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Bisphosphonates are a class of agents used for treating osteoporosis and malignant bone metastases treatment. Osteonecrosis of the jaws is the main complication in a subset of patients receiving these drugs. Based on a growing number of case reports and institutional reviews, bisphosphonate therapy can cause exposed and necrotic bone that is isolated to the jaw. This clinical investigation is aimed at analyzing the clinical effect of recombinant human bone morphogenetic protein type 2 (rhBMP-2) application in patients affected by bisphosphonates-related osteonecrosis of the jaws undergoing surgery for necrotic bone removal.A case review was made of 20 patients. The rhBMP-2 in all the cases reported here was used alone with the collagen carrier without concomitant bone materials. The cases involved osteonecrotic lesions of the upper and lower jaws. A total dose of 4 to 8 mg of rhBMP-2 was delivered to the surgical site in concentrations of 1.5 mg/mL (depending on the size of lesion). Patients were followed up over a period ranging 6 to 12 months.Patients had successful healing of the necrotic area. New bone formation in the surgical area could be clinically evaluated by palpation at the end of 3 to 4 months and confirmed by radiographic examination at the end of 12 months.This study indicated that the use of rhBMP-2 without concomitant bone grafting materials was useful in promoting healing of bisphosphonates-related osteonecrosis of the jaws. The use of growth factors, particularly rhBMP-2, should be considered a therapeutic choice in patients affected by osteonecrosis of the jaws related to bisphosphonate therapy.