Grey Andrew, Bolland Mark, Mihov Bobby, Wong Sumwai, Horne Anne, Gamble Greg, Reid Ian R
Department of Medicine, University of Auckland, Auckland, New Zealand.
J Bone Miner Res. 2014 Jan;29(1):166-72. doi: 10.1002/jbmr.2009.
Annual intravenous administration of 5 mg zoledronate decreases fracture risk, but the optimal dosing regimen for zoledronate has not been determined. We set out to evaluate the antiresorptive effects of a single administration of lower doses of zoledronate. A total of 180 postmenopausal women with osteopenia enrolled in a double-blind, randomized, placebo-controlled trial over 2 years at an academic research center. Participants were randomized to a single baseline administration of intravenous zoledronate in doses of 1 mg, 2.5 mg, or 5 mg, or placebo. The primary endpoint was change in bone mineral density(BMD) at the lumbar spine. Secondary endpoints were change in BMD at the proximal femur and total body, and changes in biochemical markers of bone turnover. After 2 years, the change in spine BMD was greater in each of the zoledronate groups than in the placebo group; values are mean (95% confidence interval [CI]) difference versus placebo: zoledronate 1 mg 4.4% [2.7% to 6.1%]; 2.5 mg 5.5% [3.9% to 7.2%]; 5 mg 5.3% [3.8% to 6.7%], p < 0.001 for each dose). Change in BMD at the total hip was greater in each of the zoledronate groups than the placebo group (mean [95% CI] difference versus placebo: zoledronate 1 mg 2.6% [1.5% to 3.7%]; 2.5 mg 4.4% [3.5% to 5.3%]; 5 mg 4.7% [3.7% to 5.7%], p < 0.001 for each dose). Each of the bone turnover markers, β-C-terminal telopeptide of type I collagen (β-CTX) and procollagen type-I N-terminal propeptide (P1NP), was lower in each of the 2.5-mg and 5-mg zoledronate groups than the placebo group throughout the trial (p < 0.001 versus placebo for each marker for each dose at each time point). For each endpoint, changes were similar in the 2.5-mg and 5-mg zoledronate groups, whereas those in the 1-mg group were smaller than those in the other zoledronate groups. These data demonstrate that single administrations of zoledronate 1 mg or 2.5 mg produce antiresorptive effects that persist for at least 2 years. Trials assessing the antifracture efficacy of intermittent low doses of zoledronate, in particular the 2.5-mg dose, are justified.
每年静脉注射5毫克唑来膦酸可降低骨折风险，但唑来膦酸的最佳给药方案尚未确定。我们着手评估单次给予较低剂量唑来膦酸的抗吸收作用。在一个学术研究中心，共有180名患有骨质减少的绝经后妇女参加了一项为期2年的双盲、随机、安慰剂对照试验。参与者被随机分为单次基线静脉注射1毫克、2.5毫克或5毫克唑来膦酸，或安慰剂。主要终点是腰椎骨密度（BMD）的变化。次要终点是股骨近端和全身BMD的变化，以及骨转换生化标志物的变化。2年后，各唑来膦酸组的脊柱BMD变化均大于安慰剂组；数值为与安慰剂相比的平均（95%置信区间[CI]）差异：唑来膦酸1毫克4.4%[2.7%至6.1%]；2.5毫克5.5%[3.9%至7.2%]；5毫克5.3%[3.8%至6.7%]，各剂量组p<0.001）。各唑来膦酸组的全髋BMD变化均大于安慰剂组（与安慰剂相比的平均[95%CI]差异：唑来膦酸1毫克2.6%[1.5%至3.7%]；2.5毫克4.4%[3.5%至5.3%]；5毫克4.7%[3.7%至5.7%]，各剂量组p<0.001）。在整个试验过程中，2.5毫克和5毫克唑来膦酸组的每种骨转换标志物，即I型胶原β-羧基末端肽（β-CTX）和I型前胶原N末端前肽（P1NP），均低于安慰剂组（各时间点各剂量组每种标志物与安慰剂相比p<0.001）。对于每个终点，2.5毫克和5毫克唑来膦酸组的变化相似，而1毫克组的变化小于其他唑来膦酸组。这些数据表明，单次给予1毫克或2.5毫克唑来膦酸可产生持续至少2年的抗吸收作用。评估间歇性低剂量唑来膦酸，特别是2.5毫克剂量的抗骨折疗效的试验是合理的。
