Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men

Abstract

A normal mineral metabolism is integral for skeletal development and preservation of bone integrity. Fibroblast growth factor 23 (FGF-23) is a bone-derived circulating factor that decreases serum concentrations of inorganic phosphorous (Pi) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Increased FGF-23 expression is a direct or indirect culprit in several skeletal disorders; however, the relation between FGF-23 and fracture risk remains undetermined. We evaluated the prospective relation between serum intact FGF-23 (measured by a two-site monoclonal antibody ELISA) and fracture risk employing the Swedish part of the population-based Osteoporotic Fractures in Men Study (MrOS; n=2868; mean age 75.4±3.2 years; median follow-up period 3.35 years). The incidence of at least one validated fracture after baseline was 20.4 per 1000 person-years. FGF-23 was directly related to the overall fracture risk [age-adjusted hazard ratio (HR) per SD increase=1.20, 95% confidence interval (CI) 1.03-1.40] and vertebral fracture risk (HR=1.33, 95% CI 1.02-1.75). Spline models revealed a nonlinear relation between FGF-23 and fracture risk, with the strongest relation at FGF-23 levels above 55.7pg/mL. FGF-23 levels above 55.7pg/mL also were associated with an increased risk for hip and nonvertebral fractures (HR=2.30, 95% CI 1.16-4.58, and HR=1.63, 95% CI 1.01-2.63, respectively). These relations remained essentially unaltered after adjustment for bodymass index (BMI), bone mineral density (BMD), glomerular filtration rate, 25(OH)2D 3, parathyroid hormone (PTH), and other fracture risk factors. In conclusion, FGF-23 is a novel predictor of fracture risk in elderly men. Copyright © 2011 American Society for Bone and Mineral Research.