The epidemiology and pathogenesis of osteoporosis.

Osteoporosis is a multifactorial disorder associated with low bone mass and enhanced skeletal fragility. Although most prevalent in older females, some men are at high risk as well. Risk factors in men and women include smoking, family history of fracture, age greater than 65 years and low BMI. Obesity has also been associated with a greater risk of fracture in men. Secondary causes of osteoporosis include chronic treatment with glucocorticoids, gastrointestinal disorders, diabetes mellitus (T1D, T2D), rheumatoid arthritis, liver disease, gluten enteropathy, multiple myeloma and other hematologic disorders. However, primary osteoporosis is most often related to either postmenopausal estrogen loss or age related deterioration of the microarchitecture; both are due to uncoupling in the remodeling unit. Reduced bone formation with age is almost certainly a function of impaired stem cell differentiation into the osteoblast lineage with a resultant increase in marrow adipogenesis. Increased bone resorption also characterizes most forms of osteoporosis but the etiology is multifactorial. Changes in local and systemic growth factors are often responsible for uncoupling between resorption and formation. However, alterations in peak bone acquisition contribute years later to low bone mass and enhanced skeletal fragility. Fracture risk (e.g. FRAX) tools found in handheld apps and computers have provided rapid assessments of future osteoporotic fractures that can be performed at the bedside. Newer methods of measuring bone quality have led to insights into micro-architectural deterioration that contributes to skeletal fragility. Notwithstanding, low areal bone mineral density by DXA remains the strongest predictor of subsequent fracture and this is potentially measurable in everyone. For complete coverage of this and related areas in Endocrinology, visit our free web-books, www.endotext.org and www.thyroidmanager.org