Genetic determinants of bone mass acquisition and risk for osteoporosis

Abstract

Osteoporosis and fragility fractures have evolved into major public health issues, particularly given the change in population demographics and the accompanying demand for better preventive as well as treatment options to avert the risk for fracture and its consequences. With the widespread availability of bone densitometry (e.g., DEXA), most studies have focused principally on determination and regulation of bone mineral density (BMD) status. From a public health perspective, bone fragility is probably of equal or greater importance; thus, increasing attention is being devoted to the determinants 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 of bone acquisition, regulation, and loss. Among the key determinants recognized to contribute most substantially to the risk for, and progression to, osteoporosis and fracture are genetic factors. These present novel opportunities for pure and applied research. Our review will summarize the evidence supporting a major role for the heritability of bone mineral status and its regulation, as well as examining other candidate genetic factors that may independently contribute to fracture risk. We will also discuss these results as they relate to our studies in several large cohorts of healthy young women as well individuals with chronic illness. Finally, we address opportunities for future research in this important and emerging field. Drug Dev. Res. 49:216–226, 2000. © 2000 Wiley-Liss, Inc.