Existing and potentially novel functional markers of vitamin D status: a systematic review

Background: Although serum 25-hydroxyvitamin D [25(OH)D] is the currently accepted vitamin D status marker of choice, use of other biomarkers or functional endpoints have been suggested. Objective: The objective was to systematically review the effectiveness of 25(OH)D, parathyroid hormone (PTH), bone turnover markers, bone mineral density (BMD), and calcium absorption as biomarkers of vitamin D status. Design: Methods included a structured search on Ovid MEDLINE, EMBASE (Ovid), and Cochrane CENTRAL; rigorous inclusion/exclusion criteria; data extraction; quality assessment; meta-analysis; and meta-regression. Results: Thirty-six vitamin D supplementation randomized controlled trials (RCTs) and 4 before-after studies were included. Vitamin D supplementation significantly raised circulating 25(OH)D in all but one RCT, but the response was highly heterogeneous [weighted mean difference (WMD): 34.1 nmol/L; 95% CI: 28.9, 39.2; 32 RCTs; I-2 = 97%). Vitamin D supplementation (without calcium) significantly lowered circulating PTH (WMD: -0.29 pmol/L; 95% CI: -0.56, -0.02; 11 RCTs; I-2 = 29%), but this was not apparent in the presence of calcium supplementation. There was a suggestion that whole-body or lumbar spine BMD may be a useful biomarker in older people but not in adolescents. Bone turnover markers were not useful biomarkers of vitamin D status, but 4 before-after studies suggested that intestinal calcium absorption may respond to vitamin D status. Conclusions: This systematic review confirmed that circulating 25(OH)D is a robust and reliable marker of vitamin D status. Further research is needed to clarify which population subgroups show responses of PTH, BMD, and/or calcium absorption in response to changes in vitamin D status. Am J Clin Nutr 2009; 89(suppl): 1997S-2008S.