Serum phosphate is associated with increased risk of bone fragility fractures in haemodialysis patients

Abstract

Background: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of chronic kidney disease-mineral and bone disorders (CKD-MBD) and bone fragility fractures in the COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) project.

Methods: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 haemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and parathyroid hormone (PTH) (exposure), was assessed using standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables.

Results: During a median follow-up of 24 months, 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months, respectively. Baseline serum phosphate >6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models {hazard ratio (HR) 1.53 [95% confidence interval (CI) 1.10-2.13] and HR 1.44 (95% CI 1.02-2.05)}. The significant association persisted after competitive risk analysis [subHR 1.42 (95% CI 1.02-1.98)] but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH >800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis.

Conclusions: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in haemodialysis patients.

Keywords: CKD, chronic kidney disease–mineral and bone disorders (CKD-MBD); bone fragility fractures; haemodialysis; serum phosphate.