The observation of the clinical cases described above could suggest that the origin of osteonecrosis has to be associated to pamidronate and zolendronate-induced insufficient vascularity. Hence, the onset of the lesions could be considered as a complication of bisphosphonate treatment as it has been shown by the literature.
In 2003 Marx and Stern were the first to describe osteonecrosis in patients suffering from multiple myeloma and treated with bisphosphonates, even though this medication had been used for more than thirty years.
No osteonecrotic lesions had been observed in the clinical trials for these drugs and this leads us to infer that other factors could contribute to the onset of lesions. The selective onset of maxillary lesions could be associated with an ecosystem of the oral cavity that can highly colonize any open wound (post-avulsion sites).
Maxillary osteonecrosis is probably due to the inability of an hypodynamic and hypovascular bone to support an increased healing demand with bone remodelling following physiological distress (chewing), iatrogenic traumas (tooth avulsions, implant surgery, periodontal operations) and tooth infections in an environment such as the oral cavity that is continuously exposed to traumas and to a strong bacterial action. Other factors could be concomitant medications with anti-angiogenic properties (such as glucocorticoids, talidomide, chemotherapeutic drugs), diabetes mellitus, maxillary irradiation, peripheral vascular disorders and clinical conditions associated with the development of osteonecrosis in any points.
The management of patients with bisphosphonate-associated maxillary osteonecrosis is particularly complicated. The surgical ablation of the necrotic bone cannot fully control the disease because of the difficulties in obtaining surgical edges with a vascularised bone or because of relapses that could expose an even larger osteonecrotic area. For this reason, resection surgery should be performed on symptomatic patients only. Antibiotics treatment administered to control the infections in exposed areas gives positive results reducing tissue inflammation and relieving pain. However, antibiotics cannot lead to a complete healing of lesions. Topic treatment with disinfectant- based mouth wash has not shown any efficacy. In our experience, hyperbaric oxygen therapy seems to give positive results on controlling inflammation of exposed areas and on improving the post-surgery course in patients that have undergone se- questrotomy. None of the treated patients has shown a dehiscence of surgical wounds.
Today, bisphosphonates are the standard treatment for patients suffering from multiple myeloma and neoplasia with bone metastasis and they give excellent results in preventing pathologic bone fractures. Nevertheless, the onset of the abovementioned complications produced a deterioration of the quality of life and led to discontinuation of treatment. Furthermore, bisphosphonates are used for treating osteoporosis: hence their use must be carefully monitored. In most cases, the diagnosis is made by the oral surgeon because the oncologist often underestimates or misunderstands this complication. Hence, the medical community as a whole should become fully aware of this risk.
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So, likewise the patients demanding radiation therapy for the heads and the neck, all patients eligible for bisphosphonate treatment should undergo a dental check up in order to detect any possible dental condition before starting therapy. As for the patients already treated, we strongly recommend dentists to collect an accurate anamnesis in order to single out not only pre-existent conditions but also the type of treatment that the patient has followed before performing any kind of oral surgery.