{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:22:55Z","timestamp":1792113775862,"version":"4.4.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[1996,12,1]],"date-time":"1996-12-01T00:00:00Z","timestamp":849398400000},"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":[[1996,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>It was predicted from the amino acid sequence of the bone anabolic peptides, parathyroid hormone (PTH) (1\u201334) and PTH related protein (PTHrP) (1\u201334), that the C-terminal amino acids form an amphipathic \u03b1-helix. Therefore, we substituted a model amphipathic \u03b1-helical peptide (MAP) sequence in the C-terminal region of hPTHrP(1\u201334), obtaining RS-66271 ([MAP1\u201310]]22\u201331 hPTHrP(1\u201334)-NH2). The anabolic activities of RS-66271 and hPTHrP(1\u201334) were evaluated in 3-month-old, ovariectomized (OVX) osteopenic rats. Subcutaneous injection of hPTHrP(1\u201334) at 80 \u03bcg\/kg\/day partially reversed estrogen depletion trabecular bone loss but was ineffective in the cortex. In contrast, RS-66271 dose-relatedly reversed loss at both sites and, at 80 \u03bcg\/kg\/day, returned both trabecular and cortical bone calcium to the level of sham-operated controls. Histomorphometric analysis showed significantly elevated bone formation rates over vehicle-treated OVX in both trabecular and cortical tibial bone following treatment with RS-66271. Electron microscopy showed an increase in the relative surface area of vertebral trabeculae covered by osteoblasts in animals treated with RS-66271. These studies demonstrate that the C-terminal amino acids of hPTHrP(1\u201334) can be replaced by a model amphipathic helix and that the new chemical entity has greater anabolic activity than the parent peptide. The results suggest that RS-66271 may be a candidate molecule for the treatment of human osteoporosis.<\/jats:p>","DOI":"10.1002\/jbmr.5650111216","type":"journal-article","created":{"date-parts":[[2010,2,24]],"date-time":"2010-02-24T19:49:47Z","timestamp":1267040987000},"page":"1943-1951","source":"Crossref","is-referenced-by-count":42,"title":["RS-66271, a C-terminally substituted analog of human parathyroid hormone-related protein (1\u201334), increases trabecular and cortical bone in ovariectomized, osteopenic rats"],"prefix":"10.1093","volume":"11","author":[{"given":"Brian H.","family":"Vickery","sequence":"first","affiliation":[{"name":"Inflammatory Disease Unit, Roche Bioscience, Palo Alto, California, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zafrira","family":"Avnur","sequence":"additional","affiliation":[{"name":"Inflammatory Disease Unit, Roche Bioscience, Palo Alto, California, 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