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

A.W. Enneman, K.M.A. Swart, J.P. van Wijngaarden, S.C. van Dijk, A.C. Ham, E.M. Brouwer-Brolsma, N.L. van der Zwaluw, R.A.M. Dhonukshe-Rutten, T.J.M. van der Cammen, C.P.G.M. de Groot, J.B.J. van Meurs, P. Lips, A.G. Uitterlinden, M.C. Zillikens, N.M. van Schoor, N. van der Velde*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

32 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)401-409
JournalCalcified Tissue International
Volume96
Issue number5
DOIs
Publication statusPublished - 2015

Keywords

  • placebo-controlled trial
  • postmenopausal women
  • fracture risk
  • turnover markers
  • elderly-women
  • metaanalysis
  • association
  • population
  • folate
  • bmd

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