Can vitamin D metabolite measurements facilitate a “treat-to-target” paradigm to guide vitamin D supplementation?

N. Binkley, J. Lappe, R. J. Singh, S. Khosla, D. Krueger, M. K. Drezner, R. D. Blank

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Summary: Substantial variability exists in the serum 25(OH)D increase observed in response to vitamin D supplementation. Measurement of circulating cholecalciferol and 24,25(OH)2D, as indicators of vitamin D absorption and degradation, respectively, account for approximately half of the variation in serum 25(OH)D observed following supplementation.Introduction: Vitamin D supplementation produces a variable response in serum 25(OH)D. This variability likely reflects, in part, differences in vitamin D absorption and/or degradation. Despite this variation in response, virtually all expert recommendations endorse a fixed vitamin D supplementation dose, an approach also used in most prospective studies. Such utilization of a single vitamin D dose does not assure attaining any pre-specified target 25(OH)D level, thereby compromising clinical care and prospective supplementation trials. This study begins addressing this weakness by exploring the feasibility of vitamin D metabolite measurements to predict serum 25(OH)D level attained following supplementation.Methods: Ninety-one community-dwelling postmenopausal women with baseline 25(OH)D of 10–30 ng/mL received oral vitamin D3, 2300 or 2500 IU, daily for 4–6 months. Serum 25(OH)D, cholecalciferol (D3), and 24,25(OH)2D were measured before and at the end of supplementation to determine if metabolite concentrations allow prediction of the 25(OH)D level attained.Results: From baseline and follow-up data, we derived a multiple linear regression model predicting posttreatment 25(OH)D as follows: final 25(OH)D = 8.3 + (1.05*initial 25(OH)D) − (7.7*initial 24,25(OH)2D) + (0.53*final D3) + (4.2*final 24,25(OH)2D). This model has an adjusted R2 = 0.55, thus accounting for approximately half of the observed variance in the final 25(OH)D level.Conclusions: The contributions of circulating cholecalciferol and 24,25(OH)2D to this predictive model can be considered as indicators of intestinal absorption and clearance, respectively. This paradigm requires further study; it may allow efficient “treat-to-25(OH)D-target” strategies useful in optimizing prospective studies and clinical practice.

Original languageEnglish (US)
Pages (from-to)1655-1660
Number of pages6
JournalOsteoporosis International
Issue number5
StatePublished - May 1 2015


  • 24,25-Dihydroxyvitamin D
  • 25-Hydroxyvitamin D
  • Cholecalciferol

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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