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Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a newly emerging condition in a long-term administration of mainly intravenous bisphosphonates for the treatment of hypercalcemia associated with malignancy, multiple myeloma, and metastatic breast and prostate cancers. The incidence of BRONJ is not so high, but it is very refractory to ordinary dental treatments, and the bone exposure, a typical symptom, continues for several months. Although many cases of BRONJ have been reported worldwide, the precise pathogenesis remains obscure. Diabetes mellitus (DM) is one of the systemic risk factors contributing in the development of BRONJ. DM is generally associated with microvascular ischemia of the bone, endothelial cell dysfunction, decreased bone turnover and remodeling, resulting in a delayed wound healing and easy to infection. In this issue, the relation of DM as a systemic risk factor with development of BRONJ as well as the incidence, clinical manifestations and prevention and treatment of BRONJ are described.

Bisphosphonates (BP) have clinically been used as a highly effective drug in the treatment of hypercalcemia of malignancy, multiple myeloma, skeletal events associated with metastatic breast cancer and prostate cancer, and osteoporosis. Despite these benefits, however, the emergence of BP-related osteonecrosis of the jaws (BRONJ) becomes a growing and significant problem in a subset of patients receiving these drugs, especially intravenous preparations. It has also been reported in the patients receiving oral BP, although the incidence is extremely low. Most of BRONJ cases occur after dental treatments such as tooth extraction, periodontal surgery, and dental implants, and are refractory to conventional treatment modalities such as debridement, antibiotics and hyperbaric oxygen therapy. As compared to EU and USA, the number of BRONJ case is still small in Japan, but it is exactly increasing year by year. The ratio of the number of BRONJ in patients receiving oral BP to that in patients receiving intravenous BP is higher in Japan than in EU and USA, speculating due to the difference of time of approval. In this communication, the practical guidelines for prevention, diagnosis and treatment of BRONJ recently released from USA and Canada were introduced. Although no effective therapy for BRONJ is established yet, the importance of oral hygiene, patient education and treatments suitable for clinical stage is emphasized. In addition, it is considered that the survey of incidence of BRONJ in Japan and the preparation of Japanese guideline are urgent need.

The osteonecrosis of the jaws (ONJ) has been reported occasionally in cancer patients treated with radiotherapy and chemotherapy. However, bisphosphonate (BP)-associated ONJ in patients with cancer such as multiple myeloma, breast cancer and prostate cancer mainly administered with intravenous BPs has been first reported in 2003. Since then, many cases over 2,500 are accumulating worldwide. Since BPs are often used for osteoporosis, cancer-associated hypercalcemia and osteolytic bone metastasis, it is speculated that ONJ cases will increase in Japan where a small number of them were reported until now. Most of ONJ in cancer patients receiving BP administration occur after dental treatments such as tooth extraction, periodontal surgery and dental implants, and do not respond to conventional treatment modalities such as debridement, antibiotic therapy and hyperbaric oxygen therapy. No effective therapy for ONJ is established yet and empirical conservative therapy is recommended in the guidelines for prevention, diagnosis, and treatment of ONJ. Therefore, dentists and oral and maxillofacial surgeons need to recognize ONJ as a serious side effect of BPs and to make informed consent to the patients and a close consultation with medical oncologists for administration of BPs.