비스포스포네이트 연관 악골 괴사(BRONJ)의 치과적 견해
Dental Considerations of the Bisphosphonate-related Osteonecrosis of the Jaw
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Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a disease entity which is rare, but is a serious side effect of bisphosphonate therapy. Several professional associations have published position papers on BRONJ; in 2009, the Korean position statement was reported as a collaborative effect between the Korean Endocrine Society, Korean Society of Bone Metabolism, Korean Society of Osteoporosis, and Korean Association of Oral and Maxillofacial Surgeons. Diagnostic criteria and treatment strategies for BRONJ are now being established through a thorough investigation and cooperation amongst numerous specialties. Still obscure, it is suggested that the pathogenesis of BRONJ is due to the inhibition of farnesyl pyrophosphate synthase of the osteoclastic mevalonate pathway, thus disturbing the cytoskeletal motility for the fusion of mononuclear cells into a multinucleated giant cell or the establishment of a ruffled border. Eventually, such changes will be followed by inactivation and apoptosis of osteoclasts, leading to decreased bone resorption. The incidence of BRONJ is known to be as low as 0.01~0.001% of the entire population, but BRONJ is as high as 1 in 300 in the case of dental intervention of patients on bisphosphonate therapy. It is important for clinicians to remember in requesting a dental consultation for a patient on bisphosphonate therapy that oral cavity has a special environment for wound healing. Routine minor trauma caused by foreignbodies, such as hard food, is compensated by an appropriate wound healing mechanism involving rapid bone turnover due to the rich vascular supply of the oral mucosa. Bisphosphonate will disturb this normal wound healing as a consequence of decreased bone turnover. It should also be kept in mind that the disturbed wound healing is further complicated by the presence of normal microflora in the oral cavity and by the unique anatomic condition of the thin oral mucosa covering the the mandible, most mobile skeleton in the head and neck area. The potency of the bisphosphonates (intravenous bisphosphonate), local factors, such as local dental intervention (especially dental extraction), and systemic factors, such as patient age (old age), have statistical significance for all BRONJ risk factors. Although the recognition of BRONJ by clinicians has been inadequate until now, the growing body of evidence is unveiling the detailed aspects of BRONJ. Continued investigation and extensive cooperation of related specialties will elucidate the nature of the disease, thus enhancing the quality of life of patients on bisphosphonate therapy.
Abstract
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a disease entity which is rare, but is a serious side effect of bisphosphonate therapy. Several professional associations have published position papers on BRONJ; in 2009, the Korean position statement was reported as a collaborative effect between the Korean Endocrine Society, Korean Society of Bone Metabolism, Korean Society of Osteoporosis, and Korean Association of Oral and Maxillofacial Surgeons. Diagnostic criteria and treatment strategies for BRONJ are now being established through a thorough investigation and cooperation amongst numerous specialties. Still obscure, it is suggested that the pathogenesis of BRONJ is due to the inhibition of farnesyl pyrophosphate synthase of the osteoclastic mevalonate pathway, thus disturbing the cytoskeletal motility for the fusion of mononuclear cells into a multinucleated giant cell or the establishment of a ruffled border. Eventually, such changes will be followed by inactivation and apoptosis of osteoclasts, leading to decreased bone resorption. The incidence of BRONJ is known to be as low as 0.01~0.001% of the entire population, but BRONJ is as high as 1 in 300 in the case of dental intervention of patients on bisphosphonate therapy. It is important for clinicians to remember in requesting a dental consultation for a patient on bisphosphonate therapy that oral cavity has a special environment for wound healing. Routine minor trauma caused by foreignbodies, such as hard food, is compensated by an appropriate wound healing mechanism involving rapid bone turnover due to the rich vascular supply of the oral mucosa. Bisphosphonate will disturb this normal wound healing as a consequence of decreased bone turnover. It should also be kept in mind that the disturbed wound healing is further complicated by the presence of normal microflora in the oral cavity and by the unique anatomic condition of the thin oral mucosa covering the the mandible, most mobile skeleton in the head and neck area. The potency of the bisphosphonates (intravenous bisphosphonate), local factors, such as local dental intervention (especially dental extraction), and systemic factors, such as patient age (old age), have statistical significance for all BRONJ risk factors. Although the recognition of BRONJ by clinicians has been inadequate until now, the growing body of evidence is unveiling the detailed aspects of BRONJ. Continued investigation and extensive cooperation of related specialties will elucidate the nature of the disease, thus enhancing the quality of life of patients on bisphosphonate therapy.
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