Bisphosphonate Therapy Associated with an Increased Incidence of Mandibular/Maxillary Osteomyelitis in Multiple Myeloma Patients.

Bisphosphonates provide a meaningful supportive skeletal benefit for patients with multiple myeloma by inhibiting the resorbtion of bone thereby effectively reducing the incidence of pathologic fractures and hypercalcemia. Recently, bisphosphonates have been linked to osteonecrosis of the jaw in breast cancer and multiple myeloma patients. We report 14 cases of multiple myeloma patients being treated with bisphosphonates who developed periodontitis/osteomyelitis of the jaw.

All 14 patients were being treated with bisphosphonates for an average of 5 months (range: 3–9 months) prior to the onset of jaw symptoms. Thirteen of the 14 patients are 51 years or older. None of the patients had been irradiated in the jaw nor had obvious osseous manifestation of multiple myeloma in the jaw. Six patients were receiving zoledronic acid and 8 pamidronate. Organisms were isolated in 6/14 patients with the most common organism being actinomycosis. All patients remain on suppressive antibiotic therapy in the form of clindamycin.

The mandible and maxilla are bisphosphonate seeking bones as evidenced by scintigraphy. The local perpetuation of an infection in the mandibular/maxillary area in association with bisphosphonates is likely multi-factorial. This environment is continually exposed to stress trauma from repetitive motions. Bisphosphonates disrupt the normal bone homeostasis and this is complicated by the fact that the oral cavity is saturated with natural flora making this area vulnerable to infection. Additionally, in an acidic environment, such as one resulting from an infection, bisphosphonates are released locally from hydroxyapatite of bone into the surrounding environment and are cytotoxic to the local stromal cells. In the presence of inflammation and infection, there is evidence to suggest that bisphosphonates, especially the nitrogen-containing compounds, may actually up regulate the host inflammatory response with stimulation of IL-1 and IL-6. This generates a continuous cycle of inflammation and release of bisphosphonates from bone comprimising the healing process as has been previously reported.

We recommend that patients have a full dental examination at the time of diagnosis of the plasma cell dyscrasia especially if bisphosphonates are to be considered as part of the therapy. In addition, we suggest to hold bisphosphonates for a period of 3 months prior to invasive dental procedures to allow for the osteoclastic activity to recover, allowing for debris removal and lessening the chance of creating a fertile bacterial medium. Patients with multiple myeloma on bisphosphonate therapy whom experience dental/jaw discomfort should have an aggressive evaluation to rule out an infectious etiology.