Skip to main content
Erschienen in: Osteoporosis International 11/2013

01.11.2013 | Original Article

Adherence to raloxifene therapy: assessment methods and relationship with efficacy

verfasst von: J. Finigan, K. Naylor, M. A. Paggiosi, N. F. Peel, R. Eastell

Erschienen in: Osteoporosis International | Ausgabe 11/2013

Einloggen, um Zugang zu erhalten

Abstract

Summary

Response to therapy depends on patient compliance but accurate assessment is difficult and adequate levels of adherence are uncertain. Adherence to raloxifene treatment may be assessed more accurately by electronic monitoring than by counting returned tablets. The level of adherence is positively associated with the degree of bone response.

Introduction

Adherence to study medication is usually estimated by counting returned tablets. This method relies on subjects’ honesty and may be inaccurate. We aimed to assess adherence more accurately, and examine its effect on measures of bone response, by using electronic monitoring.

Methods

Osteopenic women, ages 50 to 80, were prescribed daily raloxifene for 2 years. Electronic bottle caps (Medication Event Monitoring System (MEMS), Aardex) recorded the date and time on opening. Returned tablets were also counted. We measured bone mineral density (BMD) in duplicate at the spine and hip at baseline and 2 years. We also measured urinary N-terminal cross-linked telopeptide of type I collagen (NTX) at baseline, 1 and 2 years. We calculated the percentage changes in BMD and NTX from mean baseline to mean follow up measurements. Percentage adherence was assessed by both methods for 71 subjects that completed the study.

Results

The two methods correlated significantly (p <0.001, Spearman’s rho = 0.73) but the tablet count showed a higher median adherence than the MEMS caps (95.7 vs. 85.0 %, p <0.001), with greater divergence at lower adherence levels. MEMS adherence in 65 subjects with complete data correlated with NTX response (p <0.01, rho = −0.33) but with BMD response only at the femoral neck. However, adherence in the lowest quartile was associated with poorer BMD response at all sites (p <0.05).

Conclusion

Tablet counts may give similar results overall but conceal substantial individual non-adherence. Monitoring caps may assess adherence more accurately than tablet counts and would be the preferred method in clinical trials. The degree of adherence is associated with both bone turnover and BMD responses to anti-resorptive therapy.
Literatur
1.
Zurück zum Zitat Wu JR, Moser DK, De Jong MJ, Rayens MK, Chung ML, Riegel B, Lennie TA (2009) Defining an evidence-based cutpoint for medication adherence in heart failure. Am Heart J 157(2):285–291PubMedCrossRef Wu JR, Moser DK, De Jong MJ, Rayens MK, Chung ML, Riegel B, Lennie TA (2009) Defining an evidence-based cutpoint for medication adherence in heart failure. Am Heart J 157(2):285–291PubMedCrossRef
2.
Zurück zum Zitat Fielden SJ, Rusch ML, Yip B, Wood E, Shannon K, Levy AR, Montaner JS, Hogg RS (2008) Nonadherence increases the risk of hospitalization among HIV-infected antiretroviral naive patients started on HAART. J Int Assoc Physicians AIDS Care (Chic) 7(5):238–244CrossRef Fielden SJ, Rusch ML, Yip B, Wood E, Shannon K, Levy AR, Montaner JS, Hogg RS (2008) Nonadherence increases the risk of hospitalization among HIV-infected antiretroviral naive patients started on HAART. J Int Assoc Physicians AIDS Care (Chic) 7(5):238–244CrossRef
3.
Zurück zum Zitat Eastell R, Vrijens B, Cahall DL, Ringe JD, Garnero P, Watts NB (2011) Bone turnover markers and bone mineral density response with risedronate therapy: relationship with fracture risk and patient adherence. J Bone Miner Res 26(7):1662–1669PubMedCrossRef Eastell R, Vrijens B, Cahall DL, Ringe JD, Garnero P, Watts NB (2011) Bone turnover markers and bone mineral density response with risedronate therapy: relationship with fracture risk and patient adherence. J Bone Miner Res 26(7):1662–1669PubMedCrossRef
4.
Zurück zum Zitat Finigan J, Bainbridge PR, Eastell R (2001) Adherence to osteoporosis therapies. Bone 28(5):S239–S239 Finigan J, Bainbridge PR, Eastell R (2001) Adherence to osteoporosis therapies. Bone 28(5):S239–S239
5.
Zurück zum Zitat 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):1003–1008PubMedCrossRef 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):1003–1008PubMedCrossRef
6.
Zurück zum Zitat Vrijens B, Vincze G, Kristanto P, Urquhart J, Burnier M (2008) Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories. BMJ 336(7653):1114–1119PubMedCrossRef Vrijens B, Vincze G, Kristanto P, Urquhart J, Burnier M (2008) Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories. BMJ 336(7653):1114–1119PubMedCrossRef
7.
Zurück zum Zitat Horne R et al. (2005) Concordance, adherence and compliance in medicine taking. Report for the National Co-ordinating Centre for NHS Service Delivery and Organisation R & D (NCCSDO) Horne R et al. (2005) Concordance, adherence and compliance in medicine taking. Report for the National Co-ordinating Centre for NHS Service Delivery and Organisation R & D (NCCSDO)
8.
Zurück zum Zitat Grosset KA, Bone I, Reid JL, Grosset D (2006) Measuring therapy adherence in Parkinson’s disease: a comparison of methods. J Neurol Neurosurg Psychiatry 77(2):249–251PubMedCrossRef Grosset KA, Bone I, Reid JL, Grosset D (2006) Measuring therapy adherence in Parkinson’s disease: a comparison of methods. J Neurol Neurosurg Psychiatry 77(2):249–251PubMedCrossRef
9.
Zurück zum Zitat Schwed A, Fallab CL, Burnier M, Waeber B, Kappenberger L, Burnand B, Darioli R (1999) Electronic monitoring of compliance to lipid-lowering therapy in clinical practice. J Clin Pharmacol 39(4):402–409PubMedCrossRef Schwed A, Fallab CL, Burnier M, Waeber B, Kappenberger L, Burnand B, Darioli R (1999) Electronic monitoring of compliance to lipid-lowering therapy in clinical practice. J Clin Pharmacol 39(4):402–409PubMedCrossRef
10.
Zurück zum Zitat van Onzenoort HA, Verberk WJ, Kessels AG, Kroon AA, Neef C, van der Kuy PH, de Leeuw PW (2010) Assessing medication adherence simultaneously by electronic monitoring and pill count in patients with mild-to-moderate hypertension. Am J Hypertens 23(2):149–154PubMedCrossRef van Onzenoort HA, Verberk WJ, Kessels AG, Kroon AA, Neef C, van der Kuy PH, de Leeuw PW (2010) Assessing medication adherence simultaneously by electronic monitoring and pill count in patients with mild-to-moderate hypertension. Am J Hypertens 23(2):149–154PubMedCrossRef
11.
Zurück zum Zitat Ettinger B et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. JAMA 282(7):637–645PubMedCrossRef Ettinger B et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. JAMA 282(7):637–645PubMedCrossRef
12.
Zurück zum Zitat 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(3):1117–1123PubMedCrossRef 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(3):1117–1123PubMedCrossRef
13.
Zurück zum Zitat Naylor KE, Clowes JA, Finigan J, Paggiosi MA, Peel NF, Eastell R (2010) The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women. Bone 46(3):592–597PubMedCrossRef Naylor KE, Clowes JA, Finigan J, Paggiosi MA, Peel NF, Eastell R (2010) The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women. Bone 46(3):592–597PubMedCrossRef
14.
Zurück zum Zitat Baim S, Wilson CR, Lewiecki EM, Luckey MM, Downs RW Jr, Lentle BC (2005) Precision assessment and radiation safety for dual-energy x-ray absorptiometry: position paper of the International Society for Clinical Densitometry. J Clin Densitom 8(4):371–378PubMedCrossRef Baim S, Wilson CR, Lewiecki EM, Luckey MM, Downs RW Jr, Lentle BC (2005) Precision assessment and radiation safety for dual-energy x-ray absorptiometry: position paper of the International Society for Clinical Densitometry. J Clin Densitom 8(4):371–378PubMedCrossRef
15.
Zurück zum Zitat Cramer JA, Mattson RH, Prevey ML, Scheyer RD, Ouellette VL (1989) How often is medication taken as prescribed? A novel assessment technique. JAMA 261(22):3273–3277, Erratum in: JAMA 262(11):1472PubMedCrossRef Cramer JA, Mattson RH, Prevey ML, Scheyer RD, Ouellette VL (1989) How often is medication taken as prescribed? A novel assessment technique. JAMA 261(22):3273–3277, Erratum in: JAMA 262(11):1472PubMedCrossRef
16.
Zurück zum Zitat Zanchetta JR, Hakim C, Lombas C (2004) Observational study of compliance and continuance rates of raloxifene in the prevention and treatment of osteoporosis. Curr Ther Res 65(6):470–480CrossRef Zanchetta JR, Hakim C, Lombas C (2004) Observational study of compliance and continuance rates of raloxifene in the prevention and treatment of osteoporosis. Curr Ther Res 65(6):470–480CrossRef
17.
Zurück zum Zitat Wilkes MM, Navickis RJ, Chan WW, Lewiecki EM (2010) Bisphosphonates and osteoporotic fractures: a cross-design synthesis of results among compliant/persistent postmenopausal women in clinical practice versus randomized controlled trials. Osteoporos Int 21(4):679–688PubMedCrossRef Wilkes MM, Navickis RJ, Chan WW, Lewiecki EM (2010) Bisphosphonates and osteoporotic fractures: a cross-design synthesis of results among compliant/persistent postmenopausal women in clinical practice versus randomized controlled trials. Osteoporos Int 21(4):679–688PubMedCrossRef
18.
Zurück zum Zitat Chesnut CH et al (1995) Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling. am j med 99(2):144–152PubMedCrossRef Chesnut CH et al (1995) Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling. am j med 99(2):144–152PubMedCrossRef
19.
Zurück zum Zitat Simmons MS, Nides MA, Rand CS, Wise RA, Tashkin DP (2000) Unpredictability of deception in compliance with physician-prescribed bronchodilator inhaler use in a clinical trial. Chest 118(2):290–295PubMedCrossRef Simmons MS, Nides MA, Rand CS, Wise RA, Tashkin DP (2000) Unpredictability of deception in compliance with physician-prescribed bronchodilator inhaler use in a clinical trial. Chest 118(2):290–295PubMedCrossRef
20.
Zurück zum Zitat Kruse W, Weber E (1990) Dynamics of drug regimen compliance: its assessment by microprocessor-based monitoring. Eur J Clin Pharmacol 38:561–565PubMedCrossRef Kruse W, Weber E (1990) Dynamics of drug regimen compliance: its assessment by microprocessor-based monitoring. Eur J Clin Pharmacol 38:561–565PubMedCrossRef
21.
Zurück zum Zitat Schmitz JM, Sayre SL, Stotts AL, Rothfleisch J, Mooney ME (2005) Medication compliance during a smoking cessation clinical trial: a brief intervention using MEMS feedback. J Behav Med 28(2):139–147PubMedCrossRef Schmitz JM, Sayre SL, Stotts AL, Rothfleisch J, Mooney ME (2005) Medication compliance during a smoking cessation clinical trial: a brief intervention using MEMS feedback. J Behav Med 28(2):139–147PubMedCrossRef
22.
Zurück zum Zitat Cotté F-E, Mercier F, De Pouvourville G (2008) Relationship between compliance and persistence with osteoporosis medications and fracture risk in primary health care in France: a retrospective case–control analysis. Clin Ther 30(12):2410–2422PubMedCrossRef Cotté F-E, Mercier F, De Pouvourville G (2008) Relationship between compliance and persistence with osteoporosis medications and fracture risk in primary health care in France: a retrospective case–control analysis. Clin Ther 30(12):2410–2422PubMedCrossRef
23.
Zurück zum Zitat Yood RA, Emani S, Reed JI, Lewis BE, Charpentier M, Lydick E (2003) Compliance with pharmacologic therapy for osteoporosis. Osteoporos Int 14(12):965–968PubMedCrossRef Yood RA, Emani S, Reed JI, Lewis BE, Charpentier M, Lydick E (2003) Compliance with pharmacologic therapy for osteoporosis. Osteoporos Int 14(12):965–968PubMedCrossRef
24.
Zurück zum Zitat Siris ES, Selby PL, Saag KG, Borgström F, Herings RMC, Silverman SL (2009) Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med 122(2A):S3–S13PubMedCrossRef Siris ES, Selby PL, Saag KG, Borgström F, Herings RMC, Silverman SL (2009) Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med 122(2A):S3–S13PubMedCrossRef
25.
Zurück zum Zitat Siris ES, Harris ST, Rosen CJ (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 81:1013–1022PubMedCrossRef Siris ES, Harris ST, Rosen CJ (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 81:1013–1022PubMedCrossRef
26.
Zurück zum Zitat Briesacher BA, Andrade SE, Yood RA et al (2007) Consequences of poor compliance with bisphosphonates. Bone 41:882–887PubMedCrossRef Briesacher BA, Andrade SE, Yood RA et al (2007) Consequences of poor compliance with bisphosphonates. Bone 41:882–887PubMedCrossRef
27.
Zurück zum Zitat 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):571–581PubMedCrossRef 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):571–581PubMedCrossRef
28.
Zurück zum Zitat Weycker D, Macarios D, Edelsberg J, Oster G (2006) Compliance with drug therapy for postmenopausal osteoporosis. Osteoporos Int 17(11):1645–1652PubMedCrossRef Weycker D, Macarios D, Edelsberg J, Oster G (2006) Compliance with drug therapy for postmenopausal osteoporosis. Osteoporos Int 17(11):1645–1652PubMedCrossRef
29.
Zurück zum Zitat Tankó LB, Mouritzen U, Lehmann HJ, Warming L, Moelgaard A, Christgau S, Qvist P, Baumann M, Wieczorek L, Hoyle N, Christiansen C (2003) Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens. Bone 32(6):687–693PubMedCrossRef Tankó LB, Mouritzen U, Lehmann HJ, Warming L, Moelgaard A, Christgau S, Qvist P, Baumann M, Wieczorek L, Hoyle N, Christiansen C (2003) Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens. Bone 32(6):687–693PubMedCrossRef
Metadaten
Titel
Adherence to raloxifene therapy: assessment methods and relationship with efficacy
verfasst von
J. Finigan
K. Naylor
M. A. Paggiosi
N. F. Peel
R. Eastell
Publikationsdatum
01.11.2013
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 11/2013
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-013-2386-6

Weitere Artikel der Ausgabe 11/2013

Osteoporosis International 11/2013 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.