4.6 Article

Low-Energy Femoral Fractures Associated with the Long-Term Use of Bisphosphonates A Case Series from a Swiss University Hospital

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DRUG SAFETY
卷 32, 期 9, 页码 775-785

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ADIS INT LTD
DOI: 10.2165/00002018-200932090-00002

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Background: 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. Objective: We report a series of patients with a history of bisphosphonate treatment admitted to our institution with a low-energy subtrochanteric fracture. Patients and methods: 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. Results: 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 I year, respectively, after changing from alendronate, and one patient had been on pamidronate until I 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. Conclusion: 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.

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