The relationship between plasma homocysteine levels and bone mineral density in post-menopausal women

Background: Whether or not mild hyperhomocysteinemia and low serum levels of folates or vitamin B12 are risk factors for osteoporosis in the elderly is controversial. Aims and methods: To investigate whether or not plasma levels of total homocysteine (tHcy) and serum levels of folates and vitamin B12 are associated with bone mineral density (BMD), we carried out a cross-sectional study on 446 post-menopausal women (mean age: 65.1 ± 9.4 years), consecutively seen at the Siena Unit (Tuscany region, Central Italy) for BMD evaluation over a two-year period. BMD of the total femur, femoral neck and lumbar spine was detected by dual-energy X-ray absorptiometry. Results: The age-adjusted geometric mean of plasma tHcy levels (μmol/L) was 9.96 ± 1.29 in women with normal BMD, 11.06 ± 1.32 in those with osteopenia and 11.88 ± 1.35 in those with osteoporosis (p <0.0001). On multiple linear regression analysis, adjusting for age, body mass index, folates, vitamin B12, creatinine clearance, smoking habit and alcohol intake, tHcy was negatively related to BMD of the total femur [β estimate for log-homocysteine: - 0.050 (95% CI: - 0.100 to - 0.001, p = 0.048; R² = 0.02)], but not of femoral neck or lumbar spine. There was no significant association between BMD and serum levels of folates and vitamin B12. Conclusions: tHcy is negatively associated with BMD of the total femur. The contribution of tHcy to explain the variance of BMD is small (2% of the total variance) but clinically relevant, considering the high prevalence of osteoporosis among post-menopausal women and the possibility to lower tHcy by vitamin supplementation.