Burn Injury Has Skeletal Site-Specific Effects on Bone Integrity and Markers of Bone Remodeling.
Burn Injury Has Skeletal Site-Specific Effects on Bone Integrity and Markers of Bone Remodeling.
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烧伤对骨完整性和骨重塑标志物具有骨骼部位特异性影响。
DOI：
10.1097/bcr.0000000000000389
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Callaci,John
中科院分区：
文献类型：
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作者：
Hoscheit,Matthew;Conner,Grant;Roemer,James;Vuckovska,Aleksanhdra;Abbasnia,Pegah;Vana,Paul;Shankar,Ravi;Kennedy,Richard;Callaci,John
为了进一步了解严重烧伤后骨重建扰动的机制，在损伤后6周内的6个时间间隔内对啮齿动物的生物力学特性、基因表达和血清学标记物进行了评价。此外，在啮齿动物胫骨和腰椎中观察到这些效应，以探索这种病理性骨丢失的可能骨骼部位定位。啮齿动物经历热损伤（100°C水，30秒，30%BSA）或假烧伤。通过外周定量计算机断层扫描评估骨密度，并使用专用仪器测量胫骨和腰椎的承重能力。在损伤后7、14和21天测量骨吸收（RANK配体，骨钙素）和骨形成（骨保护素，1型前胶原酶α 2）的标志物，并在这些时间间隔观察血清RANK配体水平。啮齿动物的体重，骨密度和负重能力受到负面影响，急性和烧伤后几周。此外，还证实了有利于骨吸收增加和骨形成降低的基因表达谱。我们的血清分析结果显示，损伤后1周和2周RANKL显著增加，这支持骨吸收标志物表达增加。此外，这些影响发生得更快，在啮齿动物腰椎比胫骨更明显。这些结果表明，严重烧伤导致继发于骨吸收增加和骨形成减少的骨重建扰动，影响骨矿物质密度和承重能力。此外，这些过程在腰椎中具有更明显的骨骼部位效应。随着对烧伤骨丢失机制的更好理解，可以实施靶向治疗以改善长期临床结果。
To further understand the mechanisms of perturbations in bone remodeling following severe burn injury, the biomechanical properties, genetic expression, and serological markers were evaluated in rodents at six time intervals within 6 weeks following injury. Moreover, these effects were observed in rodent tibia and lumbar vertebrae to explore possible skeletal site localization of this pathologic bone loss. Rodents underwent either thermal injury (100°C water, 30 seconds, 30% BSA) or sham burn. Bone mineral density was evaluated though peripheral quantitative computer tomography, and specialized apparatus measured the weight bearing capacity of tibia and lumbar vertebrae. Markers of bone resorption (RANK ligand, osteocalcin) and bone formation (osteoprotegerin, procollagenase type 1 alpha 2) were measured at 7, 14, and 21 days following injury, and serum RANK-ligand levels were observed at these time intervals. Rodent body mass, bone mineral density, and weight bearing capacity were negatively influenced both acutely and several weeks following burn injury. Moreover, a genetic expression profile favoring increased bone resorption and lower bone formation was demonstrated. Our serum analysis findings of significantly increased RANKL 1 and 2 weeks following injury support the increased expression of bone resorption markers. Furthermore, these effects occurred sooner and were more pronounced in the rodent lumbar vertebrae than tibia. These results suggest that severe burn injury results in perturbations in bone remodeling secondary to increased bone resorption and diminished bone formation, impacting both bone mineral density and weight bearing capacity. Furthermore, these processes had a skeletal site effect more pronounced in the lumbar vertebrae. With a better understanding of the mechanisms of burn-injury bone loss, targeted therapies can be implemented to improve long-term clinical outcomes.