Skip to main content
Top
Published in: Osteoporosis International 7/2021

01-07-2021 | Bisphosphonate | Original Article

Over half of seniors who start oral bisphosphonate therapy are exposed for 3 or more years: novel rolling window approach and patterns of use

Authors: K.N. Hayes, N. He, K.A. Brown, A.M. Cheung, D.N. Juurlink, S.M. Cadarette

Published in: Osteoporosis International | Issue 7/2021

Login to get access

Abstract

Summary

Most adherence studies only consider treatment following a first prescription. Using an extended follow-up, we found that 60% of seniors starting oral bisphosphonate therapy were exposed for ≥ 3 years (48% for ≥ 5 years). Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years.

Introduction

The purpose of this study was to identify and describe patterns of long-term oral bisphosphonate use among seniors using a novel methodological approach that considers extended follow-up.

Methods

Among Ontarians aged 66 years or older, we identified subjects with a first dispensing of alendronate or risedronate between November 2000 and December 2016. We followed them until death or December 2019 to identify patients with ≥ 3 years of bisphosphonate use, defined as a proportion of days covered ≥ 80%, using 3-year rolling windows. We calculated the proportion of patients with long-term therapy (≥ 3 years of use) using Kaplan-Meier estimates. We described patterns of long-term use and compared patient characteristics between patients with and without long-term therapy.

Results

We identified 260,784 eligible seniors initiating bisphosphonate therapy. Of these, 60% continued therapy ≥ 3 years (77% women), and 48% continued ≥ 5 years. Characteristics did not meaningfully differ between patients with or without long-term therapy. The median length of long-term therapy was 7.0 (IQR 5.1) years for women and 6.1 (IQR 4.3) years for men. Only 20% experienced a treatment gap before long-term therapy, yet 50% experienced a treatment gap of ≥ 120 days after a median 5.3 years of therapy. Eighty-one percent who returned to therapy following a treatment gap re-initiated an oral bisphosphonate, with 18% switching to denosumab.

Conclusions

Among seniors initiating oral bisphosphonates, we found that 60% receive at least 3 years of therapy when using an extended follow-up. Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years.
Appendix
Available only for authorised users
Literature
1.
go back to reference Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, Hanley DA, Hodsman A, Jamal SA, Kaiser SM, Kvern B, Siminoski K, Leslie WD, for the Scientific Advisory Council of Osteoporosis Canada (2010) 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. Can Med Assoc J 182:1864–1873CrossRef Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, Hanley DA, Hodsman A, Jamal SA, Kaiser SM, Kvern B, Siminoski K, Leslie WD, for the Scientific Advisory Council of Osteoporosis Canada (2010) 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. Can Med Assoc J 182:1864–1873CrossRef
2.
go back to reference Hayes KN, Ban JK, Athanasiadis G, Burden AM, Cadarette SM (2019) Time trends in oral bisphosphonate initiation in Ontario, Canada over 20 years reflect drug policy and healthcare delivery changes. Osteoporos Int 30:2311–2319CrossRef Hayes KN, Ban JK, Athanasiadis G, Burden AM, Cadarette SM (2019) Time trends in oral bisphosphonate initiation in Ontario, Canada over 20 years reflect drug policy and healthcare delivery changes. Osteoporos Int 30:2311–2319CrossRef
3.
go back to reference Cadarette SM, Carney G, Baek D, Gunraj N, Paterson JM, Dormuth CR (2012) Osteoporosis medication prescribing in British Columbia and Ontario: impact of public drug coverage. Osteoporos Int 23:1475–1480CrossRef Cadarette SM, Carney G, Baek D, Gunraj N, Paterson JM, Dormuth CR (2012) Osteoporosis medication prescribing in British Columbia and Ontario: impact of public drug coverage. Osteoporos Int 23:1475–1480CrossRef
4.
go back to reference Friesen KJ, Bugden S, Falk J (2020) Time to benefit and the long-term persistence of new users of oral bisphosphonates. J Bone Miner Metab 38:371–377CrossRef Friesen KJ, Bugden S, Falk J (2020) Time to benefit and the long-term persistence of new users of oral bisphosphonates. J Bone Miner Metab 38:371–377CrossRef
5.
go back to reference Wells GA, Cranney A, Peterson J et al (2008) Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev:CD001155 Wells GA, Cranney A, Peterson J et al (2008) Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev:CD001155
6.
go back to reference Wells GA, Cranney A, Peterson J et al (2008) Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev:CD003376 Wells GA, Cranney A, Peterson J et al (2008) Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev:CD003376
7.
go back to reference Wells G, Cranney A, Peterson J et al (2008) Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev:CD004523 Wells G, Cranney A, Peterson J et al (2008) Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev:CD004523
8.
go back to reference Amiche MA, Lévesque LE, Gomes T, Adachi JD, Cadarette SM (2018) Effectiveness of oral bisphosphonates in reducing fracture risk among oral glucocorticoid users: three matched cohort analyses. J Bone Miner Res 33:419–429CrossRef Amiche MA, Lévesque LE, Gomes T, Adachi JD, Cadarette SM (2018) Effectiveness of oral bisphosphonates in reducing fracture risk among oral glucocorticoid users: three matched cohort analyses. J Bone Miner Res 33:419–429CrossRef
9.
go back to reference Brown J, Morin S, Leslie WD et al Bisphosphonates for treatment of osteoporosis: Expected benefits, potential harms, and drug holidays. Can Fam Physician 60:324–333 Brown J, Morin S, Leslie WD et al Bisphosphonates for treatment of osteoporosis: Expected benefits, potential harms, and drug holidays. Can Fam Physician 60:324–333
10.
go back to reference Adler RA, El-Hajj Fuleihan G, Bauer DC et al (2016) Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 31:16–35CrossRef Adler RA, El-Hajj Fuleihan G, Bauer DC et al (2016) Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 31:16–35CrossRef
11.
go back to reference Fardellone P, Lello S, Cano A, de Sá Moreira E, Watanabe de Oliveira R, Julian GS, Tang B (2019) Real-world adherence and persistence with bisphosphonate therapy in postmenopausal women: a systematic review. Clin Ther 41:1576–1588CrossRef Fardellone P, Lello S, Cano A, de Sá Moreira E, Watanabe de Oliveira R, Julian GS, Tang B (2019) Real-world adherence and persistence with bisphosphonate therapy in postmenopausal women: a systematic review. Clin Ther 41:1576–1588CrossRef
12.
go back to reference Burden AM, Paterson JM, Solomon DH, Mamdani M, Juurlink DN, Cadarette SM (2012) Bisphosphonate prescribing, persistence and cumulative exposure in Ontario, Canada. Osteoporos Int 23:1075–1082CrossRef Burden AM, Paterson JM, Solomon DH, Mamdani M, Juurlink DN, Cadarette SM (2012) Bisphosphonate prescribing, persistence and cumulative exposure in Ontario, Canada. Osteoporos Int 23:1075–1082CrossRef
13.
go back to reference Brookhart MA, Avorn J, Katz JN, Finkelstein JS, Arnold M, Polinski JM, Patrick AR, Mogun H, Solmon DH (2007) Gaps in treatment among users of osteoporosis medications: the dynamics of noncompliance. Am J Med 120:251–256CrossRef Brookhart MA, Avorn J, Katz JN, Finkelstein JS, Arnold M, Polinski JM, Patrick AR, Mogun H, Solmon DH (2007) Gaps in treatment among users of osteoporosis medications: the dynamics of noncompliance. Am J Med 120:251–256CrossRef
14.
go back to reference Tosteson ANA, Do TP, Wade SW, Anthony MS, Downs RW (2010) Persistence and switching patterns among women with varied osteoporosis medication histories: 12-month results from POSSIBLE US™. Osteoporos Int 21:1769–1780CrossRef Tosteson ANA, Do TP, Wade SW, Anthony MS, Downs RW (2010) Persistence and switching patterns among women with varied osteoporosis medication histories: 12-month results from POSSIBLE US™. Osteoporos Int 21:1769–1780CrossRef
15.
go back to reference Balasubramanian A, Goli BA et al (2013) Discontinuation and reinitiation patterns of osteoporosis treatment among commercially insured postmenopausal women. Int J Gen Med:839 Balasubramanian A, Goli BA et al (2013) Discontinuation and reinitiation patterns of osteoporosis treatment among commercially insured postmenopausal women. Int J Gen Med:839
16.
go back to reference Martin D, Miller AP, Quesnel-Vallée A, Caron NR, Vissandjée B, Marchildon GP (2018) Canada’s universal health-care system: achieving its potential. Lancet 391:1718–1735CrossRef Martin D, Miller AP, Quesnel-Vallée A, Caron NR, Vissandjée B, Marchildon GP (2018) Canada’s universal health-care system: achieving its potential. Lancet 391:1718–1735CrossRef
17.
go back to reference Burden AM, Paterson JM, Gruneir A, Cadarette SM (2015) Adherence to osteoporosis pharmacotherapy is underestimated using days supply values in electronic pharmacy claims data. Pharmacoepidemiol Drug Saf 24:67–74CrossRef Burden AM, Paterson JM, Gruneir A, Cadarette SM (2015) Adherence to osteoporosis pharmacotherapy is underestimated using days supply values in electronic pharmacy claims data. Pharmacoepidemiol Drug Saf 24:67–74CrossRef
18.
go back to reference Albaum JM, Lévesque LE, Gershon AS, Liu G, Cadarette SM (2015) Glucocorticoid-induced osteoporosis management among seniors, by year, sex, and indication, 1996–2012. Osteoporos Int 26:2845–2852CrossRef Albaum JM, Lévesque LE, Gershon AS, Liu G, Cadarette SM (2015) Glucocorticoid-induced osteoporosis management among seniors, by year, sex, and indication, 1996–2012. Osteoporos Int 26:2845–2852CrossRef
19.
go back to reference Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541CrossRef Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541CrossRef
20.
go back to reference Harris ST (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA 282:1344–1352CrossRef Harris ST (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA 282:1344–1352CrossRef
21.
go back to reference Cadarette SM, Solomon DH, Katz JN, Patrick AR, Brookhart MA (2011) Adherence to osteoporosis drugs and fracture prevention: no evidence of healthy adherer bias in a frail cohort of seniors. Osteoporos Int 22:943–954CrossRef Cadarette SM, Solomon DH, Katz JN, Patrick AR, Brookhart MA (2011) Adherence to osteoporosis drugs and fracture prevention: no evidence of healthy adherer bias in a frail cohort of seniors. Osteoporos Int 22:943–954CrossRef
22.
go back to reference 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, FLEX Research Group (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the fracture intervention trial long-term extension (FLEX): a randomized trial. JAMA 296:2927–2938CrossRef 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, FLEX Research Group (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the fracture intervention trial long-term extension (FLEX): a randomized trial. JAMA 296:2927–2938CrossRef
23.
go back to reference Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, Cummings SR, Hue TF, Lippuner K, Lakatos P, Leung PC, Man Z, Martinez RLM, Tan M, Ruzycky ME, Su G, Eastell R (2012) The effect of 3 versus 6 years of Zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-pivotal fracture trial (PFT). J Bone Miner Res 27:243–254CrossRef Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, Cummings SR, Hue TF, Lippuner K, Lakatos P, Leung PC, Man Z, Martinez RLM, Tan M, Ruzycky ME, Su G, Eastell R (2012) The effect of 3 versus 6 years of Zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-pivotal fracture trial (PFT). J Bone Miner Res 27:243–254CrossRef
24.
go back to reference Curtis JR, Saag KG, Arora T, Wright NC, Yun H, Daigle S, Matthews R, Delzell E (2020) Duration of bisphosphonate drug holidays and associated fracture risk. Med Care 58:419–426CrossRef Curtis JR, Saag KG, Arora T, Wright NC, Yun H, Daigle S, Matthews R, Delzell E (2020) Duration of bisphosphonate drug holidays and associated fracture risk. Med Care 58:419–426CrossRef
25.
go back to reference LaFleur J, DuVall SL, Willson T et al (2015) Analysis of osteoporosis treatment patterns with bisphosphonates and outcomes among postmenopausal veterans. Bone 78:174–185CrossRef LaFleur J, DuVall SL, Willson T et al (2015) Analysis of osteoporosis treatment patterns with bisphosphonates and outcomes among postmenopausal veterans. Bone 78:174–185CrossRef
26.
go back to reference Paterson JM, Suleiman A, Hux JE et al (2008) How complete are drug history profiles that are based on public drug benefit claims? Can J Clin Pharmacol 15:e108–e116PubMed Paterson JM, Suleiman A, Hux JE et al (2008) How complete are drug history profiles that are based on public drug benefit claims? Can J Clin Pharmacol 15:e108–e116PubMed
28.
go back to reference Wong L, Hayes K, Cadarette S (2018) Bad to the bone: how pharmacists can help minimize drug-induced fracture risk. Pharm Pract Bus 5:18–23 Wong L, Hayes K, Cadarette S (2018) Bad to the bone: how pharmacists can help minimize drug-induced fracture risk. Pharm Pract Bus 5:18–23
29.
go back to reference Austin PC (2009) Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research. Commun Stat Simul Comput 38:1228–1234CrossRef Austin PC (2009) Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research. Commun Stat Simul Comput 38:1228–1234CrossRef
Metadata
Title
Over half of seniors who start oral bisphosphonate therapy are exposed for 3 or more years: novel rolling window approach and patterns of use
Authors
K.N. Hayes
N. He
K.A. Brown
A.M. Cheung
D.N. Juurlink
S.M. Cadarette
Publication date
01-07-2021
Publisher
Springer London
Published in
Osteoporosis International / Issue 7/2021
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-020-05794-2

Other articles of this Issue 7/2021

Osteoporosis International 7/2021 Go to the issue