Osteoradionecrosis (ORN) consists in exposure of devitalized necrotic bone by mucosal or cutaneous ulceration in territory affected by radiation therapy, persisting without spontaneous resolution for 3 months, without tumor recurrence. It is a serious condition, usually affecting the mandible, in patients who have undergone radiation therapy for upper-airway cancer, even if its incidence has tended to stabilize since the 1980s (2%–22%). ORN does not usually show a tendency for spontaneous resolution; rather, it tends to stabilize or worsen, with onset of complications (abscess, orostoma, fracture, sepsis, malnutrition, death)
Various medical options have been tried (e.g., antibiotics, corticosteroids, hyperbaricoxygen therapy), but provide only partial results, none proving curative. Surgery, although mutilating, thus became unavoidable to arrest progression. There are three pathophysiological theories: infection, with radio-induced osteomyelitis; circulation disorder, with hypoxia and microvascular fragility; and radio-induced fibroatrophy. Considering these hypotheses, three molecules were recently assessed: tocopherol (vitamin E) as an antioxidant; pentoxifylline, which shows vascular tropism, improving local microcirculation; and clodronate, a first-generation bisphosphonate that limits bone resorption by reducing osteoclast activity, increases bone apposition by stimulating osteoblasts, and reduces production of inflammatory cytokines (e.g., interleukin [IL]-1β, IL-6, and tumor necrosis factor–α). A synergic effect of these molecules was demonstrated by Delanian et al. Associated pentoxifylline–tocopherol–clodronate (PENTOCLO) was therefore tested in mandibular ORN, with highly encouraging results. In 2005, in a retrospective clinical trial, Delanian et al. reported 89% early cure. In 2011, in a subsequent trial, Delanian et al. reported 100% cure and 96% reduction in modified SOMA (subjective, objective, management, and analytic evaluation of injury) score at 24 months. We therefore set up a prospective study with the main aim of assessing the efficacy of PENTOCLO in mandibular ORN. The study had local review board approval (South-East of France Ethics Committee VI, N°2014/CE35).