Cumulative incidence and risk factors for medication-related osteonecrosis of the jaw during long-term prostate cancer management

Sci Rep. 2024 Jun 11;14(1):13451. doi: 10.1038/s41598-024-64440-7.

Abstract

Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19 months; interquartile range, 9-43 months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93-11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01-0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13-11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68-15.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases.

Keywords: Denosumab; Jaw; Osteonecrosis; Prostate cancer; Zoledronic acid.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / epidemiology
  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / etiology
  • Bone Density Conservation Agents* / adverse effects
  • Bone Neoplasms* / drug therapy
  • Bone Neoplasms* / epidemiology
  • Bone Neoplasms* / secondary
  • Denosumab* / adverse effects
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / pathology
  • Retrospective Studies
  • Risk Factors
  • Zoledronic Acid / adverse effects
  • Zoledronic Acid / therapeutic use

Substances

  • Denosumab
  • Bone Density Conservation Agents
  • Zoledronic Acid