RANKL inhibition with denosumab does not influence 3-year progression of aortic calcification or incidence of adverse cardiovascular events in postmenopausal women with osteoporosis and high cardiovascular risk.
RANKL inhibition with denosumab does not influence 3-year progression of aortic calcification or incidence of adverse cardiovascular events in postmenopausal women with osteoporosis and high cardiovascular risk.
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DOI：
10.1002/jbmr.2043
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发表时间：
2014-02
影响因子：
6.2
通讯作者：
Kiel, Douglas P.
中科院分区：
文献类型：
--
作者：
Samelson, Elizabeth J.;Miller, Paul D.;Christiansen, Claus;Daizadeh, Nadia S.;Grazette, Luanda;Anthony, Mary S.;Egbuna, Ogo;Wang, Andrea;Siddhanti, Suresh R.;Cheung, Angela M.;Franchimont, Nathalie;Kiel, Douglas P.
动脉粥样硬化和骨质疏松是随着年龄增长而进展的慢性疾病，研究表明动脉粥样硬化的指标主动脉钙化与BMD呈负相关。OPG/RANK/RANKL系统已被提议作为骨和血管系统的共享调节系统。狄诺塞麦（DMAb），一种抗RANKL的单克隆抗体，在FREEDOM试验中改善了BMD并降低了骨折风险。我们评估了DMAb治疗是否影响主动脉钙化（AC）的进展和心血管（CV）不良事件的发生率。我们纳入了2，363名绝经后骨质疏松症女性（1，142名安慰剂，1，221名DMAb），选自FREEDOM试验的7，808名参与者（3，906名安慰剂，3，902名DMAb），根据改良的雷洛昔芬用于心脏（RUTH）标准，这些女性具有CV事件的高风险。受试者报告了CV不良事件。采用半定量方法对侧位脊柱X线片进行AC评分。AC评分从基线至12个月（N = 1，377）、24个月（N = 1，231）和36个月（N = 1，045）的变化计算为随访时的AC评分减去基线时的AC评分。AC进展定义为AC评分变化> 0。治疗组间的基线特征、CV风险因素和AC评分相似。参与者的平均年龄为74岁（范围，60-90岁），88%为白色，77%的基线AC评分> 0。安慰剂组（22%）和DMAb组（22%）女性之间3年内AC进展的频率无差异（p = 0.98）。根据基线估计肾小球滤过率或基线AC评分分析时，治疗组间AC进展无差异。安慰剂组（40%）和DMAb组（38%）之间CV不良事件的频率无差异（p = 0.26）。总之，与安慰剂相比，DMAb治疗对AC进展或CV不良事件的发生率无影响。
Atherosclerosis and osteoporosis are chronic diseases that progress with age, and studies suggest aortic calcification, an indicator of atherosclerosis, is inversely associated with BMD. The OPG/RANK/RANKL system has been proposed as a shared regulatory system for bone and vasculature. Denosumab (DMAb), a monoclonal antibody against RANKL, improved BMD and reduced fracture risk in the FREEDOM trial. We evaluated whether or not treatment with DMAb influenced progression of aortic calcification (AC) and incidence of cardiovascular (CV) adverse events. We included 2,363 postmenopausal women with osteoporosis (1,142 placebo, 1,221 DMAb), selected from 7,808 participants in the FREEDOM trial (3,906 placebo, 3,902 DMAb), at high risk of CV events according to modified Raloxifene Use for the Heart (RUTH) criteria. CV adverse events were reported by participants. AC scores were assessed using a semi-quantitative method from lateral spine x-rays. Change in AC score from baseline to 12 (N = 1,377), 24 (N = 1,231) and 36 months (N = 1,045) was calculated as AC score at follow-up minus AC score at baseline. AC progression was defined as change in AC score > 0. Baseline characteristics, CV risk factors, and AC scores were similar between treatment groups. Mean age of participants was 74 years (range, 60–90), 88% were white, and 77% had AC score > 0 at baseline. Frequency of AC progression over 3 years did not differ between women in placebo (22%) and DMAb (22%) groups (p = 0.98). AC progression did not differ between treatment groups when analyzed by baseline estimated glomerular filtration rate or by baseline AC scores. Frequency of CV adverse events did not differ between placebo (40%) and DMAb (38%) groups (p = 0.26). In conclusion, DMAb treatment had no effect on progression of AC or incidence of CV adverse events compared to placebo.
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影响因子：
6.2
作者：
Jamal, Sophie A.;Ljunggren, Osten;Miller, Paul D.
通讯作者：
Miller, Paul D.
影响因子：
5.3
作者：
Kauppila, LI;Polak, JF;Wilson, PWF
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DOI：
10.1161/01.atv.0000236428.91125.e6
发表时间：
2006-09-01
影响因子：
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作者：
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作者：
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通讯作者：
Kostenuik, PJ
影响因子：
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作者：
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通讯作者：
Nishizawa, Y