Open Access Study protocol

Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence

Janneke P van Wijngaarden1*, Rosalie AM Dhonukshe-Rutten1, Natasja M van Schoor2, Nathalie van der Velde3, Karin MA Swart2, Anke W Enneman3, Suzanne C van Dijk3, Elske M Brouwer-Brolsma1, M Carola Zillikens4, Joyce BJ van Meurs4, Johannes Brug2, André G Uitterlinden4, Paul Lips5 and Lisette CPGM de Groot1

Author Affiliations

1 Department of Human Nutrition, Wageningen University, P.O. Box 8129 6700 EV Wageningen, the Netherlands

2 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

3 Department of Internal Medicine-Section Geriatric Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands

4 Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands

5 Department of Endocrinology, VU University medical center, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands

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BMC Geriatrics 2011, 11:80  doi:10.1186/1471-2318-11-80

Published: 2 December 2011

Abstract

Background

Osteoporosis is a major health problem, and the economic burden is expected to rise due to an increase in life expectancy throughout the world. Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk. As vitamin B12 and folate intake and status play a large role in homocysteine metabolism, it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration.

Methods/Design

The B-PROOF (B-Vitamins for the PRevention Of Osteoporotic Fractures) study is a randomized double-blind placebo-controlled trial. The intervention comprises a period of two years, and includes 2919 subjects, aged 65 years and older, independently living or institutionalized, with an elevated homocysteine concentration (≥ 12 μmol/L). One group receives daily a tablet with 500 μg vitamin B12 and 400 μg folic acid and the other group receives a placebo tablet. In both tablets 15 μg (600 IU) vitamin D is included. The primary outcome of the study is osteoporotic fractures. Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers, physical performance and physical activity including falls, nutritional intake and status, cognitive function, depression, genetics and quality of life. This large multi-center project is carried out by a consortium from the Erasmus MC (Rotterdam, the Netherlands), VUmc (Amsterdam, the Netherlands) and Wageningen University, (Wageningen, the Netherlands), the latter acting as coordinator.

Discussion

To our best knowledge, the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population. We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013. The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures.

Trial Registration

The B-PROOF study is registered with the Netherlands Trial (NTR NTR1333) and with ClinicalTrials.gov (NCT00696514).