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Osteonecrosis of the maxilla and mandible: possible drug-induced complication of bisphosphonate therapy

2004; Elsevier BV; Volume: 97; Issue: 4 Linguagem: Inglês

10.1016/j.tripleo.2004.02.014

1528-395X

Cherry L. Estilo, T. Williams, E. Evtimovska, L. Tkach, Jerry Halpern, Steven Tunick, Joseph M. Huryn,

Bone and Joint Diseases

Osseous metastases are associated with skeletal complications, including bone pain, fractures, and hypercalcemia. Bisphosphonates are potent osteoclast activity inhibitors that can decrease skeletal related complications by approximately one third.1.Body J.J Bartl R Burckhardt P Delmas P.D Diel I.J Fleisch H et al.Current use of bisphosphonates in oncology. International Bone and Cancer Study Group.J Clin Oncol. 1998; 16: 3890-3899Google Scholar Hence, intravenous bisphosphonates have been incorporated into the therapy of patients with osseous metastases of various tumor types. Osteonecrosis of the maxilla has been reported in a patient with metastatic breast cancer treated for over 4 years with intravenous bisphosphonate,2.Mehrotra B, Fantasia J, Nissel-Horowitz S, Vinarsky S, Sheth M, Ruggiero S. Osteonecrosis of the maxilla: An unusual complication of prolonged bisphosphonate therapy. A case report (abstract). American Society of Clinical Oncology Annual Meeting 2003.Google Scholar and it has been postulated that bisphophonates may cause oral avascular bone necrosis due to antiangiogenic effect leading to inhibition of osteoclasts.3.Migliorati C.A Bisphosphanates and oral cavity avascular bone necrosis.J Clin Oncol. 2003; 21: 4253-4254Google Scholar To further explore this potential drug complication, we performed a retrospective chart review of patients with multiple myeloma and metastatic breast cancer who were receiving intravenous bisphosphonate therapy. The medical and dental records of all patients with multiple myeloma or breast cancer who were treated in the Dental Service of Memorial Sloan-Kettering Cancer Center between January 1, 2000, and December 10, 2003, were reviewed. Patients who presented with exposed bone or osteonecrosis of the maxilla or mandible and were previously treated with bisphosphonate were further evaluated for various clinical and pathological characteristics including sex, age, primary tumor type, presence of bony metastasis, duration of bisphosphonate therapy, symptomatology, location of osteonecrosis, history of dental extraction in the area of osteonecrosis, and dental intervention rendered. One hundred twenty-four patients were identified within the time frame and disease type of interest. Thirteen patients were found to have osteonecrosis of the maxilla or mandible. Of these patients, 9 patients had a history of breast cancer with bony metastases and 4 had multiple myeloma. There were 4 men and 9 women, with a median age of 56 years (range 27-73 years). All of the patients received intravenous pamidronate and/or zoledronic acid, with a median duration of 39 months (range 1-94 months). Nine of the fourteen patients (69%) presented with symptoms. Osteonecrosis was noted in the maxilla in 5, mandible in 6, and both maxilla and mandible in 2 patients. Nine patients had a history of dental extraction in the region of osteonecrosis. Four patients presented with spontaneous osteonecrosis. Conservative sequestrectomy was performed in 6 patients. One patient underwent surgical debridement. Six patients were managed conservatively with chlorhexidine rinse and/or antibiotics. After conservative management, resolution was achieved in one patient. The clinically relevant cancer literature on bisphosphonates is almost uniformly positive demonstrating a decrease in skeletal complications. However, there is evolving concern that bisphosphonate therapy may be associated with the development of osteonecrosis of the maxilla and mandible. Additional contributing causes of these patients' oral condition may include advanced cancer, chemotherapy, and steroids. Research to determine the mechanism of this dental phenomenon is needed to fully validate and substantiated this possible link. Until then, clinicians involved in the care of patients at risk should consider this possible complication.