Incidence and Risk Factors for Nontraumatic Osteonecrosis of the Femoral Head in Kidney Transplant Recipients: A Comparison of Two Eras (1985-2000 and 2001-2024)

Abstract

Background: Historically, osteonecrosis of the femoral head (ONFH) was a major problem following kidney transplantation, occurring in up to 5%-11% of recipients. The development of new immunosuppressive agents permitted steroid minimization protocols, and consequently, the incidence of ONFH has decreased. We studied ONFH trends over four decades and evaluated risk factors in two immunosuppressive eras, pre- and post-2001.

Patients and methods: Steroid minimization protocols at our center started in 2000. We reviewed records of 1st kidney transplants from January 1985 to May 2024 and compared ONFH incidence and risk factors between the two eras: Era 1 (January 1985-December 31, 2000) and Era 2 (January 2001-May 2024). Cox regression was used to assess for independent factors associated with a higher or lower incidence of ONFH.

Results: ONFH incidence in Era 1 was 7.2%; Era 2, 1.1% (p < 0.001). In Era 1, increased risk was associated with heavier weight (HR: 1.017, 95% CI: 1.010-1.023, p < 0.001) and mTOR inhibitors (HR: 4.258, 95% CI: 1.726-10.506, p = 0.002); and decreased risk with diabetes (HR: 0.362, 95% CI: 0.270-0.486, p < 0.001), and statins (HR: 0.452, 95% CI: 0.327-0.625, p < 0.001). In Era 2, increased risk was associated with steroid use (HR: 2.096, 95% CI: 1.071-4.100, p = 0.031) and decreased risk with mycophenolate (HR: 0.471, 95% CI: 0.237-0.935, p = 0.032).

Conclusion: The incidence of ONFH in KTRs has dramatically decreased in the modern immunosuppressive era. Diabetes, statin use, and immunosuppressive medications, specifically mTOR inhibitors and mycophenolate, appear to have varying impacts depending on the immunosuppressive era.

Keywords: immunosuppression; kidney transplant recipient; osteonecrosis of the femoral head.