Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) therapy. A critical review.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an area of uncovered bone in the maxillo-facial region that did not heal within 8 weeks after identification by health care provider, in a patient who was receiving or had been exposed to Bisphosphonate Therapy (BPT) without previous radiation therapy to the craniofacial region. Low-grade risk of ONJ is connected with oral BPT used in the treatment of osteopenia, osteoporosis and Paget's disease (from 0.01% to 0.04%) while higher-grade risk is associated with intravenous (IV) administration in the treatment of multiple myeloma and bone metastases (from 0.8% to 12%). The management of BRONJ currently is a dilemma. No effective treatment has yet been developed and interrupting BPT does not seem to be beneficial. Temporary suspension of BPs offers no short-term benefit, whilst long term discontinuation (if systemic conditions permit it) may be beneficial in stabilizing sites of ONJ and reducing clinical symptoms. The use of oral antimicrobial rinses in combination with oral systemic antibiotic therapy -penicillin, metronidazole, quinolones, clindamycin, doxycycline, erythromycin- is indicated for Stages I and II of Ruggiero's Staging. The role of hyperbaric oxygen therapy is still unclear but some benefits of this treatment have recently been described in association with discontinuation of BPT and conventional therapy (medical or/and surgical). Surgical treatment, in accordance to the AAOMS Position Paper, is reserved to patients affected by Stage III of BRONJ even if in the last version (2009) a superficial debridement is indicated to relieve soft tissue irritation also in the stage II (lesions being unresponsive to antibiotic treatment). Aggressive surgical treatment may occasionally results in even larger areas of exposed and painful infected bone. Surgical debridement or resection in combination with antibiotic therapy may offer long-term palliation with resolution of acute infection and pain. Mobile segments of bony sequestrum should be removed without exposing unaffected bone. If pathological fractures or complete mandibular involvement are observed, if the medical condition of the patients allows it the affected bone portion may be resected and primary bone reconstruction or revascularization graft may be carried out. Ozone therapy in the management of bone necrosis or in extractive sites during and after oral surgery in patients treated with BPs may stimulate cell proliferation and soft tissue healing. Laser applications at low intensity (Low Level Laser Therapy - LLLT) have been reported in the literature for the treatment of BRONJ. Biostimulant effects of laser improve reparative process, increase inorganic matrix of bone and osteoblast mitotic index and stimulate lymphatic and blood capillaries growth. Laser can be used for conservative surgery, whereby necrotic bone is vaporized, until healthy bone is reached. The Er:YAG laser wavelength has a high degree of affinity for water and hydroxyapatite, hence both soft and bone tissues can be easily treated. An additional advantage of the Er:YAG laser is its bactericidal and possible biostimulatory action, accelerating the healing of both soft and bone tissues, in comparison to conventional treatments. Long-term, prospective studies are required to establish the efficacy of drug holidays in reducing the risk of BRONJ for patients receiving oral BPs even if it has been suggested that BPT may be discontinued for three months before the surgical procedures and bone turnover markers (CTx, NTx, PTH, 1,25-dihydroxy vitamin D) may be checked. However it must be recognized that interindividual variability, gender, age, physical activity, and seasonal and circadian variation exist that can result in difficulty in interpreting these assays and more research is needed. Laser application (LLLT and laser surgery) nowadays appears to be a promising modality of BRONJ treatment, being safe and well tolerated, and it permits the minimally invasive treatment of early stages of the disease.