Background: Osteoporosis is a chronic disease and adherence can fluctuate over time. Therefore, longer observation is necessary to investigate the stability of patients' adherence. The study aim was to compare the overall adherence (OA) to supplementation with the fixed combination of calcium and vitamin D (Ca/D) in postmenopausal women at baseline and after 1 year, and to evaluate the fluctuation of the OA in individual months. Furthermore, we studied whether adherence is influenced by signing of informed consent and routine medical check-up. Methods: This was a longitudinal, observational study. The data were obtained from the Osteocenter of University Hospital in Hradec Kralove, Czech Republic. Adherence was measured using electronic bottles type Medication Events Monitoring System (MEMS). The study was carried out in two 3-month periods; the baseline in 2013 (signing of informed consent while medical check-up) and the follow-up (medical check-up) in 2014. The adherence and adherence-related outcomes were studied in patients who had initiated osteoporosis treatment and were persistent. Results: 21 (49%) out of 43 patients who avoided drug dispenser and were persistent both at baseline and at follow-up, completed the study and were included. Median age was 76. Evaluating the whole 3-month periods, the OA did not differ significantly at baseline and at follow-up, the OA was 71 and 68%, respectively. However, the adherence in month 1 at baseline was significantly higher than the adherence in month 2 at baseline (p < 0.001) and also than the adherence in month 1 at follow-up (p = 0.010). Analysing the study period without month 1, a stable adherence was observed in 48% of patients. About 33% of doses were omitted at baseline and 34% at follow-up. As many as 71% of the patients took drug holidays at baseline, and 76% at follow-up. Conclusion: The OA was insufficient, around 70% both at baseline and at follow-up. One half of the patients showed a stable adherence. The patterns of non-adherence were very similar at follow-up. Signing of the informed consent seems to act as bias more than regular medical check-up.

Department of Social and Clinical Pharmacy Faculty of Pharmacy in Hradec Kralove Charles University Prague Hradec Kralove Czech Republic

Faculty of Medicine OsteoCentre Institute of Clinical Biochemistry and Diagnostics Charles University Prague University Hospital in Hradec Kralove Hradec Kralove Czech Republic

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Castelo-Branco C., Cortés X., Ferrer M. (2010). Treatment persistence and compliance with a combination of calcium and vitamin D. Climacteric 13, 578–584. 10.3109/13697130903452804 PubMed DOI

Cheng C. W., Woo K. S., Chan J. C., Tomlinson B., You J. H. (2004). Association between adherence to statin therapy and lipid control in Hong Kong Chinese patients at high risk of coronary heart disease. Br. J. Clin. Pharmacol. 58, 528–535. 10.1111/j.1365-2125.2004.02202.x PubMed DOI PMC

Cramer J. A., Gold D. T., Silverman S. L., Lewiecki E. M. (2007). A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos. Int. 18, 1023–1031 10.1007/s00198-006-0322-8 PubMed DOI

Dezii C. M. (2001). Persistence with drug therapy: a practical approach using administrative claims data. Manag. Care 10, 42–45. PubMed

Díez A., Carbonell C., Calaf J., Caloto M. T., Nocea G. (2012). Observational study of treatment compliance in women initiating antiresorptive therapy with or without calcium and vitamin D supplements in Spain. Menopause 19, 89–95. 10.1097/gme.0b013e318223bd6b PubMed DOI

Feldman S. R., Camacho F. T., Krejci-Manwaring J., Carroll C. L., Balkrishnan R. (2007). Adherence to topical therapy increases around the time of office visits. J. Am. Acad. Dermatol. 57, 81–83. 10.1016/j.jaad.2007.04.005 PubMed DOI

Gillespie D., Hood K., Farewell D., Stenson R., Probert C., Hawthorne A. B. (2014). Electronic monitoring of medication adherence in a 1-year clinical study of 2 dosing regimens of mesalazine for adults in remission with ulcerative colitis. Inflamm Bowel Dis. 20, 82–91. 10.1097/01.MIB.0000437500.60546.2a PubMed DOI

Kanis J. A., McCloskey E. V., Johansson H., Cooper C., Rizzoli R., Reginster J. Y., et al. . (2013). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos. Int. 24, 23–57. 10.1007/s00198-012-2074-y PubMed DOI PMC

Kothawala P., Badamgarav E., Ryu S., Miller R. M., Halbert R. J. (2007). Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin. Proc. 82, 1493–1501. 10.1016/S0025-6196(11)61093-8 PubMed DOI

Osterberg L., Blasche T. (2005). Adherence to medication. N. Engl. J. Med. 353, 487–497. 10.1056/NEJMra050100 PubMed DOI

Lekkerkerker F., Kanis J. A., Alsayed J., Bouvenot G., Burlet N., Cahall D., et al. . (2007). Adherence to treatment of osteoporosis: a need for study. Osteoporos. Int. 18, 1311–1317. 10.1007/s00198-007-0410-4 PubMed DOI

Maqutu D., Zewotir T., North D., Naidoo K., Grobler A. (2011). Determinants of optimal adherence over time to antiretroviral therapy amongst HIV positive adults in South Africa: a longitudinal study. AIDS Behav. 15, 1465–1474. 10.1007/s10461-010-9688-x PubMed DOI PMC

McCambridge J., Witton J., Elbourne D. R. (2014). Systematic review of the Hawthorne effect: new concepts are needed to study research participation effects. J. Clin. Epidemiol. 67, 267–277. 10.1016/j.jclinepi.2013.08.015 PubMed DOI PMC

Ngui A. N., Vasiliadis H. M., Tempier R. (2013). Factors associated with adherence over time to antipsychotic drug treatment. Clin. Epidemiol. Glob. Health 3, 3–9 10.1016/j.cegh.2013.11.001 DOI

Parker C. S., Chen Z., Price M., Gross R., Metlay J. P., Christie J. D., et al. . (2007). Adherence to warfarin assessed by electronic pill caps, clinician assessment, and patient reports: results from the IN-RANGE study. J. Gen. Intern. Med. 22, 1254–1259. 10.1007/s11606-007-0233-1 PubMed DOI PMC

Sanfelix-Genovés J., Gil-Guillén V. F., Orozco-Beltran D., Giner-Ruiz V., Pertusa-Martínez S., Reig-Moya B., et al. . (2009). Determinant factors of osteoporosis patients' reported therapeutic adherence to calcium and/or vitamin D supplements: a cross-sectional, observational study of postmenopausal women. Drugs Aging 26, 861–869. 10.2165/11317070-000000000-00000 PubMed DOI

Shi L., Liu J., Fonseca V., Walker P., Kalsekar A., Pawaskar M. (2010a). Correlation between adherence rates measured by MEMS and self-reported questionnaires: a meta-analysis. Health Qual. Life Outcomes 8:99. 10.1186/1477-7525-8-99 PubMed DOI PMC

Shi L., Liu J., Koleva Y., Fonseca V., Kalsekar A., Pawaskar M. (2010b). Concordance of adherence measurement using self-reported adherence questionnaires and medication monitoring devices. Pharmacoeconomics 28, 1097–1107. 10.2165/11537400-000000000-00000 PubMed DOI

Shuter J., Sario J. A., Stubbs R. O., Rode R. A., Zingman B. S. (2012). Sequential antiretroviral adherence measurement using electronic bottle cap monitors in a cohort of HIV-infected adults. J. Int. Assoc. Physicians AIDS Care 11, 94–97. 10.1177/1545109711420498 PubMed DOI

Tang B. M., Eslick G. D., Nowson G. D., Smith C., Bensoussan A. (2007). Use of calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years or older: a meta-analysis. Lancet 370, 657–666. 10.1016/S0140-6736(07)61342-7 PubMed DOI

Tesoriero J., French T., Weiss L., Waters M., Finkelstein R., Agins B. (2003). Stability of adherence to highly active antiretroviral therapy over time among clients enrolled in the treatment adherence demonstration project. J. Acquir. Immune Defic. Syndr. 33, 484–493. 10.1097/00126334-200308010-00009 PubMed DOI

Touskova T., Vytrisalova M., Palicka V., Hendrychova T., Fuksa L., Holcova R., et al. . (2015). Drug holidays: the most frequent type of noncompliance with calcium plus vitamin D supplementation in persistent patients with osteoporosis. Patient Prefer. Adherence 9, 1771. 10.2147/PPA.S88630 PubMed DOI PMC

Voils C. I., Hoyle R. H., Thorpe C. T., Maciejewski M. L., Yancy W. S., Jr. (2011). Improving the measurement of self-reported medication nonadherence. J. Clin. Epidemiol. 64, 250–254. 10.1016/j.jclinepi.2010.07.014 PubMed DOI PMC

Vrijens B., De Geest S., Hughes D. A., Przemyslaw K., Demonceau J., Ruppar T., et al. . (2012). A new taxonomy for describing and defining adherence to medications. Br. J. Clin. Pharmacol. 73, 691–705. 10.1111/j.1365-2125.2012.04167.x PubMed DOI PMC

Wilson I. B., Bangsberg D. R., Shen J., Simoni J. M., Reynolds N. R., Goggin K., et al. . (2013). Heterogeneity among studies in rates of decline of ART adherence over time: results from the MACH14 study. J. Acquir. Immune Defic. Syndr. 64, 448–454. 10.1097/QAI.0000000000000025 PubMed DOI PMC

Zeller A., Ramseier E., Teagtmeyer A., Battegay E. (2008b). Patients' self-reported adherence to cardiovascular medication using electronic monitors as comparators. Hypertens Res. 31, 2037–2043. 10.1291/hypres.31.2037 PubMed DOI

Zeller A., Schroeder K., Peters T. J. (2008a). An adherence self-report questionnaire facilitated the differentiation between nonadherence and nonresponse to antihypertensive treatment. J. Clin. Epidemiol. 61, 282–288. 10.1016/j.jclinepi.2007.04.007 PubMed DOI