Grey Andrew, Bolland Mark J, Horne Anne, Mihov Borislav, Gamble Greg, Reid Ian R
Department of Medicine, University of Auckland, Auckland, New Zealand
Department of Medicine, University of Auckland, Auckland, New Zealand.
CMAJ. 2017 Sep 11;189(36):E1130-E1136. doi: 10.1503/cmaj.161207.
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.
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.
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.
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.
www.anzctr.org.au, no. ACTRN12607000576426.
每年静脉注射5毫克唑来膦酸可降低骨折风险，每两年注射5毫克可预防骨质流失，但这些适应证的最佳给药方案尚不确定。
我们对一项为期2年的随机、安慰剂对照、双盲研究进行了为期3年的开放标签扩展研究。将绝经后骨质疏松症晚期女性分为接受单次基线剂量1毫克、2.5毫克或5毫克唑来膦酸或安慰剂。主要结局是脊柱骨矿物质密度（BMD）的变化。次要结局是髋部BMD和骨转换血清标志物的变化。
该研究纳入了160名女性。唑来膦酸以剂量依赖性方式增加BMD并降低骨转换标志物。2年后，1毫克、2.5毫克和5毫克唑来膦酸剂量组的脊柱BMD较安慰剂组分别增加了5.0%（95%置信区间[CI]3.0%至7.0%）、5.7%（95%CI 3.7%至7.7%）和5.7%（95%CI 3.7%至7.6%）；5年后，相应的增加分别为2.0%（95%CI -1.1%至5.0%）、2.2%（95%CI -1.0%至5.4%）和5.1%（95%CI 2.2%至8.1%）。2年后，1毫克、2.5毫克和5毫克唑来膦酸剂量组的全髋BMD较安慰剂组分别增加了2.6%（95%CI 1.3%至3.9%）、4.1%（95%CI 2.9%至5.4%）和4.7%（95%CI 3.4%至5.9%）；5年后，相应的增加分别为1.8%（95%CI -0.1%至3.8%）、2.8%（95%CI 0.8%至4.8%）和5.4%（95%CI 3.5%至7.3%）。1毫克组的BMD在2 - 3年内保持高于基线值，2.5毫克组在3 - 4年内保持高于基线值，5毫克组至少5年内保持高于基线值。
在绝经后骨质疏松症女性中，单次1 - 5毫克唑来膦酸剂量的抗吸收活性持续至少3年。进行临床试验以评估比目前推荐剂量更低或给药频率更低的唑来膦酸对骨折风险的影响是合理的。
