Effect of vitamin B12 and folic acid supplementation on bone mineral density and quantitative ultrasound parameters in older people with an elevated plasma homocysteine level: B-PROOF, a randomized controlled trial

High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged =65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p <0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement.

Bibliographic Details

Main Authors:	Enneman, A.W., Swart, K.M.A., van Wijngaarden, J.P., van Dijk, S.C., Ham, A.C., Brouwer-Brolsma, E.M., van der Zwaluw, N.L., Dhonukshe-Rutten, R.A.M., van der Cammen, T.J.M., de Groot, C.P.G.M., van Meurs, J.B.J., Lips, P., Uitterlinden, A.G., Zillikens, M.C., van Schoor, N.M., van der Velde, N.
Format:	Article/Letter to editor biblioteca
Language:	English
Subjects:	association, bmd, elderly-women, folate, fracture risk, metaanalysis, placebo-controlled trial, population, postmenopausal women, turnover markers,
Online Access:	https://research.wur.nl/en/publications/effect-of-vitamin-b12-and-folic-acid-supplementation-on-bone-mine
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