caa a22 4500 605521514 CHVBK 20210128100740.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00223-015-9968-6 doi (NATIONALLICENCE)springer-10.1007/s00223-015-9968-6 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 [Elektronische Daten] [Anke Enneman, Karin Swart, Janneke van Wijngaarden, Suzanne van Dijk, Annelies Ham, Elske Brouwer-Brolsma, Nikita van der Zwaluw, Rosalie Dhonukshe-Rutten, Tischa van der Cammen, Lisette de Groot, Joyce van Meurs, Paul Lips, André Uitterlinden, M. Zillikens, Natasja van Schoor, Nathalie van der Velde] 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 ≥65years with plasma Hcy levels between 12 and 50µmol/L. The intervention comprised 2-year supplementation with either a combination of 500µg B12, 400µg folic acid, and 600IU vitamin D or placebo with 600IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwentQUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2years, 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 >80years (estimated marginal mean 64.4dB/MHz for the intervention group and 61.0dB/MHz for the placebo group, p=0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 andfolic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80years who were compliant in taking the supplement. The Author(s), 2015 DXA nationallicence QUS nationallicence Vitamin B12 nationallicence Folic acid nationallicence Homocysteine nationallicence Enneman Anke Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Swart Karin Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands aut van Wijngaarden Janneke Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands aut van Dijk Suzanne Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Ham Annelies Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Brouwer-Brolsma Elske Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands aut van der Zwaluw Nikita Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands aut Dhonukshe-Rutten Rosalie Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands aut van der Cammen Tischa Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut de Groot Lisette Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands aut van Meurs Joyce Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Lips Paul Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands aut Uitterlinden André Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Zillikens M. Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut van Schoor Natasja Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands aut van der Velde Nathalie Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Calcified Tissue International Springer US; http://www.springer-ny.com 96/5(2015-05-01), 401-409 0171-967X 96:5<401 2015 96 223 https://doi.org/10.1007/s00223-015-9968-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-9968-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Enneman Anke Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Swart Karin Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- van Wijngaarden Janneke Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands aut NATIONALLICENCE 700 1- van Dijk Suzanne Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Ham Annelies Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Brouwer-Brolsma Elske Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands aut NATIONALLICENCE 700 1- van der Zwaluw Nikita Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands aut NATIONALLICENCE 700 1- Dhonukshe-Rutten Rosalie Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands aut NATIONALLICENCE 700 1- van der Cammen Tischa Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- de Groot Lisette Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands aut NATIONALLICENCE 700 1- van Meurs Joyce Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Lips Paul Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Uitterlinden André Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Zillikens M. Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- van Schoor Natasja Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- van der Velde Nathalie Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 96/5(2015-05-01), 401-409 0171-967X 96:5<401 2015 96 223