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.
Highlights
A decade ago, plasma levels of homocysteine (Hcy) were discovered to be positively associated with incident osteoporotic fractures [1, 2]
We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters
The current study investigated the effects of vitamin B12 and folic acid supplementation on BMD and QUS parameters, that is broadband ultrasound attenuation (BUA) and speed of sound (SOS), in a large, mildly hyperhomocysteinemic, but otherwise general elderly population
Summary
A decade ago, plasma levels of homocysteine (Hcy) were discovered to be positively associated with incident osteoporotic fractures [1, 2]. Vitamin B12 and/or folate are important co-factors in the remethylation of Hcy to methionine, and high plasma Hcy levels are often caused by vitamin B12 and/or folate deficiency [3]. Subsequent supplementation with these vitamins has been shown to be effective in reducing levels of Hcy [4]. Two trials investigated the effect of B-vitamin supplementation on BMD, and both observed no effects [6, 12] These trials were limited either in size (n = 47) [12] or in generalizability (hemiplegic post-stroke patients) [6] and both used fairly high doses of B-vitamins
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