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.
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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
References
Vijayakumar R, Büsselberg D (2016) Osteoporosis: An under-recognized public health problem. Journal of Local and Global Health Science
Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17(12):1726–1733
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):304–313
Feurer E, Chapurlat R (2014) Emerging drugs for osteoporosis. Expert Opin Emerg Drugs 19(3):385–395
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):23–57
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):59–155
Miller PD (2016) Underdiagnoses and undertreatment of osteoporosis: the battle to be won. J Clin Endocrinol Metab 101(3):852–859
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):1374–1384
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):1809–1822
Hochberg MC (2008) Nonvertebral fracture risk reduction with nitrogen-containing bisphosphonates. Curr Osteoporos Rep 6(3):89–94
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 1
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 1
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 1
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):31–39
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):44–47
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–S132
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):268–274
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):1435–1441
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):1013–1022
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):571–581
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):1943–1951
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):2509–2517
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):213–223
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 12:155
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):870–875
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):262–269
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):3535–3541
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):223–231
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):1003–1008
Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38(6):922–928
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 83:267–275
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):767–777
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):817–824
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):321–328
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):1687–1695
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):1811–1812
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):339–346
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):893–899
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 10:231
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.
Funding
This study was funded by a non-conditional grant from MSD France.
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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.
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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).
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Belhassen, M., Cortet, B., Confavreux, C.B. et al. Impact of bisphosphonate compliance on the risk of osteoporotic fracture in France. Arch Osteoporos 13, 113 (2018). https://doi.org/10.1007/s11657-018-0530-9
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DOI: https://doi.org/10.1007/s11657-018-0530-9