Advertisement

Archives of Osteoporosis

, 13:113 | Cite as

Impact of bisphosphonate compliance on the risk of osteoporotic fracture in France

  • Manon BelhassenEmail author
  • Bernard Cortet
  • Cyrille B. Confavreux
  • Liliane Lamezec
  • Marine Ginoux
  • Eric Van Ganse
Original Article

Abstract

Summary

Limited information is available on the impact of bisphosphonate compliance levels on fracture risk in osteoporosis patients in France. The results of this nested case-control, retrospective study suggest that fracture risk did not significantly change with bisphosphonate compliance levels, except for highly compliant patients.

Purpose/introduction

This was the first study conducted in France to evaluate the impact of compliance levels for bisphosphonates, the most frequently prescribed first-line anti-osteoporotic treatment, on fracture risk.

Methods

This retrospective nested case-control study included patients ≥ 50 years old, who were recorded in a random sample of French claims data, did not die between 2006 and 2013, and received ≥ 1 reimbursement for anti-osteoporotic treatment between 2007 and 2013. Cases (patients hospitalised for osteoporosis-related fractures) were matched to 1–3 controls (patients hospitalised for other reasons). Patients hospitalised for fractures within 12 months preceding the first delivery of anti-osteoporotic treatment or during the first 24 months of follow-up were excluded. Bisphosphonate compliance during the 24 months preceding hospitalisation was calculated by the Continuous measure of Medication Acquisition version 7 (CMA7). We evaluated the impact of bisphosphonate compliance (CMA7 ≥ 80%) and very good compliance levels (CMA7 > 90%) on fracture risk.

Results

In the main analysis, the mean CMA7 values during the 24 months preceding hospitalisation were 48.4% for the 434 cases and 51.3% for the 1123 age-matched controls. An adjusted conditional logistic regression showed no significant impact (odds ratio: 0.851 [95% confidence interval: 0.668, 1.084]) of bisphosphonate compliance on fracture occurrence. In the sensitivity analysis, including one randomly selected control per case and only controls with CMA7 values > 90%, occurrence of fractures was lower (odds ratio: 0.741 [95% confidence interval: 0.608, 0.903]) among the 119 controls.

Conclusion

In conclusion, this study suggested that very high levels of compliance with bisphosphonates are necessary to induce significant decreases in fracture risk.

Keywords

Osteoporosis Treatment Epidemiology Outcomes research 

Abbreviations

BMD

Bone mineral density

CMA7

Continuous measure of Medication Acquisition version 7

COPD

Chronic obstructive pulmonary disease

EGB

Echantillon généraliste de bénéficiaires

ICD-10

International classification of diseases, 10th edition

MPR

Medication possession rate

NSAIDs

Nonsteroidal anti-inflammatory drugs

Notes

Acknowledgements

We thank the French National Health Service (Caisse Nationale de l’Assurance Maladie des Travailleurs Salariés) and the Institute of Health Data (Institut des Données de Santé) for providing data. The authors thank Claire Verbelen (XPE Pharma & Science, Wavre, Belgium) for professional medical writing support.

Author contributions

All authors critically reviewed the manuscript. E.V.G. obtained funding. E.V.G. and M.B. provided supervision, conceived and designed the study, interpreted the data, and drafted the manuscript. M.G. performed the statistical analysis. B.C. and C.B.C. conceived and designed the study and interpreted the data. L.L. contributed to study design and interpretation of data. M.B. is the guarantor of the study.

Funding

This study was funded by a non-conditional grant from MSD France.

Compliance with ethical standards

Conflicts of interest

None.

Ethics approval and consent to participate

This observational study was conducted on anonymised claims data (EGB), and the National Informatics and Liberty Committee has delivered an overall authorisation to use EGB data for research purposes. This study was performed after approval by the Institute of Health Data (Institut des Données de Santé, approval 63, June 11, 2013).

Consent to publish

Not applicable.

References

  1. 1.
    Vijayakumar R, Büsselberg D (2016) Osteoporosis: An under-recognized public health problem. Journal of Local and Global Health ScienceGoogle Scholar
  2. 2.
    Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17(12):1726–1733CrossRefGoogle Scholar
  3. 3.
    Briot K, Cortet B, Thomas T, Audran M, Blain H, Breuil V, Chapuis L, Chapurlat R, Fardellone P, Feron JM, Gauvain JB, Guggenbuhl P, Kolta S, Lespessailles E, Letombe B, Marcelli C, Orcel P, Seret P, Trémollières F, Roux C (2012) 2012 update of French guidelines for the pharmacological treatment of postmenopausal osteoporosis. Joint Bone Spine 79(3):304–313CrossRefGoogle Scholar
  4. 4.
    Feurer E, Chapurlat R (2014) Emerging drugs for osteoporosis. Expert Opin Emerg Drugs 19(3):385–395CrossRefGoogle Scholar
  5. 5.
    Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY et al (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24(1):23–57CrossRefGoogle Scholar
  6. 6.
    Ström O, Borgström F, Kanis J, Compston J, Cooper C, McCloskey E et al (2011) Osteoporosis: burden, health care provision and opportunities in the EU. Arch Osteoporos 6(1–2):59–155CrossRefGoogle Scholar
  7. 7.
    Miller PD (2016) Underdiagnoses and undertreatment of osteoporosis: the battle to be won. J Clin Endocrinol Metab 101(3):852–859CrossRefGoogle Scholar
  8. 8.
    Goldshtein I, Rouach V, Shamir-Stein N, Yu J, Chodick G (2016) Role of side effects, physician involvement, and patient perception in non-adherence with oral bisphosphonates. Adv Ther 33(8):1374–1384CrossRefGoogle Scholar
  9. 9.
    Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356(18):1809–1822CrossRefGoogle Scholar
  10. 10.
    Hochberg MC (2008) Nonvertebral fracture risk reduction with nitrogen-containing bisphosphonates. Curr Osteoporos Rep 6(3):89–94CrossRefGoogle Scholar
  11. 11.
    Wells G, Cranney A, Peterson J, Boucher M, Shea B, Robinson V et al (2008) Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 1Google Scholar
  12. 12.
    Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V et al (2008) Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 1Google Scholar
  13. 13.
    Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V et al (2008) Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 1Google Scholar
  14. 14.
    Ferguson S, Feudjo Tepie M, Taylor A, Roddam A, Critchlow C, Iqbal M, Spangler L, Bayly J (2016) The impact of persistence with bisphosphonates on health resource utilization and fracture risk in the UK: a study of patient records from the UK clinical practice research datalink. J Eval Clin Pract 22(1):31–39CrossRefGoogle Scholar
  15. 15.
    Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, Wong PK (2008) Medication compliance and persistence: terminology and definitions. Value Health 11(1):44–47CrossRefGoogle Scholar
  16. 16.
    Confavreux CB, Paccou J, David C, Mehsen N, Leboime A, Thomas T (2010) Defining treatment failure in severe osteoporosis. Joint Bone Spine 77(Suppl 2):S128–S132CrossRefGoogle Scholar
  17. 17.
    Zazzali JL, Broder MS, Omachi TA, Chang E, Sun GH, Raimundo K (2015) Risk of corticosteroid-related adverse events in asthma patients with high oral corticosteroid use. Allergy Asthma Proc 36(4):268–274CrossRefGoogle Scholar
  18. 18.
    Curtis JR, Westfall AO, Cheng H, Lyles K, Saag KG, Delzell E (2008) Benefit of adherence with bisphosphonates depends on age and fracture type: results from an analysis of 101,038 new bisphosphonate users. J Bone Miner Res 23(9):1435–1441CrossRefGoogle Scholar
  19. 19.
    Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA, Silverman S (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):1013–1022CrossRefGoogle Scholar
  20. 20.
    Ross S, Samuels E, Gairy K, Iqbal S, Badamgarav E, Siris E (2011) A meta-analysis of osteoporotic fracture risk with medication nonadherence. Value Health 14(4):571–581CrossRefGoogle Scholar
  21. 21.
    Imaz I, Zegarra P, Gonzalez-Enriquez J, Rubio B, Alcazar R, Amate JM (2010) Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis. Osteoporos Int 21(11):1943–1951CrossRefGoogle Scholar
  22. 22.
    Reynolds K, Muntner P, Cheetham TC, Harrison TN, Morisky DE, Silverman S, Gold DT, Vansomphone SS, Wei R, O’Malley CD (2013) Primary non-adherence to bisphosphonates in an integrated healthcare setting. Osteoporos Int 24(9):2509–2517CrossRefGoogle Scholar
  23. 23.
    De Roquefeuil L, Studer A, Neumann A, Merlière Y (2009) The Echantillon généraliste de bénéficiaires: representativeness, scope and limits. Pratiques et Organisation des Soins 40(3):213–223CrossRefGoogle Scholar
  24. 24.
    Vollmer WM, Xu M, Feldstein A, Smith D, Waterbury A, Rand C (2012) Comparison of pharmacy-based measures of medication adherence. BMC Health Serv Res 12:155CrossRefGoogle Scholar
  25. 25.
    Wade SW, Curtis JR, Yu J, White J, Stolshek BS, Merinar C, Balasubramanian A, Kallich JD, Adams JL, Viswanathan HN (2012) Medication adherence and fracture risk among patients on bisphosphonate therapy in a large United States health plan. Bone 50(4):870–875CrossRefGoogle Scholar
  26. 26.
    Sharman Moser S, Yu J, Goldshtein I, Ish-Shalom S, Rouach V, Shalev V et al (2016) Cost and consequences of nonadherence with oral bisphosphonate therapy: findings from a real-world data analysis. Ann Pharmacother 50(4):262–269CrossRefGoogle Scholar
  27. 27.
    Kjellberg J, Jorgensen AD, Vestergaard P, Ibsen R, Gerstoft F, Modi A (2016) Cost and health care resource use associated with noncompliance with oral bisphosphonate therapy: an analysis using Danish health registries. Osteoporos Int 27(12):3535–3541CrossRefGoogle Scholar
  28. 28.
    Hadji P, Claus V, Ziller V, Intorcia M, Kostev K, Steinle T (2012) GRAND: the German retrospective cohort analysis on compliance and persistence and the associated risk of fractures in osteoporotic women treated with oral bisphosphonates. Osteoporos Int 23(1):223–231CrossRefGoogle Scholar
  29. 29.
    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(12):1003–1008CrossRefGoogle Scholar
  30. 30.
    Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38(6):922–928CrossRefGoogle Scholar
  31. 31.
    Imel EA, Eckert G, Modi A, Li Z, Martin J, de Papp A, Allen K, Johnston CC, Hui SL, Liu Z (2016) Proportion of osteoporotic women remaining at risk for fracture despite adherence to oral bisphosphonates. Bone 83:267–275CrossRefGoogle Scholar
  32. 32.
    Modi A, Tang J, Sen S, Diez-Perez A (2015) Osteoporotic fracture rate among women with at least 1 year of adherence to osteoporosis treatment. Curr Med Res Opin 31(4):767–777CrossRefGoogle Scholar
  33. 33.
    Diez-Perez A, Olmos JM, Nogues X, Sosa M, Diaz-Curiel M, Perez-Castrillon JL et al (2012) Risk factors for prediction of inadequate response to antiresorptives. J Bone Miner Res 27(4):817–824CrossRefGoogle Scholar
  34. 34.
    Hansen L, Petersen KD, Eriksen SA, Gerstoft F, Vestergaard P (2017) Subjects with osteoporosis to remain at high risk for fracture despite benefit of prior bisphosphonate treatment-a Danish case-control study. Osteoporos Int 28(1):321–328CrossRefGoogle Scholar
  35. 35.
    Reginster JY, Felsenberg D, Boonen S, Diez-Perez A, Rizzoli R, Brandi ML, Spector TD, Brixen K, Goemaere S, Cormier C, Balogh A, Delmas PD, Meunier PJ (2008) Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis: results of a five-year, randomized, placebo-controlled trial. Arthritis Rheum 58(6):1687–1695CrossRefGoogle Scholar
  36. 36.
    Pernicova I, Middleton ET, Aye M (2008) Rash, strontium ranelate and DRESS syndrome put into perspective. European medicine agency on the alert. Osteoporos Int 19(12):1811–1812CrossRefGoogle Scholar
  37. 37.
    Sweeney J, Patterson CC, Menzies-Gow A, Niven RM, Mansur AH, Bucknall C, Chaudhuri R, Price D, Brightling CE, Heaney LG (2016) Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the optimum patient care research database and the British thoracic difficult asthma registry. Thorax 71(4):339–346CrossRefGoogle Scholar
  38. 38.
    Kanis JA, Johansson H, Oden A, Johnell O, de Laet C, Melton IL et al (2004) A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 19(6):893–899CrossRefGoogle Scholar
  39. 39.
    Kishimoto H, Maehara M (2015) Compliance and persistence with daily, weekly, and monthly bisphosphonates for osteoporosis in Japan: analysis of data from the CISA. Arch Osteoporos 10:231CrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  • Manon Belhassen
    • 1
    • 2
    Email author
  • Bernard Cortet
    • 3
  • Cyrille B. Confavreux
    • 4
  • Liliane Lamezec
    • 5
  • Marine Ginoux
    • 2
  • Eric Van Ganse
    • 1
    • 2
  1. 1.HESPER 7425, Health Services and Performance ResearchLyonFrance
  2. 2.PharmacoEpidemiology Lyon (PELyon)LyonFrance
  3. 3.Department of RheumatologyLille University HospitalLilleFrance
  4. 4.INSERM UMR 1033, Rheumatology DepartmentUniversity of LyonLyonFrance
  5. 5.Merck Sharp & DohmeParisFrance

Personalised recommendations