100 day?

Factors affecting fracture healing

Definition of fracture nonunion: After 8 months of fracture, a fracture in which both ends of the fracture fail to reach bone connection is called nonunion. The distinction between fracture healing and nonunion mainly depends on whether the materials between the fractures have ossified, and some scholars have suggested that the fracture is nonunion when it fails to heal within 6 months. ?

Definition of delayed fracture healing: The time required for normal fracture healing (generally within 4 months) has not yet reached the standard of complete fracture healing, which is called delayed bone healing. ?

1. What are the causes of delayed healing and non-healing?

Although there are many reasons for nonunion and delayed connection, they are basically the same. Most factors have different degrees and different consequences. Some only produce delayed connection, which can be connected although it takes a long time to heal. Some form nonunion, such as osteogenic factor deficiency and congenital tibial nonunion. The reasons can be divided into three categories: technical factors, biological factors and comprehensive factors. ?

(1) technical factors?

The biological process of nonunion and delayed connection caused by technical factors is normal, and the abnormal bone healing is mainly caused by improper treatment methods. ?

1. infection: infection causes necrosis of the fracture end, occlusion of nutrient vessels, destruction of the normal process of callus formation, and leads to nonunion.

2. Improper treatment?

(1) Excessive traction: it can separate the fracture ends. ?

(2) Improper fixation: it can't eliminate the unfavorable abnormal activity and stress at the fracture end. ?

(3) Muscle contractility: It can increase the gap between broken ends of fractures, such as olecranon fracture of ulna and patella fracture. ?

(4) Open comminuted fracture: bone defect caused by excessive removal of bone fragments during debridement. ?

(5) Poor alignment of fracture ends: there are often gaps or soft tissues embedded in the gaps. ?

3. Blood supply disorder: severe open fracture, large soft tissue injury, soft tissue and blood vessel injury around the fracture, affecting the blood supply at the fracture end. Therefore, open fractures heal more slowly than closed fractures, and the incidence of nonunion is higher, which can reach 5% ~ 17%. Due to excessive periosteal dissection, the incidence of nonunion can reach 4 times that of closed reduction. Periosteum plays an important role in osteogenesis and is the main source of nutrient vessels in cortical bone. ?

In the United States and Canada, delayed bone connection and nonunion caused by technical factors account for 70% ~ 80% of the total number of delayed bone connection and nonunion, and the incidence of cortical bone is higher than that of cancellous bone. It is generally believed that hypertrophic nonunion (X-ray manifestations of fracture end separation, pseudarthrosis and callus overgrowth) combined with bone grafting has a good therapeutic effect. In addition, fixation, prevention of infection and good reduction are usually effective. If synovial connection is formed at the fracture end, the cartilage covering part must be removed, because this special tissue has the function of gating barrier, and the cartilage layer divided by synovial fluid appears in the calcification process of bone healing. ?

(2) Biological factors?

The treatment of delayed bone connection and nonunion caused by biological reasons is suitable. Delayed bone connection and nonunion are caused by abnormal biological processes, including callus formation disorder, callus calcification disorder, low regional accelerator (RAP), abnormal differentiation, abnormal bone remodeling, abnormal bone formation and the influence of mechanics on bone formation. Biological factors can affect bone healing alone or together with other factors. In the United States and Canada, nonunion caused only by biological factors accounts for about 20%, and combined technical factors account for about 20%. Delayed bone connection and nonunion caused by biological factors mostly occur in cortical bone, and cancellous bone rarely occurs. ?

1. Callus formation disorder: For long bone fractures, if the amount of callus formation is insufficient or there is no callus at all, it means that the activity of local multicellular media is abnormal, and it also means that there are obstacles such as cell sensitization-stimulation-proliferation-differentiation-organization in the early stage of fracture. In the United States and Canada, callus formation obstacles account for 80% of all biological factors. The clinical manifestation is long bone fracture for more than 2 months, and X-ray film shows that there is not enough callus at the fracture end. Histopathological study showed that there were few new bone tissues in the fracture space, but a large number of fibrous tissues were replaced. This happens when X-rays and cytotoxic drugs are used to treat tumors in clinic. In addition, it can also occur in local nerve block and the application of non-steroidal anti-inflammatory and analgesic drugs. ?

2. Callus calcification disorder: Callus calcification disorder can occur in various types of rickets (but rarely in vitamin D-resistant rickets), leading to false fractures and traumatic nonunion. Once the systemic metabolic disorder is corrected, callus can be calcified normally and bone healing can be normalized. Subsequent bone reconstruction and bone shaping must wait until the callus is completely calcified. Delayed bone connection and nonunion caused by callus calcification account for less than 3% of the causes of delayed bone healing and nonunion in the United States. ?

3. Low regional acceleration phenomenon (RAP): Primary bone injury can promote normal bone healing, which is called RAP. It can shorten the various stages of bone healing. Accelerate bone healing by 2 ~ 10 times. Low RAP can reduce callus formation at the fracture end and reduce the function of lamellar bone replacing woven bone. It is generally believed that low RAP accounts for less than 3% of all delayed healing and nonunion of long bone fractures, but it accounts for about 75% of delayed healing and nonunion of bone caused by biological factors, and the incidence of cortical bone is higher than that of cancellous bone. Three months after the fracture, the clinical X-ray can clearly show that the RAP is low, which is characterized by the lack of longitudinal tunnel-like changes in local dense bone or the scarcity of trabecular bone near the metaphyseal end and osteoporosis. Once the above situation occurs, it shows that bone reconstruction will be seriously affected and the scope of bone reconstruction will be narrowed. When RAP is low or missing, scintillation photography shows local cold phase; When RAP is obvious, callus formation increases, bone remodeling increases or local blood flow increases, and bone scanning shows that local isotope absorption increases. If the fracture lasts more than 2 months, the bone scan shows that the local cold phase indicates that the RAP is low or missing, indicating that the bone healing process is slow. But RAP obviously does not mean that there are enough callus formation, and sometimes callus formation and RAP can be separated. In addition, some clinical diseases can reduce RAP, and its mechanism is not clear, including diabetes, peripheral nerve injury, regional major sensory loss caused by various reasons, diphosphate poisoning, severe radiation injury, malnutrition and so on. Nevertheless, the reason of 70% clinical low RAP is not clear. Interestingly, low RAP rarely occurs in children, healthy animals and cancellous bone fractures. ?

4. Abnormal differentiation: Abnormal differentiation means that although the sensitization-stimulation-proliferation reaction of local tissue cells in the early stage of fracture is normal, if osteoblasts and chondrocytes produced in this early stage are replaced by fibroblasts or adipocytes, the fracture end space will be filled with scar tissue or adipose tissue instead of callus. The common causes of abnormal differentiation in clinic include some metastatic tumors and improper treatment of fractures; Rare causes include chronic primary hyperparathyroidism, neurofibromatosis, diabetic neuropathy, complete local nerve resection and congenital pseudarthrosis of tibia. In the United States and Canada, delayed bone healing and nonunion caused by abnormal tissue differentiation account for less than 10% of delayed bone healing and nonunion caused by biological factors, accounting for more than 50% of technical factors. ?

5. Abnormal bone remodeling: At present, it is known that bone remodeling is based on the basic multicellular unit, which is a special organized tissue composed of many types of cells, interstitial cells and capillaries interconnected in a certain time and space. Abnormal bone remodeling can delay the process of lamellar bone replacing callus. As we all know, callus does not have biomechanical related structural characteristics, but only lamellar bone has these characteristics. Therefore, the delay of bone reconstruction can lead to the deformation of load-bearing callus and the healing of bone deformity. Frost encountered only 7 cases in his 40-year medical career, and the cause is still unknown. It is generally believed that abnormal bone remodeling is related to some drug, biochemical and endocrine factors. ?

6. Abnormal bone shaping: Abnormal bone shaping mostly occurs in children with osteogenesis imperfecta, and the ability of lamellar bone to replace woven bone or plastic bone is almost completely or completely lost. Rickets and various rickets can also cause abnormal bone remodeling, which can lead to bending of tibia or femur. This may be due to the disorder of calcification of new lamellar bone, which leads to the accumulation of uncalcified lamellar bone matrix. In addition, it may also be due to the loss of "gate barrier effect" in the process of bone reconstruction, which hinders the correction of accumulated uncalcified lamellar bone matrix. As we all know, the bone's shaping ability is basically lost after the bone matures, but X-ray films can still show some shaping effects of the cortical surface of the inner and outer membranes within a few years after the fracture healing in adults. ?

The influence of mechanics on bone shaping: the stimulation of bone shaping mainly comes from local mechanics, and there is a "mechanical use window effect" in the process of bone healing, that is, too strong or too weak mechanical stimulation is not conducive to bone healing, and only a proper range of mechanical stimulation can promote bone healing. Muscle contraction and limb bearing can enhance RAP, thus accelerating bone shaping.

Second, the mechanism?

In the process of delayed bone connection and nonunion, we should not only consider the osteoblasts themselves, but also consider whether the formation process of osteoblasts is normal. Normal bone healing is affected by the interaction of systemic factors and local factors, as well as the interaction between bone and adjacent soft tissues. Systemic factors include hormones, drugs, age, sex, race, nutrition and other factors, and their effects on bones are persistent, long-term and systematic. There are at least two local factors. One is the biological substances produced by local tissues in the early stage of injury, which can be used as local and systemic messengers in the process of bone healing, and their properties are different in different fracture sites. The abnormality of these biological substances will lead to abnormal bone healing. In addition, local denervation and severe radiation injury can also lead to delayed bone connection and nonunion. Another kind of local factor is biochemical and biophysical messenger substances released by tissues in the early stage of injury. It is generally believed that local messenger substances have a short half-life, the action time is from a few seconds to several minutes, and the release amount is extremely small. Because both local cells and intercellular substances can produce or release these messenger substances, their scope of action is limited to the cells around them, and only a very small amount overflows into the circulation.

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