title: 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.
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.
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Anke W
authors.initials: AW
authors.lastname: Enneman
authors.forename: Karin M A
authors.initials: KM
authors.lastname: Swart
authors.forename: Janneke P
authors.initials: JP
authors.lastname: van Wijngaarden
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: van Dijk
authors.forename: Annelies C
authors.initials: AC
authors.lastname: Ham
authors.forename: Elske M
authors.initials: EM
authors.lastname: Brouwer-Brolsma
authors.forename: Nikita L
authors.initials: NL
authors.lastname: van der Zwaluw
authors.forename: Rosalie A M
authors.initials: RA
authors.lastname: Dhonukshe-Rutten
authors.forename: Tischa J M
authors.initials: TJ
authors.lastname: van der Cammen
authors.forename: Lisette C P G M
authors.initials: LC
authors.lastname: de Groot
authors.forename: Joyce
authors.initials: J
authors.lastname: van Meurs
authors.forename: Paul
authors.initials: P
authors.lastname: Lips
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
authors.forename: Natasja M
authors.initials: NM
authors.lastname: van Schoor
authors.forename: Nathalie
authors.initials: N
authors.lastname: van der Velde
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects*; D002111:Calcaneus / Q000000981:diagnostic imaging; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging; D005492:Folic Acid / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000097:blood / Q000517:prevention & control*; D014463:Ultrasonography; D014805:Vitamin B 12 / Q000627:therapeutic use*
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12