Fracture Remodelling

Paget s disease is a chronic bone disorder characterized by abnormal bone remodeling. The disease disrupts the growth of new bone tissue causing the bone to thicken and become soft. This weakens the bone, which increases susceptibility of fracture even with slight trauma or collapse of the bone (eg, the vertebrae). 

ELECTROCHEMICAL ASPECTS OF BONE REMODELING AND FRACTURE REPAIR... 

Research in humans has been mainly focused either in the prevention of osteoporosis in healthy postmenopausal women or in the treatment of already osteoporotic women. Some research programs have extensively used estimates of biochemical markers of bone remodeling, while others have mostly relied on evaluations of BMD, histomorphometry, and fracture incidence. 

Prevention of osteoporosis and fracture can be achieved through limiting the resorption-remodeling process. Four main families of products can be effective in controlling bone resorption estrogens, SERMs, bisphosphonates, and calcitonin. Large, prospective randomized trials have proven the effectiveness... 

Bone tissue has a rather unique capability among human tissues in response to injury or other changes that alter its mechanical requirements it can continuously remodel itself to meet those mechanical needs best [51, 52], For example, when a bone fractures, the body creates new bone to connect the broken fragments together, and then remodels the new bone to optimize its mechanical function in the particular region of the skeleton that the fracture has occurred. Human skeletal tissue has several functions, but, when a bone is fractured by trauma, or removed surgically due to disease or tumor formation, we only seek solutions so that its mechanical function can be carried out [53, 54],... 

Calcium and phosphate, the major mineral constituents of bone, are also two of the most important minerals for general cellular function. Accordingly, the body has evolved a complex set of mechanisms by which calcium and phosphate homeostasis are carefully maintained (Figure 42-1). Approximately 98% of the 1-2 kg of calcium and 85% of the 1 kg of phosphorus in the human adult are found in bone, the principal reservoir for these minerals. These functions are dynamic, with constant remodeling of bone and ready exchange of bone mineral with that in the extracellular fluid. Bone also serves as the principal structural support for the body and provides the space for hematopoiesis. Thus, abnormalities in bone mineral homeostasis can lead not only to a wide variety of cellular dysfunctions (eg, tetany, coma, muscle weakness) but also to disturbances in structural support of the body (eg, osteoporosis with fractures) and loss of hematopoietic capacity (eg, infantile osteopetrosis). 

Bone tissue is constantly being renewed by the concerted action of osteoblasts and osteoclasts. Bone remodeling has two main phases a resorption phase consisting in the removal of old bone by osteoclasts, and a later phase of new bone formation driven by osteoblasts [6], Thus, the activity of osteoblasts and osteoclasts determines bone mass, bone geometry, bone quality, and, subsequently, bone strength [7, 8]. Osteoporosis is a prevalent disorder consisting in decreased bone mass and/or abnormal bone microarchitecture that impairs bone strength and increases the risk of fracture. Therefore, patients with osteoporosis may suffer fractures as a result of minor trauma, or even in the absence of trauma. The most common osteoporotic fractures are those of the vertebral bodies, the hip, the wrist, the shoulder, and the pelvis. 

An estimated 75 million people are affected by osteoporosis to some degree in the United States, Europe, and Japan. Osteoporosis is a systematic skeletal disease characterized by bone mass and microarchitectural deterioration with a consequent increase in bone fragility and susceptibility to fracture. Operationally, osteoporosis can be defined as a certain level of bone mineral density. The definition of osteoporosis is somewhat arbitrary and is based on epidemiological data relating fracture incidence to bone mass. Uncertainty also is introduced due to variability in bone densitometry measurements. Other clinical measures to assess the skeleton include collagen cross-links (measure of bone resorption) and levels of bone-specific alkaline phosphatase and osteocalcin (bone formation). A list of biochemical markers of bone remodeling is provided in Table 37-3. Measurement of total serum alkaline phosphatase level and urinary hydroxyproline or calcium levels is of limited value. 

Bone resorption increases with age, but changes in bone formation are not observed consistently. Increased osteocyte apoptosis may decrease responses to mechanical strain and hinder bone repair. Cortical porosity from years of remodeling and decreased trabecular connectivity, particularly of horizontal struts, promotes microarchitectural deterioration of bone that is not always reflected in BMD. Aging also increases fracture risk in other ways that are independent of BMD. 

Definition localized disorder of bone remodeling, resulting in excessive bone resorption followed by disorganized bone replacement, producing thickened but weak bone that is susceptible to deformity and fracture... 

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