Friedrich Reinhard E, Blake Felix A
Maxillofacial Surgery, Eppendorf University Hospital, University of Hamburg, Germany.
Anticancer Res. 2007 Jul-Aug;27(4A):1841-5.
Over the past three years, several reports have been published on jaw osteonecrosis possibly being associated with the administration of bisphosphonates. Bisphosphonates are highly active inhibitors of osteoclasts. These drugs are used for the treatment of multiple myeloma, bone resorption in the case of metastatic malignant diseases, tumor-associated hypercalcaemia, and in the treatment of osteoporosis. Due to the importance of this presumed side-effect of bisphosphonates for the dentist and the maxillofacial surgeon, we report four cases.
Four patients (two women and two men aged 56, 62, 67 and 75 years, respectively) were diagnosed with osteonecrosis of the mandible. These osteonecroses did not react adequately to local treatment and systemic therapy with antibiotics. One patient suffered from non-Hodgkin's lymphoma, one from breast cancer, one from prostate cancer and one from sarcoidosis. Besides cytostatic chemotherapies, all patients received bisphosphonates over an extended period.
Bisphosphonates are considered an established standard in the treatment of multiple myeloma and bone metastases. Over the past few years, a rapidly increasing number of reports have been published describing patients with a history of bisphosphonate therapy in whom therapy-resistant osteonecrosis of jaw bones occurred either after dental extractions or spontaneously. Since then, bisphosphonate therapy has come under scrutiny as a cause of osteonecrosis. However, the multiplicity of drugs prescribed for the treatment of cancer requires caution when determining a cause-and-action effect. Since patients with malignant diseases receive cytostatic therapy and a range of other drugs, including bisphosphonates, enhancement of the side-effects may be presumed. The case report of an osteonecrosis of the jaw following multi-drug therapy for sarcoidosis adds a further and non-cancerous condition to the newly described entity of bisphosphonate-associated jaw necrosis.
The probable association of the therapeutic use of bisphosphonates and the development of jaw necrosis has to be studied in further investigations. Patients who will undergo bisphosphonate therapy should receive a careful dental check-up prior to drug application. Patients receiving bisphosphonates should be followed up carefully to avoid the occurrence of extended osteonecrotic lesions. Moreover, established jaw lesions must be diagnosed precisely in order to exclude metastatic disease.
在过去三年中，已有多篇关于下颌骨坏死可能与双膦酸盐给药有关的报道发表。双膦酸盐是破骨细胞的高效抑制剂。这些药物用于治疗多发性骨髓瘤、转移性恶性疾病的骨吸收、肿瘤相关性高钙血症以及骨质疏松症。鉴于双膦酸盐这种推测的副作用对牙医和颌面外科医生的重要性，我们报告4例病例。
4例患者（2名女性和2名男性，年龄分别为56岁、62岁、67岁和75岁）被诊断为下颌骨坏死。这些骨坏死对局部治疗和抗生素全身治疗反应不佳。1例患者患有非霍奇金淋巴瘤，1例患有乳腺癌，1例患有前列腺癌，1例患有结节病。除了细胞毒性化疗外，所有患者都长期接受双膦酸盐治疗。
双膦酸盐被认为是治疗多发性骨髓瘤和骨转移的既定标准。在过去几年中，越来越多的报道发表，描述了有双膦酸盐治疗史的患者在拔牙后或自发出现对治疗有抵抗性的颌骨坏死。从那时起，双膦酸盐治疗作为骨坏死的一个原因受到了审查。然而，在确定因果关系时，由于用于治疗癌症的药物种类繁多，需要谨慎。由于患有恶性疾病的患者接受细胞毒性治疗和一系列其他药物，包括双膦酸盐，可能会推测副作用会增强。结节病多药治疗后下颌骨坏死的病例报告为新描述的双膦酸盐相关颌骨坏死实体增加了另一种非癌症情况。
双膦酸盐治疗用途与颌骨坏死发生之间的可能关联必须在进一步研究中加以探讨。将接受双膦酸盐治疗的患者在用药前应接受仔细的牙科检查。接受双膦酸盐治疗的患者应进行仔细随访，以避免发生广泛性骨坏死病变。此外，必须准确诊断已有的颌骨病变，以排除转移性疾病。
