Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures

WHI-OS prospective cohort of postmenopausal women aged 50-79 years; nested case-control design within WHI-OS; 400 incident hip fracture cases and 400 matched controls; exclusions included prior hip fracture and use of estrogen or other bone-active therapies; 40 U.S. centers; 39,793 eligible participants after exclusions; median follow-up of 7.1 years; hip fractures adjudicated by blinded central review; baseline fasting blood samples collected for biomarker analysis including serum 25(OH) vitamin D.

Lower serum 25(OH) vitamin D concentrations are associated with higher hip fracture risk. Unadjusted odds ratio (OR) per 25-nmol/L decrease: 1.30 (95% CI 1.07-1.58); multivariate adjustment had little effect. The highest risk was in the lowest vitamin D quartile versus the highest quartile (OR 1.71; 95% CI 1.05-2.79). The relationship is linear and not modified by age. Adjusting for frailty, physical function, falls, sex-steroid hormones, renal function, and bone turnover attenuated the association, with bone turnover (CTX) contributing most; full adjustment largely abolished the lowest-quartile effect, though the overall quartile trend remained significant. Conclusion: Low serum 25(OH) vitamin D concentrations are associated with higher hip fracture risk in community-dwelling women; mechanism remains unclear but may involve bone turnover and physical function; monitoring vitamin D status could help identify high-risk individuals.

Few nonwhite case-patients; bone mineral density and parathyroid hormone data not measured; potential seasonal variability in 25(OH) vitamin D; total 25(OH) vitamin D measured without distinguishing D2 vs D3; observational design with potential residual confounding.