TY - JOUR
T1 - Effect of L-000845704, an αVβ3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women
AU - Murphy, M. G.
AU - Cerchio, K.
AU - Stoch, S. A.
AU - Gottesdiener, K.
AU - Wu, M.
AU - Recker, R.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2004-2126
DO - 10.1210/jc.2004-2126
M3 - Article
C2 - 15687321
AN - SCOPUS:17844399226
VL - 90
SP - 2022
EP - 2028
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
ER -