{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T19:53:08Z","timestamp":1762458788245},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[1995,5,1]],"date-time":"1995-05-01T00:00:00Z","timestamp":799286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Wyeth Ayerst Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1995,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immunosuppressant therapy is associated with osteoporosis both clinically, post-transplantation, and experimentally. In rats, cyclosporin A (CsA) and FK506 induce a state of high turnover rapid bone loss. After 14 days of administration in immunosuppressive doses, the more recently discovered immunosuppressant, rapamycin, resulted in no change of cancellous bone volume. A longer study over 28 days has now been carried out; contrasting the new drug with CsA and FK506. Sixty, 10-week-old Sprague\u2013Dawley rats were randomly divided into five groups of 12 rats each. The first group served as an aging control. The remaining four groups received, by daily gavage, a combined vehicle placebo, CsA 15 mg\/kg, FK506 5 mg\/kg, and rapamycin 2.5 mg\/kg, respectively. CsA- and FK506-treated rats, but not those treated with rapamycin, demonstrated high turnover osteoporosis with raised serum 1,25(OH)2D (p &amp;lt; 0.05) and elevated serum osteocalcin (p &amp;lt; 0.05). The trabecular bone area was decreased by 66% (p &amp;lt; 0.01) in the CsA group and 56% (p &amp;lt; 0.05) in the FK506-treated group compared with the control animals. The CsA- and the rapamycin-treated groups failed to gain weight and developed severe hyperglycemia (&amp;gt;20 mmol\/l, p &amp;lt; 0.001) by day 14 but which largely resolved by day 28. Unlike the groups treated with CsA and FK506, rapamycin-treated rats had no loss of trabecular bone volume but there was increased modeling and remodeling and a decreased longitudinal growth rate. Rapamycin may thus confer a distinct advantage over the established immunosuppressants in not reducing bone volume in the short term. However, the increased remodeling may pose a problem with long-term use, and the decrease in longitudinal bone growth would make the drug unsuitable for growing individuals.<\/jats:p>","DOI":"10.1002\/jbmr.5650100513","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T16:07:56Z","timestamp":1265213276000},"page":"760-768","source":"Crossref","is-referenced-by-count":83,"title":["Rapamycin: A bone sparing immunosuppressant?"],"prefix":"10.1093","volume":"10","author":[{"given":"David F.","family":"Romero","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Albert Einstein Medical Center, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farrel J.","family":"Buchinsky","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Albert Einstein Medical Center, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boguslaw","family":"Rucinski","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Albert Einstein Medical Center, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirjana","family":"Cvetkovic","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Albert Einstein Medical Center, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haldon P.","family":"Bryer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Albert Einstein Medical Center, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao G.","family":"Liang","sequence":"additional","affiliation":[{"name":"Division of Radiobiology, University of Utah, Salt Lake City, Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfei F.","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Radiobiology, University of Utah, Salt Lake City, Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Webster S. S.","family":"Jee","sequence":"additional","affiliation":[{"name":"Division of Radiobiology, University of Utah, Salt Lake City, Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solomon","family":"Dr. Epstein","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Albert Einstein Medical Center, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1995,5,1]]},"reference":[{"key":"2024013113142198200_bib1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/jbmr.5650070202","article-title":"Posttransplantation bone disease.","volume":"7","author":"Katz","year":"1992","journal-title":"J Bone Miner Res"},{"key":"2024013113142198200_bib2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/hep.1840140407","article-title":"Bone loss after liver 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(CTX).","volume":"54","author":"Garcia","year":"1994","journal-title":"Calcif Tissue Int"},{"key":"2024013113142198200_bib45","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0092-8674(93)90144-F","article-title":"Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression.","volume":"73","author":"Kunz","year":"1993","journal-title":"Cell"},{"key":"2024013113142198200_bib46","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1073\/pnas.89.9.3686","article-title":"Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A.","volume":"89","author":"Fruman","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"issue":"S1","key":"2024013113142198200_bib47","first-page":"S38","article-title":"Does macrophage activating factor (Gc-MAF) mediate the bone loss caused by cyclosporin A (CsA).","volume":"25","author":"Armstrong","year":"1994","journal-title":"Bone 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