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Pathogenesis of osteoporosis

Stavros C Manolagas, MD, PhD
Section Editor
Clifford J Rosen, MD
Deputy Editor
Jean E Mulder, MD


Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fractures. Throughout life, older bone is periodically resorbed by osteoclasts at discrete sites and replaced with new bone made by osteoblasts. This process is known as remodeling. Remodeling is orchestrated and targeted to a particular site that is in need for repair by osteocytes [1]. An oversupply of osteoclasts relative to the need for remodeling or an undersupply of osteoblasts relative to the need for cavity repair are the seminal pathophysiological changes in osteoporosis [2,3].

The amount of bone mass accrued by an individual reaches a peak by the third decade of life. Low peak bone mass probably contributes to the development of osteoporosis later in life. However, old age, sex steroid deficiency, lipid oxidation, decreased physical activity, use of glucocorticoids, and a propensity to fall are the most critical determinants of increased fracture risk.

This topic will address each of these pathogenetic factors and, when it is known, how they interact with each other. Bone remodelling and osteoporotic fracture risk assessment are reviewed separately. (See "Normal skeletal development and regulation of bone formation and resorption" and "Osteoporotic fracture risk assessment".)


Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fractures. Although osteoporosis (a term used to define decreased bone mass per unit volume of anatomical bone) has become synonymous with decreased bone mineral density (BMD), this feature is not always present. Small bone size, unfavorable macro-architecture (eg, increased length of the femoral neck), disrupted micro-architecture (image 1 and figure 1), cortical porosity, compromised quality of the material, and decreased viability of osteocytes (former osteoblasts buried within mineralized bone that sense and respond to changes in mechanical forces) are some other factors contributing to decreased strength.

The diagnosis of osteoporosis or estimates of the risk for developing it in the future rely almost exclusively on measures of bone mass by imaging studies such as dual energy x-ray absorptiometry (DXA) (table 1) and quantitative computed tomography (CT). These measures are fairly good clinical surrogates, but it is important to remember that the disease is bone fragility, and decreased BMD on DXA is just one of many risk factors. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women" and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men".)

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Literature review current through: Nov 2017. | This topic last updated: Jul 20, 2017.
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