title: Low-energy femoral fractures associated with the long-term use of bisphosphonates: a case series from a Swiss university hospital.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Clinical Pharmacology and Toxicology, Regional Pharmacovigilance Centre, University Hospitals of Geneva, Geneva, Switzerland.
authors: Kuntheavy
authors: K
authors: Ing-Lorenzini
authors: Jules
authors: J
authors: Desmeules
authors: Olivier
authors: O
authors: Plachta
authors: Domizio
authors: D
authors: Suva
authors: Pierre
authors: P
authors: Dayer
authors: Robin
authors: R
authors: Peter
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000009:adverse effects / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001858:Bone Nails; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000601:surgery; D005500:Follow-Up Studies; D005598:Fractures, Spontaneous / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000150:complications / Q000188:drug therapy; D011358:Product Surveillance, Postmarketing; D011859:Radiography; D012189:Retrospective Studies; D013557:Switzerland; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D019386:Alendronate