Osteoporosis International

, Volume 17, Issue 6, pp 922–928 | Cite as

Persistence with weekly alendronate therapy among postmenopausal women

  • J. C. Lo
  • A. R. Pressman
  • M. A. Omar
  • B. Ettinger
Original Article



Although clinical trials indicate that oral bisphosphonates reduce osteoporotic fracture risk, compliance with bisphosphonate therapy in practice is suboptimal, with 1-year discontinuation rates exceeding 50%.


We conducted a retrospective cohort study among female members of a large integrated health care delivery system (Kaiser Permanente of Northern California), age 45 years and older, to determine their persistence with weekly alendronate (defined as continuous use, allowing for a refill gap of 60 days), predictors of discontinuation, and subsequent osteoporosis therapy. We also examined the effect of varying the refill gap from 30 to 120 days on the discontinuation rate. From 2002 through 2003, we identified 13,455 women (age 68.8±10.4 years) who initiated weekly oral alendronate therapy.


Using a 60-day refill gap, the 1-year discontinuation rate was 49.6% [95% confidence interval (CI) 48.8–50.4%]; this increased to 58.0% (CI 57.2–58.8%) with a 30-day gap and decreased to 42.2% (CI 41.1–43.0%) with a 120-day gap. Among those who discontinued therapy, about one-third restarted alendronate or another osteoporosis drug within 6 months. Baseline factors associated with alendronate discontinuation included prior bone mineral density testing [adjusted odds ratio (OR) 0.64, CI 0.60–0.69], prior postmenopausal hormone therapy (OR 0.78, CI 0.73–0.84), prior high-dose oral glucocorticoid therapy (OR 1.26, CI 1.05–1.51), prior gastrointestinal diagnoses (OR 1.21, CI 1.09–1.36), and high number of therapeutic classes of prescriptions filled in the prior year (OR 1.21, CI 1.10–1.32), although the final model had limited explanatory power.


We conclude that apparent discontinuation rates are high within 1 year after treatment initiation, although a subset of women appears to restart bisphosphonate or other osteoporosis therapy. Because intermittent use and/or poor adherence is common, discontinuation rates based on data from administrative databases are sensitive to the refill gap length. In addition, we identified no clinical factors highly predictive of discontinuation.


Alendronate Postmenopausal women 



This work was supported by funding from Novartis Pharmaceuticals Corporation. J.C.L. is a scholar in the Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program sponsored by the National Institute of Child Health and Human Development and the Office of Research on Women’s Health at the National Institutes of Health (9 K12HD052163-06).


  1. 1.
    Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535–1541PubMedCrossRefGoogle Scholar
  2. 2.
    Chesnut IC, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD (2004) Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 19:1241–1249CrossRefGoogle Scholar
  3. 3.
    Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the fracture intervention trial. JAMA 280:2077–2082PubMedCrossRefGoogle Scholar
  4. 4.
    Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral efficacy with risedronate therapy (VERT) study group. JAMA 282:1344–1352PubMedCrossRefGoogle Scholar
  5. 5.
    Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral efficacy with risedronate therapy (VERT) study group. Osteoporos Int 11:83–91PubMedCrossRefGoogle Scholar
  6. 6.
    Caro JJ, Ishak KJ, Huybrechts KF, Raggio G, Naujoks C (2004) The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int 15:1003–1008PubMedCrossRefGoogle Scholar
  7. 7.
    McCombs JS, Thiebaud P, McLaughlin-Miley C, Shi J (2004) Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 48:271–287PubMedCrossRefGoogle Scholar
  8. 8.
    Yood RA, Emani S, Reed JI, Lewis BE, Charpentier M, Lydick E (2003) Compliance with pharmacologic therapy for osteoporosis. Osteoporos Int 14:965–968PubMedCrossRefGoogle Scholar
  9. 9.
    Clowes JA, Peel NF, Eastell R (2004) The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 89:1117–1123PubMedCrossRefGoogle Scholar
  10. 10.
    Ettinger B, Earnshaw SR, Graham CN, Amonkar MM, Baran RW (2005) Cost-effectiveness of bisphosphonate therapies for women with postmenopausal osteoporosis: Implications of improved persistence with ibandronate. J Bone Miner Res 20(Suppl 1):S398–S399 (abstract M361)Google Scholar
  11. 11.
    MarketScan (2000) MEDSTAT Group Inc. Ann Arbor, MIGoogle Scholar
  12. 12.
    Sikka R, Xia F, Aubert RE (2005) Estimating medication persistency using administrative claims data. Am J Manag Care 11:449–457PubMedGoogle Scholar
  13. 13.
    Krieger N (1992) Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology. Am J Public Health 82:703–710PubMedCrossRefGoogle Scholar
  14. 14.
    Miller RG, Bolognese M, Worley K, Solis A, Sheer R (2004) Incidence of gastrointestinal events among bisphosphonate patients in an observational setting. Am J Manag Care 10:S207–S215Google Scholar
  15. 15.
    Ettinger B, Chidambaran P, Pressman A (2001) Prevalence and determinants of osteoporosis drug prescription among patients with high exposure to glucocorticoid drugs. Am J Manag Care 7:597–605PubMedGoogle Scholar
  16. 16.
    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 21:1453–1460PubMedCrossRefGoogle Scholar
  17. 17.
    Recker RR, Gilmore A, Hebborn A, Takemoto S (2005) Bisphosphonate dosing regimens influence adherence to treatment in women with postmenopausal osteoporosis. Presented at the 87th Annual Meeting of the Endocrine Society, June 4–7, 2005, San Diego CA, abstract P3–P372Google Scholar
  18. 18.
    Boccuzzi SJ, Foltz SH, Omar MA, Kahler KH (2005) Assessment of adherence and persistence with daily and weekly dosing regimens of oral bisphosphonates. Presented at the 87th Annual Meeting of the Endocrine Society, June 4–7, 2005, San Diego CA, abstract P1–P438Google Scholar
  19. 19.
    Ettinger B, Pressman A, Schein J, Chan J, Silver P, Connolly N (1998) Alendronate use among 812 women: prevalence of gastrointestinal complaints, noncompliance with patient instructions, and discontinuation. J Managed Care Pharm 4:488–492Google Scholar
  20. 20.
    Papaioannou A, Ioannidis G, Adachi JD, Sebaldt RJ, Ferko N, Puglia M, Brown J, Tenenhouse A, Olszynski WP, Boulos P, Hanley DA, Josse R, Murray TM, Petrie A, Goldsmith CH (2003) Adherence to bisphosphonates and hormone replacement therapy in a tertiary care setting of patients in the CANDOO database. Osteoporos Int 14:808–813PubMedCrossRefGoogle Scholar
  21. 21.
    Tosteson AN, Grove MR, Hammond CS, Moncur MM, Ray GT, Hebert GM, Pressman AR, Ettinger B (2003) Early discontinuation of treatment for osteoporosis. Am J Med 115:209–216PubMedCrossRefGoogle Scholar
  22. 22.
    Pressman A, Forsyth B, Ettinger B, Tosteson AN (2001) Initiation of osteoporosis treatment after bone mineral density testing. Osteoporos Int 12:337–342PubMedCrossRefGoogle Scholar
  23. 23.
    Karter AJ, Ahmed AT, Liu J, Moffet HH, Parker MM (2005) Pioglitazone initiation and subsequent hospitalization for congestive heart failure. Diabet Med 22:986–993PubMedCrossRefGoogle Scholar
  24. 24.
    Silverman S, Siris E, Abbott T, Barr C, Harris S, Rosen C (2005) Adherence to bisphosphonate therapy is associated with decreased nonvertebral osteoporotic fracture risk. J Bone Miner Res 20(Suppl 1):S286 (abstract SU417)Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Authors and Affiliations

  • J. C. Lo
    • 1
    • 2
  • A. R. Pressman
    • 1
  • M. A. Omar
    • 4
  • B. Ettinger
    • 1
    • 3
  1. 1.Division of ResearchKaiser Permanente Northern CaliforniaOaklandUSA
  2. 2.Division of Endocrinology, Department of MedicineUniversity of California San FranciscoSan FranciscoUSA
  3. 3.Department of MedicineUniversity of California San FranciscoSan FranciscoUSA
  4. 4.Novartis Pharmaceuticals CorporationEast HanoverUSA

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