Evaluating vitamin D status by direct measurements of free serum 25-hydroxyvitamin D (25(OH)D) is not better at determining bone mineral density (BMD) than total serum 25(OH)D, according to study findings published in JBMR Plus.

It is currently unclear whether free serum 25(OH)D is more reflective of bone health compared with total serum 25(OH)D. In a previous study, the researchers found that total serum 25(OH)D values measured during summer were more useful for predicting BMD than winter values. In this study, the researchers compared the relative importance of free and total serum 25(OH)D for BMD by season as measured by dual-energy x-ray absorptiometry; 5002 Swedish women (mean age, 68) participated in the population-based longitudinal cohort study.

The correlation between free and total serum 25(OH)D was 0.38 (P <.0001). The average free serum 25(OH)D was 5.9 pmol/L and average total serum 25(OH)D was 58 nmol/L. Findings showed that both free and total serum 25(OH)D varied according to season, with 26% and 29% higher values in August vs January to March (nadir). No differences were observed in mean BMD between categories of free or total serum 25(OH)D in samples that were collected during the winter. 

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A small positive correlation was observed between summer values of total serum 25(OH)D and total hip BMD (r =.09; 95% CI, 0.02-0.16; P =.01), but not between free serum 25(OH)D and total hip BMD (r =-.01; 95% CI, -0.08 to 0.06; P =.76).

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“Our results do not support the notion that the ‘free hormone hypothesis’ is valid for vitamin D,” concluded the researchers.

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Michaëlsson K, Rasmusson A, Wolk A, Byberg L, Mitchell A, Melhus H. The free hormone hypothesis: is free serum 25-hydroxyvitamin D a better marker for bone mineral density in older women? JBMR Plus. 2018;2(6):367-374.