Preliminary evidence of early bone resorption in a sheep model of acute burn injury: an observational study.
Preliminary evidence of early bone resorption in a sheep model of acute burn injury: an observational study.
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DOI：
10.1007/s00774-013-0483-4
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发表时间：
2014-03
影响因子：
3.3
通讯作者：
Bonewald LF
中科院分区：
文献类型：
--
作者：
Klein GL;Xie Y;Qin YX;Lin L;Hu M;Enkhbaatar P;Bonewald LF
在严重烧伤的前10天内使用双膦酸盐治疗可以完全防止骨丢失。因此，我们推测骨吸收发生在烧伤后早期，是这些患者急性骨丢失的主要原因。我们的目的是评估烧伤后早期骨吸收的组织学和生物力学证据。我们设计了一项随机对照研究，利用绵羊烧伤模型。三只绵羊在异氟烷麻醉下接受40%总体表面积烧伤，另外三只绵羊接受棉烟吸入并作为对照。烧伤绵羊在术后5天处死，对照组在术后2天处死。对死后沿着获得的髂嵴进行背散射扫描电子显微镜检查，同时进行定量组织形态测定和压缩试验，以确定骨强度（杨氏模量）。还在手术后前24小时测定了血液离子钙和尿CTx。在第5天处死的3只绵羊中，有3只存在骨表面扇贝形的证据，这是骨吸收的影响，而在术后2天处死的3只绵羊中没有一只存在扇贝形。与假手术对照组相比，在第5天处死的三只烧伤绵羊中的一只显示出侵蚀表面的定量加倍和骨体积的减半。与对照组相比，在第5天处死的烧伤绵羊的杨氏模量平均值约低三分之一，通过非配对t检验，p = 0.08，表明骨较弱。这些数据表明烧伤后早期骨吸收。在术后24小时，尿CTx标准化为肌酐在两组之间没有差异，因为烧伤绵羊接受的大量液体可能稀释了尿肌酐和CTx，并且因为烧伤绵羊产生的尿量是对照组的三倍。我们计算了24小时尿CTx排泄量，并与此计算CTx排泄量/24小时在烧伤羊几乎是对照组的两倍。此外，在前24小时内，在烧伤和对照绵羊中以3至6小时的间隔测量的全血离子化Ca在烧伤绵羊中显示出相对于基线降低6%，而在对照动物中降低<1%。该绵羊模型先前用于证明在本研究的时间范围内甲状旁腺钙敏感受体的上调。因为本研究支持的早期骨吸收和钙敏感受体上调（与观察到的血液离子化Ca减少一致）均由作为烧伤后全身炎症反应一部分存在的促炎细胞因子介导，我们可以假设，烧伤后甲状旁腺钙敏感受体的上调可能是一种适应性反应，以清除血液中由细胞因子释放的过量钙，介导的骨吸收。
Treatment with bisphosphonates within the first 10 days of severe burn injury completely prevents bone loss. We therefore postulated that bone resorption occurs early post burn and is the primary explanation for acute bone loss in these patients. Our objective was to assess bone for histological and biomechanical evidence of early resorption post burn. We designed a randomized controlled study utilizing a sheep model of burn injury. Three sheep received a 40 % total body surface area burn under isoflurane anesthesia, and three other sheep received cotton-smoke inhalation and served as control. Burned sheep were killed 5 days post procedure and controls were killed 2 days post procedure. Backscatter scanning electron microscopy was performed on iliac crests obtained immediately postmortem along with quantitative histomorphometry and compression testing to determine bone strength (Young’s modulus). Blood ionized Ca was also determined in the first 24 h post procedure as was urinary CTx. Three of three sheep killed at 5 days had evidence of scalloping of the bone surface, an effect of bone resorption, whereas none of the three sheep killed at 2 days post procedure had scalloping. One of the three burned sheep killed at 5 days showed quantitative doubling of the eroded surface and halving of the bone volume compared to sham controls. Mean values of Young’s modulus were approximately one third lower in the burned sheep killed at 5 days compared to controls, p = 0.08 by unpaired t test, suggesting weaker bone. These data suggest early post-burn bone resorption. Urine CTx normalized to creatinine did not differ between groups at 24 h post procedure because the large amounts of fluids received by the burned sheep may have diluted urine creatinine and CTx and because the urine volume produced by the burned sheep was threefold that of the controls. We calculated 24 h urinary CTx excretion, and with this calculation CTx excretion/24 h in the burned sheep was nearly twice that of the controls. Moreover, whole blood ionized Ca measured at 3- to 6-h intervals over the first 24 h in both burn and control sheep showed a 6 % reduction versus baseline in the burned sheep with <1 % reduction in the control animals. This sheep model was previously used to demonstrate upregulation of the parathyroid calcium-sensing receptor within the timeframe of the present study. Because both early bone resorption, supported by this study, and calcium-sensing receptor upregulation, consistent with the observed reduction in blood ionized Ca, are mediated by proinflammatory cytokines that are present as part of the post-burn systemic inflammatory response, we may postulate that post-burn upregulation of the parathyroid calcium-sensing receptor may be an adaptive response to clear the blood of excess calcium liberated by cytokine-mediated bone resorption.