Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is recognized as a serious
complication among patients receiving bisphosphonate therapy. However, methods for
early detection and identification of patients at risk for osteonecrosis of the jaw
(ONJ) need further investigation. The purpose of this study was to characterize BRONJ
among patients receiving intravenous bisphosphonates and to examine bone scintigraphy
findings that preceded manifestation of frank ONJ.
We identified all known cases of BRONJ (defined according to 2006 American Association
of Oral and Maxillofacial Surgeons criteria) diagnosed between January 2004 and September
2008 among patients who received intravenous bisphosphonate therapy (IVBP). The medical
records were abstracted, and the clinical and radiographic features of BRONJ and relevant
comorbidities were characterized. Technetium Tc 99 bone scintigrams were systematically
reviewed among the subset of patients who received these imaging studies for oncologic
care and imaging findings were correlated with the temporal development of ONJ.
We identified 59 cases of intravenous BRONJ (median age, 61.4 +/- 10.7 years; 57.6%
female), of whom 44.1% had breast cancer, 33.9% had multiple myeloma, and the remainder
had metastatic prostate cancer (15.3%) or other cancers (6.8%). One third (32.2%)
of the cohort was diabetic. In addition to IVBP, the vast majority (86.4%) had also
received prior systemic glucocorticoid therapy. The median cumulative number of IVBP
doses was 25 (interquartile range, 16-39) at the time of BRONJ diagnosis. Half of
the patients had prior invasive dental procedures; ONJ developed spontaneously in
27.1%, and in the remainder ONJ developed in the setting of periodontal disease (10.1%)
or local trauma (8.4%). Most patients presented with painful stage 2 disease involving
the mandible (75%), and Actinomyces was present in more than 77% of available histologic
specimens. During the median follow-up of 1.5 years, 15 patients (25.4%) regressed
to a less severe stage, with healing in 6 patients; 16 (27.1%) worsened; and the remainder
stayed within the same stage, but in almost half of these patients, the extent of
involvement progressed. Of the 38 patients who had 99Tc bone scintigraphy, 35 had
bone scans before development of BRONJ, and among these patients, 23 (67.5%) had positive
tracer uptake in areas that subsequently developed BRONJ.
In this study bone scintigraphy showed positive tracer uptake before the development
of BRONJ in almost 66% of patients who had these scans before clinical evidence of
frank osteonecrosis. BRONJ subsequently developed in the areas identified on scintigraphy
in these patients. Further studies should explore the role of bone scintigraphy in
the detection of early subclinical BRONJ.