B vitamins, homocysteine, and bone disease: epidemiology and pathophysiology

Observational studies indicate that mildly elevated homocysteine is a strong risk factor for osteoporotic fracture, yet there is no clear biologic mechanism for an effect of homocysteine on bone. The association could instead be attributed to B vitamins (folate, vitamin B(12), vitamin B(6)), as low levels of these nutrients are the primary determinants of homocysteine and may be associated with lower bone quality. Discovery of a direct effect of homocysteine or B vitamins on bone would be important in terms of interventions, as these factors can be modified with changes in diet or supplementation. This article reviews the connections of homocysteine and B vitamins to measures of bone quality and osteoporotic fracture. Although the literature suggests that these factors may be associated with bone health, most of the epidemiologic studies are observational, limiting conclusions regarding causality. More controlled -trials are needed to determine whether treatment with B vitamins would reduce fracture rates among community-dwelling cohorts.