Fibroblast Growth Factor 23, Bone Mineral Density, and Risk of Hip Fracture Among Older Adults: The Cardiovascular Health Study

Context: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that also inhibits calcitriol synthesis. Objective: Our objective was to evaluate the relationships of plasma FGF23 concentrations with bone mineral density (BMD) and hip fracture in community-dwelling older adults. Design and Setting: Linear regression and Cox proportional hazard models were used to examine the associations of plasma FGF23 concentrations with BMD and incident hip fracture, respectively. Analyses were also stratified by chronic kidney disease. Participants: Participants included 2008 women and 1329 men ≥65 years from the 1996 to 1997 Cardiovascular Health Study visit. Main Outcome Measures: Dual x-ray absorptiometry measured total hip (TH) and lumbar spine (LS) BMD in 1291 participants. Hip fracture incidence was assessed prospectively through June 30, 2008 by hospitalization records in all participants. Results: Women had higher plasma FGF23 concentrations than men (75 [56–107] vs 66 [interquartile range = 52–92] relative units/mL; P < .001). After adjustment, higher FGF23 concentrations were associated with greater total hip and lumbar spine BMD in men only (β per doubling of FGF23 = 0.02, with 95% confidence interval [CI] = 0.001–0.04 g/cm2, and 0.03 with 95% CI = 0.01–0.06 g/cm2). During 9.6 ± 5.1–11.0 years of follow-up, 328 hip fractures occurred. Higher FGF23 concentrations were not associated with hip fracture risk in women or men (adjusted hazard ratio = 0.95, with 95% CI = 0.78–1.15, and 1.09 with 95% CI = 0.82–1.46 per doubling of FGF23). Results did not differ by chronic kidney disease status (P > .4 for interactions). Conclusions: In this large prospective cohort of community-dwelling older adults, higher FGF23 concentrations were weakly associated with greater lumbar spine and total hip BMD but not with hip fracture risk.