{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:03:41Z","timestamp":1790935421755,"version":"4.1.0"},"reference-count":31,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The \u03b1V\u03b23 integrin (vitronectin receptor) plays a pivotal role in bone resorption. We hypothesized that L-000845704, an \u03b1V\u03b23 integrin antagonist, would potently inhibit bone resorption, thereby increasing bone mass as assessed by bone mineral density (BMD) in women with postmenopausal osteoporosis. In a multicenter, randomized, double-blind, placebo-controlled, 12-month study, 227 women (average 63 yr) with low lumbar spine or femoral neck BMD were randomly assigned to receive 100 or 400 mg L-000845704 once daily (qd), 200 mg L-000845704 twice daily (bid), or placebo. L-000845704 increased lumbar spine BMD (2.1, 3.1, and 3.5% for the 100-mg-qd, 400-mg-qd, and 200-mg-bid treatment groups, respectively, vs. \u22120.1% for placebo; P &amp;lt; 0.01 all treatments vs. placebo). Only 200 mg L-000845704 bid significantly increased BMD at the hip (1.7 vs. 0.3% for placebo; P &amp;lt; 0.03) and femoral neck (2.4 vs. 0.7% for placebo; P &amp;lt; 0.05). No L-000845704 group increased total body BMD. All doses of L-000845704 resulted in a similar approximately 42% decrease from baseline of N-telopeptide cross-links (P &amp;lt; 0.001 vs. placebo). L-000845704 was generally well tolerated; adverse events resulting in discontinuation from the study were relatively infrequent.<\/jats:p>\n               <jats:p>In conclusion, the antiresorptive effect of the \u03b1V\u03b23 integrin antagonist L-000845704 translated into significant increases in lumbar spine BMD. Furthermore, 200 mg L-000845704 bid provided efficacy at the hip sites. These data suggest that the \u03b1V\u03b23 integrin antagonist L-000845704 could be developed as an effective therapeutic agent for osteoporosis.<\/jats:p>","DOI":"10.1210\/jc.2004-2126","type":"journal-article","created":{"date-parts":[[2005,4,6]],"date-time":"2005-04-06T23:32:44Z","timestamp":1112830364000},"page":"2022-2028","source":"Crossref","is-referenced-by-count":117,"title":["Effect of L-000845704, an \u03b1V\u03b23 Integrin Antagonist, on Markers of Bone Turnover and Bone Mineral Density in Postmenopausal Osteoporotic Women"],"prefix":"10.1210","volume":"90","author":[{"given":"M. G.","family":"Murphy","sequence":"first","affiliation":[{"name":"Merck Research Laboratories (M.G.M., K.C., A.S., K.G., M.W.), Rahway, New Jersey 07065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Cerchio","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories (M.G.M., K.C., A.S., K.G., M.W.), Rahway, New Jersey 07065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. A.","family":"Stoch","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories (M.G.M., K.C., A.S., K.G., M.W.), Rahway, New Jersey 07065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Gottesdiener","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories (M.G.M., K.C., A.S., K.G., M.W.), Rahway, New Jersey 07065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Wu","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories (M.G.M., K.C., A.S., K.G., M.W.), Rahway, New Jersey 07065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Recker","sequence":"additional","affiliation":[{"name":"Creighton Osteoporosis Center (R.R.), Omaha, Nebraska 68131"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071618423239900_R1","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1007\/BF01623782","article-title":"Guidelines for diagnosis and management of osteoporosis.","volume":"7","author":"Kanis","year":"1997","journal-title":"Osteoporos Int"},{"key":"2020071618423239900_R2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.2165\/00003495-199753050-00001","article-title":"Prevention and management of osteoporosis.","volume":"53","author":"Compston","year":"1997","journal-title":"Drugs"},{"key":"2020071618423239900_R3","first-page":"65","article-title":"The prevention and treatment of osteoporosis.","volume":"328","author":"Riggs","year":"1992","journal-title":"N Engl J Med [Erratum (1993)"},{"key":"2020071618423239900_R4","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/jbmr.5650070608","article-title":"Appendicular bone mineral and a woman\u2019s lifetime risk of hip fracture.","volume":"7","author":"Black","year":"1992","journal-title":"J Bone Miner Res"},{"key":"2020071618423239900_R5","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/BF01623271","article-title":"Prevalence and incidence of vertebral deformities.","volume":"3","author":"Melton III","year":"1993","journal-title":"Osteoporos Int"},{"key":"2020071618423239900_R6","doi-asserted-by":"crossref","first-page":"A3","DOI":"10.1016\/S8756-3282(09)80003-3","article-title":"Introduction to bone biology","volume":"13","author":"Rodan","year":"1992","journal-title":"Bone"},{"key":"2020071618423239900_R7","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/S0140-6736(76)92217-0","article-title":"Long-term prevention of postmenopausal osteoporosis by oestrogen: evidence for an increased bone mass after delayed onset of oestrogen treatment.","volume":"1","author":"Lindsay","year":"1976","journal-title":"Lancet"},{"key":"2020071618423239900_R8","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1056\/NEJM199005033221803","article-title":"Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis.","volume":"332","author":"Storm","year":"1990","journal-title":"N Engl J Med"},{"key":"2020071618423239900_R9","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/S0140-6736(96)07088-2","article-title":"Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures.","volume":"348","author":"Black","year":"1996","journal-title":"Lancet"},{"key":"2020071618423239900_R10","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0169-6009(91)90124-I","article-title":"The ovariectomized rat model of postmenopausal bone loss.","volume":"15","author":"Kalu","year":"1991","journal-title":"Bone Miner"},{"key":"2020071618423239900_R11","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0169-6009(92)90809-R","article-title":"On the rat model of human osteopenias and osteoporosis.","volume":"18","author":"Frost","year":"1992","journal-title":"Bone Miner"},{"key":"2020071618423239900_R12","first-page":"177","article-title":"The ultrastructure of the osteoclast and its functional implications.","volume":"123","author":"Holtrop","year":"1977","journal-title":"Clin Orthop"},{"key":"2020071618423239900_R13","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1083\/jcb.106.6.1863","article-title":"Polarized secretion of lysosomal enzymes.","volume":"106","author":"Baron","year":"1988","journal-title":"J Cell Biol"},{"key":"2020071618423239900_R14","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0092-8674(92)90115-S","article-title":"Integrins, versatility, modulation and signaling in cell adhesion.","volume":"69","author":"Hynes","year":"1992","journal-title":"Cell"},{"key":"2020071618423239900_R15","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s004410100417","article-title":"Function and interaction of integrins.","volume":"305","author":"Van der Flier","year":"2001","journal-title":"Cell Tissue Res"},{"key":"2020071618423239900_R16","first-page":"S47","article-title":"Integrin function in osteoclasts","volume":"154","author":"Rodan","year":"1997","journal-title":"J Endocrinol"},{"key":"2020071618423239900_R17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s007740050055","article-title":"The role of integrins in osteoclast function.","volume":"17","author":"Duong","year":"1999","journal-title":"J Bone Miner Metab"},{"key":"2020071618423239900_R18","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","article-title":"Bone resorption by osteoclasts.","volume":"289","author":"Teitelbaum","year":"2000","journal-title":"Science"},{"key":"2020071618423239900_R19","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1210\/endo.132.3.8440195","article-title":"Inhibition of osteoclastic bone resorption in vivo by echistatin, an arginyl-glycyl-aspartyl (RGD)-containing protein.","volume":"132","author":"Fisher","year":"1993","journal-title":"Endocrinology"},{"key":"2020071618423239900_R20","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1172\/JCI119404","article-title":"A peptidomimetic antagonist of the \u03b1V\u03b23 integrin inhibits bone resorption in vitro and prevents osteoporosis in vivo.","volume":"99","author":"Engleman","year":"1997","journal-title":"J Clin Invest"},{"key":"2020071618423239900_R21","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1210\/endo.139.3.5831","article-title":"The integrin ligand echistatin prevents bone loss in ovariectomized mice and rats.","volume":"139","author":"Yamamoto","year":"1998","journal-title":"Endocrinology"},{"key":"2020071618423239900_R22","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S1359-6446(00)01545-2","article-title":"Identification and in vivo efficacy of small molecule antagonists of integrin \u03b1V\u03b23 (the vitronectin receptor).","volume":"5","author":"Miller","year":"2000","journal-title":"Drug Discov Today"},{"key":"2020071618423239900_R23","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1016\/S0960-894X(02)00743-6","article-title":"Non-peptide \u03b1V\u03b23 antagonists. Part 5: identification of potent RGD mimetics incorporating 2-aryl \u03b2 amino acids as aspartic acid replacements.","volume":"12","author":"Brashear","year":"2002","journal-title":"Bioorg Med Chem Lett"},{"key":"2020071618423239900_R24","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0960-894X(03)00254-3","article-title":"Non-peptide \u03b1V\u03b23 antagonists. Part 6: design and synthesis of \u03b1V\u03b23 antagonists containing a pyridone or pyrazinone central scaffold.","volume":"13","author":"Breslin","year":"2003","journal-title":"Bioorg Med Chem Lett"},{"key":"2020071618423239900_R25","doi-asserted-by":"crossref","first-page":"4790","DOI":"10.1021\/jm030306r","article-title":"Nonpeptide \u03b1V\u03b23 antagonists. 8. In vitro and in vivo evaluation of a potent \u03b1V\u03b23 antagonist for the prevention and treatment of osteoporosis.","volume":"46","author":"Hutchinson,","year":"2003","journal-title":"J Med Chem"},{"key":"2020071618423239900_R26","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0002-9343(99)80134-X","article-title":"Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling.","volume":"99","author":"Chesnut","year":"1995","journal-title":"Am J Med"},{"key":"2020071618423239900_R27","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1172\/JCI118722","article-title":"Bisphosphonates: mechanisms of action. J.","volume":"97","author":"Rodan","year":"1996","journal-title":"Clin Invest"},{"key":"2020071618423239900_R28","first-page":"711","article-title":"Therapeutic equivalence of alendronate 35 milligrams once weekly and 5 milligrams daily in the prevention of postmenopausal osteoporosis.","volume":"10","author":"Luckey","year":"2003","journal-title":"Obstet-Gynecol"},{"key":"2020071618423239900_R29","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1185\/030079904125003566","article-title":"Two-year efficacy and tolerability of risedronate once a year for the treatment of women with postmenopausal osteoporosis.","volume":"20","author":"Harris","year":"2004","journal-title":"Curr Med Res Opin"},{"key":"2020071618423239900_R30","first-page":"1","article-title":"Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis.","volume":"12","author":"Schnitzer","year":"2000","journal-title":"Aging"},{"key":"2020071618423239900_R31","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1359\/jbmr.2002.17.11.1988","article-title":"Two-year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis.","volume":"17","author":"Rizzoli","year":"2002","journal-title":"J Bone Miner Res"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/90\/4\/2022\/10775359\/jcem2022.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/90\/4\/2022\/10775359\/jcem2022.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T03:58:12Z","timestamp":1594958292000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/90\/4\/2022\/2836638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4,1]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2005,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2004-2126","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4,1]]}}}