Risk factors for osteonecrosis of the jaw in patients with chronic kidney disease: a nested case-control study

Osteonecrosis of the jaw (ONJ) is a severe disease leading to decreased quality of life, but risk factors for ONJ in chronic kidney disease (CKD) patients remain unclear. We conducted a nested case-control study using a large Japanese administrative database to investigate. CKD patients were identified based on estimated glomerular filtration rate (eGFR) measurements, and ONJ cases were identified using ICD-10 codes and diagnostic terms. Controls were matched 1:4 by age and sex. Among 597 026 CKD patients, 75 ONJ cases were identified during a median follow-up of 2.9 yr (incidence rate: 3.27 per 100 000 patient-years). A total of 375 patients (250 males, 66.7%) with a median age of 72 yr (interquartile range (IQR), 64-78) were included after matching controls. The use of bisphosphonates and denosumab for tumor-related disorders in the case group was significantly higher compared to the control group. There was no significant association between kidney functions and the ONJ risk. Multivariate analysis revealed that anti-resorptive drugs for tumor-related disorders [odds ratio (OR): 74.74, 95% confidence interval (CI): 8.81-634.39, p<.001] and oral corticosteroids (OR: 13.23, 95% CI: 3.34-52.33, p<.001) were significantly associated with increased ONJ risk, while anti-resorptive drugs for osteoporosis and injectable corticosteroid use were not. Other relevant factors such as diabetes, liver disease, anabolic drugs, and radiation therapy did not have a significant association with ONJ risk. When stratified by indications for bisphosphonate use (known to be eliminated by renal excretion), bisphosphonate use for tumor-related disorders showed a significant association with ONJ risk (OR: 27.80, 95% CI: 2.47-313.29, p<.01), while bisphosphonates use for osteoporosis did not (OR: 0.74, 95% CI: 0.19-2.92, p=.67). These findings suggest that anti-resorptive drugs for tumor-related disorders and oral corticosteroids are associated with ONJ risk in CKD patients. Heightened surveillance may be necessary for CKD patients receiving these treatments to prevent or detect ONJ early.