Wenger Karl H, Zumbrun Steven D, Rosas Militza, Dickinson Douglas P, McPherson James C
Department of Clinical Investigation, Dwight D. Eisenhower Army Medical Center, Fort Gordon, 30905, Georgia.
General Dynamics Information Technology, Frederick, MD, 21703, USA.
J Orthop. 2020 Jan 28;20:251-256. doi: 10.1016/j.jor.2020.01.036. eCollection 2020 Jul-Aug.
Fracture healing often requires extended convalescence as the bony fragments consolidate into restored viable tissue for load-bearing. Development of interventions to improve healing remains a priority for orthopaedic research. The goal of this study was to evaluate the ability of a naturally occurring matrix of amorphous calcium carbonate to affect fracture healing in an uninstrumented long bone model.
Complete transverse fracture was induced in the fibula of mature mice, followed by daily gavage of crushed gastrolith from crayfish at doses of 0 (control), 1 (1 MG), and 5 (5 MG) mg/kg. At Day 17, bones and sera were harvested.
Morphologically, the 1 MG treated group had greater bone volume (BV), and both 1 MG and 5 MG had greater tissue volume (TV) than control (p < 0.05), as determined by μCT; BV/TV and mineral density did not yield a statistical difference. Histologically, regional variations in mineralized matrix were evident in all specimens, indicating a broad continuum of healing within the callus. Among serum proteins, bone-specific alkaline phosphatase, indicative of active mineralization, was greater in 5 MG than control (p < 0.05). Sclerostin, an inhibitor of osteogenesis, was lower in 5 MG than control (p < 0.05), also suggestive of enhanced healing.
An increase in bone volume, tissue volume and cellular signaling for osteogenesis at 17 days following fibula fracture in this mouse model suggests that gastrolith treatment holds potential for improving fracture healing. Further study at subsequent time points is warranted to determine the extent to which the increase in callus size with gastrolith treatment may accelerate restoration of tissue integrity.
骨折愈合通常需要较长的康复期，因为骨碎片要巩固成恢复活力的组织以承受负荷。开发改善愈合的干预措施仍然是骨科研究的重点。本研究的目的是评估天然存在的无定形碳酸钙基质在未植入器械的长骨模型中影响骨折愈合的能力。
在成熟小鼠的腓骨上造成完全横断骨折，然后每天以0（对照）、1（1毫克）和5（5毫克）毫克/千克的剂量对小鼠进行小龙虾胃石灌胃。在第17天，采集骨骼和血清。
通过μCT测定，形态学上，1毫克治疗组的骨体积（BV）更大，1毫克和5毫克组的组织体积（TV）均大于对照组（p < 0.05）；骨体积分数（BV/TV）和矿物质密度无统计学差异。组织学上，所有标本中矿化基质的区域差异明显，表明骨痂内愈合过程广泛连续。在血清蛋白中，指示活跃矿化的骨特异性碱性磷酸酶在5毫克组高于对照组（p < 0.05）。骨硬化蛋白是一种成骨抑制剂，在5毫克组低于对照组（p < 0.05），也提示愈合增强。
在该小鼠模型中，腓骨骨折后17天骨体积、组织体积和成骨细胞信号增加，表明胃石治疗具有改善骨折愈合的潜力。有必要在后续时间点进行进一步研究，以确定胃石治疗导致的骨痂大小增加在多大程度上可能加速组织完整性的恢复。
