Fracture risk prediction using bone mineral density and biochemical markers of bone and mineral metabolism in dialysis and non-dialysis CKD patients

BACKGROUND: Bone mineral density (BMD) is a recognized predictor of fracture risk in the general population, but its utility in chronic kidney disease (CKD) remains uncertain. This study evaluated BMD and biochemical markers of bone and mineral metabolism (BMMs)-parathyroid hormone (PTH) and bone-specific alkaline phosphatase (bone ALP)-as fracture predictors in CKD patients, both with and without dialysis. METHODS: We retrospectively analyzed 918 adult patients with CKD who underwent BMD and BMM assessments between 2010 and 2024. Patients were stratified by dialysis status (RRT: n = 514; non-RRT: n = 404); non-RRT patients who initiated RRT during follow-up were censored at the date of RRT initiation. Cox proportional hazards models (Firth correction) and Fine-Gray competing-risk models were applied, with adjustment for age, sex, BMI, and diabetes mellitus. Time-dependent receiver operating characteristic (ROC) curves were used to compare predictive performance for 5-year fracture risk. RESULTS: Over a median follow-up of 1,694 days (IQR 751-2,314), 83 fracture events occurred. Fracture risk did not significantly differ across tertiles of PTH or bone ALP in either group. In contrast, BMD was significantly associated with fracture risk in both groups: patients with osteoporosis (T-score ≤ - 2.5) had directionally elevated fracture risk in both groups, although the extremely wide confidence intervals around the categorical hazard ratios preclude precise interpretation of effect magnitude. More stable estimates from Fine-Gray competing-risk models showed that each one-unit increase in BMD T-score was associated with an approximately 45% lower fracture risk in both groups (RRT: SHR 0.54, 95% CI 0.38-0.75; non-RRT: SHR 0.57, 95% CI 0.41-0.79). Time-dependent ROC analysis confirmed BMD significantly outperformed BMMs for 5-year fracture risk prediction, with AUCs of 0.712 (RRT) and 0.658 (non-RRT). CONCLUSION: BMD was strongly associated with fracture risk in CKD patients, regardless of dialysis status, and significantly outperformed BMMs in predicting fracture risk. In contrast, BMMs were not associated with fracture risk. These results support the role of BMD assessment in fracture risk evaluation across the full spectrum of CKD.