Pathophysiology of osteoporosis.

As with many chronic diseases that express themselves late in life, osteoporosis is distinctly multifactorial, both in etiology and pathophysiology. Osteoporotic fractures occur because of a combination of injury and intrinsic bony fragility. Injury comes most often from a combination of falls, falling to the side, poor postural reflexes that fail to protect bony parts from impact, and reduced soft-tissue padding over bony prominences. The bony fragility itself is a composite of geometry, low mass density, severance of microarchitectural connections in trabecular structures, and altered bone material quality. The latter is primarily the result of accumulated fatigue damage, but reduced collagen cross-links and other intrinsic material defects may play a role as well. Reduced bone mass, in turn, is the result of varying combinations of gonadal hormone deficiency, inadequate intakes of calcium and vitamin D, decreased physical activity, comorbidity, and the effects of drugs used to treat various unrelated medical conditions. Finally, the often poor outcome from hip fracture in the elderly is partly due to associated protein-calorie malnutrition. An adequate preventive program for osteoporotic fracture must address as many of these factors as possible and be as multifaceted as the disease is multifactorial.