{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:52:21Z","timestamp":1753883541471,"version":"3.41.2"},"reference-count":21,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2021,11,20]],"date-time":"2021-11-20T00:00:00Z","timestamp":1637366400000},"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\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["151806","ICE17006"],"award-info":[{"award-number":["151806","ICE17006"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Parathyroid hormone (PTH) replacement is a promising approach in the management of hypoparathyroidism but long-acting analogues need to be developed. To date, animal models for testing PTH required parathyroidectomy by surgery. We have developed a nonsurgical rodent hypoparathyroid model and tested a delayed-clearance PTH molecule (DC-PTH).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The aim of this study was to use cinacalcet to suppress calcium levels in normal rats and to reverse these effects with the administration of PTH or PTH analogues<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Male Wistar rats were gavaged with either 30 mg\/kg cinacalcet-HCl (cinacalcet) or vehicle only. Animals were then dosed with either single or repeated subcutaneous doses of PTH 1-34 or a DC-PTH at 20 nmol\/kg. Control animals received vehicle only. Serum samples were analyzed for ionized calcium (iCa), phosphate, PTH, and DC-PTH. A pharmacokinetic-pharmacodynamic (PK-PD) model was built for cinacalcet, PTH 1-34, and DC-PTH using Phoenix64.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Cinacalcet reduced iCa levels between 2 and 24 hours, returning to baseline by 72 hours post dose with nadir at 8 hours (analysis of variance P\u2005&amp;lt;\u2005.001), associated with a fall in rat PTH. For phosphate there was a variable biphasic response. Single-dose PTH abrogated the cinacalcet-induced fall in iCa for up to 2 hours. DC-PTH prevented the fall in iCa from 4 hours post dose and gave a prolonged response, with iCa levels quicker to return to baseline than controls. DC-PTH has a half-life of 11.5 hours, approximately 44 times longer than human PTH 1-34. The PK-PD models defined the reproducible effect of cinacalcet on iCa and that DC-PTH had prolonged biological activity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The administration of cinacalcet provides a robust and reproducible nonsurgical animal model of hypoparathyroidism. DC-PTH holds promise for the treatment of hypoparathyroidism in the future.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/endocr\/bqab239","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T05:36:31Z","timestamp":1640324191000},"source":"Crossref","is-referenced-by-count":1,"title":["Development of a Hypoparathyroid Male Rodent Model for Testing Delayed-Clearance PTH Molecules"],"prefix":"10.1210","volume":"163","author":[{"given":"Narjes","family":"Ramezanipour","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 81746-73695, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayyed Hamid Zarkesh","family":"Esfahani","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 81746-73695, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-3366","authenticated-orcid":false,"given":"Richard","family":"Eastell","sequence":"additional","affiliation":[{"name":"Department of Oncology & Metabolism, University of Sheffield, Sheffield S10 2RX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Newell-Price","sequence":"additional","affiliation":[{"name":"Department of Oncology & Metabolism, University of Sheffield, Sheffield S10 2RX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham","family":"Trevitt","sequence":"additional","affiliation":[{"name":"XenoGesis Ltd, Nottingham NG1 1GF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Oncology & Metabolism, University of Sheffield, Sheffield S10 2RX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6236-2419","authenticated-orcid":false,"given":"Ian R","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Department of Oncology & Metabolism, University of Sheffield, Sheffield S10 2RX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2021,11,20]]},"reference":[{"issue":"6","key":"2021122314445992700_CIT0001","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1210\/clinem\/dgaa113","article-title":"Hypoparathyroidism","volume":"105","author":"Bilezikian","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2021122314445992700_CIT0002","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1210\/endrev\/bnab005","article-title":"Physiological and pharmacological roles of PTH and PTHrP in bone using their shared receptor, 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