Intravenous Bisphosphonate-Related Osteonecrosis of the Jaw: Bone Scintigraphy as an Early Indicator

Abstract

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.