Maxilla osseus sequestre and oral exposure: effects of the treatment of multiple myeloma with bisphosphonates.

Abstract

Multiple myeloma, the second most common haematopoietic cancer, represents a collection of plasma-cell neoplasms that invariably become fatal when self-renewing myeloma cells begin unrestrained proliferation. The major clinical manifestation of multiple myeloma is related to loss of bone through osteolysis. The bone disease can lead to pathologic fractures, spinal cord compression, hypercalcemia, and pain. It is also a major cause of morbidity and mortality in these patients. These patients frequently require radiation therapy, surgery and analgesic medications. Bisphosphonates are specific inhibitors of osteoclastic activity, and are currently used to prevent bone complications and to treat malignant hypercalcemia in patients with multiple myeloma, or bone metastases from breast and prostate cancers. Recent published reports have documented a possible link between treatment with intravenous bisphosphonates and osteonecrosis of the jaw. Bisphosphonates have been demonstrated to alter the normal bone microenvironment and appear to have direct effects on tumours as well. These changes may contribute to the development of osteonecrosis of the jaw in these patients, particularly after tooth extractions or other invasive dental procedures. Osteonecrosis of the mandible has been reported in 3 patients from Centro Hospitalar de Vila Nova de Gaia (CHVNG) with multiple myeloma treated for over 18 to 48 months with intravenous bisphosphonate zoledronate. It has been postulated that bisphosphonates may cause oral avascular bone necrosis due to antiangiogenic effect leading to disruption of osteoclast-mediated bone resorption. Although this report serves to alert clinicians about the potential complication of bone necrosis in patients receiving bisphosphonates therapy, many questions remain concerning the underlying pathogenesis of this process. In these 3 described clinical cases, surgical debridment without flap elevation, intensive antibiotherapy and zolendronate treatment arrest made possible the partial recovery of the patients. We purpose this type of clinical approach in patients suffering from multiple myeloma and bone osteonecrosis induced by bisphosphonate treatment. Research to determine the mechanism of this dental phenomenon is needed to fully validate and substantiated the possible link between bisphosphonates treatment of multiple myeloma or other cancer diseases with avascular osteonecrosis of the jaws. Until then, clinicians involved in the care of patients at risk should consider this possible complication.