Severe Osteomyelitis of the Jaws in Long Term Survivorsmultiple Myeloma Patients Treated with Biphosphonates.A New Clinical Entity.

Multiple Myeloma is a frequent and usually fatal lymphoproliferative disorder with a median survival of around 30 months.Supportive therapy includes monthly intravenous injections of biphosphonates as prevention, or therapy,of lytic bone disease.

We report three cases of Multiple Myeloma patients who developed severe osteomyelitis of the jaws while receiving prolonged biphosphonate therapy.All three patients are very long survivors of Myeloma,being alive 6 to 12 years after diagnosis.They have been treated with biphosphonates for more than 4 years, receiving large doses of Pamidronate(3420 to 4680 mg) and lesser doses of Zoledronate(16 to 72 mg).Jaw infection was unprovoked in wo parients and was cused by dental extraction in the third.Diagnosis of osteomyelitis was confirmed by histology in all three patients, while in two we could demonstrate the presence of Actinomyces.Therapy with hyperbaric oxygen of osteomyelitis refractory to prolonged antibiotherapy, was curative in one patient. To the best of our knowledge, these are the first cases of osteomyelitis of the jaw reported in the literature in Myeloma patients treated with chronic administration of intravenous biphosphonates.Recent reports have alerted physicians of a ’’ growing epidemics’’ of Pamidronate and Zoledronate induced avascular necrosis of the jaw, most of them provoked by teeth removal.Both of these biphosphonates have strong antiosteoclastic activity, and Zoledronate is antiangeogenic, all properties which contribute to the development of bone necrosis.Since the jaws are the only bones in the skeleton exposed to the external environment, the association of bone necrosis with secondary chronic infections may lead to osteomyelitis.Even though it is not possible to prove beyond doubt an etiological link between biphosphonate therapy and the occurrence of osteomyelitis of the jaws, the association of Myeloma with severe immunosupression, the very prolonged biphosphonate therapy in our three patients, and the localization to the jaw, are in favor of a clear relationship between therapy with Zolandronate, Pamidronate and osteomyelitis of the jaws. With the expected life prolongation of Myeloma patients due to recent therapeutic breakthroughs and the increasing use of antiangeogenic agents, it is crucial to be aware of the possibility of a rise in the number of osteomyelitis of the jaws in Myeloma patients.