Vitamin B12 and folic acid for preventing fractures in elderly people.

Osteoporotic fractures are a major health problem in the industrialized nations. It is likely that this problem will become even greater throughout the world as the population ages. Thus there is a growing need for inexpensive and low-risk strategies for preventing osteoporosis and fracture risk. Addressing dietary risk factors is particularly important because these factors are modifiable. While calcium and vitamin D have received the most attention, new research links B-vitamin status with fracture risk. There is growing evidence that an elevated homocysteine level is a risk factor for fracture risk. The most common cause of homocysteine elevation is poor B vitamin status, most notably of vitamin B12 and folate, which leaves a role of both homocysteine and vitamin B12/folate in the biological mechanism linking B-vitamin status to fractures. Whatever the mechanism, reducing homocysteine levels with supplements would be the required dietary intervention. In old age both hyperhomocysteinemia and vitamin B12 deficiency are highly prevalent (up to 50% of the elderly population). These conditions can easily be reverted with supplementation of folic acid and vitamin B12. Both in vitro and epidemiological studies in various populations and patient groups underpin the likely importance of homocysteine for bone quality. A consortium from Erasmus, VU and Wageningen Universities (1) showed in two large cohorts that elderly Dutch subjects in the highest homocysteine quartile had an osteoporotic fracture risk twice as high as subjects in the other quartiles. An American study confirmed these results (2). Despite the biological plausibility for effects on fracture incidence, the efficacy of homocysteine reduction via supplementation with B-vitamins is yet to be demonstrated in properly designed clinical trials. In the proposed study three academic centres with many years of expertise in bone health (VU University Amsterdam and Erasmus University Rotterdam) and nutrition (Wageningen University) aim to fill this knowledge gap jointly by assessing the effect of B-vitamin supplementation on fracture incidence in apparently healthy elderly people of 70 years and over in a double-blind, randomized placebo-controlled trial. The three centres have recognized experience with clinical trials and large prospective cohort studies. The Netherlands provide a suitable and still unique site for the proposed study since food fortification with folic acid is as yet not allowed in the Netherlands. In view of the implementation of the trial results, findings emerging from the proposed research will be discussed with representatives in several key areas (e.g. policy-makers, research workers, gerontologists, public health and dissemination platforms including the elderly).