Homocysteine oxidative stress and relation to bone mineral density in post-menopausal osteoporosis

Background and aims: Mildly elevated homocysteine (Hcy) and oxidative stress are novel and potentially modifiable risk factors for post-menopausal osteoporosis. We hypothesized that imbalance of oxidant/antioxidant status and increased Hcy concentration stimulates osteoporotic activity, leading to increased collagen I breakdown in post-menopausal women. Methods: Patients were divided into 2 groups (NOP and OP). Group NOP had normal bone mineral density (BMD) and group OP low BMD. Thirty-four (69%) were in group OP and 15 (31%) in group NOP. Serum Total Antioxidant Status (TAS) and Total Peroxide (TPx) levels were determined with new automated methods. The study included measurement of Deoxypyridinoline (DPD). Results: In OP patients plasma t-Hcy, urine deoxypyridinoline and plasma TPx were significantly higher than those in NOP controls. In addition, OP patients also had lower TAS levels than controls, which represent the oxidative imbalance. Pearson’s correlation analysis revealed a negative correlation between t-Hcy and TAS (p<0.038). A significant negative correlation was also found between TAS level and BMD values for the spine in OP patients (p<0.035). In contrast, a positive correlation between t-Hcy and TPx in OP patients was demonstrated significantly, r=0.52, p<0.029. Conclusions: We show that the OP group had reduced TAS, whereas the elevated TPx was different from that in the NOP group. Slightly elevated homocysteinemia may contribute to increasing TPx and reducing TAS in the OP group. However, our results suggest a weak but negative relationship between TAS and BMD. Further investigations are needed to examine the relationship of oxidative stress as an endogenous bioactive agent to bone loss in post-menopausal women. Since oxidative stress is the imbalance between total oxidants and antioxidants in the body, any single oxidant/antioxidant parameter may not reflect overall oxidative stress. Further studies are needed to understand the underlying mechanisms of these findings.