Homocysteine and bone metabolism markers in osteoporotic patients: A secondary analysis

Homocysteine (Hcy) is considered a new indicator of bone disease. However, the effect of homocysteine on bone turnover remains controversial, and its relationship with bone metabolism markers remains unclear. To further investigate this, we conducted a secondary analysis utilizing data from our previously published cross-sectional study. The study aims to explore the relationship between Hcy and bone turnover markers in newly diagnosed osteoporosis patients based on a cross-sectional study and then verify the effect of different Hcy concentrations on bone turnover markers in cells. The cross-sectional study was a cross-sectional design of 518 newly diagnosed osteoporotic patients. The independent correlation between homocysteine level and bone metabolism markers was analyzed by multiple regression analysis. A linear regression model was applied to assess the threshold effect of homocysteine on bone metabolism markers. Osteoclasts from rats and MG63 were cultured and treated with homocysteine at different concentrations to determine the effects of homocysteine on osteogenic and osteoclast differentiation in vitro. We found that the correlations between Hcy and bone-alkaline phosphatase (B-ALP, β = 0.67, 95% CI = 0.28-1.07, P = .00) and tartrate-resistant acid phosphatase.5B (TRACP.5B, β = 0.49, 95% CI = 0.10-0.89, P = .01) were significant. The adjusted smoothed plots show that Hcy had a linear relationship with B-ALP and TRACP.5B levels. Furthermore, there was a nonlinear relationship between Hcy and osteocalcin (OC) as well as Hcy and 25-OHD. In in vitro cell experiments, we found that at an Hcy level of 10-5 mol/L, there was a promotion of alkaline phosphatase activity, osteocalcin in osteoblasts, and a significant increase in mineralized nodules on the 14th day. The Hcy level of 10-5 mol/L was likewise seen to have promoted TRACP.5B activity, and tartrate resistant acid phosphatase staining demonstrated an increase in osteoclast formation. The cross-sectional study revealed that Hcy was positively linearly correlated with TRACP.5B and B-ALP and nonlinearly related to OC in osteoporotic patients. A moderate concentration of Hcy promoted bone turnover marker expression in vitro, which may be one of the mechanisms of Hcy-related osteoporosis.