The remodeling phase is the final phase of the five-phase secondary fracture healing process. During this phase, old bone mass is removed and new bone substance is built up through the simultaneous activity of osteoclasts and osteoblasts. In osteoporosis, the activity of osteoblasts and osteoclasts is impaired.
What is the remodeling phase?
The remodeling phase is the final phase of the five-phase secondary fracture healing process. It involves the simultaneous activity of osteoclasts and osteoblasts to remove old bone mass and build up new bone substance. The complete severing of a bone by indirect or direct force is also called a fracture. In the case of a bone fracture, two or more fragments are formed, which can usually be rejoined therapeutically. Bone fractures are either direct primary or indirect secondary fractures. In direct fractures, the ends of the fracture are directly adjacent to each other. Indirect fractures, on the other hand, are characterized by a gap between the fracture ends. Fracture healing is either primary or secondary depending on the fracture type. Secondary fracture healing results in the formation of a visible callus, also known as a bone scar. Secondary fracture healing occurs in five phases. The injury and inflammation phase are followed by the granulation phase and callus hardening. At the end of secondary fracture healing is the so-called remodeling phase, which consists of modeling and remodeling processes. In this process, the bone grows exactly as much as it is resorbed. Thus, a stable skeletal system is maintained in the organism even after fractures with good healing.
Function and task
Redomodelling of bone tissue is used to build up new bone tissue and to remove old bone tissue. The process is relevant to the healing of indirect fractures. However, it also occurs in the body independently of fractures to adapt bone structures to stresses. In addition to osteoclasts, osteoblasts are involved in the process. Osteoclasts are cells with multiple nuclei. They are formed by the fusion of mononuclear progenitor cells in the bone marrow and are part of the mononuclear-phagocytic system. Thus, they belong to the cells of the reticular connective tissue. Their tasks mainly include degradation work on bone substance. Bone formation, on the other hand, is carried out by osteoblasts. These cells arise from undifferentiated cells of the mesenchyme and are thus embryonic connective tissue cells. They attach themselves to the bone in a skin layer-like manner and thus form the basis for new bone substance. This basic framework is also called bone matrix and is formed by the secretion of type 1 collagen and calcium phosphates or carbonates into the interstitial space. During bone formation, osteoblasts become a scaffold of osteocytes with no ability to divide. This scaffold mineralizes and becomes filled with calcium. The network of osteocytes is incorporated into the newly formed bone. As a repair mechanism, the remodeling phase minimizes bone wear and maintains a stable and functional skeleton for humans. Structural damage from everyday stresses is corrected by remodeling, and the microarchitecture of the bone is adapted to the stress conditions. In fracture healing, remodeling plays a role mainly in the form of callus remodeling. The remodeling processes result in a fully load-bearing bone. During remodeling, the osteoclasts break down the bone matrix and the osteoblasts build up new bone substance via the intermediate osteoid stage. The osteoclasts burrow into the bone matrix through lytic enzymes such as cathepsin K, MMP-3 and ALP, where they form resorption lacunae. In fields of about 50 cells, osteoblasts secrete the new bone matrix. As the process continues, this collagenous matrix is calcified, resulting in stable bone. Presumably, the remodeling processes are subject to a superordinate control, which is also called coupling. However, the exact regulatory mechanisms of remodeling are not yet known.
Diseases and disorders
Remodeling plays a role in disease conditions such as senile osteoporosis. Bone density decreases in this disease. Bone substance breaks down excessively fast in osteoporosis. The osteoblasts can hardly keep up with the build-up of new substance. This makes patients more susceptible to fractures.In addition to vertebral body fractures, fractures of the femur near the hip joint, fractures of the radius near the wrist, and fractures of the humeral head frequently occur. Pelvic fractures are also a common symptom of osteoporosis. The most common cause of osteoporosis is insufficient bone formation during the first three decades of life. Up to the age of about 30 years, bone substance increases permanently due to the activity of osteoblasts. A healthy person builds up so much bone substance in the first three decades of life that the increased breakdown in the later decades of life does not cause any complications. The fact that osteoporosis patients have built up too little bone substance in the earlier decades of life can have various reasons. Nutrition, for example, may play a role. Other conceivable causes are inflammatory or hormonal diseases. Osteoporosis is not the only disease that can cause problems in modeling and remodeling. The processes of osteoclasts or osteblasts can also be disturbed, for example, due to genetic factors. In pycnodysostosis, for example, osteoclast activity is severely diminished. The same applies to polycystic lipomembranous osteodysplasia or Nasu-Hakola disease. Increased osteoclast activity is present in hyperparathyroidism, Paget’s disease, or aseptic bone necrosis. Rheumatoid arthritis, osteogenesis imperfecta or giant cell tumors can also cause the overactivity. Dysregulated activities of osteoblasts, on the other hand, play a role predominantly in bone proliferation. For example, degeneration of osteoblasts can cause osteoblastomas and thus a type of bone cancer.
