**6. Uneventful and disturbed fracture healing**

From the clinical point of view, the fracture is considered to be healed, when its mechanical properties are restored allowing carrying the body weight. Thus, the main indicators of successful healing are lack of the pathological mobility corresponding with a resolution of pain and restored the ability to carry mechanical loads confirmed by radiographic images showing callus mineralization and remodeling.

The only examination that may be useful in the monitoring of the healing process and predicting its outcome is limb lymphoscintigraphy [34]. Observation of the lymphatic system showed that regional lymph node draining the fracture is a subject of molecules released from its gap. Thus, increased lymph drainage and enlargement of the lymph node (accumulation of cells) reflect molecular and cellular events taking place at the fracture gap that may be used

**Figure 2.** Lymphoscintigrams of the uneventful (left) and disturbed (right) healings of the fractures of the right extremities. Uneventful healing is characterized by enlarged regional lymph nodes and lymphatic outflow, when compared with contralateral limb. If the healing is disturbed, decreased lymph outflow, and regional lymph nodes, are

Fracture Repair: Its Pathomechanism and Disturbances http://dx.doi.org/10.5772/intechopen.76252 9

**2.** Reparative-replacement of hematoma with cartilaginous tissue and its endochondral os-

**3.** Remodeling-formation of mature bone with the structure analogous to that prior to the

The first phase lasts up to several (3–7) days, the second up to 4 weeks and the third may last up to 2 (or even more) years after the fracture. However, the advance of the healing may differ even in adjacent areas; especially, when proceeds in comminuted fractures. In consequence, remodeling already proceeding in between some bone fragments may coexist with

as an indicator of the quality of reparative processes (**Figure 2**).

**1.** Reactive- colonization of posttraumatic hematoma by inflammatory cells,

Uneventful healing may be divided into three phases:

sification (primary callus),

early, reactive phase between others.

fracture.

observed.

It was estimated that up to 15% of fractures display some kind of healing disturbances [32]. Depending on the severity of the pathological changes, it ranges from slow fracture healing (slow union), delayed union or non-union, if complete inhibition of the reparative processes occurs. The lack of union and the resultant non-union (pseudoarthrosis) are diagnosed when callus was not formed in-between bone fragments in an assumed period of time and all regenerative processes have stopped.

According to the recommendations of the food and drug administration, a non-union could be diagnosed, when the fracture is not healed in the 9th post-injury month, or any evidence of the healing progress could be observed on X-rays during the three consecutive months. However, the number of orthopedists that diagnose non-union as early as at the 6th post-fracture month implementing procedures that improve reparative processes increases. However, it is also believed that the time of the healing of a given bone should be determined arbitrarily, based on the clinical experience [33].

The varying opinions that concern the definition of disturbed fracture healing come from the lack of diagnostic tools that could demonstrate the moment of cessation of regenerative processes. The very important flaw of radiographic monitoring is the possibility to assess the status of the healing after a sufficiently long period of follow-up. Moreover, it does not allow predicting the final result.

**Figure 2.** Lymphoscintigrams of the uneventful (left) and disturbed (right) healings of the fractures of the right extremities. Uneventful healing is characterized by enlarged regional lymph nodes and lymphatic outflow, when compared with contralateral limb. If the healing is disturbed, decreased lymph outflow, and regional lymph nodes, are observed.

The only examination that may be useful in the monitoring of the healing process and predicting its outcome is limb lymphoscintigraphy [34]. Observation of the lymphatic system showed that regional lymph node draining the fracture is a subject of molecules released from its gap. Thus, increased lymph drainage and enlargement of the lymph node (accumulation of cells) reflect molecular and cellular events taking place at the fracture gap that may be used as an indicator of the quality of reparative processes (**Figure 2**).

Uneventful healing may be divided into three phases:

**5. Remodeling**

8 Trauma Surgery

excreting ECM proteins and mineralizing them.

**6. Uneventful and disturbed fracture healing**

callus mineralization and remodeling.

erative processes have stopped.

based on the clinical experience [33].

Remodeling proceeds in consequence of osteolysis and forthcoming osteogenesis. In the beginning, a group of activated osteoclasts, acidifying ECM, dissolve the osteoid and enzymatically (MMPs) digest its proteins. In consequence, resorptive (Howship) lacuna is formed. Released molecules that are stored in the latent form bound to ECM heparan sulfate (BMPs, Vascular endothelial growth factor (VEGF), FGF, and EGF) activate proliferation and folding into three-dimensional structures of endothelial cells originating from neighboring blood vessels [30]. Those form vascular loops (sprouts) in-growing into the lacunae, providing its blood supply. Inflowing MSCs differentiate into osteoblasts that repopulate lacunae as osteocytes

Osteoclasts at the top (cutting cone) gradually move across the bone as far as they reach its borderline (osteoclastic tunneling; remaining as Haversian canal), and finally undergo apoptosis. Passing across the fracture, they restore bone continuity (osteonal fracture healing), but only when the distance between bone fragments does not exceed 1 mm [31]. If the distance is higher, each bone fragment is remodeled alone and the fracture gap remains intact, that is not healed.

From the clinical point of view, the fracture is considered to be healed, when its mechanical properties are restored allowing carrying the body weight. Thus, the main indicators of successful healing are lack of the pathological mobility corresponding with a resolution of pain and restored the ability to carry mechanical loads confirmed by radiographic images showing

It was estimated that up to 15% of fractures display some kind of healing disturbances [32]. Depending on the severity of the pathological changes, it ranges from slow fracture healing (slow union), delayed union or non-union, if complete inhibition of the reparative processes occurs. The lack of union and the resultant non-union (pseudoarthrosis) are diagnosed when callus was not formed in-between bone fragments in an assumed period of time and all regen-

According to the recommendations of the food and drug administration, a non-union could be diagnosed, when the fracture is not healed in the 9th post-injury month, or any evidence of the healing progress could be observed on X-rays during the three consecutive months. However, the number of orthopedists that diagnose non-union as early as at the 6th post-fracture month implementing procedures that improve reparative processes increases. However, it is also believed that the time of the healing of a given bone should be determined arbitrarily,

The varying opinions that concern the definition of disturbed fracture healing come from the lack of diagnostic tools that could demonstrate the moment of cessation of regenerative processes. The very important flaw of radiographic monitoring is the possibility to assess the status of the healing after a sufficiently long period of follow-up. Moreover, it does not allow predicting the final result.


The first phase lasts up to several (3–7) days, the second up to 4 weeks and the third may last up to 2 (or even more) years after the fracture. However, the advance of the healing may differ even in adjacent areas; especially, when proceeds in comminuted fractures. In consequence, remodeling already proceeding in between some bone fragments may coexist with early, reactive phase between others.

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

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