{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:43:37Z","timestamp":1780458217389,"version":"3.54.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2006,12,1]],"date-time":"2006-12-01T00:00:00Z","timestamp":1164931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although the pharmacological action of calcitonin (CT) as an inhibitor of bone resorption is well established, there is still some controversy regarding its physiological function. Unexpectedly, Calca-deficient mice lacking CT and \u03b1-calcitonin gene-related peptide (\u03b1CGRP) were described to have a high bone mass phenotype caused by increased bone formation with normal bone resorption. Here we show that these mice develop a phenotype of high bone turnover with age, suggesting that CT is a physiological inhibitor of bone remodeling.<\/jats:p>\n               <jats:p>Introduction: The absence of significant changes in bone mineral density caused by decline or overproduction of CT in humans has raised the question, whether the pharmacological action of CT as an inhibitor of bone resorption is also of physiological relevance. To study the physiological role of mammalian CT, we have analyzed the age-dependent bone phenotype of two mouse models, one lacking CT and \u03b1CGRP (Calca\u2212\/\u2212), the other one lacking only \u03b1CGRP (\u03b1CGRP\u2212\/\u2212).<\/jats:p>\n               <jats:p>Materials and Methods: Bones from wildtype, Calca\u2212\/\u2212-mice and \u03b1CGRP\u2212\/\u2212-mice were analyzed at the ages of 6, 12 and 18 months using undecalcified histology. Differences of bone remodeling were quantified by static and dynamic histomorphometry as well as by measuring the urinary collagen degradation products. To rule out secondary mechanisms underlying the observed phenotype, we determined serum concentrations of relevant hormones using commercially available antibody-based detection kits.<\/jats:p>\n               <jats:p>Results: Whereas \u03b1CGRP\u2212\/\u2212-mice display an osteopenia at all ages analyzed, the Calca\u2212\/\u2212-mice develop a phenotype of high bone turnover with age. Histomorphometric analysis performed at the age of 12 months revealed significant increases of bone formation and bone resorption specifically in the Calca\u2212\/\u2212-mice. This severe phenotype that can result in hyperostotic lesions, can not be explained by obvious endocrine abnormalities other than the absence of CT.<\/jats:p>\n               <jats:p>Conclusions: In addition to the previously described increase of bone formation in the Calca-deficient mice, we have observed that there is also an increase of bone resorption with age. This suggests that CT has a dual action as an inhibitor of bone remodeling, which may explain why alterations of CT serum levels in humans do not result in major changes of bone mineral density.<\/jats:p>","DOI":"10.1359\/jbmr.060820","type":"journal-article","created":{"date-parts":[[2006,9,29]],"date-time":"2006-09-29T14:58:12Z","timestamp":1159541892000},"page":"1924-1934","source":"Crossref","is-referenced-by-count":71,"title":["Calcitonin Deficiency in Mice Progressively Results in High Bone Turnover"],"prefix":"10.1093","volume":"21","author":[{"given":"Antje K","family":"Huebner","sequence":"first","affiliation":[{"name":"Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany"},{"name":"Center for Biomechanics and Skeletal Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Schinke","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany"},{"name":"Center for Biomechanics and Skeletal Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Priemel","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany"},{"name":"Center for Biomechanics and Skeletal Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Schilling","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany"},{"name":"Center for Biomechanics and Skeletal Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt F","family":"Schilling","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany"},{"name":"Center for Biomechanics and Skeletal Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald B","family":"Emeson","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology, Molecular Physiology, and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M","family":"Rueger","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany"},{"name":"Center for Biomechanics and Skeletal Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Amling","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany"},{"name":"Center for Biomechanics and Skeletal Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024013019374001300_bib1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/193381a0","article-title":"Calcitonin-a hormone from the parathyroid which lowers the calcium-level of the blood","volume":"193","author":"Copp","year":"1962","journal-title":"Nature"},{"key":"2024013019374001300_bib2","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/2021303a0","article-title":"Thyroid origin of calcitonin","volume":"202","author":"Foster","year":"1964","journal-title":"Nature"},{"key":"2024013019374001300_bib3","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1126\/science.150.3702.1465","article-title":"Thyrocalcitonin: Inhibitor of bone resorption in tissue culture","volume":"150","author":"Friedmann","year":"1965","journal-title":"Science"},{"key":"2024013019374001300_bib4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/path.1711360104","article-title":"Calcitonin alters behaviour of isolated osteoclasts","volume":"136","author":"Chambers","year":"1982","journal-title":"J Pathol"},{"key":"2024013019374001300_bib5","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1172\/JCI112584","article-title":"Abundant calcitonin receptors in isolated rat osteoclasts. 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