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Effects of vitamin D on biochemical markers of osteoporosis: a meta-analysis of randomised trials

Alber CS, Halsey J, Emberson J, Hin H, Hill M, Armitage J, Clarke RJ

The British journal of nutrition, 2026

2,695 participants

Abstract

Plasma levels of procollagen type 1 N-propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) are bone turnover markers (BTMs) used to predict risk of fracture. We compared effects of vitamin D supplements on plasma levels of P1NP and CTX in the BEST-D trial (305 participants) after treatment with 2000 IU/day or 4000 IU/day vitamin D3 or placebo. The results of BEST-D were combined in a meta-analysis of all trials of vitamin D vs placebo on levels of P1NP (12 trials, 2654 participants) or CTX (16 trials, 2695 participants). In BEST-D, allocation to vitamin D3 resulted in a dose-dependent increase in 25-hydroxy-vitamin D (25[OH]D) levels, but had no effects on P1NP or CTX. Geometric mean (SE) levels at 12 months were similar for P1NP (41.7 [0.7] vs 42.9 [1.0] ng/mL; p=0.29: either dose vs placebo) and likewise for CTX (0.23 [0.01] vs 0.23 [0.01] ng/mL; p=0.98). In a meta-analysis of 18 trials, the average difference between the within-trial change in P1NP for allocated vitamin D and control was -3.3% (95% CI -5.6 to -1.0, p<0.005). For CTX, this difference was slightly greater (-3.8% [-6.8 to -0.8]; p=0.01). There was no significant heterogeneity between these trials after stratifying trials with or without calcium, higher or lower doses of vitamin D, or lower vs higher pre-treatment levels of 25(OH)D. Overall, vitamin D supplementation was associated with modest reductions in both P1NP and CTX and results provide support for further trials of vitamin D for…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 2,695 participants or records.

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