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Low-Energy Femoral Fractures Associated with the Long-Term Use of Bisphosphonates

A Case Series from a Swiss University Hospital

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Abstract

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 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.

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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Acknowledgements The authors wish to thank Dr Richard Stern and Dr Victoria Rollason Gumprecht for their helpful comments during the manuscript preparation, and Joan Stalder for technical support. ## No external sources of funding were used to conduct this study. None of the authors have any conflicts of interest to declare that are directly relevant to the content of this study.

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Correspondence to Robin Peter.

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Ing-Lorenzini, K., Desmeules, J., Plachta, O. et al. Low-Energy Femoral Fractures Associated with the Long-Term Use of Bisphosphonates. Drug-Safety 32, 775–785 (2009). https://doi.org/10.2165/00002018-200932090-00002

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