Jaw avascular osteonecrosis after treatment of multiple myeloma with zoledronate

Summary 

Purpose

Multiple myeloma, the second most common haematopoietic cancer, which represents the collection of plasma-cell neoplasms that invariably becomes fatal when self-renewing myeloma cells begin unrestrained proliferation. The major clinical manifestation of multiple myeloma is related to the loss of bone through osteolysis. This can lead to pathologic fractures, spinal cord compression, hypercalcaemia, and pain. It is also a major cause of morbidity and mortality in these patients, who 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 hypercalcaemia in patients with multiple myeloma, or bone metastases from breast and prostate cancers. Hence, osteonecrosis of the mandible has been reported in three patients from Centro Hospitalar de Vila Nova de Gaia (CHVNG) with multiple myeloma treated for over 18–48 months with intravenous zoledronate, commonly prescribed for multiple myeloma therapy. Although, this report alerts clinicians about the potential complication of bone necrosis in patients receiving bisphosphonate therapy, many questions remain concerning the underlying pathogenesis of this process.

Patients and methods

The medical and dental records of three patients with multiple myeloma, who were treated in CHVNG in the past 4 years, were reviewed. These three patients presented exposed bone and osteonecrosis of the mandible, and shared one common clinical feature: all of them were treated with bisphosphonate zoledronate, administered intravenously for long periods. Sequential orthopantomograms (OPGs) and histological evaluation have been analysed from the biopsies of the non healing dental extraction sites of these patients.

Results

After a routine dental extraction, these patients developed avascular osteonecrosis of the mandible and secondary bone infection with Actinomyces israelii (actinomycotic osteomyelitis), with no evidence of metastatic disease evaluated by biopsy. In these three described clinical cases, surgical debridment without flap elevation, intensive antibiotherapy and the suspension of the zoledronate treatment allowed a partial recovery of the patients.

The purpose of this clinical report is to point out that patients suffering from multiple myeloma can develop bone osteonecrosis induced by treatment with bisphosphonates. Research to determine the mechanism of this dental phenomenon is needed to fully validate and substantiate the possible link between bisphosphonate treatment of multiple myeloma or other cancer diseases and avascular osteonecrosis of the jaws. Until then, clinicians involved in the care of patients at risk should consider this possible complication.

Keywords: Bisphosphonates, Multiple myeloma, Avascular osteonecrosis, Jaw