Background/Purpose: Bone health in SLE is adversely affected by vitamin D deficiency, inflammatory cytokines including interferon (IFN)-α, and glucocorticoid use. We tested the hypothesis that vitamin D supplementation would increase bone formation and decrease bone resorption in an SLE clinical trial.

Methods: Vitamin D-deficient SLE subjects had completed a randomized controlled trial (NCT00710021) testing the effect of 2000 IU/d or 4000 IU/d vitamin D supplementation vs. placebo for 12 weeks upon the IFN gene signature. For this analysis, low- and high-dose vitamin D groups were analyzed together. All subjects met 1997 ACR SLE Classification Criteria, had inactive disease (SELENA-SLEDAI <=4), and were taking <20 mg of prednisone daily at baseline. Serum 25(OH) vitamin D and bone turnover markers (N-terminal propeptide of type 1 collagen [P1NP], a marker of bone formation, and C-telopeptide [CTX], a marker of bone resorption), were assayed in baseline and week 12 blood samples. Change in (Δ) P1NP, CTX, and 25(OH)D were calculated as week 12 minus baseline. Spearman rho estimated the correlation between Δ25(OH)D and Δbone turnover markers. We tested the effect of vitamin D supplementation vs. placebo on ΔP1NP and ΔCTX using Wilcoxon rank-sum tests in an intention-to-treat analysis. Subgroup analyses tested the effect of vitamin D among subjects with current glucocorticoid use and with a detectable IFN signature. Secondary analyses excluded bisphosphonate users and tested the effect of achieving vitamin D repletion (>=30 ng/mL).

Results: We analyzed 28 subjects randomized to vitamin D and 15 randomized to placebo. Baseline characteristics including P1NP and CTX were similar between groups. Mean age was 39.0 (SD 11.5) years, 93.0% were female, 48.8% Black, 41.8% White, and 39.5% used glucocorticoids at baseline. IFN signature was present in 83.7% at baseline. Sixty-five percent of subjects in the vitamin D group achieved repletion compared to none in the placebo group. Mean increase in 25(OH)D was 17.7 (SD 8.2) ng/mL in the vitamin D group vs. 2.9 (SD 4.9) ng/mL in the placebo group (p <0.01). Changes in 25(OH)D were not significantly correlated with ΔP1NP or ΔCTX. Changes in bone turnover markers were not significantly different in the vitamin D group vs. placebo group in the primary analysis (Table). The effect of vitamin D vs. placebo did not differ by glucocorticoid use. An increase in P1NP, suggesting bone formation, was observed in subjects without baseline IFN signature assigned to vitamin D, but this was not significantly different from placebo (p 0.16). Results from the primary analysis were similar after excluding bisphosphonate users (n=4). Changes in bone turnover markers were not significantly different in those who did vs. did not achieve vitamin D repletion.

Conclusion: Vitamin D supplementation did not affect the 12-week change in bone turnover markers among SLE subjects in this trial.