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

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 prevention of fracture in older people.