The relationship of 25-hydroxyvitamin D values and risk of fracture: a population-based retrospective cohort study

Summary: Our study investigates 25-hydroxyvitamin D levels and fracture risk using population-level data. 25-Hydroxyvitamin D values < 12, 12–19, and > 50 ng/mL were not associated with increased risk of fractures overall compared with values 20–50 ng/mL. Severely low levels may be associated with increased risk of osteoporotic fracture, particularly of the wrist. Introduction: Studies of the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and fracture risk have been inconsistent. We hypothesized that high 25(OH)D concentrations (> 50 ng/mL) would be associated with increased risk of fracture. Methods: We identified all adult patients living in Olmsted County, Minnesota, between January 1, 2005 and December 31, 2011, who had at least one 25(OH)D measurement. Fracture outcomes were retrieved starting 30 days after 25(OH)D measurement and until patients’ final clinical visit as an Olmsted County resident, December 31, 2014, or death. Data were analyzed using Cox proportional hazard regression. Results: Of 11,002 individuals with a 25(OH)D measurement, 5.8% had a 25(OH)D value ˂ 12 ng/mL, and 5.1% had a value > 50 ng/mL. Compared with subjects with 25(OH)D values 20–50 ng/mL (reference group), values < 12, 12–19, and > 50 ng/mL displayed no association with overall fracture risk. After adjusting for a prior diagnosis of osteoporosis/osteopenia, only individuals with values ˂ 12 ng/mL had increased risk of any osteoporotic fracture (aHR = 1.41; 95% CI 1.05–1.89) and wrist fracture (aHR = 2.11; 95% CI 1.27–3.48) compared with the reference group. Compared with the reference group, values ˂ 12 ng/mL were associated with increased risk of any fracture (aHR = 1.35; 95% CI 1.01–1.80), osteoporotic fracture (aHR = 2.18; 95% CI 1.44–3.31), and wrist fracture (aHR = 2.39; 95% CI 1.19–4.81) in subjects without a prior diagnosis of osteoporosis/osteopenia, but not in those with a prior diagnosis of osteoporosis/osteopenia. Conclusion: Severely low 25(OH)D levels may be associated with increased risk of osteoporotic fracture, particularly of the wrist, but 25(OH)D values > 50 ng/mL were not associated with increased fracture risk.