Improvement of Zoledronic Acid-Induced Jaw Osteonecrosis with Bortezomib

month, but the painful mass on her mandible did not recover. The clinical course, CT and biopsy findings suggested that our patient had a zoledronic acid-induced jaw osteonecrosis [3, 4] . Two months after the cessation of antibiotic therapy, MM also relapsed. Bortezomib was started on days 1, 4, 8 and 11 at a dose of 1.3 mg/m 2 as monotherapy. After the first cycle of bortezomib, clinically regression of the mass and pain relief in her left jaw were observed in the absence of dexamethasone, antibiotic or any other drug treatment that could cause the improvement in osteonecrosis. This was an unexpected and surprising finding. If it were a plasmacytoma, it would reasonably respond to bortezomib therapy, but a biopsy specimen of the involved tissue did not reveal plasmacytoma. A control CT after three cycles of bortezomib also showed improvement in the soft tissue mass with a moderate callus formation and, as a result, moderately improved osteonecrosis ( fig. 1 b). In total, four cycles of bortezomib were given without bisphosphonates. The patient responded to bortezomib therapy with a significant decrease in M-protein. She is still on follow-up with no MM-related complaints, but has neuropathic pain due to bortezomib. The exact mechanism of bisphosphonate-induced jaw osteonecrosis has not been elucidated yet, however, the cumulative ischemic effect was suggested to be the causative event. It was reported that osteonecrosis induced by bisphosphonates did not improve following surgical resection or antibiotics [4, 5] . Bortezomib is the first proThe proteasome is an enzyme complex that degrades many targeted intracellular proteins. Inhibition of this enzyme complex affects the levels of various intracellular proteins that regulate the cell cycle, leading to a decrease in cell proliferation. Bortezomib is the first proteasome inhibitor to be used in cancer therapy, especially in multiple myeloma (MM) [1, 2] . However, we report a different effect of bortezomib in a patient with relapsed MM. A 58-year-old female patient was diagnosed as having IgG MM. She received three cycles of VAD (vincristine, adriamycin and dexamethasone) chemotherapy and high-dose melphalan with autologous peripheral blood stem cell support, followed by monthly zoledronic acid. One year after high-dose chemotherapy, she had a tooth extraction from the left jaw and sometime later, she was admitted with gum hyperplasia. Since no clinically associated disease was found to explain the gum hyperplasia, it was surgically resected. Histopathological examination of this material revealed normal histological findings. One year after the tooth extraction, a painful mass appeared on her left jaw and a few days later, an inflammatory material began to drain. Computerized tomography (CT) revealed osteitis and a widespread periosteal reaction in her mandible ( fig. 1 a). Biopsy of the involved bone disclosed osteonecrosis and a mixed inflammatory reaction, but there was no evidence of plasmacytoma. With a clinical suspicion of osteomyelitis, ampicillin/sulbactam therapy was given empirically and zoledronic acid was stopped. The fistula was successfully treated after 1 Received: July 4, 2007 Accepted after revision: September 6, 2007 Published online: November 9, 2007