RANK hypomethylation is associated with primary osteoporosis in elderly men in Xinjiang: a case-control study

RANK is a candidate gene for osteoporosis based on both functional and genetic mechanisms. This study investigated the association between RANK methylation and osteoporosis among community-dwelling elderly people in Xinjiang, China. This case-control study was based on an epidemiological investigation. Initially, methylated cytosine-rich cytosine phosphate-guanine sites (CpGs) were identified within the RANK promoter region using a screening cohort. Subsequently, selected CpGs were detected via bisulfite sequencing in the primary cohort comprising 90 elderly men (47 with osteoporosis and 43 without). Finally, the correlations between osteoporosis and the methylation rates of the identified CpGs were assessed. Age and prevalence of diabetes differed significantly between individuals with and without osteoporosis (P = 0.025 and P = 0.005, respectively), while other factors showed no statistically significant differences between the case and control groups (P > 0.05). The RANK methylation rate was significantly higher in the control group than in the osteoporosis group (P < 0.001). Furthermore, after covariance analysis to adjust for age, smoking, drinking, and diabetes, a significantly higher RANK methylation rate was observed in control individuals versus those with osteoporosis among elderly men from Xinjiang (P = 0.001). Multivariate logistic regression analysis, adjusted for confounding factors (age, smoking, alcohol consumption, and diabetes), further demonstrated that RANK hypomethylation was significantly associated with osteoporosis (odds ratio = 0.310, 95% confidence interval: 0.886–0.976). RANK hypomethylation shows a significant association with osteoporosis in elderly male residents in Xinjiang communities. These results support that RANK hypomethylation may play a role in the pathogenesis of osteoporosis.