Ing-Lorenzini Kuntheavy, Desmeules Jules, Plachta Olivier, Suva Domizio, Dayer Pierre, Peter Robin
Division of Clinical Pharmacology and Toxicology, Regional Pharmacovigilance Centre, University Hospitals of Geneva, Geneva, Switzerland.
Drug Saf. 2009;32(9):775-85. doi: 10.2165/00002018-200932090-00002.
Bisphosphonates are effective and well tolerated anti-resorptive drugs used for the treatment of osteoporosis. However, some concerns about their potential long-term negative effects are emerging.
We report a series of patients with a history of bisphosphonate treatment admitted to our institution with a low-energy subtrochanteric fracture.
Eight patients fulfilling these two criteria within the last 2 years were included in our retrospective analysis. All cases were reported to the Swiss National Pharmacovigilance Centre.
All patients presented with a typical radiological pattern consisting of a cortical thickening at the lateral femoral subtrochanteric cortex with a horizontal fracture line originating precisely at this level. Four patients eventually developed a stress fracture or complete fracture of the contralateral femur. Two patients demonstrated delayed healing of their fracture. Five patients had been on alendronate therapy for a period ranging from 16 months to 8 years, two had been on ibandronate for 4 months and 1 year, respectively, after changing from alendronate, and one patient had been on pamidronate until 1 year before the fracture occurred. Seven patients were also receiving long-term proton pump inhibitor (PPI) treatment which could have contributed to the increased risk of fracture. Four patients were receiving both PPI and long-term corticosteroid treatment. The hypothesis of a negative pharmacodynamic interaction between bisphosphonates, PPIs and corticosteroids which could lead to a decrease in bone strength after long-term use needs further investigation.
Prescribers should be aware of the possibility of these rare adverse reactions and the prolonged use of bisphosphonates should be reconsidered until long-term robust safety data are available.
双膦酸盐是用于治疗骨质疏松症的有效且耐受性良好的抗吸收药物。然而,关于其潜在长期负面影响的一些担忧正在出现。
我们报告了一系列有双膦酸盐治疗史并因低能量转子下骨折入住我院的患者。
在过去2年内符合这两个标准的8例患者纳入我们的回顾性分析。所有病例均报告给瑞士国家药物警戒中心。
所有患者均呈现典型的放射学表现,包括股骨转子下外侧皮质增厚,水平骨折线恰好起源于此水平。4例患者最终对侧股骨发生应力性骨折或完全骨折。2例患者骨折愈合延迟。5例患者接受阿仑膦酸盐治疗16个月至8年不等,2例在从阿仑膦酸盐换用后分别接受伊班膦酸盐治疗4个月和1年,1例患者在骨折发生前1年一直在接受帕米膦酸盐治疗。7例患者还接受长期质子泵抑制剂(PPI)治疗,这可能增加了骨折风险。4例患者同时接受PPI和长期皮质类固醇治疗。双膦酸盐、PPI和皮质类固醇之间可能存在负面药效学相互作用,长期使用可能导致骨强度下降,这一假设需要进一步研究。
处方医生应意识到这些罕见不良反应的可能性,在获得长期可靠的安全数据之前,应重新考虑双膦酸盐的长期使用。