{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:26:11Z","timestamp":1764332771569,"version":"3.37.3"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":1641,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T00:00:00Z","timestamp":1568160000000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>In the randomized, placebo-controlled, double-blind phase 3 ACTIVE study (NCT01343004), 18\u2009months of abaloparatide 80\u2009\u03bcg daily (subcutaneous injection) in postmenopausal women at risk of osteoporotic fracture significantly reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and significantly increased bone mineral density (BMD) versus placebo regardless of baseline risk factors. Women from the abaloparatide and placebo groups who completed ACTIVE were eligible for ACTIVExtend (NCT01657162), in which all enrollees received sequential, open-label monotherapy with alendronate 70\u2009mg once weekly for up to 24\u2009months. This prespecified analysis evaluated whether fracture risk reductions and bone mineral density (BMD) gains associated with abaloparatide during ACTIVE persisted through the full 43-month ACTIVE\u2013ACTIVExtend study period in nine prespecified baseline risk subgroups. Baseline risk subgroups included BMD T-score at the lumbar spine, total hip, and femoral neck (\u2264\u2009\u2212\u20092.5 versus &amp;gt;\u2009\u2212\u20092.5 and\u2009\u2264\u2009\u22123.0 versus &amp;gt;\u2009\u2212\u20093.0), history of nonvertebral fracture (yes\/no), prevalent vertebral fracture (yes\/no), and age (&amp;lt;65 versus 65 to &amp;lt;75 versus \u226575\u2009years). Forest plots display treatment effect. Treatment-by-subgroup interactions were tested using the Breslow-Day test, Cox proportional hazards model, and ANCOVA model. After the combined ACTIVE\u2013ACTIVExtend study period, reductions in relative risk for new vertebral, nonvertebral, clinical, and major osteoporotic fractures were greater among patients in the abaloparatide\/alendronate group than among those in the placebo\/alendronate group across all nine baseline risk subgroups. BMD gains at the lumbar spine, total hip, and femoral neck were greater in the abaloparatide\/alendronate group versus the placebo\/alendronate group. No clinically meaningful interaction between treatment assignment and any baseline risk variable was observed. The sequence of abaloparatide for 18\u2009months followed by alendronate for up to 24\u2009months appears to be an effective treatment option for a wide range of postmenopausal women at risk for osteoporotic fractures. \u00a9 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jbmr.3848","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T14:16:30Z","timestamp":1565792190000},"page":"2213-2219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Fracture and Bone Mineral Density Response by Baseline Risk in Patients Treated With Abaloparatide Followed by Alendronate: Results From the Phase 3 ACTIVExtend Trial"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2051-0505","authenticated-orcid":false,"given":"Benjamin Z","family":"Leder","sequence":"first","affiliation":[{"name":"Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Zapalowski","sequence":"additional","affiliation":[{"name":"Radius Health, Inc. Waltham MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Yi","family":"Hu","sequence":"additional","affiliation":[{"name":"Radius Health, Inc. Waltham MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Hattersley","sequence":"additional","affiliation":[{"name":"Radius Health, Inc. Waltham MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy E","family":"Lane","sequence":"additional","affiliation":[{"name":"School of Medicine University of California at Davis Sacramento CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea J","family":"Singer","sequence":"additional","affiliation":[{"name":"Medstar Georgetown University Hospital Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin K","family":"Dore","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine University of California at Los Angeles Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,8,14]]},"reference":[{"year":"2017","author":"Radius Health, Inc. Tymlos (abaloparatide) [prescribing information]","key":"2024021014411284000_jbmr3848-bib-0001"},{"issue":"7","key":"2024021014411284000_jbmr3848-bib-0002","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1001\/jama.2016.11136","article-title":"Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial","volume":"316","author":"Miller","year":"2016","journal-title":"JAMA."},{"issue":"1","key":"2024021014411284000_jbmr3848-bib-0003","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/jbmr.2991","article-title":"Effects of abaloparatide-SC on fractures and bone mineral density in subgroups of postmenopausal women with osteoporosis and varying baseline risk factors","volume":"32","author":"Cosman","year":"2017","journal-title":"J Bone Miner Res."},{"issue":"8","key":"2024021014411284000_jbmr3848-bib-0004","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1002\/jbmr.3163","article-title":"The effect of abaloparatide-SC on fracture risk is independent of baseline FRAX fracture probability: a post hoc analysis of the ACTIVE study","volume":"32","author":"McCloskey","year":"2017","journal-title":"J Bone Miner Res."},{"issue":"8","key":"2024021014411284000_jbmr3848-bib-0005","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1210\/jc.2018-00163","article-title":"ACTIVExtend: 24 months of alendronate after 18 months of abaloparatide or placebo for postmenopausal osteoporosis","volume":"103","author":"Bone","year":"2018","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2024021014411284000_jbmr3848-bib-0006","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1056\/NEJMoa050336","article-title":"One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis","volume":"353","author":"Black","year":"2005","journal-title":"N Engl J Med."},{"issue":"9999","key":"2024021014411284000_jbmr3848-bib-0007","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0140-6736(15)61120-5","article-title":"Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-switch study): extension of a randomised controlled trial","volume":"386","author":"Leder","year":"2015","journal-title":"Lancet."},{"issue":"4","key":"2024021014411284000_jbmr3848-bib-0008","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1359\/jbmr.081215","article-title":"Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final results of the randomized, controlled European Study of Forsteo (EUROFORS)","volume":"24","author":"Eastell","year":"2009","journal-title":"J Bone Miner Res."},{"issue":"1","key":"2024021014411284000_jbmr3848-bib-0009","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1359\/jbmr.2003.18.1.18","article-title":"The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis","volume":"18","author":"Marcus","year":"2003","journal-title":"J Bone Miner Res."},{"key":"2024021014411284000_jbmr3848-bib-0010","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00774-013-0505-2","article-title":"Once-weekly teriparatide reduces the risk of vertebral fracture in patients with various fracture risks: subgroup analysis of the Teriparatide Once-Weekly Efficacy Research (TOWER) trial","volume":"32","author":"Nagano","year":"2014","journal-title":"J Bone Miner Metab"},{"issue":"9","key":"2024021014411284000_jbmr3848-bib-0011","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1210\/jc.2008-2765","article-title":"Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density","volume":"94","author":"Eastell","year":"2009","journal-title":"J Clin Endocrinol Metab."},{"issue":"1","key":"2024021014411284000_jbmr3848-bib-0012","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/jbmr.536","article-title":"Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis","volume":"27","author":"McClung","year":"2012","journal-title":"J Bone Miner Res."},{"key":"2024021014411284000_jbmr3848-bib-0013","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","article-title":"Romosozumab treatment in postmenopausal women with osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"N Engl J Med."},{"issue":"6","key":"2024021014411284000_jbmr3848-bib-0014","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00223-017-0375-z","article-title":"Geography of fracture incidence in postmenopausal women with osteoporosis treated with abaloparatide","volume":"102","author":"McClung","year":"2018","journal-title":"Calcif Tissue Int."}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.3848","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbmr.3848","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbmr.3848","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/34\/12\/2213\/56653800\/jbmr3848.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/34\/12\/2213\/56653800\/jbmr3848.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:04:45Z","timestamp":1710342285000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/34\/12\/2213-2219\/7380871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,14]]},"references-count":14,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,8,14]]},"published-print":{"date-parts":[[2019,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.3848","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"type":"print","value":"0884-0431"},{"type":"electronic","value":"1523-4681"}],"subject":[],"published-other":{"date-parts":[[2019,12,1]]},"published":{"date-parts":[[2019,8,14]]},"assertion":[{"value":"2019-04-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}