Hip fractures are the most serious outcome of osteoporosis and one of the most disabling consequences of aging. In order to reduce the burden of this disease, the Healthy People 2010 objectives establish a national target to reduce the proportion of adults who have osteoporosis during the current decade. The overarching goal of this study is to further explore the relationship between genetically identified single nucleotide polymorphisms (SNPs) for hip fracture and putative causal pathways and biomarkers for hip fracture. We also propose to extend the genetic associations to a major skeletal phenotype associated with fracture risk, bone mineral density. The objectives of the study wil be to: (1) determine whether the genetic variants for hip fracture are similar to or differ from SNPs associated with bone mass and lean body mass by analyzing the most promising panel of SNPs from the Phase 1-2 hip fracture GWAS in a subset of postmenopausal women from the BMD cohort;(2) identify the association of a reproducible set of SNP's from the GWAS for hip fracture with putative novel biomarkers reflecting bone remodeling-osteoblast regulation, calcium balance, and inflammatory pathways;and (3) to analyze the set of genetic and serum/plasma biomarkers for hip fracture to determine whether two or more risk factors together predict hip fracture increased or decreased risk beyond what would be expected from the main effects of each risk factor. At the conclusion of the study, we wil have significantly advanced our understanding of the putative functional significance of genetic variants associated with hip fracture.
