Marx Robert E, Sawatari Yoh, Fortin Michel, Broumand Vishtasb
Miller School of Medicine, Division of Oral and Maxillofacial Surgery, University of Miami, 9380 SW 150th Street, Miami, FL 33157, USA.
J Oral Maxillofac Surg. 2005 Nov;63(11):1567-75. doi: 10.1016/j.joms.2005.07.010.
Bisphosphonates inhibit bone resorption and thus bone renewal by suppressing the recruitment and activity of osteoclasts thus shortening their life span. Recently three bisphosphonates, Pamidronate (Aredia; Novartis Pharmaceuticals, East Haven, NJ), Zoledronate (Zometa; Novartis Pharmaceuticals), and Alendronate (Fosamax; Merck Co, West Point, VA) have been linked to painful refractory bone exposures in the jaws.
One hundred-nineteen total cases of bisphosphonate-related bone exposure were reviewed.
Thirty-two of 119 patients (26%) received Aredia, 48 (40.3%) received Zometa, 36 (30.2%) received Aredia later changed to Zometa, and 3 (2.5%) received Fosamax. The mean induction time for clinical bone exposure and symptoms was 14.3 months for those who received Aredia, 12.1 months for those who received both, 9.4 months for those who received Zometa, and 3 years for those who received Fosamax. Sixty-two (52.1%) were treated for multiple myeloma, 50 (42%) for metastatic breast cancer, 4 (3.4%) for metastatic prostate cancer and 3 (2.5%) for osteoporosis. Presenting findings in addition to exposed bone were 37 (31.1%) asymptomatic, 82 (68.9%) with pain, 28 (23.5%) mobile teeth, and 21 (17.6%) with nonhealing fistulas. Eighty-one (68.1%) bone exposures occurred in the mandible alone, 33 (27.7%) in the maxilla, and 5 (4.2%) occurred in both jaws. Medical comorbidities included the malignancy itself 97.5%, previous and/or maintenance chemotherapy 97.5%, Dexamethasone 59.7%. Dental comorbidities included the presence of periodontitis 84%, dental caries 28.6%, abscessed teeth 13.4% root canal treatments 10.9%, and the presence of mandibular tori 9.2%. The precipitating event that produced the bone exposures were spontaneous 25.2%, tooth removals 37.8%, advanced periodontitis 28.6%, periodontal surgery 11.2%, dental implants 3.4% and root canal surgery 0.8%.
Complete prevention of this complication in not currently possible. However, pre-therapy dental care reduces this incidence, and non-surgical dental procedures can prevent new cases. For those who present with painful exposed bone, effective control to a pain free state without resolution of the exposed bone is 90.1% effective using a regimen of antibiotics along with 0.12% chlorohexidine antiseptic mouth.
双膦酸盐通过抑制破骨细胞的募集和活性来抑制骨吸收，从而抑制骨更新，进而缩短其寿命。最近，三种双膦酸盐，帕米膦酸二钠（阿可达；诺华制药公司，东黑文，新泽西州）、唑来膦酸（择泰；诺华制药公司）和阿仑膦酸钠（福善美；默克公司，西点，弗吉尼亚州）已被证实与颌骨难治性疼痛性骨暴露有关。
回顾了119例双膦酸盐相关骨暴露的病例。
119例患者中，32例（26%）接受了阿可达治疗，48例（40.3%）接受了择泰治疗，36例（30.2%）先接受阿可达治疗后改为择泰治疗，3例（2.5%）接受了福善美治疗。接受阿可达治疗的患者临床骨暴露和出现症状的平均诱导时间为14.3个月，接受两种药物治疗的患者为12.1个月，接受择泰治疗的患者为9.4个月，接受福善美治疗的患者为3年。62例（52.1%）患者因多发性骨髓瘤接受治疗，50例（42%）因转移性乳腺癌接受治疗，4例（3.4%）因转移性前列腺癌接受治疗，3例（2.5%）因骨质疏松症接受治疗。除骨暴露外，其他表现包括37例（31.1%）无症状，82例（68.9%）有疼痛，28例（23.5%）牙齿松动，21例（17.6%）有不愈合瘘管。81例（68.1%）骨暴露仅发生在下颌骨，33例（27.7%）发生在上颌骨，5例（4.2%）上下颌骨均有发生。内科合并症包括恶性肿瘤本身97.5%，既往和/或维持化疗97.5%，地塞米松59.7%。牙科合并症包括牙周炎84%，龋齿28.6%，牙齿脓肿13.4%，根管治疗10.9%，下颌隆突9.2%。导致骨暴露的诱发事件为自发事件占25.2%，拔牙占37.8%，重度牙周炎占28.6%，牙周手术占11.2%，牙种植占3.4%，根管手术占0.8%。
目前尚无法完全预防这种并发症。然而，治疗前的牙科护理可降低其发生率，非手术牙科治疗可预防新病例的发生。对于出现疼痛性骨暴露的患者，使用抗生素联合0.12%氯己定抗菌漱口水的方案将疼痛有效控制至无痛状态且骨暴露未缓解的有效率为90.1%。
