Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans

Recent studies have found a connection between hyperhomocysteinemia and hip fracture. If this association is causal, it could be mediated through detrimental effects of low B-vitamin status on bone mineral density (BMD). Studies have linked homocysteine (Hcy) and the established Hcy determinants folate and vitamin B12, to BMD, but results have been inconsistent. Furthermore, only one study considered the specific marker of tissue vitamin B12 status, methylmalonic acid (MMA), and none have considered red blood cell (RBC) folate. To further explore associations between Hcy and B-vitamin status indicators and bone health, we used data collected on older (i.e., aged >55 years) men and women who underwent DEXA scans of the hip as participants in phase 2 of the third U.S. National Health and Nutrition Examination Survey (n = 1550). We used BMD at the total hip as a continuous outcome variable in some analyses. In others, we used osteoporosis defined on a sex- and race/ethnicity-specific basis according to World Health Organization (WHO) guidelines. After adjusting for demographic factors, body mass index, and other osteoporosis risk factors, BMD decreased and osteoporosis increased significantly with increasing serum MMA quartile category (P < 0.01). Serum vitamin B12 was related to BMD in dose-response fashion up to about 200 pmol/L, and subjects with serum Hcy > or = 20 micromol/L had significantly lower BMD than subjects with serum Hcy < 10 micromol/L. Furthermore, the OR (95% CI) relating a serum vitamin B12 concentration below the 25th percentile to osteoporosis/osteopenia was 2.0 (1.0-3.9), and dose-response trends relating both serum B12 and Hcy to this outcome were marginally statistically significant. Neither serum nor RBC folate was related to BMD or osteoporosis. We conclude that Hcy and vitamin B12 status indicators are associated with BMD in older Americans. Whether this association reflects a causal relation remains unclear and merits further study in light of age-related declines in B12 status and BMD, and the need for low-risk, easily implemented strategies for osteoporosis prevention.