Osteoporosis International

, 19:1613 | Cite as

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

  • J. R. Curtis
  • A. O. Westfall
  • H. Cheng
  • E. Delzell
  • K. G. Saag
Original Article



Based upon interest in a bisphosphonate drug holiday, we evaluate the risk for hip fracture after bisphosphonate discontinuation. Among women compliant with bisphosphonates for ≥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.


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 ≥2 years to evaluate the risk of hip fracture after bisphosphonate discontinuation.


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


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 ≥80%) or compliant for 3 years, there were no significant differences in risk associated with discontinuation.


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.


Adherence Bisphosphonates Compliance Discontinuation Fracture 


Conflicts of interest

The authors make the following disclosures:

J.R.C.: grant support: Merck, Procter & Gamble, Lilly, Roche, Amgen, Novartis; consulting/honorarium: Merck, Procter & Gamble, Roche, Lilly

A.O.W.: grant support: Novartis

H.C.: grant support: Amgen

E.D.: grant support: Amgen

K.G.S.: grant support: Merck, Procter & Gamble, Lilly, Amgen, Novartis, Roche; consulting/honorarium: Merck, Procter & Gamble, Lilly, Amgen, Novartis, Roche


  1. 1.
    Black DM, Schwartz AV, Ensrud KE et al (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296(24):2927–2938CrossRefPubMedGoogle Scholar
  2. 2.
    Bone HG, Hosking D, Devogelaer J-P et al (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350(12):1189–1199CrossRefPubMedGoogle Scholar
  3. 3.
    Mortensen L, Charles P, Bekker PJ, DiGennaro J Jr (1998) JCC: Risedronate increases bone mass in an early postmenopausal population: two years of treatment plus one year of follow-up. J Clin Endocrinol Metab 83:396–402PubMedGoogle Scholar
  4. 4.
    Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY (2005) Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 90(3):1294–1301CrossRefPubMedGoogle Scholar
  5. 5.
    Cramer JA, Amonkar MM, Hebborn A, Altman R (2005) Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis. Curr Med Res Opin 21(9):1453–1460CrossRefPubMedGoogle Scholar
  6. 6.
    Curtis JR, Westfall AO, Allison JJ, Freeman A, Saag KG (2006) Channeling and adherence with alendronate and risedronate among chronic glucocorticoid users. Osteoporos Int 17(8):1268–1274CrossRefPubMedGoogle Scholar
  7. 7.
    Brookhart MA, Avorn J, Katz JN et al (2007) Gaps in treatment among users of osteoporosis medications: the dynamics of noncompliance. Am J Med 120(3):251–256CrossRefPubMedGoogle Scholar
  8. 8.
    Yood RA, Emani S, Reed JI, Lewis BE, Charpentier M, Lydick E (2003) Compliance with pharmacologic therapy for osteoporosis. Osteoporos Int 14(12):965–968CrossRefPubMedGoogle Scholar
  9. 9.
    Siris ES, Harris ST, Rosen CJ et al (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 81(8):1013–1022CrossRefPubMedGoogle Scholar
  10. 10.
    Ray WA, Griffin MR, Fought RL, Adams ML (1992) Identification of fractures from computerized Medicare files. J Clin Epidemiol 45(7):703–714CrossRefPubMedGoogle Scholar
  11. 11.
    Silverman SL, Watts NB, Delmas PD, Lange JL, Lindsay R (2007) Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study. Osteoporos Int 18(1):25–34CrossRefPubMedGoogle Scholar
  12. 12.
    Curtis JR, Westfall AO, Allison JJ, Freeman A, Kovac SH, Saag KG (2006) Agreement and validity of pharmacy data and self-report for use of osteoporosis medications among chronic glucocorticoid users. Pharmacoepi Drug Safety 15(10):710–718Google Scholar
  13. 13.
    Nancollas GH, Tang R, Phipps RJ et al (2006) Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone 38(5):617–627CrossRefPubMedGoogle Scholar
  14. 14.
    Curtis JR, Mudano A, Solomon DH, Kim Y, Saag KG (2007) Identifying clinical vertebral fractures using administrative claims data: a validation study. J Bone Miner Res 22(1):S199Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2008

Authors and Affiliations

  • J. R. Curtis
    • 1
  • A. O. Westfall
    • 2
  • H. Cheng
    • 3
  • E. Delzell
    • 3
  • K. G. Saag
    • 1
    • 3
  1. 1.Center for Education and Research on Therapeutics (CERTs) of Musculoskeletal DisordersUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of BiostatisticsUniversity of Alabama at Birmingham School of Public HealthBirminghamUSA
  3. 3.Department of EpidemiologyUniversity of Alabama at Birmingham School of Public HealthBirminghamUSA

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