Puthucheary Zudin A, Sun Yao, Zeng Kaiyang, Vu Lien Hong, Zhang Zhi Wei, Lim Ryan Z L, Chew Nicholas S Y, Cove Matthew E
Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore.
Adult Intensive Care Unit, Royal Brompton Hospital, London, United Kingdom.
Crit Care Med. 2017 Dec;45(12):e1254-e1261. doi: 10.1097/CCM.0000000000002732.
Survivors of critical illness have an increased prevalence of bone fractures. However, early changes in bone strength, and their relationship to structural changes, have not been described. We aimed to characterize early changes in bone functional properties in critical illness and their relationship to changes in bone structure, using a sepsis rodent model.
Experimental study.
Animal research laboratory.
Adult Sprague-Dawley rats.
Forty Sprague-Dawley rats were randomized to cecal ligation and puncture or sham surgery. Twenty rodents (10 cecal ligation and puncture, 10 sham) were killed at 24 hours, and 20 more at 96 hours.
Femoral bones were harvested for strength testing, microCT imaging, histologic analysis, and multifrequency scanning probe microscopy. Fracture loads at the femoral neck were significantly reduced for cecal ligation and puncture-exposed rodents at 24 hours (83.39 ± 10.1 vs 103.1 ± 17.6 N; p = 0.014) and 96 hours (81.60 ± 14.2 vs 95.66 ± 14.3 N; p = 0.047). Using multifrequency scanning probe microscopy, collagen elastic modulus was lower in cecal ligation and puncture-exposed rats at 24 hours (1.37 ± 0.2 vs 6.13 ± 0.3 GPa; p = 0.001) and 96 hours (5.57 ± 0.5 vs 6.13 ± 0.3 GPa; p = 0.006). Bone mineral elastic modulus was similar at 24 hours but reduced in cecal ligation and puncture-exposed rodents at 96 hours (75.34 ± 13.2 vs 134.4 ± 8.2 GPa; p < 0.001). There were no bone architectural or bone mineral density differences by microCT. Similarly, histologic analysis demonstrated no difference in collagen and elastin staining, and C-X-C chemokine receptor type 4, nuclear factor kappa beta, and tartrate-resistant acid phosphatase immunostaining.
In a rodent sepsis model, trabecular bone strength is functionally reduced within 24 hours and is associated with a reduction in collagen and mineral elastic modulus. This is likely to be the result of altered biomechanical properties, rather than increased bone mineral turnover. These data offer both mechanistic insights and may potentially guide development of therapeutic interventions.
危重症幸存者骨折患病率增加。然而，骨强度的早期变化及其与结构变化的关系尚未得到描述。我们旨在利用脓毒症啮齿动物模型，描述危重症时骨功能特性的早期变化及其与骨结构变化的关系。
实验研究。
动物研究实验室。
成年Sprague-Dawley大鼠。
40只Sprague-Dawley大鼠被随机分为盲肠结扎穿刺组或假手术组。20只啮齿动物（10只盲肠结扎穿刺，10只假手术）在24小时时处死，另外20只在96小时时处死。
采集股骨进行强度测试、显微CT成像、组织学分析和多频扫描探针显微镜检查。盲肠结扎穿刺组啮齿动物在24小时（83.39±10.1 vs 103.1±17.6 N；p = 0.014）和96小时（81.60±14.2 vs 95.66±14.3 N；p = 0.047）时股骨颈骨折负荷显著降低。使用多频扫描探针显微镜检查，盲肠结扎穿刺组大鼠在24小时（1.37±0.2 vs 6.13±0.3 GPa；p = 0.001）和96小时（5.57±0.5 vs 6.13±0.3 GPa；p = 0.006）时胶原弹性模量较低。骨矿物质弹性模量在2�小时时相似，但在盲肠结扎穿刺组啮齿动物96小时时降低（75.34±13.2 vs 134.4±8.2 GPa；p<0.001）。显微CT检查未见骨结构或骨密度差异。同样，组织学分析显示胶原和弹性蛋白染色、C-X-C趋化因子受体4、核因子κB和抗酒石酸酸性磷酸酶免疫染色均无差异。
在啮齿动物脓毒症模型中，小梁骨强度在24小时内功能降低，且与胶原和矿物质弹性模量降低有关。这可能是生物力学特性改变的结果，而非骨矿物质周转率增加。这些数据提供了机制性见解，并可能潜在指导治疗干预措施的开发。
