Effect of L-000845704, an αVβ3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women

M. G. Murphy, K. Cerchio, S. A. Stoch, K. Gottesdiener, M. Wu, Robert R. Recker

Research output: Contribution to journalArticle

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Abstract

The αVβ3 integrin (vitronectin receptor) plays a pivotal role in bone resorption. We hypothesized that L-000845704, an αVβ3 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 αVβ3 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 αVβ3 integrin antagonist L-000845704 could be developed as an effective therapeutic agent for osteoporosis.

Original languageEnglish
Pages (from-to)2022-2028
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number4
DOIs
StatePublished - Apr 2005

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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