Source:http://linkedlifedata.com/resource/pubmed/id/15687321
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2005-4-7
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pubmed:abstractText |
The alphaVbeta3 integrin (vitronectin receptor) plays a pivotal role in bone resorption. We hypothesized that L-000845704, an alphaVbeta3 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. -0.1% for placebo; P < 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 < 0.03) and femoral neck (2.4 vs. 0.7% for placebo; P < 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 < 0.001 vs. placebo). L-000845704 was generally well tolerated; adverse events resulting in discontinuation from the study were relatively infrequent. In conclusion, the antiresorptive effect of the alphaVbeta3 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 alphaVbeta3 integrin antagonist L-000845704 could be developed as an effective therapeutic agent for osteoporosis.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-972X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
90
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2022-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15687321-Aged,
pubmed-meshheading:15687321-Bone Density,
pubmed-meshheading:15687321-Bone Remodeling,
pubmed-meshheading:15687321-Bone Resorption,
pubmed-meshheading:15687321-Double-Blind Method,
pubmed-meshheading:15687321-Female,
pubmed-meshheading:15687321-Humans,
pubmed-meshheading:15687321-Integrin alphaVbeta3,
pubmed-meshheading:15687321-Middle Aged,
pubmed-meshheading:15687321-Osteogenesis,
pubmed-meshheading:15687321-Osteoporosis, Postmenopausal
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pubmed:year |
2005
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pubmed:articleTitle |
Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women.
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pubmed:affiliation |
Merck Research Laboratories, Building 5W, Sentry Rahway, NJ 07065, USA. Gail_Murphy@Merck.com
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Randomized Controlled Trial,
Research Support, Non-U.S. Gov't,
Multicenter Study
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