Vitamin D supplementation for 12 months in older adults alters regulators of bone metabolism but does not change Wnt signalling pathway markers

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Vitamin D status and supplementation regulates bone metabolism and may modulate Wnt-signalling.

We studied the response of hormonal regulators of bone metabolism, markers of Wnt signalling and bone turnover and BMD and BMC in a randomised vitamin D intervention trial (12,000IU, 24,000IU, 48,000IU/month for 1 year; men and women >70y; n=379; ISRCTN35648481). Associations with total and free 25(OH)D concentrations were analysed by linear regression.

Baseline vitamin D status was (mean ± SD) 25(OH)D: 40.0 +/- 20.1 nmol/L. Supplementation dose-dependently increased total and free 25(OH)D concentrations and decreased plasma phosphate and PTH (all p<0.05). The PINP:CTX ratio, cFGF23 and iFGF23 significantly increased with no between-group differences, while Klotho was unchanged. 1,25(OH)2D and PINP significantly increased in the 24 and 48,000IU groups. SOST, OPG, RANKL, BMD, BMC and CTX remained unchanged. Subgroup analyses with baseline 25(OH)D<25nmol/L (n= 94) provided similar results.

Baseline total and free 25(OH)D concentrations were positively associated with 1,25(OH)2D, 24,25(OH)2D (p<0.001), DBP (p<0.05), BMD and BMC (P<0.05). Associations with PTH (p<0.001), cFGF23 (p<0.01) and BAP (p<0.05) were negative. After supplementation, total and free 25(OH)D concentrations remained positively associated only with 24,25(OH)2D (p<0.001), DBP (p<0.001) and negatively with eGFR (p<0.01). PTH and SOST were significantly associated only with free 25(OH)D. There were no significant relationships with BMD and BMC after supplementation.

The decrease in PTH and increase in PINP:CTX ratio suggest a protective effect of supplementation on bone metabolism although no significant effect on BMD or pronounced changes in regulators of Wnt signalling were found. The increase in FGF23 warrants caution due to its negative association with skeletal and cardiovascular health. Associations of total and free 25(OH)D with biomarkers were similar and known positive associations between vitamin D status and BMD were confirmed. The change in associations after supplementation might suggest a threshold effect.
Original languageEnglish
Article numbere10619
JournalJBMR Plus
Issue number5
Early online date5 Mar 2022
Publication statusPublished - May 2022

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