Searching for genes underlying susceptibility to osteoporotic fracture: current progress and future prospect.

INTRODUCTION: Osteoporotic fracture (OF) is a public health problem. It is a common practice in the genetics of osteoporosis that bone mineral density (BMD) was studied as a major surrogate phenotype in gene search for risk of OF (ROF) because of their high phenotypic correlation. However, some studies indicate that the genetic correlation between BMD and ROF is very low. This implies that most genes found important for BMD may not be relevant to ROF. Ideally, employing OF per se as a direct study phenotype can directly find the relevant genes underlying ROF. EVIDENCE: Here, we summarized some evidence supporting ROF under moderate genetic control, and the current progress of molecular genetic studies employing OF as the direct study phenotype, then give our consideration on the future prospects in the genetics of ROF.