Evolution of Bisphosphonates Related Osteonecrosis of the Jaw (BRONJ) in Patients with Multiple Myeloma (MM): A Retrospective Study
Authors: Andriani Alessandro AA Alessandro , Petrucci Maria Teresa MTP , Caravita Tommaso , Montanaro Marco , Pisani Francesco , Coppetelli Ugo , De Muro Marianna , Bongarzoni Velia , Avvisati Giuseppe , Villivà Nicoletta , Levi Anna , Siniscalchi A. , Agrillo Alessandro , Gaglioti Domenico 
Published: April 2020

Abstract
INTRODUCTION: Bisphosphonates (Bsf) are a recognized and effective class of drugs used intravenously to treat cancer-related conditions, such as multiple myeloma (MM) and others solid tumours for the prevention of pathologic fractures, and in oral form to prevent osteoporosis and osteopenia. Some other activities are described as immunomodulating effects. Evolution of bisphosphonates related osteonecrosis of the jaw (BRONJ) is a rare complication with the risk increasing the longer the patient uses the drug. Pamidronate and Zolendronic acid can induce BRONJ in 0,8% – 12% of patients as described in different casistics. In this study we want describe the evolution and outcome of the BRONJ in a multicentric casistic.
MATERIAL AND METHODS: In our group we observed 55 pts with Multiple Myeloma (MM) who developed BRONJ; immunoglobulin isotype was: 25 pts IgG-κ; 6 pts IgG-λ, 12 pts IgA-κ; 3 pt IgA-λ, 5 pts IgM-κ, 3 pts MM light chain κ and 1 pt MM light chain λ. Median age was 72 years (range 56–95), male 16/female 39. All patients were treated with Bsf: Pamidronate 1 pts (1,8 %), Zolendronate 36 pts (65,5 %), Pamidronate/zolendronate 18 pts (32,7 %). The average dose of Pamidronate was 2.022 mg (range 90–6.750 mg) and of zoledronate was 84 mg (range 4–256 mg). Anatomic localisation of the BRONJ was: mandible 29 pts (52,7%); maxilla 22 pts (40%); mandible/maxilla 4 cases (7,3 %). The most common trigger for BRONJ was dentoalveolar surgery, including extractions (43 cases-78, 4%), dental implant placement (3 patients-5, 4%), periodontal disease (5 cases-9 %), and in 3 patients with dental prothesis (5, 4%); 1 patient (1,8%) developed BRONJ spontaneously. All patients stopped bsf therapy after BRONJ diagnosis.
RESULTS: All patients were treated with conservative treatment such as antibiotic therapy. In 18 patients (32,7%) antibiotic therapy was the only treatment used. Six patients (10,9%) received antibiotic associated with surgical debridement of necrotic bone. Sixteen patients (29%) were treated with antibiotic therapy in combination with hyperbaric oxygen therapy/ozonotherapy and curettage; twelve patients (21, 8%) required sequestrectomy in association with antibiotic and oxygen/hyperbaric therapy. Three patients (5,4%) refused any therapy. Resolution was observed in 19 cases (34,5%); 24 patients (43,6%) improved as pain and as control of infection of the soft and hard tissue. The osteonecrosis was invariated in 9 patients (16,3%); three patients (5, 4%) did not responde to treatment.
CONCLUSIONS: Our retrospective study demonstrate that, in established BRONJ, clinical improvement can be obtained in a high percentage (78%), with a complete resolution of bone necrosis in one third of patients. Surgical treatment, associated with antibiotic therapy, is the most effective treatment to eradicate the necrotic bone. The effectiveness of hyperbaric oxygen therapy is not nowadays well determined, but in our experience it demonstrated its utility. Because the most common trigger for BRONJ was dental extractions, prior to treatment with bsf, all patients should have a thorough oral examination and should be completed all invasive dental procedures, achieving optimal periodontal health. With increased recognition and follow up of the BRONJ, it is likely that our knowledge will improve the risk of developing BRONJ and obtaining in more patients a complete remission.