Background: Chronic kidney disease (CKD) is a known risk factor for fragility fractures, in particular the first fragility fracture. It is known that patients with a recent fragility fracture after the age of 50 are at increased risk of sustaining a subsequent fracture.

Objective: to evaluate the association between CKD (stages G3-G5 versus G1-G2) and the risk of a subsequent non-hip major fragility fracture (humerus, distal forearm and vertebral fracture) following a hip fracture (HF).

Methods: A retrospective cohort study using data from the UK Clinical Practice Research Datalink (CPRD) (2004-2016) was conducted. All patients with a first HF and ≥ 50 years were included. eGFR was assessed time-dependently and was used to determine the KDIGO CKD stage. Cox proportional hazard analyses were used to estimate cause specific (cs)- hazard ratio (HR).To explore the potential competing risk of mortality, a cause-specific HR for mortality was estimated.

Results: We included 37,820 patients with a first HF during the study period. Patients with CKD stage G1-G2 were younger than patients with CKD stage G3-G5 (79.2 vs. 84.2 years). CKD G3-G5 was not associated with risk of subsequent major fragility fractures (adjusted cs-HR: 0.89, 95%CI 0.79-1.00). Stratification of kidney function by CKD resulted in a cs-HR of 0.89 (95%CI 0.79-1.01) for CKD G3, 0.88 (95%CI 0.64-1.20) for CKD G4 and 0.56 (95%CI 0.20-1.56) for CKD G5. CKD G3-G5 was associated with a small increased risk of mortality (cs-HR 1.05 (95%CI 1.01-1.09)). Stratification by CKD stage resulted in a 1.5 and 3-fold increased mortality risk for CKD G4 and CKD G5, respectively (cs-HR CKD G4 1.50, 95%CI 1.38-1.62; CKD G5 2.93, 95% CI 2.48-3.46).

Conclusion: This study did not demonstrate an increased risk of subsequent fractures following a HF in patients with CKD G3-G5 compared to CKD G1-2. However, mortality risk was increased in patients with CKD G4 and G5 as compared to CKD G1-2. The higher mortality risk may, as competing risk, explain our main finding of no increased subsequent fracture risk with CKD stage 3-5.