Risk of Osteonecrosis of the Jaw Under Denosumab Compared to Bisphosphonates in Patients With Osteoporosis

Judith Everts-Graber; Daniel Lehmann; John-Patrik Burkard; Benoît Schaller; Brigitta Gahl; HansJörg Häuselmann; Ueli Studer; Hans-Rudolf Ziswiler; Stephan Reichenbach; Thomas Lehmann

doi:10.1002/jbmr.4472

Risk of Osteonecrosis of the Jaw Under Denosumab Compared to Bisphosphonates in Patients With Osteoporosis

J Bone Miner Res. 2022 Feb;37(2):340-348. doi: 10.1002/jbmr.4472. Epub 2021 Nov 30.

Authors

Affiliations

¹ OsteoRheuma Bern, Bern, Switzerland.
² Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
³ Faculty of Medicine, University of Bern, Bern, Switzerland.
⁴ Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁵ Clinical Trial Unit, University of Bern, Bern, Switzerland.
⁶ Zentrum für Rheuma- und Knochenerkrankungen, Zürich, Switzerland.
⁷ Institute for Social and Preventive Medicine, University of Bern, Bern, Switzerland.

^# Contributed equally.

PMID: 34787342
DOI: 10.1002/jbmr.4472

Abstract

Osteonecrosis of the jaw (ONJ) is a rare but serious adverse event associated with antiresorptive treatment. There is little evidence regarding the incidence of ONJ among patients with osteoporosis who are treated with denosumab versus bisphosphonates (BPs). The aim of this study was to determine the risk of ONJ in a real-world population. Subjects who underwent at least one dual-energy X-ray absorptiometry (DXA) examination were included in the osteoporosis register of the Swiss Society of Rheumatology between January 1, 2015, and September 30, 2019. Statistical analyses included incidence rates, rate ratios, and hazard ratios for ONJ, considering sequential therapies and drug holidays as covariates. Among 9956 registered patients, 3068 (89% female, median age 69 years [63 to 76]) were treated with BPs or denosumab for a cumulative duration of 11,101 and 4236 patient-years, respectively. Seventeen cases of ONJ were identified: 12 in patients receiving denosumab at the time of ONJ diagnosis and 5 in patients receiving oral or intravenous BP therapy. The diagnosis of ONJ was confirmed by independent and blinded maxillofacial surgeons, using the American Association of Oral and Maxillofacial Surgeons case definition of ONJ. The incidence of ONJ per 10,000 observed patient-years was 28.3 in patients receiving denosumab and 4.5 in patients with BP-associated ONJ, yielding a rate ratio of 6.3 (95% confidence interval [CI] 2.1 to 22.8), p < 0.001. Nine of 12 patients who developed ONJ during denosumab treatment had been pretreated with BPs, but none of the 5 patients with BP-related ONJ had previously received denosumab. The risk of ONJ was higher in patients receiving denosumab therapy compared with BPs (hazard ratio 3.49, 95% CI 1.16 to 10.47, p = 0.026). Previous BP therapy before switching to denosumab may be an additional risk factor for ONJ development. © 2021 American Society for Bone and Mineral Research (ASBMR).

Keywords: BISPHOSPHONATES; DENOSUMAB; ONJ; OSTEONECROSIS OF THE JAW; OSTEOPOROSIS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Bisphosphonate-Associated Osteonecrosis of the Jaw* / epidemiology
Bisphosphonate-Associated Osteonecrosis of the Jaw* / etiology
Bone Density Conservation Agents* / adverse effects
Denosumab / adverse effects
Diphosphonates / adverse effects
Female
Humans
Male
Osteonecrosis* / chemically induced
Osteonecrosis* / epidemiology
Osteoporosis* / complications
Risk Factors

Substances

Bone Density Conservation Agents
Diphosphonates
Denosumab