**7. Factors disturbing healing of the fracture**

As the goal of reparative events is to fill the fracture gap with cells possessing osteogenic potential, the participation of their precursors, the MSCs, is crucial. As MSCs are widely distributed in the body, the risk of their deficiency is rather not feasible. Nevertheless, those cells exert some specific features that may reduce their number and activity.

First of all, they are very sensitive to unfavorable conditions, distinctly responding to inordinate mechanical stimuli, hypoxia, and malnutrition [38]. They are also very prone to injury, regardless of its mechanism: mechanical, thermal (burns, frostbites), chemical (acids, bases, toxins), electric, or radiative. Thus, massive traumatization of tissues neighboring the fracture deprives them of progenitors resulting in cessation of reparative processes. Moreover, their loss, exposing the bone to the outer environment, favor its drying that promotes intravascular coagulation depriving the fracture of blood supply. Also, iatrogenic injuries, including vast surgical approach, wide periosteal stripping, excessive cauterization, or just brutal operative technique, superimpose traumatic changes impairing the healing.

Second of all, removal or drainage of hematoma or cellular infiltrates from the fracture, especially, when performed repeatedly, deprives it of molecular regulators [7].

Third of all, under hypoxia MSCs have been shown to differentiate into chondrocytes, instead of osteoblasts. This process, being natural at early stages of reparative processes, when prolongs, results in the formation of cartilaginous pseudoarthrosis. The problem usually occurs, when the fracture is immobilized inadequately or is not immobilized at all, as excessive movements between bone fragments disrupt newly formed vasculature depriving it of blood supply [39].

infection [41, 42]. An inadequate blood supply may also originate from central cardiovascular (stroke, cardiac arrest) insufficiency and peripheral vascular (i.e. atherosclerosis, venous

Fracture Repair: Its Pathomechanism and Disturbances http://dx.doi.org/10.5772/intechopen.76252 11

Satisfactory healing requires an appropriate oxygenation and nutrition. Bone fracture corresponds with the disruption of its vasculature leading to the necrosis of 5 to 10 mm-width bone fragments adjacent to the fracture gap [44]. The area of necrosis may spread on the damage of the neighboring soft tissues, cardiovascular insufficiency (decompensated heart failure, arterial damage, or occlusion, venous thrombosis), anemia, or infection [45, 46]. Hypothermia

also exerts an impact on local circulation constricting blood vessels [47].

thrombosis) diseases [43] (**Figure 3**).

**Figure 3.** Oxygenation and nourishment of the fracture gap.

An especially unappreciated is the contribution of the shock in the cessation of fracture gap perfusion. Centralizing the circulation to protect the circulation of vital organs, it deprives the perfusion of peripheral tissues, including the fractured gap and surrounding it tissues [40]. When prolongs, shock aggravates tissue injury, impairs the healing, and increases the risk of

Fracture Repair: Its Pathomechanism and Disturbances http://dx.doi.org/10.5772/intechopen.76252 11

**Figure 3.** Oxygenation and nourishment of the fracture gap.

Histologically, uneventful healing is characterized by soft callus filling the fracture gap in the 2nd week after injury (soft callus). In the 4th week, the callus should already be replaced by spongy bone (hard callus), and in the 8th-be a subject of remodeling. Non-union is characterized by the lack of ossification at the 4th post-fracture week, despite the fact that similarly to uneventful healing, the fracture's gap is filled with an excess of cartilage "flowing" out of it. In the 8th week, young fibrous tissue with scarce and loose foci of cartilaginous tissue is

On a molecular level, there are no differences in the expression of PDGF, TGF-β, and FGF-2 in the 1st week after the fracture in both uneventfully and healing with delay fracture gaps. But in the 8th week, in contrary to uneventful healing, whose osteocytes express all these factors, none of them is expressed [36]. It was proved that lack of the mentioned above molecular stimuli leading to non-union could also be produced surgically removing tissues from the

As the goal of reparative events is to fill the fracture gap with cells possessing osteogenic potential, the participation of their precursors, the MSCs, is crucial. As MSCs are widely distributed in the body, the risk of their deficiency is rather not feasible. Nevertheless, those cells

First of all, they are very sensitive to unfavorable conditions, distinctly responding to inordinate mechanical stimuli, hypoxia, and malnutrition [38]. They are also very prone to injury, regardless of its mechanism: mechanical, thermal (burns, frostbites), chemical (acids, bases, toxins), electric, or radiative. Thus, massive traumatization of tissues neighboring the fracture deprives them of progenitors resulting in cessation of reparative processes. Moreover, their loss, exposing the bone to the outer environment, favor its drying that promotes intravascular coagulation depriving the fracture of blood supply. Also, iatrogenic injuries, including vast surgical approach, wide periosteal stripping, excessive cauterization, or just brutal operative

Second of all, removal or drainage of hematoma or cellular infiltrates from the fracture, espe-

Third of all, under hypoxia MSCs have been shown to differentiate into chondrocytes, instead of osteoblasts. This process, being natural at early stages of reparative processes, when prolongs, results in the formation of cartilaginous pseudoarthrosis. The problem usually occurs, when the fracture is immobilized inadequately or is not immobilized at all, as excessive movements between bone fragments disrupt newly formed vasculature depriving it of blood supply [39].

An especially unappreciated is the contribution of the shock in the cessation of fracture gap perfusion. Centralizing the circulation to protect the circulation of vital organs, it deprives the perfusion of peripheral tissues, including the fractured gap and surrounding it tissues [40]. When prolongs, shock aggravates tissue injury, impairs the healing, and increases the risk of

fracture gap that may result from repeated debridement or rinsing drainage [37].

exert some specific features that may reduce their number and activity.

technique, superimpose traumatic changes impairing the healing.

cially, when performed repeatedly, deprives it of molecular regulators [7].

observed and finally, the pseudoarthrosis is formed [35].

10 Trauma Surgery

**7. Factors disturbing healing of the fracture**

infection [41, 42]. An inadequate blood supply may also originate from central cardiovascular (stroke, cardiac arrest) insufficiency and peripheral vascular (i.e. atherosclerosis, venous thrombosis) diseases [43] (**Figure 3**).

Satisfactory healing requires an appropriate oxygenation and nutrition. Bone fracture corresponds with the disruption of its vasculature leading to the necrosis of 5 to 10 mm-width bone fragments adjacent to the fracture gap [44]. The area of necrosis may spread on the damage of the neighboring soft tissues, cardiovascular insufficiency (decompensated heart failure, arterial damage, or occlusion, venous thrombosis), anemia, or infection [45, 46]. Hypothermia also exerts an impact on local circulation constricting blood vessels [47].

Properly balanced diet provides all the nutrients, vitamins, and minerals that are necessary for healing. In case of bone fracture, an attention has to be paid over calcium, phosphates (osteoid formation), proteins (source of amino acids for collagen synthesis), and vitamin D3 that may, in some cases, require supplementation.

Starvation is nowadays relatively seldom in developed societies, whose overweight and obese population alarmingly increases. Nevertheless, it could not be forgotten that it pertains only ca one-fourth of the Earth's population, whereas the next three-fourth suffers from hunger. Moreover, starvation and malnutrition may result from other than just a food shortage, reasons.

At the risk are especially elder, handicapped (also mentally) persons, drugs or alcohol abused, patients suffering from anorexia, and all others suffering from disturbed food intake, digestion, absorption, or processing. Thus, at risk are all those suffering from various digestive disorders, including short bowel syndrome, Hirschsprung's or Crohn's diseases, liver cirrhosis, pancreatitis and many others. Diabetes also leads to some type of starvation, as intracellular hypoglycemia deprives cells of glucose, the most important source of energy [48].

An increasing number of population implementing restrictive diet to reduce the body weight may present various nutritional deficiencies. Nevertheless, so far any religious (i.e. exclusion from the diet some kind of a meat) nor ideological (i.e. growing population of vegetarians and vegans) dietary restrictions nor customs were reported to influence bone healing. However, their negative insult, especially on young individuals, should be considered [49].
