Surgical treatment of bisphosphonate-associated osteonecrosis: Prognostic score and long-term results

Abstract

Over a century after the first synthesis of bisphosphonates (1897) and a decade (2003) since the initial report on bisphosphonate-related osteonecrosis of the jaw (ONJ), this osteopathy remains a serious clinical challenge. A single center longitudinal study (2005-2014) was carried out to prospectively characterize inpatients with manifest ONJ and to evaluate their outcomes. The data recorded were: medical history, bisphosphonate treatment, localization, imaging, treatment, histomorphological features, and complications. A prognostic score (modified UCONN-Score) was adopted to predict outcomes. Eighty patients were included (mean age 69.4 years; 40 male, 40 female). Breast cancer (n = 25), multiple myeloma (n = 16), and prostate cancer (n = 15) were the three most common malignancies; and cardiovascular disease (n = 31), diabetes mellitus (16), and renal disorders (6) were the most important comorbidities. The severity of ONJ was stage I in three patients, stage II in 37, and stage III in 40, being predominantly localized in the posterior mandible and needing gradual resection. The average duration of bisphosphonate treatment was 38.3 months. The typical histological aspects of ONJ were predominantly osteonecrosis, bone marrow fibrosis, and bacterial colonization (Actinomyces) with suppurative inflammation. Within the resected jawbone a primary malignancy was diagnosed in two cases. The overall success rate was 83.6% (follow-up 23.5 months), with a UCONN-Score ≥15 predicting unfavorable treatment results (OR = 5.2). The past decade has enhanced experience with ONJ treatment and knowledge about its pathogenesis, which seems to be a multistep process. This study demonstrates the importance of bone and multilayer soft tissue management, preferably as an early intervention. The UCONN-Score might help to assess individual prognosis in ONJ surgery and the potential benefit of an antiresorptive drug holiday. To our knowledge it is the first use of a prognostic score in ONJ surgery.

Keywords: Bisphosphonate; Histopathology; Osteonecrosis; Outcome; Radiology; Score.