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

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.