{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:13:08Z","timestamp":1768569188998,"version":"3.49.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T00:00:00Z","timestamp":1476662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100015831","name":"Radius Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015831","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Abaloparatide is a novel 34-amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor (PTH1R) signaling pathway with 41% homology to PTH(1-34) and 76% homology to PTHrP(1-34). A 12-month treatment study was conducted in osteopenic ovariectomized (OVX) rats to characterize the mechanisms by which abaloparatide increases bone mass. Sprague-Dawley (SD) rats were subjected to OVX or sham surgery at age 6 months and left untreated for 3 months to allow OVX-induced bone loss. Ten OVX rats were euthanized after this bone depletion period, and the remaining OVX rats received daily subcutaneous injections of vehicle (n\u2009=\u200918) or abaloparatide at 1, 5, or 25\u2009\u03bcg\/kg\/d (n\u2009=\u200918\/dose level) for 12 months. Sham controls (n\u2009=\u200918) received vehicle daily. Bone densitometry and biochemical markers of bone formation and resorption were assessed longitudinally, and L3 vertebra and tibia were collected at necropsy for histomorphometry. Abaloparatide increased biochemical bone formation markers without increasing bone resorption markers or causing hypercalcemia. Abaloparatide increased histomorphometric indices of bone formation on trabecular, endocortical, and periosteal surfaces without increasing osteoclasts or eroded surfaces. Abaloparatide induced substantial increases in trabecular bone volume and density and improvements in trabecular microarchitecture. Abaloparatide stimulated periosteal expansion and endocortical bone apposition at the tibial diaphysis, leading to marked increases in cortical bone volume and density. Whole-body bone mineral density (BMD) remained stable in OVX-Vehicle controls while increasing 25% after 12 months of abaloparatide (25\u2009\u03bcg\/kg). Histomorphometry and biomarker data suggest that gains in cortical and trabecular bone mass were attributable to selective anabolic effects of abaloparatide, without evidence for stimulated bone resorption. \u00a9 2016 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3003","type":"journal-article","created":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T11:53:23Z","timestamp":1476705203000},"page":"24-33","source":"Crossref","is-referenced-by-count":74,"title":["One Year of Abaloparatide, a Selective Activator of the PTH1 Receptor, Increased Bone Formation and Bone Mass in Osteopenic Ovariectomized Rats Without Increasing Bone Resorption"],"prefix":"10.1093","volume":"32","author":[{"given":"Aurore","family":"Varela","sequence":"first","affiliation":[{"name":"Charles River LaboratoriesMontrealCanada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Chouinard","sequence":"additional","affiliation":[{"name":"Charles River LaboratoriesMontrealCanada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Lesage","sequence":"additional","affiliation":[{"name":"Charles River LaboratoriesMontrealCanada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan Y","family":"Smith","sequence":"additional","affiliation":[{"name":"Charles River LaboratoriesMontrealCanada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Hattersley","sequence":"additional","affiliation":[{"name":"Radius Health Inc.WalthamMA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,10,17]]},"reference":[{"issue":"2","key":"2024031419333524900_jbmr3003-bib-0001","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1210\/jc.2014-3718","article-title":"Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis","volume":"100","author":"Leder","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"2024031419333524900_jbmr3003-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"},{"key":"2024031419333524900_jbmr3003-bib-0003","year":"2015"},{"key":"2024031419333524900_jbmr3003-bib-0004","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1359\/jbmr.2000.15.8.1517","article-title":"Six month daily administration of parathyroid hormone and parathyroid hormone-related protein peptides to adult ovariectomized rats markedly enhances bone mass and biomechanical properties: a comparison of human parathyroid hormone 1-34, parathyroid hormone-related protein 1-36, and SDZ-parathyroid hormone 893","volume":"15","author":"Stewart","year":"2000","journal-title":"J Bone Miner Res"},{"issue":"4","key":"2024031419333524900_jbmr3003-bib-0005","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s00223-006-0108-1","article-title":"Daily treatment of aged ovariectomized rats with human parathyroid hormone (1-84) for 12 months reverses bone loss and enhances trabecular and cortical bone strength","volume":"79","author":"Fox","year":"2006","journal-title":"Calcif Tissue Int"},{"issue":"8","key":"2024031419333524900_jbmr3003-bib-0006","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1359\/jbmr.090315","article-title":"Comparative effects of teriparatide and strontium ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis","volume":"24","author":"Recker","year":"2009","journal-title":"J Bone Miner Res"},{"issue":"8","key":"2024031419333524900_jbmr3003-bib-0007","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1210\/jc.2012-1262","article-title":"Skeletal histomorphometry in subjects on teriparatide or zoledronic acid therapy (SHOTZ) study: a randomized controlled trial","volume":"97","author":"Dempster","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"issue":"36","key":"2024031419333524900_jbmr3003-bib-0008","doi-asserted-by":"crossref","first-page":"28164","DOI":"10.1074\/jbc.M110.101964","article-title":"Are osteoclasts needed for the bone anabolic response to parathyroid hormone? 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