Inderjeeth Charles A, Glendenning Paul, Ratnagobal Shoba, Inderjeeth Diren Che, Ondhia Chandni
Department of Geriatric Medicine and Rheumatology, North Metropolitan Health Service, WA, Australia ; School of Medicine and Pharmacology, University of Western Australia, WA, Australia.
School of Medicine and Pharmacology, University of Western Australia, WA, Australia ; Department of Clinical Biochemistry, PathWest Royal Perth Hospital, Perth, WA, Australia.
Int J Womens Health. 2014 Dec 17;7:7-17. doi: 10.2147/IJWH.S73944. eCollection 2015.
Several second-generation bisphosphonates (BPs) are approved in osteoporosis treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate synthase (FPPS) inhibition, hydroxyapatite affinity, compliance and adherence. The latter may be influenced by frequency and route of administration. A literature search using "ibandronate", "postmenopausal osteoporosis", "fracture", and "bone mineral density" (BMD) revealed 168 publications. The Phase III BONE study, using low dose 2.5 mg daily oral ibandronate demonstrated 49% relative risk reduction (RRR) in clinical vertebral fracture after 3 years. Non-vertebral fracture (NVF) reduction was demonstrated in a subgroup (pretreatment T-score ≤ -3.0; RRR 69%) and a meta-analysis of high annual doses (150 mg oral monthly or intravenous equivalent of ibandronate; RRR 38%). Hip fracture reduction was not demonstrated. Long-term treatment efficacy has been confirmed over 5 years. Long term safety is comparable to placebo over 3 years apart from flu-like symptoms which are more common with oral monthly and intravenous treatments. No cases of atypical femoral fracture or osteonecrosis of the jaw have been reported in randomized controlled trial studies. Ibandronate inhibits FPPS more than alendronate but less than other BPs which could explain rate of action onset. Ibandronate has a higher affinity for hydroxyapatite compared with risedronate but less than other BPs which could affect skeletal distribution and rate of action offset. High doses (150 mg oral monthly or intravenous equivalent) were superior to low doses (oral 2.5 mg daily) according to 1 year BMD change. Data are limited by patient selection, statistical power, under-dosing, and absence of placebo groups in high dose studies. Ibandronate treatment offers different doses and modalities of administration which could translate into higher adherence rates, an important factor when the two main limitations of BP treatment are initiation and adherence rates. However, lack of consistency in NVF reduction and absence of hip fracture data limits more generalized use of this agent.
几种第二代双膦酸盐（BP）已被批准用于骨质疏松症治疗。疗效和安全性取决于法尼基焦磷酸合酶（FPPS）抑制的效力、对羟基磷灰石的亲和力、依从性和坚持性。后者可能受给药频率和途径的影响。使用“伊班膦酸钠”、“绝经后骨质疏松症”、“骨折”和“骨密度”（BMD）进行的文献检索共找到168篇出版物。III期BONE研究使用低剂量每日口服2.5毫克伊班膦酸钠，结果显示3年后临床椎体骨折的相对风险降低（RRR）49%。在一个亚组（治疗前T值≤ -3.0；RRR 69%）以及对高年剂量（每月口服150毫克或伊班膦酸钠静脉注射等效剂量；RRR 38%）的荟萃分析中显示非椎体骨折（NVF）减少。未显示髋部骨折减少。超过5年的长期治疗疗效已得到证实。除了口服每月一次和静脉注射治疗更常见的类流感症状外，3年的长期安全性与安慰剂相当。在随机对照试验研究中未报告非典型股骨骨折或颌骨坏死病例。伊班膦酸钠对FPPS的抑制作用比对阿仑膦酸钠强，但比其他双膦酸盐弱，这可能解释了作用起效速度。与利塞膦酸钠相比，伊班膦酸钠对羟基磷灰石的亲和力更高，但比其他双膦酸盐低，这可能影响骨骼分布和作用抵消速度。根据1年的骨密度变化，高剂量（每月口服150毫克或静脉注射等效剂量）优于低剂量（每日口服2.5毫克）。数据受到患者选择、统计效力、剂量不足以及高剂量研究中缺乏安慰剂组的限制。伊班膦酸钠治疗提供了不同的剂量和给药方式，这可能转化为更高的依从率，而依从率是双膦酸盐治疗的两个主要限制因素即起始治疗和依从率中的一个重要因素。然而，非椎体骨折减少缺乏一致性以及缺乏髋部骨折数据限制了该药物更广泛的应用。
