Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday

Osteoporos Int. 2008 Nov;19(11):1613-20. doi: 10.1007/s00198-008-0604-4. Epub 2008 May 16.

Abstract

Based upon interest in a bisphosphonate drug holiday, we evaluate the risk for hip fracture after bisphosphonate discontinuation. Among women compliant with bisphosphonates for > or = 2 years, the risk of hip fracture was increased after discontinuation, although with higher compliance and a longer duration of preceding bisphosphonate therapy, this risk was attenuated.

Introduction: Recent data suggest that hip fracture risk was not significantly increased among women receiving 5 years of bisphosphonate therapy who were subsequently randomized to placebo. We studied older women compliant with bisphosphonates > or = 2 years to evaluate the risk of hip fracture after bisphosphonate discontinuation.

Methods: Using administrative databases from a large U.S. healthcare organization, we identified women initiating bisphosphonate therapy compliant (Medication Possession Ratio, MPR > or = 66%) for 2 years. We examined the rate of hip fracture among women who discontinued bisphosphonates versus those who remained on therapy.

Results: At 2 years, 9,063 women were eligible for analysis. Hip fracture incidence among women who discontinued bisphosphonates versus those who did not was 8.43 versus 4.67 per 1000 person years (p = 0.016). The adjusted hazard ratio of hip fracture per 90 days following discontinuation was 1.2 (1.1-1.3). For women with higher compliance at 2 years (MPR > or = 80%) or compliant for 3 years, there were no significant differences in risk associated with discontinuation.

Conclusions: The rate of hip fracture was increased among women compliant with bisphosphonate therapy for 2 years who subsequently discontinued, suggesting that discontinuation is not advisable under these conditions. This association was attenuated with higher compliance and a longer duration of previous bisphosphonate therapy.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Density Conservation Agents / therapeutic use
  • Diphosphonates / administration & dosage*
  • Diphosphonates / therapeutic use
  • Drug Administration Schedule
  • Epidemiologic Methods
  • Female
  • Health Services / statistics & numerical data
  • Hip Fractures / epidemiology
  • Hip Fractures / etiology*
  • Hip Fractures / prevention & control
  • Humans
  • Middle Aged
  • Osteoporosis, Postmenopausal / complications
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / epidemiology
  • Patient Compliance / statistics & numerical data
  • United States / epidemiology

Substances

  • Bone Density Conservation Agents
  • Diphosphonates