Bisphosphonate-Induced Osteonecrosis of the Jaws, Bone Markers, and a Hypothesized Candidate Gene
Bisphosphonate-Induced Osteonecrosis of the Jaws, Bone Markers, and a Hypothesized Candidate Gene
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DOI：
10.1016/j.joms.2008.09.015
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发表时间：
2009-01-01
影响因子：
1.9
通讯作者：
Kogan, Rita
中科院分区：
文献类型：
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作者：
Lehrer, Steven;Montazem, Andre;Kogan, Rita
目的：确定血清骨标志物异常是否与双膦酸盐引起的颌骨坏死有关。材料与方法：我们对7例颌骨骨坏死（ONJ）患者进行了血清骨标志物和其他相关内分泌检测。检测项目为 C-端肽、N-端肽、骨特异性碱性磷酸酶、骨钙素、完整甲状旁腺激素、T3、T4、TSH 和维生素 D 25 羟基。 ONJ 的诊断标准是由美国口腔颌面外科医师协会制定的标准。结果：我们的患者中有 5 名是女性。其中两人患有转移性乳腺癌，并接受了唑来膦酸治疗；我还接受了帕米膦酸钠。另外三人患有骨质疏松症，每天接受阿仑膦酸钠治疗。一名男子患有转移性前列腺癌，接受唑来膦酸治疗。另一名男子患有戈谢病，接受唑来膦酸治疗。所有患者均已停用双磷酸盐至少 6 个月。没有人正在服用或曾经服用过皮质类固醇。没有一个病灶显示出任何明显的愈合，并且仍然给患者带来相当大的痛苦，但根据我们实验室的测量，骨标志物都在正常范围内，除了完整的甲状旁腺激素，在转移性乳腺癌的一例中，甲状旁腺激素略有升高（177 pg/mL）。结论：我们假设基质金属蛋白酶 2 (MMP2) 是双磷酸盐诱导 ONJ 的候选基因，原因有 3 个：1) MMP2 与骨异常相关，这可能与骨异常有关。到ONJ。 2）双磷酸盐与心房颤动相关，而MMP2是唯一已知与骨异常和心房颤动相关的基因。 3) 由已知的疾病-基因关联联系起来的疾病和疾病基因网络表明，心血管疾病和骨骼疾病密切相关，这表明单一药物（例如双膦酸盐）作用于单一基因MMP2，可能具有与双膦酸盐特征的破骨细胞抑制不同的骨骼和心血管副作用。 (c) 2009 年美国口腔颌面外科医师协会
Purpose: To determine whether any abnormality in serum bone markers is related to bisphosphonate-induced osteonecrosis of the jaw.Materials and Methods: we obtained serum bone markers and other relevant endocrine assays on 7 patients with osteonecrosis of the jaws (ONJ). The assays were C-telopeptide, N-telopeptide, bone specific alkaline phosphatase, osteocalcin, intact parathyroid hormone, T3, T4, TSH, and vitamin D 25 hydroxy. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons.Results: Five of our patients were women. Two had metastatic breast cancer and had been treated with zoledronic acid; I had also received pamidronate. Three others had osteoporosis and had been treated with daily alendronate. One man had metastatic prostate cancer treated with zoledronic acid. Another man had Gaucher's disease treated with zoledronic acid. All patients had been withdrawn from bisphosphonate for at least 6 months. None was taking or had taken corticosteroids. None of the lesions had shown any significant healing and all were still causing the patients considerable distress, yet the bone markers were within the normal range as measured in our laboratory, except for intact parathyroid hormone, which was slightly elevated in I case of metastatic breast cancer (177 pg/mL).Conclusions: We hypothesize that matrix metalloproteinase 2 (MMP2) is a candidate gene for bisphosphonate-induced ONJ for 3 reasons: 1) MMP2 is associated with bone abnormalities which could be related to ONJ. 2) Bisphosphonates are associated with atrial fibrillation, and MMP2 is the only gene known to be associated with both bone abnormalities and atrial fibrillation. 3) A network of disorders and disease genes linked by known disorder-gene associations indicates that cardiovascular disease and bone disease are closely related, suggesting that a single drug such as bisphosphonate, acting on a single gene, MMP2, could have both bone and cardiovascular side effects different from the osteoclast inhibition that is characteristic of bisphosphonate. (c) 2009 American Association of Oral and Maxillofacial Surgeons