Osteonecrosis of the Jaw – Relationship to Bisphosphonate Use: Commentary and Perspective

Abstract

Osteonecrosis of the jaw (ONJ) has traditonally been known to occur following head and neck irradiation in cancer patients. It has also been associated with other important risk factors, such as chemotherapy, glucocorticoid therapy, local trauma, malignancy and periodontal disease. This avascular bone necrosis, or dead bone, develops due to an inadequate blood supply and has recently been described as occuring in oncology patients receiving high-dose intravenous bisphosphonates. In 2003, the first cases of ONJ in cancer patients receiving bisphosphonates were reported [1]. Subsequent publications have essentially consisted of case reports, case series or surveys, and have demonstrated a temporal relationship between high-dose intravenous bisphosphonate use and the development of ONJ [2–5]. To date, there are only two prospective observational studies evaluating bisphosphonate-associated ONJ. These lesions often involve mandibular bone, in particular the mylohyoid ridge, unlike osteoradionecrosis, and have presented with painful or painless exposure of the bone in the oral cavity. Presenting features of ONJ include pain, softtissue swelling and local infection or abscess formation with development of fistulas. Loosening of teeth may also occur in addition to the exposed bone in the oral cavity. ONJ most commonly occurs at sites of previous tooth extraction or areas of trauma. However, it may occur spontaneously. In a study by Marx et al., 76 consecutive patients referred to the University of Miami, FL, USA, were reviewed in addition to 43 patients from other centers. Approximately a third had presented with asymptomatic exposed bone, which had been self identified or noted on routine examination. Approximately two-thirds of patients presented with exposed bone in the presence of pain [6]. High doses of intravenous bisphosphonates in the oncology population have been associated with an increased risk of osteonecrosis in published data to date. Durie and colleagues reviewed 1203 patients from a web-based survey with multiple myeloma or breast cancer and 75 patients were reported to have ONJ. The likelihood of ONJ appeared to be related to both the potency and duration of therapy [4]. Bamias and colleagues published a case series of 252 patients with bone metastases and those developing ONJ had received a median of 35 infusions of pamidronate or zoldedronic acid, whereas those who were not affected had received a median of 15 infusions (p < 0.001) [5]. Duration of therapy appears to be an important risk factor in the development of ONJ in oncology patients.