Clinical and biomarker modifiers of vitamin D treatment response: the multi-ethnic study of atherosclerosis.

BACKGROUND Different 25-hydroxyvitamin D (25(OH)D) thresholds for treatment with vitamin D supplementation have been suggested, and are derived almost exclusively from observational studies. Whether other characteristics including race/ethnicity, body mass index (BMI), and estimated glomerular filtration rate (eGFR) should also influence the threshold for treatment is unknown. OBJECTIVE Identify clinical and biomarker characteristics that modify the response to vitamin D supplementation. METHODS 666 older adults in the Multi-Ethnic Study of Atherosclerosis (MESA) were randomized to 16 weeks of oral vitamin D3 (2000 IU/d; n = 499) or placebo (n = 167). Primary outcomes were changes in serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D) concentrations from baseline to 16 weeks. RESULTS Among 666 participants randomized (mean age 72 years, 53% female, 66% racial/ethnic minority), 611 (92%) completed the study. Mean (SD) change in PTH was -3 (16) pg/mL with vitamin D3 vs 2 (18) pg/mL with placebo (estimated mean difference, -5 (95% CI: -8, -2) pg/mL). Within the vitamin D3 group, lower baseline 25(OH)D was associated with a larger decline in PTH in a non-linear fashion. With baseline 25(OH)D ≥30 ng/mL as the reference, 25(OH)D <20 ng/mL was associated with a larger decline in PTH with vitamin D3 supplementation (-10 (95% CI: -15, -6) pg/mL) whereas 25(OH)D 20-30 ng/mL was not (-2 (95% CI: -6, 1) pg/mL). A segmented threshold model identified a baseline 25(OH)D concentration of 21 (95% CI: 13, 31) ng/mL as an inflection point for difference in change in PTH. Race/ethnicity, BMI and eGFR did not modify vitamin D treatment response. There was no significant change in 1,25(OH)2D in either treatment group. CONCLUSIONS Of characteristics most commonly associated with vitamin D metabolism, only baseline 25(OH)D <20 ng/mL modified the PTH response to vitamin D supplementation, providing support from a clinical trial to use this threshold to define insufficiency. Clinicaltrials.gov NCT02925195.