Osteonecrosis of the jaw associated with pamidronate therapy

Bisphosphonates are commonly used in the treatment and prevention of osteoporosis, and they are also an important therapeutic adjunct in multiple myeloma and other cancers metastatic to bone. Bisphosphonates are generally well tolerated and associated with minimal adverse effects; however, there exists a growing concern that intravenous bisphosphonate use is associated with osteonecrosis of the jaw (ONJ). We report the occurrence of osteonecrosis of the jaw associated with pamidronate therapy in 12 patients diagnosed with multiple myeloma, breast carcinoma, or renal cell carcinoma, all involving bone. At the onset of jaw osteonecrosis, pamidronate therapy was the single medication common to all 12 patients. The duration of therapy varied from 12 to 77 months before osteonecrosis was observed; 92% (11/12) of cases involved the posterior mandible and all cases have been refractory to a variety of medical therapies, including surgical debridement and systemic antibiotics. Available tissue biopsies revealed inflammation consistent with osteomyelitis. In one biopsy, Actinomyces spp. were recovered from culture, but treatment with an extended course of clindamycin conferred no clinical benefit. The persistence of exposed bone remains a significant source of morbidity and pain for each surviving patient. Discontinuation of pamidronate therapy has not helped reverse the presence of osteonecrosis, and surgical manipulation of the involved site appears to worsen the underlying bone pathology. ONJ is an important adverse outcome associated with bisphosphonate therapy, and physicians prescribing pamidronate or zoledronate must be aware of the association between these drugs and this serious clinical entity. Failure to recognize the signs of ONJ can lead to unnecessary surgical procedures, which ultimately exacerbate the condition and impact quality of life. The unremitting nature of this clinical development, and the long-lasting morbidity associated with it suggests that patients should be counseled regarding the possible occurrence of ONJ prior to initiating therapy with pamidronate.