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

Meta-analysis integrating the BEST-D factorial vitamin D3 RCT (2000 vs 4000 IU/day vs placebo; n=305) with global placebo-controlled trials reports pooled average differences in procollagen type-1 N-propeptide (P1NP) of −3.3% (95% CI −5.6 to −1.0; p<0.005) and in C-terminal telopeptide of type-I collagen (CTX) of −3.8% (95% CI −6.8 to −0.8; p=0.01) for vitamin D versus control, with BEST-D itself showing no clear P1NP/CTX shift at 12 months in the trial-specific abstract summary.

Design

  • Anchor trial: BEST-D — vitamin D₃ 2000 IU/day or 4000 IU/day vs placebo (n = 305)
  • Meta-analysis: pooled vitamin D vs placebo effects on P1NP and CTX turnover markers
  • Corpus sizes (abstract): P1NP meta-analysis 18 trials; CTX meta-analysis 16 trials (participant counts reported in abstract)

BEST-D–specific 12-month geometric means (abstract)

25(OH)D rose dose-dependently on vitamin D, but P1NP and CTX did not materially differ vs placebo in BEST-D’s primary biomarker contrasts (p ≈ 0.29 and p = 0.98 respectively in abstract summary)

Pooled trial-average differences (vitamin D vs control)

  • P1NP: −3.3% average difference in within-trial change (95% CI −5.6 to −1.0; p < 0.005)
  • CTX: −3.8% (95% CI −6.8 to −0.8; p = 0.01)
  • Authors note no significant heterogeneity after stratifying by calcium co-supplementation, dose, or baseline 25(OH)D

Evidence hygiene

BTM shifts are surrogate endpoints—pair with fracture RCTs (VITAL ancillary fracture row on this wiki) before inferring hard outcomes.

Publication

Sandford Alber C, Halsey J, Emberson J, et al. Br J Nutr. 2026 Apr 27:1-22. doi: 10.1017/S0007114526107193. Epub ahead of print. PMID 42036999.

Outcomes

  • Pooled meta-analysis of vitamin D vs placebo: average difference in within-trial change for P1NP −3.3% (95% CI −5.6 to −1.0; p<0.005).
  • Pooled meta-analysis for CTX: −3.8% (95% CI −6.8 to −0.8; p=0.01); BEST-D trial itself reported no significant P1NP/CTX shift at 12 months in abstract summary.
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