Background: Recently, increased plasma homocysteine (Hcy) has been suggested as an independent risk factor for osteoporotic fractures. Therefore, it is tempting to speculate that Hcy adversely affects bone metabolism. This study aimed to analyze the relation between Hcy and biochemical markers of bone metabolism and bone mineral density (BMD). Materials and methods: We investigated 143 peri-and post-menopausal women wmedian age (25th-75th percentile), 67 (57-75) yearsx. All subjects underwent a detailed medical examination, measurement of bone mineral density at lumbar spine (BMD-LS) and total hip (BMD-HIP), and fasting venous blood and urine sampling. Osteocalcin (OC), serum calcium (Ca), urinary desoxypyridinoline cross-links (DPD), osteoprotegerin (OPG) and soluble receptor activator of NFkB ligand (sRANKL) were studied. Results: According to BMD subjects were classified as normal (ns24), osteopenic (ns51) or osteoporotic (ns68). Median Hcy did not differ between normal, osteopenic and osteoporotic subjects (ps0.647). Partial correlation analysis, controlling for the major confounders, age, creatinine, menopause and previous fractures, revealed significant correlations between Hcy and DPD (rs0.193, ps0.022), as well as between Hcy and Ca (rs0.170, ps0.045). After adjustment for the same confounders, subsequent regression analysis confirmed significant associations of Hcy with DPD and Ca. No significant relations could be observed between Hcy and BMD-LS, BMD-HIP, OC, OPG or sRANKL. Conclusion: Our results demonstrate weak, but significant, relations between Hcy and markers of organic and inorganic bone resorption, suggesting a mechanistic role of Hcy in bone metabolism. The rela-