Possible Role of Ozone Therapy in the Treatment of Osteonecrosis of the Jaws in Multiple Myeloma Patients.
Authors: Gallucci Cristiano , Agrillo Alessandro , Iannetti Giorgio , Foà Robert , Petrucci Maria Teresa 
Published: April 2020

Abstract
Multiple Myeloma (MM) is a haematological malignancy clinically characterized by a frequent involvement of the bone from osteoporosis up to lytic lesions. Therapy with bisphosphonates (Pamidronate and/or Zoledronate) is commonly prescribed for the prevention and cure of pathological fractures in these patients. Among the several properties of this drug, its osteoclastic inhibition results in reduction of bone resorption. Since 2003, a possible association between the use of bisphosphonates and the appearance of osteonecrosis of the jaws, especially in long-term treated patients undergoing invasive oral procedures, has been reported. Histologic examinations show these lesions to be the result of an avascular necrosis of the bone, due, in first hypothesis, to bisphosphonates osteoclastic and angiogenetic inhibition, which impairs healing and exposes to infections by oral bacteria. At present, the treatment options reported (antibiotics with or without surgery and hyperbaric oxygen therapy) have not led to a complete resolution. Since 1998, at our Institute we have treated 311 MM patients with Pamidronate 90 mg i.v. and/or Zoledronate 4 mg i.v. monthly. Twenty-four patients (8%) referred toothache, impaired healing after teeth extractions, dental abscesses and bone exposure; bisphosphonates were withdrawn and antibiotics administered. In view of the limited benefits in this subset of patients with standard therapy, we decided to utilize a 15 day treatment protocol that included antibiotics (amoxicillin-clavulanic acid 2 gr/daily plus metronidazole 1 gr/daily), surgery (from simple curettage to bone reseption) and ozone therapy (administered previous, during and after surgery). Of the 11 patients with dental abscesses or jawbone exposition after teeth extraction, followed so far, 4 are evaluable for response because they completed the program. All patients symptomatic for MM were also treated with chemotherapy, 3 are women and 1 man, aged 61, 62, 69 and 79. Two patients are IgG, 1 IgA, 1 light chain MM. Three patients have received Zoledronate and 1 Pamidronate followed by Zoledronate for a median time of 19 months (range 6–27). One patient had a wide bone exposition with oro-sinusal fistula, 3 had difficult healing after teeth extractions or oral cleaning. Osteonecrosis of the jaw was histologically confirmed in 1 patient. Patients were treated with antibiotic therapy, underwent surgery (1 emimaxillectomy, 1 curettage, 1 tooth extraction and 1 extraction plus curettage) and local ozone applications according to the schedule. All patients obtained a complete resolution of the problem with the total riepithelialization of the lesions. These preliminary results add further evidence that ozone therapy, with its antimicrobic action and neoangiogenetic properties, results in an improved tissue oxygenation making healing easier. The association of ozone therapy with antibiotics and surgery could be considered an effective treatment of avascular necrosis of the bone. Still, the focus should be on prevention, through attending to any necessary dental treatment before bisphosphonates therapy begins. This kind of protocol could prove useful both for established lesions and in controlling the extension of new ones at their onset. Updated results on a greater number of treated patients will be available at the time of presentation