Prevalence of Osteonecrosis of the Jaw in Patients With Oral Bisphosphonate Exposure

These data were presented in part at the 90th Annual Meeting of the Endocrine Society, San Francisco, CA, June 15-18, 2008.

published online 03 July 2009.

Purpose

Osteonecrosis of the jaw (ONJ) is a serious complication associated with bisphosphonate therapy, but its epidemiology in the setting of oral bisphosphonate therapy is poorly understood. The present study examined the prevalence of ONJ in patients receiving chronic oral bisphosphonate therapy.

Materials and Methods

We mailed a survey to 13,946 members who had received chronic oral bisphosphonate therapy as of 2006 within a large integrated health care delivery system in Northern California. Respondents who reported ONJ, exposed bone or gingival sores, moderate periodontal disease, persistent symptoms, or complications after dental procedures were invited for examination or to have their dental records reviewed. ONJ was defined as exposed bone (of >8 weeks' duration) in the maxillofacial region in the absence of previous radiotherapy.

Results

Of the 8,572 survey respondents (71 ± 9 years, 93% women), 2,159 (25%) reported pertinent dental symptoms. Of these 2,159 patients, 1,005 were examined and an additional 536 provided dental records. Nine ONJ cases were identified, representing a prevalence of 0.10% (95% confidence interval 0.05% to 0.20%) among the survey respondents. Of the 9 cases, 5 had occurred spontaneously (3 in palatal tori) and 4 occurred in previous extraction sites. An additional 3 patients had mandibular osteomyelitis (2 after extraction and 1 with implant failure) but without exposed bone. Finally, 7 other patients had bone exposure that did not fulfill the criteria for ONJ.

Conclusions

ONJ occurred in 1 of 952 survey respondents with oral bisphosphonate exposure (minimum prevalence of 1 in 1,537 of the entire mailed cohort). A similar number had select features concerning for ONJ that did not meet the criteria. The results of the present study provide important data on the spectrum of jaw complications among patients with oral bisphosphonate exposure.

⁎ Research Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, and Associate Clinical Professor, Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA

† Director, Division of Maxillofacial Surgery, Kaiser Permanente Oakland Medical Center, Oakland, CA

‡ Research Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, CA

§ Data Consultant, Division of Research, Kaiser Permanente Northern California, Oakland, CA

¶ Outcomes Research Scientist, Pharmacy Outcomes Research Group, Drug Information Services, Kaiser Permanente California, Oakland, CA

∥ Resident, Division of Maxillofacial Surgery, Kaiser Permanente Oakland Medical Center, and Department of Oral and Maxillofacial Surgery, Highland General Hospital, Oakland, CA

# Resident, Division of Maxillofacial Surgery, Kaiser Permanente Oakland Medical Center, and Department of Oral and Maxillofacial Surgery, Highland General Hospital, Oakland, CA

⁎⁎ Project Manager, Division of Research, Kaiser Permanente Northern California, Oakland, CA

†† Project Manager, Division of Research, Kaiser Permanente Northern California, Oakland, CA

‡‡ Project Manager, Division of Research, Kaiser Permanente Northern California, Oakland, CA

§§ Senior Consulting Data Analyst, Division of Research, Kaiser Permanente Northern California, Oakland, CA

¶¶ Epidemiologist, US Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Silver Spring, MD

∥∥ Associate Director for Regulatory Research, US Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Silver Spring, MD

## Senior Risk Analyst, US Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Silver Spring, MD

⁎⁎⁎ Director, Division of Research, Kaiser Permanente Northern California, Oakland, CA

††† Research Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, and Associate Professor, Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, School of Medicine, San Francisco, CA

Address correspondence and reprint requests to Dr Lo: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612

This study was funded by the US Food and Drug Administration (HHSF223200510008C), the National Institute of Child Health and Human Development at the National Institutes of Health (K12 HD052163), and the Kaiser Permanente Community Benefit Program; a portion of this study was also supported by the National Center for Research Resources at the National Institutes of Health (UCSF-CTSI UL1 RR024131).

J. Lo previously received research funding from Novartis; D. Martin previously owned stock in Merck & Company, Incorporated; a household family member of N. Gordon previously owned stock in Novartis Pharmaceuticals; a nonhousehold family member of F. O'Ryan is employed by Roche Laboratories; A. Go previously received research funding from Amgen and currently receives research funding from GlaxoSmithKline.

The contents of this publication are solely the responsibility of the authors and do not represent the official views of the Food and Drug Administration or the National Institutes of Health.

PII: S0278-2391(09)00441-8

doi:10.1016/j.joms.2009.03.050

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