B-PROOF: B-vitamins for the prevention of osteoporotic fractures, a randomized placebo-controlled double-blind trial

Introduction: Current observational evidence strongly suggests that B-vitamins play a role in the prevention of fractures. Poor vitamin B12 and folate status contribute largely to homocysteine elevation. It is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people. Objective: To determine the effect of vitamin B12 and folic acid supplementation on fracture incidence in hyperhomocysteinemic elderly people, in a double-blind, placebo-controlled trial. Methods: The B-PROOF (B-Vitamins for the Prevention Of Osteoporotic Fractures) study is a randomized double-blind placebocontrolled trial. The intervention comprises a period of two years, and aims for the inclusion of 3000 subjects, aged 65 years and older, free living and institutionalized, with elevated homocysteine levels (=12µmol/L). One group receives a tablet with 500 µg vitamin B12 and 400 µg folic acid daily and the other group receives a placebo tablet. In both tablets 15 µg (600 IE) of vitamin D is included. Measurements are performed at baseline and after two years and cover bone health, physical activity and functioning, cognitive function, nutritional intake and status, depression and quality of life. This large multi-center project is carried out by a consortium from the Erasmus MC (Rotterdam), VUmc (Amsterdam) and Wageningen University, acting as coordinator. Relevance: It is of major importance to prevent osteoporosis from entering the clinical state, preferably through non-invasive interventions, such as ensuring adequate nutrient intakes, i.e. vitamin B12 and folic acid. Because of the high prevalence of elevated homocysteine levels (10%- 50%) in the elderly population, many elderly may benefit from possibly beneficial effects emerging from this trial, reduce their risk of fracture and improve their health status in a relative simple way, once implementation strategies are applied.