Osteoporosis International

, Volume 23, Issue 12, pp 2873–2884

Incidence of fractures of the femur, including subtrochanteric, up to 8 years since initiation of oral bisphosphonate therapy: a register-based cohort study using the US MarketScan claims databases

  • M. Pazianas
  • B. Abrahamsen
  • Y. Wang
  • R. G. G. Russell
Original Article

DOI: 10.1007/s00198-012-1952-7

Cite this article as:
Pazianas, M., Abrahamsen, B., Wang, Y. et al. Osteoporos Int (2012) 23: 2873. doi:10.1007/s00198-012-1952-7



In a cohort study of users of bisphosphonates, we evaluated the incidence of fragility fractures at all sites on the femur following for up to 8 years of therapy with alendronate or risedronate. We did not find evidence for a reversal of fracture protection with long-term use of bisphosphonates.


Few studies have acquired adequate data with prolonged follow-up on bisphosphonate users in the general population to evaluate their long-term effects on the risk of hip fractures including those in the subtrochanteric region.


This cohort study utilizes a large USA database (January 1, 2000 to June 30, 2009). We compared patients with higher versus lower degrees of compliance [medication possession ratio, MPR <1/3 (the reference), 1/3–<2/3, or ≥2/3]. Radiographic adjudication of fracture site and features were not performed. Hazard ratios (HR) for fracture were estimated using time-dependent Cox models. Restricted cubic splines (RCS) were used to plot HRs for fracture against duration of therapy.


There were 3,655 incident cases of femoral fracture (764 subtrochanteric/shaft, 2,769 hip) identified during 917,741 person-years of follow-up (median = 3 years) on 287,099 patients (267,374 were women) from the date when they initiated oral bisphosphonate therapy. The corresponding HRs (95% confidence interval, CI) for overall femoral fractures associated with each additional year of therapy were 0.93 (0.86–1.01) within 5 years, and 0.89 (0.77–1.03) beyond 5 years for risedronate and 0.86 (0.81–0.91) and 0.95 (0.84–1.07) for alendronate, respectively. The corresponding estimates for subtrochanteric/shaft fractures were 1.05 (0.87–1.26) and 0.89 (0.60–1.33) for risedronate and 0.99 (0.92–1.05) and 1.05 (0.92–1.20) for alendronate, respectively. The HRs (95% CI) for overall femoral fractures associated with each additional year of alendronate or risedronate therapy within 5 and beyond 5 years were not significantly different.


Our study showed persistence of overall hip fracture protection with long-term use of alendronate or risedronate.


Atypical femur fracturesFemoral shaft fracturesFragility fracturesLow-energy femoral fracturesMedication possession ratioOral bisphosphonatesSubtrochanteric fractures

Supplementary material

198_2012_1952_MOESM1_ESM.doc (320 kb)
Appendix 1Baseline variables that were considered but did not make any appreciable difference in results included nutrient deficiency, diseases of the digestive system, genitourinary diseases, muskuloskeletal disorders, knee or hip surgeries, COPD, other respiratory diseases, disorders in the artery or vein systems, cerebral vascular disorders, other heart disease, pulmonary diseases, circulatory and ischemic heart disease separately, HBP, Parkinson’s, alcoholism, smoking, dementia, blood system disease, use of ACE inhibitors, anti-arrhythmic drugs, antibiotics, anticoagulants, ARBs, beta-blockers, BDZs, calcitonin, calcium channel blockers, anticonvulsants, digitalis, diuretics, hypoglycemics, NSAIDS, PPIs, psychotherapy, raloxifene, SSRIs, STATINS, and thyroxin. (DOC 319 kb)

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2012

Authors and Affiliations

  • M. Pazianas
    • 1
    • 6
  • B. Abrahamsen
    • 2
    • 3
  • Y. Wang
    • 4
  • R. G. G. Russell
    • 1
    • 5
  1. 1.The Botnar Research CentreOxford UniversityOxfordUK
  2. 2.Department of Medicine FGentofte HospitalCopenhagenDenmark
  3. 3.OPEN, Institute of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
  4. 4.P&G Pharmaceuticals, Epidemiology & Health OutcomesMasonUSA
  5. 5.The Mellanby Centre for Bone ResearchSheffield UniversitySheffieldUK
  6. 6.Oxford University Institute of Musculoskeletal Sciences, the Botnar Research Centre and Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal DiseasesOxford UniversityOxfordUK