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.


METHODS
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; I2 = 97%). Vitamin D supplementation (without calcium) significantly lowered circulating PTH (WMD: -0.29 pmol/L; 95% CI: -0.56, -0.02; 11 RCTs; I2 = 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.
Seamans
Kelly M
KM
Department of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
Cashman
Kevin D
KD
D015415:Biomarkers / Q000097:blood*; D015519:Bone Density; D002118:Calcium / Q000493:pharmacokinetics*; D019587:Dietary Supplements; D006801:Humans; D007408:Intestinal Absorption; D008722:Methods; D015596:Nutrition Assessment; D009752:Nutritional Status; D010281:Parathyroid Hormone / Q000097:blood; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood*; D014815:Vitamins / Q000097:blood
D015415:Biomarkers; D010281:Parathyroid Hormone; D014815:Vitamins; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002118:Calcium