Oral Cavity Avascular Bone Necrosis - a Newly Recognized Complication of Intravenous (IV) Bisphosphonate Therapy in Cancer Patients.

Cancer patients with skeletal complications are frequently treated monthly with intravenous bisphosphonates over an extended period of time. The bisphosphonates have been useful in strengthening the bone, in pain control, and in some cases, decreasing the incidence of further skeletal -related events (SRE’s), including the hypercalcemia of malignancy. Although bisphosphonate treatment is remarkably well tolerated, recently, a serious complication has been reported in the dental literature - oral cavity avascular bone necrosis. We report on 2 cases of intraoral osteonecrosis in patients treated for more than 2 years with, initially, pamidronate (Aredia; Novartis) and later zoledronic acid (Zometa; Novartis). Patient JG is a 65 year-old man with a 7-year history of IgG kappa multiple myeloma. The patient was originally treated with vincristine, adriamycin and Decadron (VAD) chemotherapy along with monthly pamidronate infusions followed by high-dose melphalan (HDM) and autologous peripheral stem cell transplantation (PBSCT). At the time of relapse < 1 year after the PBSCT, he was maintained on Thalidomide along with monthly infusions of zoledronic acid at a dose of 4mg. Almost 3 years after starting zoledronic acid therapy, the patient began experiencing severe dental pain. He was repeatedly evaluated by his dentist, treated with antibiotics for recurrent dental abscesses and underwent numerous root-canal procedures. A tooth was extracted, and he was subsequently diagnosed with oral cavity avascular bone necrosis in the molar region. Bisphosphonate infusions were discontinued. He has required repeated courses of antibiotics, root canal, and narcotic pain medications to treat the condition. FC is a 60 year-old woman, also with a 7-year history of IgG kappa multiple myeloma treated initially with VAD along with monthly pamidronate infusions followed by HDM and PBSCT. Additionally, she was subsequently treated for ovarian cancer with 6 ycles of carboplatin and paclitaxel. Following this, she was also treated with thalidomide and zoledronic acid. for 2 years after relapsing 2 years post PBSCT. At the end of this time, she noted a purulent drainage arising from a lesion in the mental region of the jaw. The area was biopsied and revealed only necrotic material. A subsequent CAT scan revealed osteonecrosis of the jaw. She has also required therapy with antibiotics and narcotic pain control. The zoledronic acid has been discontinued. Oral cavity avascular bone necrosis is becoming an increasingly more recognized complication of intravenous bisphosphonate treatment in cancer patients. The etiology is not understood although it has been postulated to be secondary to the antiangiogenic effect of the bisphosphonates on inhibiting osteoclasts. Treatment has included discontinuation of the offending drug, antibiotics, pain control, regional débridement, and bone trimming. Hematologists/oncologists should now be alert to this new complication of intravenous bisphosphonates in cancer patients who complain of dental pain.