The Vitamin D Metabolite Ratio Is Associated With Changes in Bone Density and Fracture Risk in Older Adults

Recent studies have suggested that 25-hydroxyvitamin D (25(OH)D) may be a poor biomarker of bone health, in part because measured levels incorporate both protein-bound and free vitamin D. The ratio of its catabolic product (24,25-dihydroxyvitamin D [24,25(OH)₂ D]) to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide more information on sufficient vitamin D stores and is not influenced by vitamin D-binding protein concentrations. We evaluated whether the VMR or 25(OH)D are more strongly associated with bone loss and fracture risk in older adults. We performed a retrospective cohort study of 786 community-dwelling adults aged 70 to 79 years who participated in the Health Aging and Body Composition study. Our primary outcomes were annual changes in bone density and incident fracture. The mean age of these participants was 75 ± 3 years, 49% were female, 42% were Black, and 23% had an estimated glomerular filtration rate (eGFR) <60 mL/mL/1.73m² . In fully adjusted models, a 50% lower VMR was associated with 0.3% (0.2%, 0.6%) more rapid decline in total hip bone mineral density (BMD). We found similar relationships with thoracic and lumbar spine BMD. In contrast, 25(OH)D₃ concentrations were not associated with longitudinal change in BMD. There were 178 fractures during a mean follow-up of 10 years. Each 50% lower VMR was associated with a 49% (95% confidence interval [CI] 1.06, 2.08) greater fracture risk, whereas lower 25(OH)D₃ concentrations were not significantly associated with fracture risk (hazard ratio [HR] per 50% lower 1.07 [0.80, 1.43]). In conclusion, among a diverse cohort of community-dwelling older adults, a lower VMR was more strongly associated with both loss of BMD and fracture risk compared with 25(OH)D₃ . Trials are needed to evaluate the VMR as a therapeutic target in persons at risk for worsening BMD and fracture. © 2021 American Society for Bone and Mineral Research (ASBMR).