Bisphosphonates and Osteonecrosis of the Jaw: A Case Report

Abstract

The incidence of bone metastases is high among patients with advanced cancer. Bone metastases occur in about 80% of men with advanced prostate cancer,1 75% of patients with metastatic breast cancer2 and 30% to 60% of patients with advanced metastatic lung cancer,3 and are present in 35% of patients with renal cell carcinoma at the time of diagnosis4. Bone metastases cause considerable skeletal morbidity with severe bone pain in some cases, pathologic fractures, spinal cord compression and hypercalcemia. In addition, patients frequently need radiotherapy or surgery to treat bone pain or to prevent pathological fractures.3,5 Because of this, complications from bone metastases heavily impact the quality of life of patients with cancer. Therefore, the prevention or delay of these complications would be of significant benefit to patients with advanced cancer.6 The bisphosphonates represent a major advance in helping patients with bone metastases.7 They have been largely used in the treatment of this condition, since they inhibit osteoclastic activity, proliferation of tumor cells and angiogenesis. Bisphosphonates are also used in the treatment of other bone diseases, such as osteoporosis, Paget’s disease and malignancy-related hypercalcemia.8–10 In 1995, intravenous pamidronate was approved for treating patients with multiple myeloma or metastatic breast cancer based on study findings that pamidronate reduces the risk of skeletal complications. In 2002, intravenous zoledronic acid was approved for the treatment and prevention of skeletal complications in patients with multiple myeloma or with bone metastases from any solid tumor type.11,12 This was the first bisphosphonate with proven efficacy in the treatment of bone metastases from solid tumors, in addition to breast carcinoma.6 Currently, therapy with bisphosphonates is considered standard in the prevention of skeletal complications in patients with bone metastases.13 Although serious side-effects have been reported, including acute renal failure after intravenous administration and gastrointestinal toxicities such as esophagitis when used orally, these drugs are generally well tolerated14. Recently, however, a new complication associated with the use of bisphosphonates has been described: osteonecrosis of the jaw. This condition was initially associated with the use of zoledronic acid, but occurrences after pamidronate use have also been reported.15, 16