Among patients with established infection in the bone

Among patients with established infection in the bone or surrounding tissue (Stage II) antibiotic penicillin-based therapy in addition to mouthwash may result in healing in patients with minor ONJ lesions. However, a large proportion of cases tend to show chronically infected necrotic process in jaw bones with very limited response to any treatment. Prior to commencement of antimicrobial (penicillin-based) and antifungal therapy, wound and pus culture samples, including those for Actinomyces species should be taken [55,56]. Generally, surgical debridement has been variably effective in eradicating necrotic bone and is not recommended for early stages of ONJ due to the concern of possible exacerbation of the necrotic process [57]. However, in patients with advanced process (Stage III) with pathological fracture, extra oral fistula, osteolysis extending to the xpo 1 of the jaw or recurrent infections, complete removal of the necrotic bone and where possible immediate reconstruction in addition to systemic antibiotic treatment is indicated [58,59]. Several authors reported successful outcome with surgical treatment of ONJ [9,60,61]. As alternative for conventional conservative surgery, laser applications at low intensity (low level laser therapy—LLLT) have been reported in the literature for the treatment of ONJ with promising results [54,62]. Biostimulatory effects of laser improve reparative processes, increase inorganic matrix of bone and stimulate lymphatic and blood capillary growth, as well as having a bactericidal effect. Hyperbaric oxygenation therapy has shown inconsistent results and is now under investigation in an ongoing randomised trial as an addition to surgical or non-surgical treatment [63]. As a result, its use is not presently recommended outside of clinical trials. Pentoxifylline (blood viscosity reducer agent) and oral vitamin E has shown efficacy in a small case series [64]. Ozone (O3) therapy in the management of bone necrosis or in extractive sites during and after oral surgery in patients treated with bisphosphonate may stimulate cell proliferation and soft tissue healing resulting in alleviation of symptoms [6]. However, several case reports and small uncontrolled studies reported controversial efficacy of O3 gas formulation in addition to conventional in treatment of ONJ [65,66] In a phase I and II study, medical O3 has been shown to heal ONJ if antibiotic therapy (azithromycin) is administered 10 days prior to O3 oil formulation, where more than half of the patients showing a complete response with radiologic lesion disappearance following reconstruction of the oral tissue [67]. Teriparatide (synthetic peptide that corresponds to the N-terminal residues of human parathyroid hormone) therapy has been recommended to adjust the mechanisms of failed bone remodelling and have anabolic effects on osteoblasts. Teriparatide has been shown to help remove necrotic bone for new healthy bone to be laid down in order to resolve periodontal osseous defects [68]. Subramanian et al. [69] reported on the off-label use of teriparatide for ONJ in 6 patients treated with bisphosphonates for osteoporosis. In this report healing occurred in all cases within 5 months of initiating treatment. In contrast, Narvaez [70] reported a case of lack of response to teriparatide treatment. Of note, teriparatide is contraindicated in patients with osteosarcoma or metastatic bone disease following reports that osteosarcoma has occurred in rats and people who took the drug [71]. Other treatments such as administration of platelet rich plasma, and bone morphogenic proteins have been published as possible procedures in ONJ treatment in small case reports. Clearly the efficacy of these strategies needs to be established in additional prospective studies [72].
Should bisphosphonate therapy be discontinued if osteonecrosis of the jaw is present? Decisions about to continue or stop bisphosphonates in face of established osteonecrosis of the jaw remains controversial.