Maldaptation of the link between inflammation and bone turnover may be a key determinant of osteoporosis.

Currently the etiology of osteoporosis is attributed to various endocrine, metabolic, and mechanical factors. We hypothesize that many cases of osteoporosis are also partially attributable to a maladaptation of the link between inflammation and bone turnover. We explore the spatial and temporal link between inflammation and osteoporosis in conditions such as aging, menopause, reflex sympathetic dystrophy, HIV, pregnancy, transplantation, and steroid administration. While nutritional and mechanical factors clearly play a role in many of these situations, the spatial and temporal concordance of osteoporosis and inflammation is buttressed by emerging molecular evidence. Modern bone biology of humans may reflect dual functional legacies of mineral storage and structural support. Osteoporosis may result from disequilibrium between structural demand for key minerals and their biologic demand during maladaptive states of inflammation. Copyright 2004 Elsevier Ltd.