Association of aberrant mineral metabolic markers with fracture risk in chronic kidney disease: a comprehensive meta-analysis.

Background: This meta-analysis aims to investigate the impact of abnormalities in mineral metabolic markers, including serum phosphate and calcium, intact parathyroid hormone (iPTH), and fibroblast growth factor 23 (FGF23) on the risk of fractures in patients with chronic kidney disease (CKD).
Methods: A systematic search was conducted across MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Controlled Trials. The outcomes were association of mineral metabolic markers with the risk of fractures in patients with chronic kidney disease. Pooled risk estimates and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models.
Results: Thirty-two studies were included in the meta-analysis. High and low levels of serum phosphate in hemodialysis (HD) patients were both associated with an increased risk of fractures (RR = 1.08, 95% CI 1.02-1.15, P = 0.013; RR = 1.13, 95% CI 1.02-1.25, P = 0.022, respectively). Similarly, abnormal levels of iPTH in CKD patients, both high and low, were associated with increased fracture risk (RR = 1.25, 95% CI 1.20-1.31, P < 0.001; RR = 1.41, 95% CI 1.10-1.82, P = 0.007, respectively). Elevated FGF23 levels were also linked to an increased risk of fractures (RR = 1.32, 95% CI 1.06-1.66, P = 0.015). While a higher level of calcium exhibited a trend towards reduced fracture incidence without statistical significance (RR = 0.90, 95% CI 0.77-1.05, P = 0.181), lower calcium levels tended to increase fracture risk without statistical significance (RR = 1.11, 95% CI 0.99-1.24, P = 0.087). Notably, subjects treated with calcium and phosphorus modulating drugs demonstrated a statistically significant reduction in fractures among CKD patients undergoing dialysis (phosphate binders, RR = 0.79, 95% CI 0.70-0.89; cinacalcet, RR = 0.74, 95% CI 0.59-0.93; vitamin D analogues, RR = 0.82, 95% CI 0.74-0.92, respectively).
Conclusion: This meta-analysis underscores the association between abnormal mineral metabolic markers, including high serum phosphate, iPTH, and FGF23, and an increased risk of fractures in CKD patients. Notably, both elevated and decreased levels of phosphate and iPTH contribute to fracture risk. The efficacy of active vitamin D, phosphorus binders, and cinacalcet in preventing fractures was observed in HD patients but not in the non-dialysis CKD population.
Trial Registration: PROSPERO CRD42023493951.
Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2025. The Author(s).)