Basic and patient-oriented research
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.
https://doi.org/10.1016/j.joms.2009.03.050Get rights and content

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.

Section snippets

Source Population

Kaiser Permanente of Northern California is a large integrated health care delivery system that provides comprehensive care to 3.3 million members, representing more than one third of insured adults in the greater San Francisco Bay Area. Its diverse membership is generally representative of the surrounding local and statewide population, except for a somewhat lower representation of the extremes of age and income.

The institutional review boards of the Kaiser Foundation Research Institute and

Results

We initially identified 31,680 eligible persons who met the minimal treatment criteria, including ≥1 bisphosphonate prescription in 2006. We excluded 5,108 patients because of intravenous bisphosphonate treatment (n = 98), oral cavity neoplasm (n = 81), no written or spoken English (n = 2,185), diagnosed dementia (n = 1,185), human immunodeficiency virus infection (n = 36), not meeting membership criteria (n = 1,759), and death or admission to hospice care (n = 650). Of the remaining 26,572

Discussion

Among the nearly 14,000 patients who had received chronic oral bisphosphonate therapy, we identified 9 cases of ONJ, for a minimum prevalence of 1 (0.10%) in 952 survey respondents or 1 (0.07%) in 1,537 in the target population who received the mailed survey. Among the survey respondents, we estimated a frequency of ONJ of 28 per 100,000 person-years of treatment. These estimates might be conservative because they did not include 3 cases of osteomyelitis without bone exposure. However, they do

Acknowledgments

We wish to thank the other members of the PROBE Study Team for their support: Donald Liberty, DDS, Julia Townsend, DDS, Sudheer Surpure, DDS, Jeffrey Caputo, DDS, Vicente Chavez, DDS, A. Thomas Indresano, DMD, David Baer, MD, Pete Bogdanos, Alice Ansfield, Marvella Villasenor, Beatriz Monjaras, Joelle Ebalo, Benjamin Wang, Virginia Browning, Colanda Grier, Teresa Lin, Maryanne Armstrong, Mohammad Hararah, and Joel Gonzalez. Our sincere appreciation to the Maxillofacial Clinics at Kaiser

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    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.

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