Effect of vitamin D supplementation or fortification on bone turnover markers in women: A systematic review and meta-analysis.

Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomized clinical trials (RCTs) reported changes in bone resorption markers (serum C-terminal Telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP), and Procollagen type-1 intact N-terminal Propeptide (P1NP)) following vitamin D administration in women (aged ≥18 years old) were considered. Mean differences (MDs) and their respective 95% confidence intervals (CIs) were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias, and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0.038, n= 22) and OC (MD: -0.610, n=24) with high heterogeneity and uNTX (MD: -8.188, n= 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region, and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600IU/day and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.