Abstract
Summary
Osteoporosis treatments reduce the risk of fractures. The objective of this study was to investigate adherence to treatment of osteoporosis and its association to fractures in Sweden. Adherence to treatment of osteoporosis in Sweden is poor, and time on treatment was found to be significantly associated with fracture incidence.
Introduction
The objective of this study was to estimate persistence and compliance to treatment of primary osteoporosis in Sweden. A second aim was to investigate the determinants of non-persistence and the association between adherence and fracture incidence.
Methods
Patients were identified through filled prescriptions for alendronate, risedronate, strontium ranelate, and raloxifene between 2005 and 2009 from the Swedish Prescribed Drug Register. Persistence was investigated using survival analysis. Medication possession ratio (MPR) was used to measure compliance in persistent patients. The outcome measure in the analysis of adherence and fracture incidence was hospitalized osteoporotic fractures.
Results
The final cohort consisted of 56,586 treatment-naïve patients (mean age 71, 86% women). A total of 51%, 35%, 25%, and 14% were still on treatment (switching allowed) after 1, 2, 3, and 4 years, respectively. Average MPR in persistent patients was 94.2% (CI95 94.2–94.3%). Compared with <1 month of therapy, treatment for 1 month to 1 year, 1 to 2 years, and 2 to 3 years was associated with a lower 3-year fracture incidence (HR 0.86, p = 0.091; HR 0.67, p < 0.001; and HR 0.59, p < 0.001, respectively). No significant relationship was identified between MPR and fracture risk.
Conclusions
Persistence to treatment of osteoporosis in Sweden is poor and approximately 50% of all treatment-naïve patients discontinue therapy within 1 year. Average refill compliance, estimated only while the patients were persistent, was found to be close to perfect. A strong association was identified between treatment persistence and fracture incidence, which calls for action to improve the current situation.
Similar content being viewed by others
References
Reginster JY, Burlet N (2006) Osteoporosis: a still increasing prevalence. Bone 38:S4–S9
EFFO, NOF (1997) Who are candidates for prevention and treatment for osteoporosis. Osteoporos Int 7:1–6
Kothawala P, Badamgarav E, Ryu S, Miller RM, Halbert RJ (2007) Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin Proc 82:1493–1501
Cramer JA, Gold DT, Silverman SL, Lewiecki EM (2007) A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int 18:1023–1031
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 115:209–216
Lamberg L (2000) Patient-physician relationship critical even during brief “medication checks”. Jama 284:29–31
Eraker SA, Kirscht JP, Becker MH (1984) Understanding and improving patient compliance. Ann Intern Med 100:258–268
Cramer JA (1995) Relationship between medication compliance and medical outcomes. Am J Health-Syst Pharm 52:S27–S29
Claxton AJ, Cramer J, Pierce C (2001) A systematic review of the associations between dose regimens and medication compliance. Clin Ther 23:1296–1310
Carr AJ, Thompson PW, Cooper C (2006) Factors associated with adherence and persistence to bisphosphonate therapy in osteoporosis: a cross-sectional survey. Osteoporos Int 17:1638–1644
SCB, Statistics Sweden. Available from: http://www.scb.se
The Swedish Medical Products Agency (2007) Behandling av osteoporos. Information från Läkemedelsverket 18:19–38
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 7:597–605
The National Board of Health and Welfare. Available from: http://www.socialstyrelsen.se
Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, Wong PK (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47
Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, Saunders LD, Beck CA, Feasby TE, Ghali WA (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 43:1130–1139
Hosmer D, Lemeshow S (1999) Applied survival analysis: regression modeling of time to event data. Wiley, New York, p 386
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 81:1013–1022
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 21:1453–1460
Brankin E, Walker M, Lynch N, Aspray T, Lis Y, Cowell W (2006) The impact of dosing frequency on compliance and persistence with bisphosphonates among postmenopausal women in the UK: evidence from three databases. Curr Med Res Opin 22:1249–1256
Cramer JA, Lynch NO, Gaudin AF, Walker M, Cowell W (2006) The effect of dosing frequency on compliance and persistence with bisphosphonate therapy in postmenopausal women: a comparison of studies in the United States, the United Kingdom, and France. Clin Ther 28:1686–1694
Ideguchi H, Ohno S, Takase K, Ueda A, Ishigatsubo Y (2008) Outcomes after switching from one bisphosphonate to another in 146 patients at a single university hospital. Osteoporos Int 19:1777–1783
Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR (2000) Fracture risk reduction with alendronate in women with osteoporosis: the fracture intervention trial. FIT Research Group. J Clin Endocrinol Metab 85:4118–4124
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 280:2077–2082
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 11:83–91
van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford) 39:1383–1389
Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38:922–928
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 15:1003–1008
McCloskey E, de Takats D, Orgee J (2005) Characteristics associated with non-persistence during daily therapy. Experience from the placebo wing of a community based clinical trial. J Bone Miner Res 20(suppl 1):S282
Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the fracture intervention trial long-term extension (FLEX): a randomized trial. Jama 296:2927–2938
Strewler GJ (2004) Decimal point–osteoporosis therapy at the 10-year mark. N Engl J Med 350:1172–1174
Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189–1199
Iizuka T, Matsukawa M (2008) Potential excessive suppression of bone turnover with long-term oral bisphosphonate therapy in postmenopausal osteoporotic patients. Climacteric 11:287–295
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 90:1294–1301
De Geest S, Sabate E (2003) Adherence to long-term therapies: evidence for action. Eur J Cardiovasc Nurs 2:323
Conflicts of interest
This study was sponsored by Amgen. EL, OS, and FB have previously received funding from several pharmaceutical companies involved in marketing products for treatment of osteoporosis. SR is an employee of Amgen (Europe) GmbH, Zug, Switzerland.
Author information
Authors and Affiliations
Corresponding author
Additional information
Erik Landfeldt and Oskar Ström made equal contributions to this work.
Rights and permissions
About this article
Cite this article
Landfeldt, E., Ström, O., Robbins, S. et al. Adherence to treatment of primary osteoporosis and its association to fractures—the Swedish Adherence Register Analysis (SARA). Osteoporos Int 23, 433–443 (2012). https://doi.org/10.1007/s00198-011-1549-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-011-1549-6