A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate
A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate
复制标题
双膦酸盐治疗的新概念：开发每月口服伊班膦酸盐的基本原理
作者：
J. Reginster;D. Felsenberg;C. Cooper;J. Stakkestad;P. Miller;D. Kendler;S. Adami;M. McClung;M. Bolognese;R. Civitelli;E. Dumont;B. Bonvoisin;R. Recker;P. Delmas
每日和每周口服双膦酸盐是目前治疗绝经后骨质疏松症（PMO）的主要方法。然而，已知频繁给药的不便会对长期治疗依从性产生负面影响。这促使了方便的口服双膦酸盐方案的发展，其特点是简单，频率较低的给药方案。这样的方案需要高效力的药剂，其可以以低有效剂量给予并且还具有良好的耐受性。伊班膦酸盐是一种强效的含氮双膦酸盐，在雌激素耗竭的比格犬、大鼠和食蟹猴中间歇给药时具有已证实的疗效。在临床上，一项关键的前瞻性研究已经确定，口服伊班膦酸盐对PMO具有显著的椎骨骨折疗效，无论是每日给药（2.5 mg）还是间歇给药（每隔一天20 mg，每3个月给药12次;延长给药间隔>2个月）。两种口服方案均耐受良好，值得注意的是，未特别排除有胃肠道（GI）紊乱病史的患者。由于这些发现，一项大型、多国、随机、双盲研究（每月一次口服伊班膦酸钠：移动的）目前正在探索每月一次口服伊班膦酸钠（100或150 mg）与每日一次口服伊班膦酸钠（2.5 mg）方案在腰椎骨密度（BMD）变化方面的非劣效性，该方案已被证明具有抗骨折疗效。与研究其他双膦酸盐每周给药的试验一样，如果研究证明每月一次的伊班膦酸盐在脊柱BMD变化方面非劣效于经证实的每日口服方案，则可推断椎体骨折疗效。这种每月一次的伊班膦酸盐方案的可用性预计将在方便性（必须遵循每月一次与每日或每周一次的给药建议）和潜在的耐受性（通过减少频繁重复暴露可能导致的上消化道刺激的可能性）方面提供益处。更大的便利性和耐受性可能会提高治疗依从性，从而改善PMO的长期治疗结果。
Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Such regimens require high potency agents, which can be given at low effective doses and that also have good tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats and cynomolgus monkeys. Clinically, a pivotal prospective study has established that oral ibandronate has significant vertebral fracture efficacy in PMO, whether given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months; extended between-dose interval >2 months). Both oral regimens were well tolerated, which is noteworthy as patients with a history of gastrointestinal (GI) disturbance were not specifically excluded. As a result of these findings, a large, multinational, randomized, double-blind study (Monthly Oral iBandronate In LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with proven anti-fracture efficacy, in terms of lumbar spine bone mineral density (BMD) change. As with the trials investigating the weekly administration of other bisphosphonates, vertebral fracture efficacy will be inferred if the study demonstrates the non-inferiority of once-monthly ibandronate to the proven oral daily regimen in terms of spinal BMD change. The availability of this once-monthly ibandronate regimen is expected to offer benefits in terms of convenience (by having to follow dosing recommendations once a month vs. once daily or weekly) and potentially tolerability (by reducing the potential for upper GI irritation that can result from frequent, repeated exposure). Greater convenience and tolerability may enhance the therapy adherence and, hence, improve long-term therapeutic outcomes in PMO.
影响因子：
5.9
作者：
Tosteson, ANA;Grove, MR;Ettinger, B
通讯作者：
Ettinger, B