How Are Diabetes, Statins, and Immunosuppressive Medications Linked to Non-Traumatic Osteonecrosis of the Femoral Head in Kidney Transplant Recipients?

Abstract

Identifying the factors associated with the risk of osteonecrosis of the femoral head (ONFH) is crucial for implementing effective preventive measures. However, there is currently no consensus on whether a correlation exists between the incidence of ONFH and diabetes, statins, or immunosuppressive medications. We studied the associations between these factors and ONFH risk in a large cohort of kidney transplant recipients (KTRs). Medical records of KTRs who underwent transplantation between 1985 and 2024 were gathered from a prospectively collected database. Collected data included demographic variables, immunosuppressive regimens, diabetes statuses, transplantation details, smoking histories, and statin usages. In total, 262 recipients who had ONFH were recorded in 6,926 KTRs (3.8%). Variables with a P-value < 0.1 in the univariate analyses or those considered clinically significant were included in a multivariate Cox regression model. In the multivariate analyses, the following factors were significantly associated with an increased risk of ONFH: older age (hazard ratio [HR]: 1.01, 95% confidence interval [CI]: 1.00 to 1.02, P = 0.018), men (HR: 1.40, 95% CI: 1.08 to 1.82, P = 0.010), mammalian target of rapamycin inhibitors (HR: 4.42, 95% CI: 2.10 to 9.32, P < 0.001), corticosteroids for maintenance immunosuppression (HR: 3.54, 95% CI: 2.02 to 6.23, P < 0.001), and cyclosporine (HR = 2.53, 95% CI: 1.12 to 5.71, P = 0.025). The following factors were significantly associated with a reduced risk of ONFH: diabetes (HR: 0.49, 95% CI: 0.38 to 0.63, P < 0.001) and statin use (HR: 0.59, 95% CI: 0.45 to 0.78). In addition to recipient characteristics, diabetes or statin use reduces the risk of ONFH, whereas certain immunosuppressive medications increase the risk of ONFH. These findings underscore the importance of thorough patient evaluation and the implementation of immunosuppressive strategies to reduce the risk of post-transplant ONFH. III.