{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:45:34Z","timestamp":1788864334664,"version":"build-2803163510"},"reference-count":29,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"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\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education Korea government","award":["NRF-2018R1D1A1A02086061"],"award-info":[{"award-number":["NRF-2018R1D1A1A02086061"]}]},{"name":"Ministry of Science and ICT","award":["NRF-2018R15A2023217"],"award-info":[{"award-number":["NRF-2018R15A2023217"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Postsurgical hypoparathyroidism is the most common complication of thyroid surgery. Conventional therapy with high-dose calcium and vitamin D can correct hypocalcemia but can increase the risk of hypercalciuria, renal stones, or ectopic calcification. The aim of the present study was to investigate the efficacy of a calcium-sensing receptor antagonist, also called a calcilytic (AXT914), in rat models of postsurgical hypoparathyroidism. Two postsurgical hypoparathyroidism rat models were made by hemi-parathyroidectomy or total parathyroidectomy with autotransplantation in 10-week-old female Wistar rats. AXT914 or vehicle was administered orally for 2 to 3 weeks. Serum PTH, calcium, and phosphorus levels, and the urinary excretion of calcium were measured. Autotransplanted parathyroid tissues were collected and examined histologically. In the hemi-parathyroidectomy model, the oral administration of the calcilytic AXT914 (5 and 10 mg\/kg) for 2 weeks increased serum PTH and calcium levels and decreased serum phosphorus levels and urinary calcium excretion. In the total parathyroidectomy with autotransplantation model, the oral administration of AXT914 (10 mg\/kg) for 3 weeks increased serum PTH and calcium levels and decreased serum phosphorus levels. The serum PTH and calcium levels increased by AXT914 were maintained for 1 week, even after discontinuation of the drug. In conclusion, AXT914 increased PTH secretion in rat models of postsurgical hypoparathyroidism, thereby correcting abnormal calcium and phosphorus homeostasis. Furthermore, AXT914 improved the functional recovery of autotransplanted parathyroid tissues.<\/jats:p>","DOI":"10.1210\/endocr\/bqaa145","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T12:47:14Z","timestamp":1598532434000},"source":"Crossref","is-referenced-by-count":5,"title":["A New Therapeutic Approach Using a Calcilytic (AXT914) for Postsurgical Hypoparathyroidism in Female Rats"],"prefix":"10.1210","volume":"161","author":[{"given":"Yun-Sung","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Dongguk University Ilsan Hospital, Koyang-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Hoon","family":"You","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Koyang-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Bok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Dongguk University Ilsan Hospital, Koyang-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Hyun","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Dongguk University Ilsan Hospital, Koyang-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Geun","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Koyang-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Goo","family":"Bae","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Koyang-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Kyung","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Koyang-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Koyang-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6506-4342","authenticated-orcid":false,"given":"Han Seok","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Dongguk University Ilsan Hospital, Koyang-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,8,27]]},"reference":[{"issue":"7","key":"2021121718164373400_CIT0001","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1007\/s002689900459","article-title":"Hypocalcemia following thyroid surgery: incidence and prediction of outcome","volume":"22","author":"Pattou","year":"1998","journal-title":"World J Surg."},{"issue":"4","key":"2021121718164373400_CIT0002","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1001\/archotol.128.4.389","article-title":"Assessment of the morbidity and complications of total thyroidectomy","volume":"128","author":"Bhattacharyya","year":"2002","journal-title":"Arch Otolaryngol Head Neck Surg."},{"issue":"4","key":"2021121718164373400_CIT0003","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00423-006-0097-6","article-title":"Scandinavian quality register for thyroid and parathyroid surgery: audit of surgery for primary hyperparathyroidism","volume":"392","author":"Bergenfelz","year":"2007","journal-title":"Langenbecks Arch Surg."},{"issue":"5","key":"2021121718164373400_CIT0004","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1002\/lary.24429","article-title":"Hypocalcemia after total laryngectomy: incidence and risk factors","volume":"124","author":"Basheeth","year":"2014","journal-title":"Laryngoscope."},{"key":"2021121718164373400_CIT0005","doi-asserted-by":"crossref","first-page":"17055","DOI":"10.1038\/nrdp.2017.55","article-title":"Hypoparathyroidism","volume":"3","author":"Mannstadt","year":"2017","journal-title":"Nat Rev Dis Primers."},{"issue":"4","key":"2021121718164373400_CIT0006","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1056\/NEJMcp0803050","article-title":"Clinical practice. Hypoparathyroidism","volume":"359","author":"Shoback","year":"2008","journal-title":"N Engl J Med."},{"issue":"1","key":"2021121718164373400_CIT0007","first-page":"82","article-title":"Defining the syndromes of parathyroid failure after total thyroidectomy","volume":"4","author":"Lorente-Poch","year":"2015","journal-title":"Gland Surg."},{"issue":"4","key":"2021121718164373400_CIT0008","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/bjs.9384","article-title":"Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia","volume":"101","author":"Edafe","year":"2014","journal-title":"Br J Surg."},{"issue":"1","key":"2021121718164373400_CIT0009","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/1097-0142(20000701)89:1<202::AID-CNCR27>3.0.CO;2-A","article-title":"Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the united states during 1996. U.S. and German Thyroid Cancer Study Group. An American College of Surgeons Commission on Cancer Patient Care Evaluation study","volume":"89","author":"Hundahl","year":"2000","journal-title":"Cancer."},{"issue":"6","key":"2021121718164373400_CIT0010","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1210\/jc.2015-3910","article-title":"Management of hypoparathyroidism: present and future","volume":"101","author":"Bilezikian","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021121718164373400_CIT0011","doi-asserted-by":"crossref","first-page":"535","DOI":"10.4155\/fmc.11.17","article-title":"Calcilytics: antagonists of the calcium-sensing receptor for the treatment of osteoporosis","volume":"3","author":"Widler","year":"2011","journal-title":"Future Med Chem."},{"key":"2021121718164373400_CIT0012","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.bone.2014.04.015","article-title":"AXT914 a novel, orally-active parathyroid hormone-releasing drug in two early studies of healthy volunteers and postmenopausal women","volume":"64","author":"John","year":"2014","journal-title":"Bone."},{"issue":"8","key":"2021121718164373400_CIT0013","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1210\/jc.2010-2855","article-title":"The effects of ronacaleret, a calcium-sensing receptor antagonist, on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mineral density","volume":"96","author":"Fitzpatrick","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"issue":"11","key":"2021121718164373400_CIT0014","doi-asserted-by":"crossref","first-page":"E2207","DOI":"10.1210\/jc.2013-4009","article-title":"A phase 2, randomized, placebo-controlled, dose-ranging study of the calcium-sensing receptor antagonist MK-5442 in the treatment of postmenopausal women with osteoporosis","volume":"99","author":"Halse","year":"2014","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2021121718164373400_CIT0015","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1097\/MLG.0b013e3181671b61","article-title":"Fluorescent detection of rat parathyroid glands via 5-aminolevulinic acid","volume":"118","author":"Asher","year":"2008","journal-title":"Laryngoscope."},{"issue":"10","key":"2021121718164373400_CIT0016","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1007\/s00405-014-3262-5","article-title":"Development of hypoparathyroidism animal model and the feasibility of small intestinal submucosa application on the parathyroid autotransplantation","volume":"272","author":"Park","year":"2015","journal-title":"Eur Arch Otorhinolaryngol."},{"issue":"5","key":"2021121718164373400_CIT0017","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1021\/jm901811v","article-title":"1-Alkyl-4-phenyl-6-alkoxy-1H-quinazolin-2-ones: a novel series of potent calcium-sensing receptor antagonists","volume":"53","author":"Widler","year":"2010","journal-title":"J Med Chem."},{"key":"2021121718164373400_CIT0018","volume-title":"Data from: RRID:AB_2827505"},{"key":"2021121718164373400_CIT0019","volume-title":"Data from: RRID:AB_2861347"},{"issue":"11","key":"2021121718164373400_CIT0020","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1002\/bjs.7219","article-title":"Outcome of protracted hypoparathyroidism after total thyroidectomy","volume":"97","author":"Sitges-Serra","year":"2010","journal-title":"Br J Surg."},{"issue":"7","key":"2021121718164373400_CIT0021","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nrneph.2016.59","article-title":"Localization and function of the renal calcium-sensing receptor","volume":"12","author":"Riccardi","year":"2016","journal-title":"Nat Rev Nephrol."},{"issue":"12","key":"2021121718164373400_CIT0022","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.1210\/jc.2012-1808","article-title":"Long-term follow-up of patients with hypoparathyroidism","volume":"97","author":"Mitchell","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"issue":"11","key":"2021121718164373400_CIT0023","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1002\/jbmr.1979","article-title":"Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study","volume":"28","author":"Underbjerg","year":"2013","journal-title":"J Bone Miner Res."},{"issue":"10","key":"2021121718164373400_CIT0024","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1002\/jbmr.483","article-title":"Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research","volume":"26","author":"Bilezikian","year":"2011","journal-title":"J Bone Miner Res."},{"issue":"2","key":"2021121718164373400_CIT0025","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1530\/eje.0.1460215","article-title":"Well-being, mood and calcium homeostasis in patients with hypoparathyroidism receiving standard treatment with calcium and vitamin D","volume":"146","author":"Arlt","year":"2002","journal-title":"Eur J Endocrinol."},{"issue":"4","key":"2021121718164373400_CIT0026","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S2213-8587(13)70106-2","article-title":"Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study","volume":"1","author":"Mannstadt","year":"2013","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"10","key":"2021121718164373400_CIT0027","doi-asserted-by":"crossref","first-page":"3694","DOI":"10.1210\/jc.2014-2267","article-title":"PTH(1-84) is associated with improved quality of life in hypoparathyroidism through 5 years of therapy","volume":"99","author":"Cusano","year":"2014","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021121718164373400_CIT0028","doi-asserted-by":"crossref","first-page":"617","DOI":"10.2131\/jts.37.617","article-title":"Osteosarcoma in Sprague-Dawley rats after long-term treatment with teriparatide (human parathyroid hormone (1-34))","volume":"37","author":"Watanabe","year":"2012","journal-title":"J Toxicol Sci."},{"issue":"5","key":"2021121718164373400_CIT0029","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1093\/ndt\/gfm850","article-title":"Highly concentrated calcitriol and its analogues induce apoptosis of parathyroid cells and regression of the hyperplastic gland\u2013study in rats","volume":"23","author":"Shiizaki","year":"2008","journal-title":"Nephrol Dial Transplant."}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/advance-article-pdf\/doi\/10.1210\/endocr\/bqaa145\/33688755\/bqaa145.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/161\/10\/bqaa145\/41812478\/endo_161_10_bqaa145.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/161\/10\/bqaa145\/41812478\/endo_161_10_bqaa145.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T19:40:16Z","timestamp":1639770016000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/doi\/10.1210\/endocr\/bqaa145\/5898117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,27]]},"references-count":29,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/endocr\/bqaa145","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,10]]},"published":{"date-parts":[[2020,8,27]]},"article-number":"bqaa145"}}