Relationship of Sympathetic Activity to Bone Microstructure, Turnover, and Plasma Osteopontin Levels in Women
Relationship of Sympathetic Activity to Bone Microstructure, Turnover, and Plasma Osteopontin Levels in Women
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DOI：
10.1210/jc.2012-2381
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发表时间：
2012-11-01
影响因子：
5.8
通讯作者：
Khosla, Sundeep
中科院分区：
文献类型：
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作者：
Farr, Joshua N.;Charkoudian, Nisha;Khosla, Sundeep
背景：对啮齿动物的研究表明，交感神经活动减少骨形成和骨量；这些效应是由非胶原基质蛋白骨桥蛋白介导的。目的：本研究的目的是将交感神经活性(通过腓神经显微神经成像测量)与骨微结构(通过高分辨率外周定量计算机断层扫描进行评估)、骨转换和血浆骨桥蛋白水平之间的关系。设计、背景和患者：在临床研究单元中有23名年龄在20-72岁的女性(10名绝经前和13名绝经后)。结果：与绝经前女性相比，绝经后女性的交感神经活性(每百次心跳爆发次数)高2.4倍(P<；0.001)。两组合并年龄调整后，交感神经活性与骨小梁体积分数(r=-0.55，P<；0.01)和厚度(r=-0.59，P<；0.01)呈负相关，与骨小梁间距(r=0.45，P<；0.05)呈正相关。交感神经活性与血清I型胶原氨基端前肽呈负相关(r=-0.65，P=0.015)，绝经前妇女交感神经活性与血清I型胶原氨基端前肽呈负相关(r=-0.58，P=0.082)。交感神经活性与血浆骨桥蛋白水平也呈负相关(r=-0.43，P=0.045)，这主要是由绝经后妇女的相关性驱动的(r=-0.76，P=0.002)。结论：这些发现首次证实了交感神经活性与骨微结构和循环中I型胶原氨基末端前肽和骨桥蛋白水平的关系。鉴于骨桥蛋白在调节β-肾上腺素能信号对骨的作用中的关键作用，交感神经活性与血浆骨桥蛋白水平之间的负关联可能反映了一个负反馈回路，以限制交感神经活动对骨代谢的有害影响。基于在绝经后妇女中观察到的较高的交感神经活性，需要更多的人类研究来确定交感神经活性增加在调节绝经后骨丢失中的作用。(临床内分泌代谢酶97：4219-4227,2012)
Context: Studies in rodents have demonstrated that sympathetic activity reduces bone formation and bone mass; these effects are mediated by the noncollagenous matrix protein, osteopontin.Objective: The objective of the study was to relate sympathetic activity (measured using micro-neurography at the peroneal nerve) to bone microstructure (assessed by high resolution peripheral quantitative computed tomography), bone turnover, and plasma osteopontin levels.Design, Setting, and Patients: Twenty-three women aged 20-72 yr (10 premenopausal and 13 postmenopausal) were studied in the Clinical Research Unit.Results: Sympathetic activity (bursts per 100 heart beats) was 2.4-fold higher in postmenopausal as compared with premenopausal women (P < 0.001). In the two groups combined and after age adjustment, sympathetic activity was inversely correlated with trabecular bone volume fraction (r = -0.55, P < 0.01) and thickness (r = -0.59, P < 0.01) and positively correlated with trabecular separation (r = 0.45, P < 0.05). Sympathetic activity was negatively correlated with serum amino-terminal propeptide of type I collagen in postmenopausal women (r = -0.65, P = 0.015), with a similar trend in premenopausal women (r = -0.58, P = 0.082). Sympathetic activity was also negatively correlated with plasma osteopontin levels (r = -0.43, P = 0.045), driven mainly by the correlation in postmenopausal women (r = -0.76, P = 0.002).Conclusion: These findings represent the first demonstration in humans of a relationship between sympathetic activity and bone microstructure and circulating levels of amino-terminal propeptide of type I collagen and osteopontin. Given the critical role of osteopontin in mediating the effects of beta-adrenergic signaling on bone, the inverse association between sympathetic activity and plasma osteopontin levels may reflect a negative feedback loop to limit the deleterious effects of sympathetic activity on bone metabolism. Based on the higher sympathetic activity observed in postmenopausal women, additional human studies are needed to define the role of increased sympathetic activity in mediating postmenopausal bone loss. (J Clin Endocrinol Metab 97:4219-4227, 2012)