Genetic determinants of bone mass acquisition and risk for osteoporosis

Osteoporosis and fragility fractures have evolved into major public health issues, particularly given the change in population demographics and the ac companying demand for better preventive as well as treatment options to ave rt the risk for fracture and its consequences. With the widespread availabi lity of bone densitometry (e.g., DEXA), most studies have focused principal ly on determination and regulation of bone mineral density (BMD) status. Fr om a public health perspective, bone fragility is probably of equal or grea ter importance; thus, increasing attention is being devoted to the determin ants of fracture risk, which is, in part, but not entirely addressed by BMD status. integral to any discussion of BMD and bone strength is the issue o f bone acquisition, regulation, and loss. Among the key determinants recogn ized to contribute most substantially to the risk for, and progression to, osteoporosis and fracture are genetic factors. These present novel opportun ities for pure and applied research. Our review will summarize the evidence supporting a major role for the heritability of bone mineral status and it s regulation, as well as examining other candidate genetic factors that may independently contribute to fracture risk. We will also discuss these resu lts as they relate to our studies in several large cohorts of healthy young women as well individuals with chronic illness. Finally, we address opport unities for future research in this important and emerging field. Drug Dev. Res. 49:216-226, 2000. (C) 2000 Wiley-Liss, Inc.