الفهرس 
Bone Composition and StructureOnly 14 pages are availabe for public view
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Abstract
Osteoporosis is an impairment in bone strength due to an abnormal quantity, quality of bone, or both.
Osteoporosis is a major public health problem through its association with fragility fractures which is The most significant complication of osteoporosis. While fractures may occur at many sites, they most commonly occur in the hip, spine, and wrist.
Fractures associated with osteoporosis have a high predilection in females and are related to the patient’s age. While vertebral fracture is the most common type of osteoporotic fracture, hip fractures have a particularly high morbidity and mortality rate. Fracturing a hip is a major concern in many older people, in that it makes it difficult for the individual to perform necessary activities of day living (ADLs) and limits independence, and secondary complications may even lead to death.
Despite the availability of preventative therapeutic agents, the incidence of osteoporosis and its associated costs continue to rise globally.
Pathogenesis
The three mechanisms underlying osteoporosis are: (a) failure to achieve a skeleton of optimal strength during growth and development; (b) excessive bone resorption resulting in loss of bone mass and disruption of architecture; and (c) failure to replace lost bone due to defects in bone formation.
During growth, the balance between the volume of bone that is resorbed and the volume that is formed in the bone multicellular unit is positive. An equal balance between bone formation and resorbtion is reached by the late 20s to the med 30s, so that the bone structure remains stable. A negative balance in the bone multicellular unit, which causes bone loss, an increased remodeling rate, or both, compromises the strength of bone. The rate of gain in bone during growth and loss during aging is driven more by a high remodeling rate than by the magnitude of the positive or negative balance in the bone multicellular unit.
Estrogen has a central role in the pathogenesis of osteoporosis. This concept was based on the higher risk of osteoporosis incidence in postmenopausal women. Estrogen deficiency increases and estrogen treatment decreases the rate of bone remodeling, as well as the amount of bone lost with each remodeling cycle. Estrogen mediates its effects by diffusing through the plasma membrane of the cells and then binding to specific estrogen receptors in the target cell. The activated complex then translocates to the nucleus of the target cell and leads to stimulation or inhibition of specific genes, resulting in the synthesis of specific proteins. These intracellular proteins cause cell growth and differentiation.
Vitamin D is vital for bone health because it assists in the absorption and utilization of calcium. Also it exerts a tonic inhibitory effect on parathyroid hormone synthesis.Supplementation of both calcium and vitamin D can reverse secondary hyperparathyroidism, decrease bone resorption, increase bone mass, decrease fracture rates, and even decrease the frequency of falling. Although an excess of PTH, as in severe hyperparathyroidism, is often catabolic for bone, intermittent exposure of bone to PTH can increase bone formation and bone mass in humans.
RANK/ RANKL/OPG system has been implicated in the pathophysiology of osteoporosis. Osteoblasts produce RANKL, a ligand for RANK on hematopoietic cells, which activates the differentiation of osteoclasts and maintains their function. Osteoblasts also produce and secrete osteoprotegerin, a decoy receptor that can block RANKL/RANK interactions. Stimulators of bone resorption have been found to increase R ANKL expression in osteoblasts, and some also decrease OPG expression.
The critical recent discoveries of signal transduction pathways and transcription factors for osteoblast differentiation and function have opened up new approaches to understanding the pathogenesis of osteoporosis.
Osteoporosis is likely to be caused by complex interactions among local and systemic regulators of bone cell function. The heterogeneity of osteoporosis may be due not only to differences in the production of systemic and local regulators, but also to changes in receptors, signal transduction mechanisms, nuclear transcription factors, and enzymes that produce or inactivate local regulators.
Leptin has direct posetive effect on bone mass by stimulating the bone marrow stromal cells proliferation and differentiation to osteoblasts. Also leptin has a central negative effect on bone mass through the stimulation of ventromedial hypothalamic expression of Lepr, triggering norepinephrine release by sympathetic nervous system fibers and activation of 2-adrenergic receptors in osteoblasts, leading to suppression of osteoblast activity and bone formation, and increases bone resorption via RANKL.