Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial
Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial
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DOI：
10.1503/cmaj.161207
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发表时间：
2017-09-11
影响因子：
14.6
通讯作者：
Reid, Ian R.
中科院分区：
文献类型：
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作者：
Grey, Andrew;Bolland, Mark J.;Reid, Ian R.
背景：每年静脉注射唑来膦酸盐5 mg可降低骨折风险，每两年静脉注射5 mg可防止骨丢失，但这些适应症的最佳剂量方案尚不确定。方法：我们进行了一项为期2年的随机、安慰剂对照、双盲研究的3年开放标签延长研究。有骨量减少的绝经后晚期妇女被分配接受1毫克、2.5毫克或5毫克的单次基线剂量的唑来磷酸钠或安慰剂。主要结果是脊柱骨密度(BMD)的变化。次要结果是髋部骨密度和血清骨转换标志物的变化。结果：这项研究涉及160名女性。唑来膦酸盐以剂量依赖的方式增加骨密度，降低骨转换标志物。2年后，与安慰剂相比，1 mg、2.5 mg和5 mg的唑来磷酸钠使脊柱骨密度分别增加了5.0%(95%可信区间3.0%至7.0%)、5.7%(95%可信区间3.7%至7.7%)和5.7%(95%可信区间3.7%至7.6%)；5年后分别增加2.0%(95%可信区间-1.1%~5.0%)、2.2%(95%可信区间-1.0%~5.4%)和5.1%(95%可信区间2.2%~8.1%)。2年后，与安慰剂相比，1 mg、2.5 mg和5 mg的唑来膦酸盐组的总髋部骨密度分别增加了2.6%(95%可信区间1.3%至3.9%)、4.1%(95%可信区间2.9%至5.4%)和4.7%(95%可信区间3.4%至5.9%)；5年后分别增加1.8%(95%可信区间-0.1%~3.8%)、2.8%(95%可信区间0.8%~4.8%)和5.4%(95%可信区间3.5%~7.3%)。1-mg组BMD持续高于基线2-3年，2.5-mg组3-4年，5-mg组至少5年。干预：1-5 mg单剂唑来磷酸钠的抗吸收活性在绝经后骨质疏松症患者中持续至少3年。临床试验将有理由评估比目前推荐的更少频率或更低剂量的唑来磷酸钠对骨折风险的影响。
BACKGROUND: Intravenous zoledronate 5 mg annually reduces fracture risk, and 5 mg every 2 years prevents bone loss, but the optimal dosing regimens for these indications are uncertain.METHODS: We conducted a 3-year open-label extension of a 2-year randomized, placebo-controlled, double-blind study. Late postmenopausal women with osteopenia were assigned to receive a single baseline dose of 1 mg, 2.5 mg or 5 mg of zoledronate or placebo. The primary outcome was change in spine bone mineral density (BMD). Secondary outcomes were changes in hip BMD and serum markers of bone turnover.RESULTS: The study involved 160 women. Zoledronate increased BMD and reduced markers of bone turnover in a dose-dependent manner. After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased spine BMD over placebo by 5.0% (95% confidence interval [CI] 3.0% to 7.0%), 5.7% (95% CI 3.7% to 7.7%) and 5.7% (95% CI 3.7% to 7.6%), respectively; after 5 years, the respective increases were 2.0% (95% CI -1.1% to 5.0%), 2.2% (95% CI -1.0% to 5.4%) and 5.1% (95% CI 2.2% to 8.1%). After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased total hip BMD over placebo by 2.6% (95% CI 1.3% to 3.9%), 4.1% (95% CI 2.9% to 5.4%) and 4.7% (95% CI 3.4% to 5.9%), respectively; after 5 years, the respective increases were 1.8% (95% CI -0.1% to 3.8%), 2.8% (95% CI 0.8% to 4.8%) and 5.4% (95% CI 3.5% to 7.3%). BMD remained above baseline values for 2-3 years in the 1-mg group, 3-4 years in the 2.5-mg group and at least 5 years in the 5-mg group.INTERPRETATION: The antiresorptive activity of single zoledronate doses of 1-5 mg persist for at least 3 years in postmenopausal women with osteopenia. Clinical trials would be justified to evaluate the effects on fracture risk of less frequent or lower doses of zoledronate than are currently recommended.