Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges

Bisphosphonate-related osteonecrosis of the jaw (BONJ) is an adverse effect of bisphosphonate use with a poorly described epidemiology in osteoporosis patients. We examined the literature and two new cohorts for BONJ. The literature suggests an incidence rate of 0.028 % to 4.3 %. Our cohort studies found an incidence of 0.02 % (95 % CI 0.004 %-0.11 %). We examined the epidemiology of BONJ associated with osteoporosis dosing of bisphosphonates. First, we systematically searched the literature about osteoporosis BONJ. Identified studies were abstracted by two authors. Second, we attempted to estimate the relative risk of BONJ among bisphosphonate users with osteoporosis. Two different large insurance databases, one from 2005-2007 and another from 2007-2010, combined with medical record review, were searched. The older dataset did not include the International Classification of Diagnoses (ICD) diagnosis code for osteonecrosis of the jaw (ONJ; ICD 733.45). Incidence rates and relative risks were estimated using Cox regression. The literature review produced nine studies of varying quality. The incidence rates for BONJ among osteoporosis patients varied from 0.028 % to 4.3 %. Two prior studies estimated the relative risk of ONJ related to bisphosphonates and found odds ratios of 7.2 and 9.2. Our attempts to estimate the incidence rate of BONJ encompassed 41,957 in the dataset from 2005-2007 and 466,645 in a separate dataset from 2007-2010. From the older dataset, we found 51 potential cases of BONJ using a broad definition of possible ONJ. One case was confirmed by a dentist for a prevalence of 0.02 % (95 % CI 0.004 %-0.11 %) among bisphosphonate users. From the newer dataset, we found 13 possible cases, but none could be confirmed. Most subjects with the ONJ diagnosis code appeared to have had an osteoporosis-related fracture and not ONJ. The literature suggests a broad range of possible values for the prevalence of BONJ; our estimate fell within the range from prior literature.