Top

Archives of Osteoporosis

Published in:

01-12-2021 | Care | Original Article

Insufficient persistence to pharmacotherapy in Japanese patients with osteoporosis: an analysis of the National Database of Health Insurance Claims and Specific Health Checkups in Japan

Authors: Shinichi Nakatoh, Kenji Fujimori, Shigeyuki Ishii, Junko Tamaki, Nobukazu Okimoto, Sumito Ogawa, Masayuki Iki

Published in: Archives of Osteoporosis | Issue 1/2021

Abstract

Summary

In Japan, persistence and the 2-year MPR were inadequate in increasing fracture control efficacy despite a high adherence rate during the treatment period. Both factors were higher in females and those with polypharmacy but worsened with increasing age.

Purpose

Only a few large-scale studies have examined the care gap between the patients who need osteoporosis treatment and those who receive them in Japan. The aim of this study was to investigate the persistence and adherence to osteoporosis pharmacotherapy in Japan.

Methods

Continuation (persistence) rates and adherence to osteoporosis pharmacotherapy were investigated using medical insurance data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, between April 2012 and March 2019.

Results

The study included 528,806 male and 3,064,410 female patients. Persistence proportions were 56.6% in the first year and 46.3% in the second year. The medication possession ratio (MPR) from start to discontinuation of treatment (MPR_discon) was 94.5%, and 92.7% of patients had an MPR_discon ≥ 80%. The 2-year MPR (MPR₇₃₀) was 61.9%, and 49.6% of patients had an MPR₇₃₀ ≥ 80%. Both the persistence proportion and MPR₇₃₀ were higher in females than in males, whereas MPR_discon was higher in males. The persistence proportion and MPR₇₃₀ were highest in the 70–79 years age group, whereas MPR_discon improved with increasing age. The MPR_discon and MPR₇₃₀ were higher in the mixed-fracture and vertebral-fracture groups, respectively. The persistence proportion, MPR_discon, and MPR₇₃₀ were higher in patients with polypharmacy than in those without.

Conclusion

In Japan, persistence and the 2-year MPR were inadequate in increasing fracture control efficacy despite a high adherence rate during the treatment period. To bridge the care gap following osteoporosis pharmacotherapy, improvements are required for males, the elderly, and those without polypharmacy.

Melton LJ 3rd, Achenbach SJ, Atkinson EJ, Therneau TM, Amin S (2013) Long-term mortality following fractures at different skeletal sites: a population-based cohort study. Osteoporos Int 24:1689–1696. https://doi.org/10.1007/s00198-012-2225-1CrossRefPubMed

Svedbom A, Borgstöm F, Hernlund E, Ström O, Alekna V, Bianchi ML, Clark P, Curiel MD, Dimai HP, Jürisson M, Kallikorm R, Lember M, Lesnyak O, McCloskey E, Sanders KM, Silverman S, Solodovnikov A, Tamulaitiene M, Thomas T, Toroptsova N, Uusküla A, Tosteson ANA, Jönsson B, Kanis JA (2018) Quality of life for up to 18 months after low-energy hip, vertebral, and distal forearm fractures-results from the ICUROS. Osteoporos Int 29:557–566. https://doi.org/10.1007/s00198-017-4317-4CrossRefPubMed

Orimo H, Yaegashi Y, Hosoi T, Fukushima Y, Onoda T, Hashimoto T, Sakata K (2016) Hip fracture incidence in Japan: estimates of new patients in 2012 and 25-year trends. Osteoporos Int 27:1777–1784. https://doi.org/10.1007/s00198-015-3464-8CrossRefPubMedPubMedCentral

Cheung CL, Ang SB, Chadha M, Chow ES, Chung YS, Hew FL, Jaisamrarn U, Ng H, Takeuchi Y, Wu CH, Xia W, Yu J, Fujiwara S (2018) An updated hip fracture projection in Asia: The Asian Federation of Osteoporosis Societies study. Osteoporos Sarcopenia 4:16–21. https://doi.org/10.1016/j.afos.2018.03.003CrossRefPubMedPubMedCentral

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. Fracture Intervention Trial Research Group. Lancet 348:1535–1541. https://doi.org/10.1016/s0140-6736(96)07088-2CrossRefPubMed

McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY, Hip Intervention Program Study Group (2001) Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 344:333–340. https://doi.org/10.1056/NEJM200102013440503CrossRefPubMed

Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C, FREEDOM Trial (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765. https://doi.org/10.1056/NEJMoa0809493CrossRefPubMed

Kanis JA, Cooper C, Rizzoli R, Reginster JY, Scientific Advisory Board of the European Society for C, Economic Aspects of O (2019) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 30:3–44. https://doi.org/10.1007/s00198-018-4704-5CrossRefPubMed

Chen YC, Lin WC (2017) Poor 1st-year adherence to anti-osteoporotic therapy increases the risk of mortality in patients with magnetic resonance imaging-proven acute osteoporotic vertebral fractures. Patient Prefer Adherence 11:839–843. https://doi.org/10.2147/PPA.S131564CrossRefPubMedPubMedCentral

10.

Kanis JA, Cooper C, Hiligsmann M, Rabenda V, Reginster JY, Rizzoli R (2011) Partial adherence: a new perspective on health economic assessment in osteoporosis. Osteoporos Int 22:2565–2573. https://doi.org/10.1007/s00198-011-1668-0CrossRefPubMed

11.

Hiligsmann M, McGowan B, Bennett K, Barry M, Reginster JY (2012) The clinical and economic burden of poor adherence and persistence with osteoporosis medications in Ireland. Value Health 15:604–612. https://doi.org/10.1016/j.jval.2012.02.001CrossRefPubMed

12.

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 14:571–581. https://doi.org/10.1016/j.jval.2010.11.010CrossRefPubMed

13.

Imaz I, Zegarra P, González-Enríquez 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 21:1943–1951. https://doi.org/10.1007/s00198-009-1134-4CrossRefPubMed

14.

Fatoye F, Smith P, Gebrye T, Yeowell G (2019) Real-world persistence and adherence with oral bisphosphonates for osteoporosis: a systematic review. BMJ Open 9:e027049. https://doi.org/10.1136/bmjopen-2018-027049CrossRefPubMedPubMedCentral

15.

Yeam CT, Chia S, Tan HCC, Kwan YH, Fong W, Seng JJB (2018) A systematic review of factors affecting medication adherence among patients with osteoporosis. Osteoporos Int 29:2623–2637. https://doi.org/10.1007/s00198-018-4759-3CrossRefPubMed

16.

Fardellone P, Lello S, Cano A, de Sá ME, 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 41:1576–1588. https://doi.org/10.1016/j.clinthera.2019.05.001CrossRefPubMed

17.

van Boven JF, de Boer PT, Postma MJ, Vegter S (2013) Persistence with osteoporosis medication among newly-treated osteoporotic patients. J Bone Miner Metab 31:562–570. https://doi.org/10.1007/s00774-013-0440-2CrossRefPubMed

18.

Keshishian A, Boytsov N, Burge R, Krohn K, Lombard L, Zhang X, Xie L, Baser O (2017) Examining the effect of medication adherence on risk of subsequent fracture among women with a fragility fracture in the U.S. Medicare population. J Manag Care Spec Pharm 23:1178–1190. https://doi.org/10.18553/jmcp.2017.17054CrossRefPubMed

19.

Nakatoh S, Fujimori K, Tamaki J, Okimoto N, Ogawa S, Iki M (2021) Insufficient persistence of and adherence to osteoporosis pharmacotherapy in Japan. J Bone Miner Metab. https://doi.org/10.1007/s00774-020-01188-wCrossRefPubMed

20.

Sato M, Tsujimoto M, Kajimoto K, Uetake H, Shimoda H, Fujiwara S (2018) Effect of a patient-support program on once-daily teriparatide adherence and persistence in the Japan Fracture Observational Study (JFOS). Arch Osteoporos 13:74. https://doi.org/10.1007/s11657-018-0487-8CrossRefPubMedPubMedCentral

21.

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. https://doi.org/10.1007/s11657-015-0231-6CrossRefPubMed

22.

Sakai A, Ikeda S, Okimoto N, Matsumoto H, Teshima K, Okazaki Y, Fukuda F, Arita S, Tsurukami H, Nagashima M, Yoshioka T (2014) Clinical efficacy and treatment persistence of monthly minodronate for osteoporotic patients unsatisfied with, and shifted from, daily or weekly bisphosphonates: the BP-MUSASHI study. Osteoporos Int 25:2245–2253. https://doi.org/10.1007/s00198-014-2756-8CrossRefPubMedPubMedCentral

23.

Ministry of Health, Labour, and Welfare. The popularization and state of electronic receipt claims https://www.mhlw.go.jp/file/06-Seisakujouhou-12400000-Hokenkyoku/0000099002.pdf. (in Japanese) Accessed March 09, 2021

24.

Desai RJ, Mahesri M, Abdia Y, Barberio J, Tong A, Zhang D, Mavros P, Kim SC, Franklin JM (2018) Association of osteoporosis medication use after hip fracture with prevention of subsequent nonvertebral fractures: an instrumental variable analysis. JAMA Netw Open 1:e180826. https://doi.org/10.1001/jamanetworkopen.2018.0826CrossRefPubMedPubMedCentral

25.

Cheung MY, Ho AW, Wong SH (2018) Post-fracture care gap: a retrospective population-based analysis of Hong Kong from 2009 to 2012. Hong Kong Med J 24:579–583. https://doi.org/10.12809/hkmj187227CrossRefPubMed

26.

Nakatoh S, Fujimori K, Tamaki J, Okimoto N, Ogawa S, Iki M (2020) Insufficient increase in bone mineral density testing rates and pharmacotherapy after hip fracture in Japan Journal of Bone and Mineral Metabolism. J Bone Miner Metab 38:589–596. https://doi.org/10.1007/s00774-020-01093-2CrossRefPubMed

27.

Durden E, Pinto L, Lopez-Gonzalez L, Juneau P, Barron R (2017) Two-year persistence and compliance with osteoporosis therapies among postmenopausal women in a commercially insured population in the United States. Arch Osteoporos 12:22. https://doi.org/10.1007/s11657-017-0316-5CrossRefPubMedPubMedCentral

28.

Reyes C, Tebe C, Martinez-Laguna D, Ali MS, Soria-Castro A, Carbonell C, Prieto-Alhambra D (2017) One and two-year persistence with different anti-osteoporosis medications: a retrospective cohort study. Osteoporos Int 28:2997–3004. https://doi.org/10.1007/s00198-017-4144-7CrossRefPubMed

29.

Neele SJ, Evertz R, De Valk-De RG, Roos JC, Netelenbos JC (2002) Effect of 1 year of discontinuation of raloxifene or estrogen therapy on bone mineral density after 5 years of treatment in healthy postmenopausal women. Bone 30:599–603. https://doi.org/10.1016/s8756-3282(01)00706-2CrossRefPubMed

30.

Prince R, Sipos A, Hossain A, Syversen U, Ish-Shalom S, Marcinowska E, Halse J, Lindsay R, Dalsky GP, Mitlak BH (2005) Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res 20:1507–1513. https://doi.org/10.1359/JBMR.050501CrossRefPubMed

31.

Watts NB, Chines A, Olszynski WP, McKeever CD, McClung MR, Zhou X, Grauer A (2008) Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporos Int 19:365–372. https://doi.org/10.1007/s00198-007-0460-7CrossRefPubMed

32.

Nakatoh S (2017) Bone turnover rate and bone formation/resorption balance during the early stage after switching from a bone resorption inhibitor to denosumab are predictive factors of bone mineral density change. Osteoporos Sarcopenia 3:45–52. https://doi.org/10.1016/j.afos.2016.12.001CrossRefPubMedPubMedCentral

33.

Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O (2017) Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases. J Bone Miner Res 32:1291–1296. https://doi.org/10.1002/jbmr.3110CrossRefPubMed

34.

McClung MR, Wagman RB, Miller PD, Wang A, Lewiecki EM (2017) Observations following discontinuation of long-term denosumab therapy. Osteoporos Int 28:1723–1732. https://doi.org/10.1007/s00198-017-3919-1CrossRefPubMedPubMedCentral

35.

Modi A, Sajjan S, Insinga R, Weaver J, Lewiecki EM, Harris ST (2017) Frequency of discontinuation of injectable osteoporosis therapies in US patients over 2 years. Osteoporos Int 28:1355–1363. https://doi.org/10.1007/s00198-016-3886-yCrossRefPubMed

36.

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. https://doi.org/10.4065/81.8.1013CrossRefPubMed

37.

Papaioannou A, Kennedy CC, Dolovich L, Lau E, Adachi JD (2007) Patient adherence to osteoporosis medications: problems, consequences and management strategies. Drugs Aging 24:37–55. https://doi.org/10.2165/00002512-200724010-00003CrossRefPubMed

38.

Dyer SM, Crotty M, Fairhall N, Magaziner J, Beaupre LA, Cameron ID, Sherrington C, Fragility Fracture Network (FFN) Rehabilitation Research Special Interest Group (2016) A critical review of the long-term disability outcomes following hip fracture. BMC Geriatr 16:158. https://doi.org/10.1186/s12877-016-0332-0CrossRefPubMedPubMedCentral

39.

Roerholt C, Eiken P, Abrahamsen B (2009) Initiation of anti-osteoporotic therapy in patients with recent fractures: a nationwide analysis of prescription rates and persistence. Osteoporos Int 20:299–307. https://doi.org/10.1007/s00198-008-0651-xCrossRefPubMed

40.

Cooper C, Atkinson EJ, Jacobsen SJ, O’Fallon WM, Melton LJ 3rd (1993) Population-based study of survival after osteoporotic fractures. Am J Epidemiol 137:1001–1005. https://doi.org/10.1093/oxfordjournals.aje.a116756CrossRefPubMed

41.

Lee SB, Park Y, Kim DW, Kwon JW, Ha JW, Yang JH, Lee BH, Suk KS, Moon SH, Kim HS, Lee HM (2020) Association between mortality risk and the number, location, and sequence of subsequent fractures in the elderly. Osteoporos Int. https://doi.org/10.1007/s00198-020-05602-xCrossRefPubMedPubMedCentral

42.

Iversen MD, Vora RR, Servi A, Solomon DH (2011) Factors affecting adherence to osteoporosis medications: a focus group approach examining viewpoints of patients and providers. J Geriatr Phys Ther 34:72–81. https://doi.org/10.1097/JPT.0b013e3181ff03b4CrossRefPubMedPubMedCentral

43.

Forbes CA, Deshpande S, Sorio-Vilela F, Kutikova L, Duffy S, Gouni-Berthold I, Hagström E (2018) A systematic literature review comparing methods for the measurement of patient persistence and adherence. Curr Med Res Opin 34:1613–1625. https://doi.org/10.1080/03007995.2018.1477747CrossRefPubMed

44.

Cornelissen D, de Kunder S, Si L, Reginster JY, Evers S, Boonen A, Hiligsmann M, European Society for Clinical and Economic Aspect of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) (2020) Interventions to improve adherence to anti-osteoporosis medications: an updated systematic review. Osteoporos Int 31:1645–1669. https://doi.org/10.1007/s00198-020-05378-0CrossRefPubMedPubMedCentral

Title: Insufficient persistence to pharmacotherapy in Japanese patients with osteoporosis: an analysis of the National Database of Health Insurance Claims and Specific Health Checkups in Japan
Authors: Shinichi Nakatoh
Kenji Fujimori
Shigeyuki Ishii
Junko Tamaki
Nobukazu Okimoto
Sumito Ogawa
Masayuki Iki
Publication date: 01-12-2021
Publisher: Springer London
Keywords: Care
Osteoporosis
Osteoporosis
Published in: Archives of Osteoporosis / Issue 1/2021
Print ISSN: 1862-3522
Electronic ISSN: 1862-3514
DOI: https://doi.org/10.1007/s11657-021-00993-8

At a glance: The STEP trials

Springer Medicine

Insufficient persistence to pharmacotherapy in Japanese patients with osteoporosis: an analysis of the National Database of Health Insurance Claims and Specific Health Checkups in Japan

Abstract

Summary

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

Does the relationship between 25-hydroxyvitamin D status and bone mass vary according to skin color in adults? Results of a Brazilian population-based study

Joint position statement on management of patient with osteoporosis during COVID-19 contingency from the AMMOM, CONAMEGER, FELAEN, FEMECOG, FEMECOT, and ICAAFYD

Comparison of the NOF and NOGG guidelines for spinal radiographic examination in postmenopausal Chinese women

Predictors of hip fracture mortality in Ghana: a single-center prospective study

Performance of HR-pQCT, DXA, and FRAX in the discrimination of asymptomatic vertebral fracture in postmenopausal Chinese women

Correlation of oxidative stress-related biomarkers with postmenopausal osteoporosis: a systematic review and meta-analysis