{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:22:31Z","timestamp":1760235751007,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Only a few studies are available on the effect of the dosing interval of bisphosphonate on drug compliance. We analyzed the data of patients who were newly prescribed bisphosphonate using a national insurance claims database. Drug compliance was assessed by calculating medication possession ratio (MPR) over a minimum of a 1-year follow-up. This analysis included 281,996 new bisphosphonate users with a mean age of 68.9 years (92% women). The patients were divided into daily, weekly, monthly, 3-monthly, and switch groups (who changed the drug to other dosing intervals). The average MPR was the highest in the switch group (66%), and the longer the dosing interval, the higher the compliance (3-monthly, 56% vs. daily, 37%). \u201cNon-compliant\u201d was defined as an MPR under 80%. Various factors which were possibly associated with \u201cnon-compliant\u201d MPR were investigated using multiple regression analysis. Multivariate analysis showed that male patients were more likely to be non-compliant with pharmacotherapy than female patients, with as odds ratio of 1.389. Younger patients had a significantly lower likelihood of being non-compliant than older patients for age 60\u201369 vs. age 80+. Long dosing intervals were recommended to improve compliance and special attention was given to older and male patients.<\/jats:p>","DOI":"10.3390\/jcm10194350","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T20:15:32Z","timestamp":1632514532000},"page":"4350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Dosing Interval on Compliance of Osteoporosis Patients on Bisphosphonate Therapy: Observational Study Using Nationwide Insurance Claims Data"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0957-0988","authenticated-orcid":false,"given":"Hyunil","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Ilsan Paik Hospital, Inje University, Goyang 10380, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangcheol","family":"Lee","sequence":"additional","affiliation":[{"name":"CHA Bundang Medical Center, Department of Orthopaedic Surgery, CHA University School of Medicine, Pocheon-si 13488, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dokyung","family":"Kim","sequence":"additional","affiliation":[{"name":"CHA Bundang Medical Center, Department of Orthopaedic Surgery, CHA University School of Medicine, Pocheon-si 13488, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weonmin","family":"Cho","sequence":"additional","affiliation":[{"name":"CHA Bundang Medical Center, Department of Orthopaedic Surgery, CHA University School of Medicine, Pocheon-si 13488, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungtan","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Ilsan Paik Hospital, Inje University, Goyang 10380, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyeong","family":"Yoon","sequence":"additional","affiliation":[{"name":"CHA Bundang Medical Center, Department of Orthopaedic Surgery, CHA University School of Medicine, Pocheon-si 13488, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soonchul","family":"Lee","sequence":"additional","affiliation":[{"name":"CHA Bundang Medical Center, Department of Orthopaedic Surgery, CHA University School of Medicine, Pocheon-si 13488, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1007\/s00198-006-0172-4","article-title":"An estimate of the worldwide prevalence and disability associated with osteoporotic fractures","volume":"17","author":"Johnell","year":"2006","journal-title":"Osteoporos Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1359\/jbmr.061113","article-title":"Incidence and economic burden of osteoporosis-related fractures in the United States, 2005\u20132025","volume":"22","author":"Burge","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.bone.2012.02.007","article-title":"Prevalence, awareness, and treatment of osteoporosis among Korean women: The Fourth Korea National Health and Nutrition Examination Survey","volume":"50","author":"Kim","year":"2012","journal-title":"Bone"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.4055\/cios.2014.6.1.56","article-title":"Prevalence of Osteoporotic Vertebral Compression Fractures in Korean Post Menopausal Women Study, G. Influence of insurance benefit criteria on the administration rate of osteoporosis drugs in postmenopausal females","volume":"6","author":"Lee","year":"2014","journal-title":"Clin. Orthop. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.amjmed.2008.12.002","article-title":"Impact of osteoporosis treatment adherence on fracture rates in North America and Europe","volume":"122","author":"Siris","year":"2009","journal-title":"Am. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1001\/archinte.165.20.2414","article-title":"Compliance with osteoporosis medications","volume":"165","author":"Solomon","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00198-011-1620-3","article-title":"Treatment satisfaction and persistence among postmenopausal women on osteoporosis medications: 12-month results from POSSIBLE US","volume":"23","author":"Wade","year":"2012","journal-title":"Osteoporos Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jsps.2017.12.005","article-title":"Changes in the utilization of osteoporosis drugs after the 2010 FDA bisphosphonate drug safety communication","volume":"26","author":"Balkhi","year":"2018","journal-title":"Saudi Pharm. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00223-012-9668-4","article-title":"A novel monthly dosing regimen of risedronate for the treatment of postmenopausal osteoporosis: 2-year data","volume":"92","author":"McClung","year":"2013","journal-title":"Calcif. Tissue Int."},{"key":"ref_10","first-page":"12","article-title":"Preventing nonvertebral osteoporotic fractures with extended-interval bisphosphonates: Regimen selection and clinical application","volume":"11","author":"Cole","year":"2009","journal-title":"Medscape J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12933-020-01060-1","article-title":"Comparison of heart failure risk and medical costs between patients with type 2 diabetes mellitus treated with dapagliflozin and dipeptidyl peptidase-4 inhibitors: A nationwide population-based cohort study","volume":"19","author":"Seong","year":"2020","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"200","DOI":"10.4055\/cios19095","article-title":"Comparison of the Prevalence of Low Back Pain and Related Spinal Diseases among Smokers and Nonsmokers: Using Korean National Health Insurance Database","volume":"12","author":"Kwon","year":"2020","journal-title":"Clin. Orthop. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/iid3.316","article-title":"Seasonality of allergic diseases: Real-world evidence from a nationwide population-based study","volume":"8","author":"Lee","year":"2020","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"730","DOI":"10.3340\/jkns.2020.0007","article-title":"The Influence of Comorbidities on Reoperations Following Primary Surgery of Lumbar Degenerative Diseases: A Nationwide Population-Based Retrospective Cohort Study from 2009\u20132016","volume":"63","author":"Park","year":"2020","journal-title":"J. Korean Neurosurg. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1524-4733.2007.00213.x","article-title":"Medication compliance and persistence: Terminology and definitions","volume":"11","author":"Cramer","year":"2008","journal-title":"Value Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1524-4733.2006.00139.x","article-title":"A checklist for medication compliance and persistence studies using retrospective databases","volume":"10","author":"Peterson","year":"2007","journal-title":"Value Health"},{"key":"ref_17","first-page":"450","article-title":"Medication adherence and use of generic drug therapies","volume":"15","author":"Briesacher","year":"2009","journal-title":"Am. J. Manag. Care."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1185\/03007990903126833","article-title":"Good and poor adherence: Optimal cut-point for adherence measures using administrative claims data","volume":"25","author":"Karve","year":"2009","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/00031305.2015.1069760","article-title":"The p-Value You Can\u2019t Buy","volume":"70","author":"Demidenko","year":"2016","journal-title":"Am. Stat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1517\/14656560903140533","article-title":"Poor adherence to oral bisphosphonate treatment and its consequences: A review of the evidence","volume":"10","author":"Rabenda","year":"2009","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s11657-015-0231-6","article-title":"Compliance and persistence with daily, weekly, and monthly bisphosphonates for osteoporosis in Japan: Analysis of data from the CISA","volume":"10","author":"Kishimoto","year":"2015","journal-title":"Arch. Osteoporosis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"856","DOI":"10.4065\/80.7.856","article-title":"Effect of dosing frequency on bisphosphonate medication adherence in a large longitudinal cohort of women","volume":"80","author":"Recker","year":"2005","journal-title":"Mayo Clin. Proc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1185\/030079905X61875","article-title":"Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis","volume":"21","author":"Cramer","year":"2005","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00198-007-0506-x","article-title":"Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women","volume":"19","author":"Rabenda","year":"2008","journal-title":"Osteoporos Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1185\/030079906X112688","article-title":"The impact of dosing frequency on compliance and persistence with bisphosphonates among postmenopausal women in the UK: Evidence from three databases","volume":"22","author":"Brankin","year":"2006","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.aott.2016.07.001","article-title":"Influence of patient training on persistence, compliance, and tolerability of different dosing frequency regimens of bisphosphonate therapy: An observational study in Turkish patients with postmenopausal osteoporosis","volume":"50","author":"Akarirmak","year":"2016","journal-title":"Acta Orthop. Traumatol. Turc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1111\/j.1742-1241.2006.01059.x","article-title":"Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: Results from the PERSIST study","volume":"60","author":"Cooper","year":"2006","journal-title":"Int. J. Clin. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s00198-011-1729-4","article-title":"A retrospective analysis of extended-interval dosing and the impact on bisphosphonate compliance in the US Military Health System","volume":"23","author":"Devine","year":"2012","journal-title":"Osteoporos Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.amjmed.2009.05.017","article-title":"Adoption of once-monthly oral bisphosphonates and the impact on adherence","volume":"123","author":"Briesacher","year":"2010","journal-title":"Am. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1185\/030079907X226069","article-title":"Persistence across weekly and monthly bisphosphonates: Analysis of US retail pharmacy prescription refills","volume":"23","author":"Weiss","year":"2007","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.bone.2011.12.021","article-title":"Medication adherence and fracture risk among patients on bisphosphonate therapy in a large United States health plan","volume":"50","author":"Wade","year":"2012","journal-title":"Bone"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s11657-017-0316-5","article-title":"Two-year persistence and compliance with osteoporosis therapies among postmenopausal women in a commercially insured population in the United States","volume":"12","author":"Durden","year":"2017","journal-title":"Arch. Osteoporos."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/S0149-2918(01)80109-0","article-title":"A systematic review of the associations between dose regimens and medication compliance","volume":"23","author":"Claxton","year":"2001","journal-title":"Clin. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1097\/MLR.0b013e31829b1d2a","article-title":"Standardizing terminology and definitions of medication adherence and persistence in research employing electronic databases","volume":"51","author":"Raebel","year":"2013","journal-title":"Med. Care"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/pds.1230","article-title":"Methods for evaluation of medication adherence and persistence using automated databases","volume":"15","author":"Andrade","year":"2006","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/dme.12651","article-title":"Adherence to diabetes medication: A systematic review","volume":"32","author":"Krass","year":"2015","journal-title":"Diabet Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1007\/s00198-015-3084-3","article-title":"Long-term persistence with anti-osteoporosis drugs after fracture","volume":"26","author":"Klop","year":"2015","journal-title":"Osteoporos. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11657-017-0331-6","article-title":"Cessation rate of anti-osteoporosis treatments and risk factors in Spanish primary care settings: A population-based cohort analysis","volume":"12","year":"2017","journal-title":"Arch. Osteoporos."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"McCarney, R., Warner, J., Iliffe, S., van Haselen, R., Griffin, M., and Fisher, P. (2007). The Hawthorne Effect: A randomised, controlled trial. BMC Med. Res. Methodol., 7.","DOI":"10.1186\/1471-2288-7-30"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1089\/jwh.2012.3972","article-title":"Influence of patient sex and gender on medication use, adherence, and prescribing alignment with guidelines","volume":"23","author":"Manteuffel","year":"2014","journal-title":"J. Womens Health"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"293","DOI":"10.4040\/jkan.2015.45.2.293","article-title":"Gender difference in osteoporosis prevalence, awareness and treatment: Based on the Korea national health and nutrition examination survey 2008\u20132011","volume":"45","author":"Kim","year":"2015","journal-title":"J. Korean Acad. Nurs."},{"key":"ref_42","first-page":"319","article-title":"Trends in drug prescribing for osteoporosis after hip fracture, 1995\u20132004","volume":"35","author":"Cadarette","year":"2008","journal-title":"J. Rheumatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s00774-018-0904-5","article-title":"Gender differences in anti-osteoporosis drug treatment after osteoporotic fractures","volume":"37","author":"Jung","year":"2019","journal-title":"J. Bone Miner. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00198-008-0651-x","article-title":"Initiation of anti-osteoporotic therapy in patients with recent fractures: A nationwide analysis of prescription rates and persistence","volume":"20","author":"Roerholt","year":"2009","journal-title":"Osteoporos Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"194","DOI":"10.4065\/80.2.194","article-title":"Medication use patterns for osteoporosis: An assessment of guidelines, treatment rates, and quality improvement interventions","volume":"80","author":"Solomon","year":"2005","journal-title":"Mayo Clin. Proc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1177\/1090198107301331","article-title":"Osteoporosis health beliefs among younger and older men and women","volume":"35","author":"McLeod","year":"2008","journal-title":"Health Educ Behav."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/00006416-200019030-00006","article-title":"Osteoporosis in older men: Knowledge and health beliefs","volume":"19","author":"Sedlak","year":"2000","journal-title":"Orthop Nurs."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/S0140-6736(98)09075-8","article-title":"Mortality after all major types of osteoporotic fracture in men and women: An observational study","volume":"353","author":"Center","year":"1999","journal-title":"Lancet"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.2106\/JBJS.G.00864","article-title":"Low incidence of anti-osteoporosis treatment after hip fracture","volume":"90","author":"Rabenda","year":"2008","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1359\/jbmr.080606","article-title":"Long-term survival and fracture risk after hip fracture: A 22-year follow-up in women","volume":"23","author":"Besjakov","year":"2008","journal-title":"J. Bone Miner. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s11914-011-0064-1","article-title":"Minor, major, low-trauma, and high-trauma fractures: What are the subsequent fracture risks and how do they vary?","volume":"9","author":"Warriner","year":"2011","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00198-014-2871-6","article-title":"Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: Interim results from a prospective observational study","volume":"26","author":"Silverman","year":"2015","journal-title":"Osteoporos. Int."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/19\/4350\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:04:23Z","timestamp":1760166263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/19\/4350"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,24]]},"references-count":52,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["jcm10194350"],"URL":"https:\/\/doi.org\/10.3390\/jcm10194350","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2021,9,24]]}}}