title: Intravenous bisphosphonate-related osteonecrosis of the jaw: bone scintigraphy as an early indicator.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Maxillofacial Surgery, Kaiser Permanente Oakland Medical Center, Oakland, CA 94611, USA. Felice.O'Ryan@kp.org
authors.forename: Felice S
authors.initials: FS
authors.lastname: O'Ryan
authors.forename: Sam
authors.initials: S
authors.lastname: Khoury
authors.forename: Wendy
authors.initials: W
authors.lastname: Liao
authors.forename: Myo M
authors.initials: MM
authors.lastname: Han
authors.forename: Rita L
authors.initials: RL
authors.lastname: Hui
authors.forename: David
authors.initials: D
authors.lastname: Baer
authors.forename: Daniel
authors.initials: D
authors.lastname: Martin
authors.forename: Donald
authors.initials: D
authors.lastname: Liberty
authors.forename: Joan C
authors.initials: JC
authors.lastname: Lo
mesh_terms: D000284:Administration, Oral; D019386:Alendronate / Q000008:administration & dosage / Q000009:adverse effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D007275:Injections, Intravenous; D007571:Jaw Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D010020:Osteonecrosis / Q000139:chemically induced / Q000000981:diagnostic imaging*; D000077268:Pamidronate; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012189:Retrospective Studies; D017556:Technetium Compounds; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D019275:Radiopharmaceuticals; D017556:Technetium Compounds; D000077211:Zoledronic Acid; C029045:technetium Tc 99m diphosphonate; D000077268:Pamidronate; D019386:Alendronate