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.