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Osteonecrosis of the jaw among patients with cancer treated with denosumab or zoledronic acid: Results of a regulator-mandated cohort postauthorization safety study in Denmark, Norway, and Sweden

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  • Vera Ehrenstein
  • Uffe Heide-Jørgensen
  • Morten Schiødt, University of Copenhagen
  • ,
  • Olof Akre, Karolinska Institutet
  • ,
  • Bente Brokstad Herlofson, University of Oslo
  • ,
  • Svein Hansen, Cancer Registry of Norway
  • ,
  • Cecilia Larsson Wexell, Lund University, University of Gothenburg
  • ,
  • Sven Erik Nørholt
  • Steinar Tretli, Cancer Registry of Norway
  • ,
  • Anders Kjellman, Karolinska Institutet
  • ,
  • Anthony Glennane, Amgen Incorporated
  • ,
  • Kimberly A. Lowe, Amgen Incorporated
  • ,
  • Henrik T. Sørensen

BACKGROUND: Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptive treatment. This study estimated incidence proportions and incidence rates of ONJ in cancer patients with bone metastases from solid tumors treated for the prevention of skeletal-related events in routine clinical practice. METHODS: This cohort study in Denmark, Norway, and Sweden in 2011-2018 included 3 treatment cohorts: a denosumab inception cohort (DEIC), a zoledronic acid inception cohort (ZAIC), and a denosumab-switch cohort (DESC). The authors estimated 1- to 5-year incidence proportions and incidence rates of ONJ overall, by cancer site (breast, prostate, or other solid tumor), and by country. ONJ diagnoses were confirmed by adjudication. RESULTS: There were 1340 patients in the DEIC, 1352 in the ZAIC, and 408 in the DESC. The median ages of the 3 cohorts were 70, 69, and 70 years, respectively; the proportions of men were 72.6%, 53.8%, and 48.3%, respectively; and the median follow-up was 19.8, 12.9, and 13.3 months, respectively. The 5-year incidence proportions of ONJ were 5.7% (95% confidence interval [CI], 4.4%-7.3%) in the DEIC, 1.4% (95% CI, 0.8%-2.3%) in the ZAIC, and 6.6% (95% CI, 4.2%-10.0%) in the DESC. The corresponding ONJ incidence rates per 100 person-years were 3.0 (95% CI, 2.3-3.7), 1.0 (95% CI, 0.6-1.5), and 4.3 (95% CI, 2.8-6.3). Incidence proportions and incidence rates were highest in patients with prostate cancer and in Denmark. CONCLUSIONS: This study provides estimates of the risk of medically confirmed ONJ among patients initiating denosumab or zoledronic acid in routine clinical practice in 3 Scandinavian countries. The results varied by cancer site and by country. LAY SUMMARY: Denosumab and zoledronic acid reduce the risk of bone fractures, pain, and surgery in patients with advanced cancers involving bone. Osteonecrosis of the jaw (ONJ)—death of a jawbone—is a known side effect of treatment with denosumab or zoledronic acid. The authors examined almost 2900 denosumab- or zoledronic acid–treated patients with cancer in Denmark, Norway, and Sweden. Over the course of 5 years, ONJ developed in 5.7% of the patients whose initial treatment was denosumab, in 1.4% of the patients whose initial treatment was zoledronic acid, and in 6.6% of the patients who switched from zoledronic acid to denosumab.

Original languageEnglish
Pages (from-to)4050-4058
Publication statusPublished - Nov 2021

Bibliographical note

Publisher Copyright:
© 2021 American Cancer Society

    Research areas

  • bisphosphonates, cohort study, denosumab, osteonecrosis of the jaw, real-world data, routinely collected health data

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