Ibandronate treatment for osteoporosis: Rationale, preclinical, and clinical development of extended dosing regimens

被引:6
作者
Epstein S. [1 ]
机构
[1] Mount Sinai Medical Center, New York, NY 10029, One Gustave Levy Place
关键词
Bone Mineral Density; Vertebral Fracture; Bone Turnover; Alendronate; Ibandronate;
D O I
10.1007/s11914-006-0010-9
中图分类号
学科分类号
摘要
Ibandronate is a potent nitrogen-containing bisphosphonate available as a once-monthly oral formulation for the treatment and prevention of osteoporosis. Preclinical experiments with estrogen-depleted rats, dogs, and monkeys demonstrated the efficacy of daily and intermittent ibandronate dosing. Initial clinical trials explored the optimal dosing regimens for oral administration in humans. The Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE) and Monthly Oral Ibandronate in Ladies (MOBILE) trials demonstrated that long-term daily and intermittent administration of ibandronate was efficacious for increasing bone mineral density, reducing markers of bone turnover, and preventing fractures, while maintaining bone quality. These preclinical and clinical ibandronate trials provided progressive evidence that a simple, long interval dosing regimen could offer efficacy and safety comparable with currently available bisphosphonates. It is anticipated that once-monthly ibandronate may have a positive impact on patient adherence, and ultimately, on fracture protection in osteoporotic women. Copyright © 2006 by Current Science Inc.
引用
收藏
页码:14 / 20
页数:6
相关论文
共 50 条
[1]
Fleisch H.A., Bisphosphonates: Preclinical aspects and use in osteoporosis, Ann Med, 29, pp. 55-62, (1997)
[2]
Rogers M.J., New insights into the molecular mechanisms of action of bisphosphonates, Curr Pharm des, 9, pp. 2643-2658, (2003)
[3]
Fleisch H., Bisphosphonates: Mechanisms of action, Endocr Rev, 19, pp. 80-100, (1998)
[4]
Sato M., Grasser W., Endo N., Et al., Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure, J Clin Invest, 88, pp. 2095-2105, (1991)
[5]
Frith J.C., Monkkonen J., Auriola S., Et al., The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: Evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis, Arthritis Rheum, 44, pp. 2201-2210, (2001)
[6]
Coxon F.P., Rogers M.J., The role of prenylated small GTP-binding proteins in the regulation of osteoclast function, Calcif Tissue Int, 72, pp. 80-84, (2003)
[7]
Reszka A.A., Rodan G.A., Mechanism of action of bisphosphonates, Curr Osteoporos Rep, 1, pp. 45-52, (2003)
[8]
Balena R., Toolan B.C., Shea M., Et al., The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates, J Clin Invest, 92, pp. 2577-2586, (1993)
[9]
Ott S.M., Clinical effects of bisphosphonates in involutional osteoporosis, J Bone Miner Res, 8, SUPPL. 2, (1993)
[10]
Flora L., Hassing G.S., Cloyd G.G., Et al., The long-term skeletal effects of EHDP in dogs, Metab Bone Dis Relat Res, 3, pp. 289-300, (1981)