{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T06:30:35Z","timestamp":1767162635741,"version":"build-2238731810"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Decline of bone mineral density (BMD) during menopause is related to increased risk of fractures in postmenopausal women, however, this relationship in premenopausal women has not been established. To quantify this relationship, real\u2010world data (RWD) from the National Health and Nutrition Examination Survey (NHANES), and longitudinal data from the elagolix phase III clinical trials were modeled across a wide age range, and covariates were evaluated. The natural changes in femoral neck BMD (FN\u2010BMD) were well\u2010described by a bi\u2010exponential relationship with first\u2010order BMD formation (k\n                    <jats:sub>1<\/jats:sub>\n                    ) and resorption (k\n                    <jats:sub>2<\/jats:sub>\n                    ) rate constants. Body mass index (BMI) and race (i.e., Black) were significant predictors indicating that patients with high BMI or Black race experience a relatively lower BMD loss. Simulations suggest that untreated premenopausal women with uterine fibroids (UFs) from elagolix phase III clinical trials (median age 43 years [minimum 25\u2013maximum 53]) lose 0.6% FN\u2010BMD each year up to menopausal age. For clinical relevance, the epidemiological FRAX model was informed by the simulation results to predict the 10\u2010year risk of major osteoporotic fracture (MOF). Premenopausal women with UFs, who received placebo only in the elagolix phase III trials, have a projected FN\u2010BMD of 0.975\u00a0g\/cm\n                    <jats:sup>2<\/jats:sup>\n                    at menopause, associated with a 10\u2010year risk of MOF of 2.3%. Integration of modeling, RWD, and clinical trials data provides a quantitative framework for projecting long\u2010term postmenopausal risk of fractures, based on natural history of BMD changes in premenopausal women. This framework enables quantitative evaluation of the future risk of MOF for women receiving medical therapies (i.e., GnRH modulators) that adversely affect BMD.\n                  <\/jats:p>","DOI":"10.1111\/cts.13006","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:18:31Z","timestamp":1614644311000},"page":"1452-1463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Integrating real\u2010world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women"],"prefix":"10.1111","volume":"14","author":[{"given":"Denise","family":"Beck","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Deutschland GmbH &amp; Co. KG Ludwigshafen am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Insa","family":"Winzenborg","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Deutschland GmbH &amp; Co. KG Ludwigshafen am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"Analysis Group Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nael M.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie North Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Noertersheuser","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Deutschland GmbH &amp; Co. KG Ludwigshafen am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie E.","family":"Chiuve","sequence":"additional","affiliation":[{"name":"Global Epidemiology AbbVie North Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Owens","sequence":"additional","affiliation":[{"name":"Clinical Development, General Medicine AbbVie North Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamad","family":"Shebley","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie North Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,4,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000400"},{"key":"e_1_2_10_3_1","volume-title":"Bone Health and Osteoporosis: A Report of the Surgeon General","author":"Office of the Surgeon General (US)","year":"2004"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-013-0161-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.08.106"},{"key":"e_1_2_10_6_1","volume-title":"DEPO\u2010PROVERA CI (medroxyprogesterone acetate) [US package insert]","year":"2016"},{"key":"e_1_2_10_7_1","volume-title":"Lupron Depot\u00ae 11.25 mg [US prescribing information]","author":"AbbVie","year":"2013"},{"key":"e_1_2_10_8_1","volume-title":"Orilissa\u2122 (elagolix) [US package insert]","year":"2018"},{"key":"e_1_2_10_9_1","unstructured":"FRAX\u00ae Fracture Risk Assessment Tool.https:\/\/www.sheffield.ac.uk\/FRAX\/tool.aspx. 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Accessed May 12 2020.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01620528."},{"key":"e_1_2_10_14_1","unstructured":"AbbVie Inc.A Global Phase 3 Study to Evaluate the Safety and Efficacy of Elagolix in Subjects With Moderate to Severe Endometriosis\u2010Associated Pain (ELARIS EM\u2010II). ClincialTrials.gov identifier: NCT01931670. Updated September 7 2018. Accessed May 12 2020.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01931670."},{"key":"e_1_2_10_15_1","unstructured":"AbbVie Inc.Efficacy and Safety of Elagolix in Combination With Estradiol\/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women. ClinicalTrials.gov identifier: NCT02654054. Last updated February 11 2019. Accessed May 12 2020.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02654054."},{"key":"e_1_2_10_16_1","unstructured":"AbbVie Inc.Efficacy and Safety of Elagolix in Combination With Estradiol\/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women (Replicate Study). ClinicalTrials.gov identifier: NCT02691494. Updated February 11 2019. Accessed May 12 2020.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02691494."},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1904351"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1700089"},{"key":"e_1_2_10_19_1","unstructured":"Centers for Disease Control and Prevention (CDC).National Center for Health Statistics (NCHS). 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