title: 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.
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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  The B-PROOF study is registered with the Netherlands Trial (NTR NTR1333) and with ClinicalTrials.gov (NCT00696514).
authors.affiliation: Department of Human Nutrition, Wageningen University, P,O, Box 8129 6700 EV Wageningen, the Netherlands. janneke.vanwijngaarden@wur.nl
authors.forename: Janneke P
authors.initials: JP
authors.lastname: van Wijngaarden
authors.forename: Rosalie A M
authors.initials: RA
authors.lastname: Dhonukshe-Rutten
authors.forename: Natasja M
authors.initials: NM
authors.lastname: van Schoor
authors.forename: Nathalie
authors.initials: N
authors.lastname: van der Velde
authors.forename: Karin M A
authors.initials: KM
authors.lastname: Swart
authors.forename: Anke W
authors.initials: AW
authors.lastname: Enneman
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: van Dijk
authors.forename: Elske M
authors.initials: EM
authors.lastname: Brouwer-Brolsma
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
authors.forename: Joyce B J
authors.initials: JB
authors.lastname: van Meurs
authors.forename: Johannes
authors.initials: J
authors.lastname: Brug
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Paul
authors.initials: P
authors.lastname: Lips
authors.forename: Lisette C P G M
authors.initials: LC
authors.lastname: de Groot
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008297:Male; D010024:Osteoporosis / Q000188:drug therapy* / Q000453:epidemiology; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000627:therapeutic use*
chemical_list: D005492:Folic Acid; D014805:Vitamin B 12