{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T04:36:39Z","timestamp":1772858199719,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Oral bisphosphonates (BPs) are highly effective in preventing fractures and are recommended first-line therapies for patients with osteoporosis. We identified the incidence and predictors of oral BP treatment failure, defined as the incidence of two or more fractures while on treatment (\u22652 FWOT) among users with high adherence. Fractures were considered from 6 months after treatment initiation and up to 6 months after discontinuation. Data from computerized records and pharmacy invoices were obtained from Sistema d\u2018Informaci\u00f3 per al Desenvolupament de l\u2018Investigaci\u00f3 en Atenci\u00f3 Prim\u00e0ria (SIDIAP; Catalonia, Spain) and Danish Health Registries (Denmark) for all incident users of oral BPs in 2006-2007 and 2000-2001, respectively. Fine and Gray survival models using backward-stepwise selection (p-entry 0.049; p- exit 0.10) and accounting for the competing risk of therapy cessation were used to identify predictors of \u22652 FWOT among patients having persisted with treatment \u22656 months with overall medication possession ratio (MPR) \u226580%. Incidence of \u22652 FWOT was 2.4 (95% confidence interval [CI], 1.8 to 3.2) and 1.7 (95% CI, 1.2 to 2.2) per 1000 patient-years (PYs) within Catalonia and Denmark, respectively. Older age was predictive of \u22652 FWOT in both Catalonian and Danish cohorts: subhazard ratio (SHR)\u2009=\u20092.28 (95% CI, 1.11 to 4.68) and SHR\u2009=\u20092.61 (95% CI, 0.98 to 6.95), respectively, for 65 to &amp;lt;80 years; and SHR\u2009=\u20093.19 (95% CI, 1.33 to 7.69) and SHR\u2009=\u20094.88 (95% CI, 1.74 to 13.7), respectively, for \u226580 years. Further significant predictors of \u22652 FWOT identified within only one cohort were dementia, SHR\u2009=\u20094.46 (95% CI, 1.02 to 19.4) (SIDIAP); and history of recent or older fracture, SHR\u2009=\u20093.40 (95% CI, 1.50 to 7.68) and SHR\u2009=\u20092.08 (95% CI: 1.04-4.15), respectively (Denmark). Even among highly adherent users of oral BP therapy, a minority sustain multiple fractures while on treatment. Older age was predictive of increased risk within both study populations, as was history of recent\/old fracture and dementia within one but not both populations. Additional and\/or alternative strategies should be investigated for these patients. \u00a9 2015 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2595","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T23:24:03Z","timestamp":1436916243000},"page":"234-244","source":"Crossref","is-referenced-by-count":21,"title":["Incidence and Predictors of Multiple Fractures Despite High Adherence to Oral Bisphosphonates: A Binational Population-Based Cohort Study"],"prefix":"10.1093","volume":"31","author":[{"given":"Samuel","family":"Hawley","sequence":"first","affiliation":[{"name":"Oxford National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal SciencesUniversity of OxfordOxfordUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Kassim","family":"Javaid","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK"},{"name":"Oxford National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal SciencesUniversity of OxfordOxfordUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrine H","family":"Rubin","sequence":"additional","affiliation":[{"name":"Odense Patient Data Explorative Network (OPEN), Institute of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Judge","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK"},{"name":"Oxford National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal SciencesUniversity of OxfordOxfordUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel K","family":"Arden","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK"},{"name":"Oxford National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal SciencesUniversity of OxfordOxfordUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Vestergaard","sequence":"additional","affiliation":[{"name":"Departments of Clinical Medicine and EndocrinologyAalborg University HospitalAalborgDenmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Eastell","sequence":"additional","affiliation":[{"name":"Department of Human MetabolismUniversity of SheffieldSheffieldUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adolfo","family":"Diez-Perez","sequence":"additional","affiliation":[{"name":"Hospital del Mar Medical Research Institute (IMIM), Universitat Aut\u00f2noma de Barcelona and Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa en Envejecimiento y Fragilidad (RETICEF)Instituto de Salud Carlos IIIBarcelonaSpain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyrus","family":"Cooper","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK"},{"name":"Oxford National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal SciencesUniversity of OxfordOxfordUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Abrahamsen","sequence":"additional","affiliation":[{"name":"Research Centre for Ageing and OsteoporosisGlostrup HospitalGlostrupDenmark"},{"name":"Odense Patient Data Explorative Network (OPEN), Institute of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Prieto-Alhambra","sequence":"additional","affiliation":[{"name":"Grup de Recerca en Malalties Prevalents de l'Aparell Locomotor (GREMPAL) Research Group, Institut d'Investigaci\u00f3 en Atenci\u00f3 Prim\u00e0ria (IDIAP) Jordi Gol Primary Care Research InstituteUniversitat Aut\u00f2noma de BarcelonaBarcelonaSpain"},{"name":"Hospital del Mar Medical Research Institute (IMIM), Universitat Aut\u00f2noma de Barcelona and Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa en Envejecimiento y Fragilidad (RETICEF)Instituto de Salud Carlos IIIBarcelonaSpain"},{"name":"Medical Research Council (MRC) Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK"},{"name":"Oxford National Institute for Health Research 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