Avascular necrosis of the jaw in multiple myeloma (MM) patients (pts) treated with bisphosphonates (BP)

Abstract

18538 Background: Oral cavity avascular bone necrosis (ABN) has been recently reported as an emerging serious complication in pts receiving BP for the treatment of hypercalcemia related to MM or metastatic solid tumors. Methods: We report the cases of 6 pts with MM treated initially with pamidronate and later with zoledronic acid (ZA). Results: Pts characteristics : M/F 3/3; mean age 58.4 (46–78); 4 IgG κ,1 γ and 1 κ MM; 5 St IIIA and 1 IIIB; mean history of disease 61.3 mo. (23–103); 5 pts had a relapsing MM refractory to several lines of therapy but 1 pt had received only high dose dexametazone (D); 2 pts had received autologous stem cell transplantation and 1 pt allogenic bone marrow transplantation; mean n.° of BP doses was 41.3 (17–81). At the time of ABN onset all pts were receiving ZA along with, respectively: D (2 pts); cyclophosphamide plus D (1 pt), bortezomib plus D (2 pts) and oral melphalan (1 pt). ABN was localized in 2 pts at alveolar bone of the right maxilla and presented as an inflammation of the gum, followed by a painful bone exposure. In the other 4 pts ABN was localized at mandible and presented as dental abscesses followed in 2/4 pts by cutaneous fistulization. Treatment has included in all pts discontinuation of ZA, antibiotics, chlorhexidine mouthwashes, pain control, minor regional débridement, and bone trimming. In 1 pt a more aggressive surgical approach was attempted at an other Institution and postoperative course was complicated by massive haemorrhage and complete loss of chewing. Four pts dead with progressive disease with a mean overall survival after ABN presentation of 6 mo.; 2 pts are alive after 3 and 4 mo. after ABN presentation; however in all pts ABN significantly worsened quality of life. Conclusions: Oral cavity ABN is a severe complication in refractory MM pts receiving BP. Mechanisms of action of BP that determine a reduction in osteoclastic activity and an accumulation of nonvital osteocytes with microfractures of old mineral matrix appear to play an important role. However other causes may be involved as a long history of disease; an uncontrolled progressive disease; type and doses of previous and present therapies, primarily steroids; status of oral cavity and teeth of pts and possibly the n.° of doses of BP. No significant financial relationships to disclose.