Compared with total 25(OH)D, calculated free and bioavailable 25(OH)D are not superior in predicting indices of bone health in a population of older adults, according to research published in The Journal of Clinical Endocrinology and Metabolism.

Using data from a 1-year double-blind, randomized clinical trial ( identifier NCT01315366), researchers sought to investigate the impact of vitamin D-specific variables on indices of bone and mineral metabolism in response to 2 doses of vitamin D. Older adult participants (>65 years of age) who were overweight and had serum 25(OH)D levels between 10 ng/mL and 30 ng/mL were included (N=221; 55% women; mean 71.1±4.7 years of age; mean body mass index [BMI], 30.2±4.5 kg/m2).

All participants received a daily total of 1000 mg elemental calcium and a daily total intake of vitamin D equivalent to 600 IU/day or 3750 IU/day in the low- and high-dose groups, respectively.

At baseline, there were no differences in age, BMI, calcium and vitamin D supplementation, dietary calcium intake, serum 25(OH)D, bone mineral density, or other biochemical, skeletal, or hormone levels.

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At 12 months, investigators found an increase in total, bioavailable, and free 25(OH)D in both the low- and high-dose supplementation groups. Those in the high-dose group had higher levels of all 3 serum variables compared with those in the low-dose group (P <.001). In particular, bioavailable and free 25(OH)D levels were associated with total 25(OH)D (estimated r value, 0.942 and 0.943, respectively).

All 3 variables — serum total, bioavailable, and free 25(OH)D — were negatively correlated with parathyroid hormone (P <.001); correlation coefficients were similar, ranging from -0.22 to -0.25. A consistent trend for a negative relationship between mean parathyroid hormone level and mean 25(OH)D levels was established, stratified by quartiles of all 3 variables. In the first quartile, mean parathyroid hormone values were 1.27- to 1.29-fold higher compared with the fourth quartiles of each 25(OH)D variable.

Serum total, bioavailable, and free 25(OH)D levels were not correlated with either serum calcium levels or with indices of bone remodeling including C-terminal telopeptide and osteocalcin. When correlated with each other, there was no correlation between serum total, bioavailable, and free 25(OH)D and bone mineral density, either at study entry or at 12 months.

Study limitations include a lack of directly measured free 25(OH)D and the inclusion of overweight, older adult participants, which may limit the generalizability of results across other age ranges.

“Vitamin D supplementation at a dose of 3750 IU/day resulted in serum levels of total, bioavailable, and free 25(OH)D that were 1.28- to 1.38-fold higher than levels reached with [a] 600 IU/day dose,” the researchers concluded. “Additional studies are needed to determine the accuracy of calculated and measured free bioavailable 25(OH)D, as well as establish their normal range of reference using international calibration standards.”


El Sabeh M, Ghanem P, Al-Shaar L, et al. Total, bioavailable, and free 25(OH)D relationship with indices of bone health in elderly: a randomized controlled trial. Published online December 6, 2020. J Clin Endocrinol Metab. doi:10.1210/climem/dgaa780