Avascular mandibular osteonecrosis in association with bisphosphonate therapy: a report on four patients.
Over the past three years, several reports have been published on jaw osteonecrosis possibly being associated with the administration of bisphosphonates. Bisphosphonates are highly active inhibitors of osteoclasts. These drugs are used for the treatment of multiple myeloma, bone resorption in the case of metastatic malignant diseases, tumor-associated hypercalcaemia, and in the treatment of osteoporosis. Due to the importance of this presumed side-effect of bisphosphonates for the dentist and the maxillofacial surgeon, we report four cases.


METHODS
Four patients (two women and two men aged 56, 62, 67 and 75 years, respectively) were diagnosed with osteonecrosis of the mandible. These osteonecroses did not react adequately to local treatment and systemic therapy with antibiotics. One patient suffered from non-Hodgkin's lymphoma, one from breast cancer, one from prostate cancer and one from sarcoidosis. Besides cytostatic chemotherapies, all patients received bisphosphonates over an extended period.


CONCLUSIONS
Bisphosphonates are considered an established standard in the treatment of multiple myeloma and bone metastases. Over the past few years, a rapidly increasing number of reports have been published describing patients with a history of bisphosphonate therapy in whom therapy-resistant osteonecrosis of jaw bones occurred either after dental extractions or spontaneously. Since then, bisphosphonate therapy has come under scrutiny as a cause of osteonecrosis. However, the multiplicity of drugs prescribed for the treatment of cancer requires caution when determining a cause-and-action effect. Since patients with malignant diseases receive cytostatic therapy and a range of other drugs, including bisphosphonates, enhancement of the side-effects may be presumed. The case report of an osteonecrosis of the jaw following multi-drug therapy for sarcoidosis adds a further and non-cancerous condition to the newly described entity of bisphosphonate-associated jaw necrosis.


CONCLUSIONS
The probable association of the therapeutic use of bisphosphonates and the development of jaw necrosis has to be studied in further investigations. Patients who will undergo bisphosphonate therapy should receive a careful dental check-up prior to drug application. Patients receiving bisphosphonates should be followed up carefully to avoid the occurrence of extended osteonecrotic lesions. Moreover, established jaw lesions must be diagnosed precisely in order to exclude metastatic disease.
Friedrich
Reinhard E
RE
Maxillofacial Surgery, Eppendorf University Hospital, University of Hamburg, Germany. rfriedri@uke.uni-hamburg.de
Blake
Felix A
FA
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008297:Male; D008336:Mandibular Diseases / Q000139:chemically induced*; D008875:Middle Aged; D010020:Osteonecrosis / Q000139:chemically induced*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012507:Sarcoidosis / Q000188:drug therapy
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates