Osteoporosis is a disorder in which loss of bone strength leads to fragility fractures. This review examines the fundamental pathogenetic mechanisms underlying this disorder, which include: (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. Estrogen deficiency is known to play a critical role in the development of osteoporosis, while calcium and vitamin D deficiencies and secondary hyperparathyroidism also contribute. There are multiple mechanisms underlying the regulation of bone remodeling, and these involve not only the osteoblastic and osteoclastic cell lineages but also other marrow cells, in addition to the interaction of systemic hormones, local cytokines, growth factors, and transcription factors. Polymorphisms of a large number of genes have been associated with differences in bone mass and fragility. It is now possible to diagnose osteoporosis, assess fracture risk, and reduce that risk with antiresorptive or other available therapies. However, new and more effective approaches are likely to emerge from a better understanding of the regulators of bone cell function.Osteoporosis, characterized by the loss of bone mass and strength that leads to fragility fractures, has probably existed throughout human history but only recently became a major clinical problem as human lifespan increased. In the early 19th century, Sir Astley Cooper, a distinguished English surgeon, noted "the lightness and softness that (bones) acquire in the more advanced stages of life" and that "this state of bone . . . favors much the production of fractures" (1). The term osteoporosis was coined by Johann Lobstein at about the same time, but the disorder he described was probably osteogenesis imperfecta (2). In 1940, the American physician and endocrinologist Fuller Albright described postmenopausal osteoporosis and proposed that it was the consequence of impaired bone formation due to estrogen deficiency (3). Subsequently, the concept that there are 2 forms of osteoporosis, one related to estrogen deficiency at the menopause and the other to calcium deficiency and aging of the skeleton, was proposed (4). This has been replaced by the current concept that osteoporosis represents a continuum, in which multiple pathogenetic mechanisms converge to cause loss of bone mass and microarchitectural deterioration of skeletal structure. These factors, coupled with an increased risk of falls, contribute to a high incidence of fragility fractures in osteoporotic patients.There is a rapidly expanding amount of information, based on laboratory studies, that indicates that 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 tra...

ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force.

Osteoporosis is common in patients requiring long-term treatment with glucocorticoids. Careful attention to preventive management may minimize the severity of this serious complication.

Transdermal testosterone (5 mg/d) prevented bone loss at the femoral neck, decreased body fat, and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels. In addition, both testosterone and placebo groups demonstrated gains in lower extremity muscle strength, possibly due to the beneficial effects of vitamin D. Testosterone did result in a modest increase in PSA levels but resulted in no change in signs or symptoms of prostate hyperplasia.

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