Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women.
J Clin Endocrinol Metab
; 90(4): 2022-8, 2005 Apr.
Article
em En
| MEDLINE
| ID: mdl-15687321
ABSTRACT
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Densidade Óssea
/
Osteoporose Pós-Menopausa
/
Remodelação Óssea
/
Integrina alfaVbeta3
Tipo de estudo:
Clinical_trials
Limite:
Aged
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos