Abstract
PURPOSE: This study aimed to explore relationships between baseline bone metabolism markers and long-term outcomes, collectively referred to as fractures, cardiovascular diseases, diabetes and all-cause death (FCDD), in healthy women at baseline and identify predictive markers for outcome. METHODS: This study included 356 healthy women and assessed baseline bone turnover markers-osteocalcin, C-telopeptide of type I collagen-as well as bone mineral densities (BMDs) at lumbar spine (L1-4), femoral neck (FN) and total hip (TH). A 16-year retrospective follow-up via telephone questionnaire tracked FCDD occurrence. Statistical tests, including univariate analysis, forward stepwise regression and logistic regression analysis, were used to determine correlations between baseline markers and FCDD. RESULTS: Among 356 participants, 291 (81.7%) completed follow-up; among these 291 subjects, 109 (37.5%) experienced FCDD. 47 participants experienced fractures (16.2%), 27 developed diabetes (9.3%), 25 experienced cardiovascular events or mortality (8.6%). Stepwise regression identified osteocalcin (odds ratio: 0.938, 95% confidence interval: 0.895-0.980, P = 0.006) and FN BMD (odds ratio: 0.066, 95% confidence interval: 0.008-0.490, P = 0.009) as independent predictors. However, logistic regression revealed that the protective effect of FN BMD was attenuated after adjusting for age, body mass index, years since menopause, whereas osteocalcin remained significant (P < 0.05). Heatmap visualization revealed the lowest FCDD risk among both markers in the highest tertiles (P = 0.002). CONCLUSION: Our study shows that baseline osteocalcin is independently associated with long-term FCDD outcomes in healthy women. These insights offer valuable guidance for the development of personalized health prevention and intervention strategies.