term follow-up. The Journal of Bone and Joint Surgery. American Volume. 2000;**82**:70-79

[57] Dewilde TR, Dauw J, Vandenneucker H, et al. Opening wedge distal femoral varus osteotomy using the Puddu plate and calcium phosphate bone cement. Knee Surgery, Sports Traumatology, Arthroscopy. 2013;**21**:249-254

[58] Giuseffi SA, Replogle WH, Shelton WR. Opening-wedge high tibial osteotomy: Review of 100 consecutive cases. Arthroscopy. 2015;**31**:2128-2137

[59] Martin R, Birmingham TB, Willits K, et al. Adverse event rates and classifications in medial opening wedge high tibial osteotomy. The American Journal of Sports Medicine. 2014;**42**:1118-1126

[60] Harris JD, McNeilan R, Siston RA, et al. Survival and clinical outcome of isolated high tibial osteotomy and combined biological knee reconstruction. The Knee. 2013;**20**:154-161

[61] Bode G, Schmal H, Pestka JM, et al. A non-randomized controlled clinical trial on autologous chondrocyte implantation (ACI) in cartilage defects of the medial femoral condyle with or without high tibial osteotomy in patients with varus deformity of less than 5 degrees. Archives of Orthopaedic and Trauma Surgery. 2013;**133**:43-49

[62] Laprade RF, Spiridonov SI, Nystrom LM, et al. Prospective outcomes of young and middle-aged adults with medial compartment osteoarthritis

**131**

*High Tibial Osteotomy*

2012;**28**:354-364

2014;**96-B**:1491-1497

*DOI: http://dx.doi.org/10.5772/intechopen.92887*

treated with a proximal tibial opening wedge osteotomy. Arthroscopy.

[63] Howells NR, Salmon L, Waller A, et al. The outcome at ten years of lateral closing-wedge high tibial osteotomy: Determinants of survival and functional outcome. The Bone & Joint Journal.

*High Tibial Osteotomy DOI: http://dx.doi.org/10.5772/intechopen.92887*

*Tibia Pathology and Fractures*

[48] Meidinger G, Imhoff AB, Paul J, et al. May smokers and overweight patients be treated with a medial openwedge HTO? Risk factors for non-union. Knee Surgery, Sports Traumatology, Arthroscopy. 2011;**19**:333-339

Bone and Joint Surgery. British Volume

[56] Billings A, Scott DF, Camargo MP, et al. High tibial osteotomy with a calibrated osteotomy guide, rigid internal fixation, and early motion. Long-term follow-up. The Journal of Bone and Joint Surgery. American

Vandenneucker H, et al. Opening wedge

Shelton WR. Opening-wedge high tibial osteotomy: Review of 100 consecutive cases. Arthroscopy. 2015;**31**:2128-2137

(London). 2008;**90**:592-596

Volume. 2000;**82**:70-79

[57] Dewilde TR, Dauw J,

2013;**21**:249-254

2014;**42**:1118-1126

2013;**20**:154-161

[60] Harris JD, McNeilan R,

Siston RA, et al. Survival and clinical outcome of isolated high tibial osteotomy and combined biological knee reconstruction. The Knee.

[61] Bode G, Schmal H, Pestka JM, et al. A non-randomized controlled clinical trial on autologous chondrocyte implantation (ACI) in cartilage defects of the medial femoral condyle with or without high tibial osteotomy in patients with varus deformity of less than 5 degrees. Archives of Orthopaedic and Trauma Surgery. 2013;**133**:43-49

[62] Laprade RF, Spiridonov SI,

Nystrom LM, et al. Prospective outcomes of young and middle-aged adults with medial compartment osteoarthritis

distal femoral varus osteotomy using the Puddu plate and calcium phosphate bone cement. Knee Surgery, Sports Traumatology, Arthroscopy.

[58] Giuseffi SA, Replogle WH,

[59] Martin R, Birmingham TB, Willits K, et al. Adverse event rates and classifications in medial opening wedge high tibial osteotomy. The American Journal of Sports Medicine.

[49] Kuremsky MA, Schaller TM, Hall CC, et al. Comparison of autograft vs allograft in opening-wedge high tibial osteotomy. The Journal of Arthroplasty.

[50] Koshino T, Yoshida T, Ara Y, et al. Fifteen to twenty-eight years' follow-up results of high tibial valgus osteotomy for osteoarthritic knee. The Knee.

[51] Weale AE, Lee AS, MacEachern AG. High tibial osteotomy using a dynamic

axial external fixator. Clinical Orthopaedics and Related Research.

[52] Hernigou P, Ma W. Open wedge tibial osteotomy with acrylic bone cement as bone substitute. The Knee.

[53] Schallberger A, Jacobi M, Wahl P, et al. High tibial valgus osteotomy in unicompartmental medial osteoarthritis of the knee: A retrospective follow-up study over 13-21 years. Knee Surgery, Sports Traumatology, Arthroscopy.

[54] Duivenvoorden T, Brouwer RW, Baan A, et al. Comparison of closingwedge and opening-wedge high tibial osteotomy for medial compartment

osteoarthritis of the knee: A randomized controlled trial with a six-year follow-up. The Journal of Bone and Joint Surgery. American Volume.

[55] Akizuki S, Shibakawa A, Takizawa T, et al. The long-term outcome of high tibial osteotomy: A ten- to 20-year follow-up. Journal of

2010;**25**:951-957

2004;**11**:439-444

2001;**382**:154-167

2001;**8**:103-110

2011;**19**:122-127

2014;**96**:1425-1432

**130**

treated with a proximal tibial opening wedge osteotomy. Arthroscopy. 2012;**28**:354-364

[63] Howells NR, Salmon L, Waller A, et al. The outcome at ten years of lateral closing-wedge high tibial osteotomy: Determinants of survival and functional outcome. The Bone & Joint Journal. 2014;**96-B**:1491-1497

## *Edited by Dimitrios D. Nikolopoulos, George K. Safos and John Michos*

The tibia is the larger, stronger, and anterior (frontal) of the two bones in the leg, which connects the knee with the ankle bones. The tibia, or shinbone, is the most fractured long bone in the body. In recent years, high-energy accidents result in comminuted tibia fractures or intraarticular fractures of the knee (plateau) or ankle (platform) that need immediate open reduction and internal fixation with anatomical plates or intramedullary nails. Intraarticular fractures with comminution or fractures with non-appropriate internal fixation predispose to post-traumatic knee or ankle arthritis. Conservative current therapies (injections of plate-rich plasma or stems cells) or high tibia osteotomies may delay the need of total knee arthroplasty. Tibia Pathology and Fractures analyzes all the up-to-date internal fixation or other operative or conservative therapies.

Published in London, UK © 2020 IntechOpen © ChooChin / iStock

Tibia Pathology and Fractures

Tibia Pathology and Fractures

*Edited by Dimitrios D. Nikolopoulos, George K. Safos and John Michos*