骨水泥成形术治疗骨转移瘤的临床观察

目的 观察应用微创技术治疗骨转移瘤引起疼痛的效果.方法 17例骨转移患者,59处骨转移病灶(55处在椎体,3处在四肢骨,1处在骨盆),其中男性5例,女性12例,年龄30～78岁,平均年龄58.9岁,影像学检查均证实有骨转移瘤(X线片、CT及MRI).临床伴有明显持续性骨痛,症状持续时间为2～18个月,平均5.7个月.17例患者59处骨转移灶均给予骨水泥成形术治疗.观察治疗前后患者的疼痛强度的变化情况、镇痛药使用评分并行SF-12健康状况调查.结果 17例59处病灶手术顺利完成.患者的疼痛评分由治疗前的5.0～9.5(平均7.9±1.2)减少为治疗后的3.1～6.8(平均5.1±1.0)(P＜0.01).患者的止痛药使用评分由治疗前的3～4(平均3.6±0.6),减少为治疗后的1～3(平均2.4±1.1)(P＜0.01).SF-12健康调查评分治疗前为-17～-33,平均-30.00±4.03,治疗后为-18～-33,平均-26.00±3.94(P＜0.05).术后随访6～17个月,平均12.3个月,患者疼痛均较术前减轻,17例患者中1例在治疗期间出现1个椎体新发的压缩性骨折.结论 应用骨水泥成形术治疗骨转移瘤可有效地缓解疼痛,改善患者后期生活质量.     

Theoretical study of bone sialoprotein in bone biomineralization

Bone sialoprotein (BSP) is an acidic, non-collagenous protein specific to bone proposed previously to promote hydroxyapatite (HAP) nucleation and modulate HAP nanocrystal growth. Specifically, two phosphorylated acidic amino acid sequences in BSP, highly conserved across several vertebrates, are the proposed active sites. We selected one of these sites, i.e. (Sp)(2)E(8), where Sp represents a phosphoserine as a model peptide to study the role of BSP. We used molecular dynamics simulations to determine whether an α-helix or a random coil peptide conformation promotes templated HAP nucleation. A bioinformatics method helps infer preferential crystal growth directions by predicting the likely peptide conformations adsorbed on the (001), (100), and (110) crystal faces of HAP. Results suggest that, independent of conformation, no stable nucleating template is formed and, thus, the ion distributions in the vicinity of the peptide that eventually lead to a stable nucleus start out with disordered arrangements of ions. When adsorbed on all three faces, the Sp residues bind strongly regardless of the peptide conformation, and the Glu residues show different propensities to form helical conformations. The lack of geometrical templating between the peptide residues and all HAP surface sites indicates that adsorption and subsequent crystal growth modulation may be structurally nonspecific.     

Replacement of bone marrow by bone in rat femurs: the bone bioreactor

During development and repair of bone, two distinct yet complementary mechanisms, intramembranous and endochondral, mediate new bone formation via osteoblasts. Because mechanical bone marrow ablation leads to the rapid and transient formation of new bone in the marrow cavity, we postulated that parathyroid hormone (PTH), which is a bone anabolic hormone, enhances the formation of new bone that forms after marrow ablation. We subjected the left femur of rats to mechanical marrow ablation, or sham operation, and injected the animals daily with PTH or vehicle for 1, 2, or 3 weeks in a first experiment, then with PTH, parathyroid hormone-related peptide (PTHrP), or vehicle for 3 weeks in a second experiment. We subjected both femurs from each rat to soft X-ray, peripheral quantitative computed tomography, computed tomography on a microscale, and histological analysis, and determined the concentration of serum osteocalcin. In addition, in the second experiment, we determined the serum concentration of calcium, tartrate-resistant acid phosphatase (TRAP), and receptor activator of NF-kappaB ligand (RANKL) at 3 weeks, and subjected femurs to biomechanical testing. Following treatment with PTH or PTHrP for 3 weeks, bone filled the marrow cavity of the shafts whose marrow had been ablated. PTH increased trabecular density in the right femur, but failed to induce bone formation in the medullary region of the right unoperated femoral shafts. The newly formed bone endowed left femoral shafts with improved biomechanical properties when compared to those of right femurs and left femurs from control, sham-operated, and vehicle-treated rats. PTHrP, like PTH, increased serum osteocalcin, but neither increased serum calcium, TRAP, or RANKL at 3 weeks. Our results reveal that the newly formed bone that follows marrow ablation is responsive to PTH, expand the role of PTH in bone, and might open new avenues of investigations to the field of regenerative medicine and tissue engineering. Local bone marrow removal in conjunction with pharmacologic intervention with an anabolic agent might provide a technique for rapid preferential site-directed bone growth in areas of high bone loss.     

生物衍生骨在骨组织工程研究中的应用

支架材料的选取是骨组织工程研究的关键 ,生物衍生骨具有较好的生物相容性和材料界面 ,三维立体孔隙 -网架合理 ,可塑性强 ,可降解 ,并具备一定的力学强度 ,兼备良好的骨传导及一定的骨诱导能力。可作为种子细胞的支架材料应用于骨组织工程研究。     

Bioactive glass and autogenous bone as bone graft substitutes in benign bone tumors

In a prospective randomized study, 25 patients with benign bone tumors were surgically treated with either bioactive glass S53P4 (BG) or autogenous bone (AB) as bone graft material. X-rays were taken preoperatively and postoperatively at 2 weeks and at 3, 8, 12, 18, 24, and 36 months. In addition, for most of the patients, CT scans were performed at the same time-points. No infections or material-related adverse reactions occurred in any patient. The filled cavity was replaced faster by new bone in the AB group than in the BG group (p = 0.0001). However, at 36 months, no statistical difference in cavity volume between the two groups was observed on X-rays (p = 0.7881) or on CT scans (p = 0.9117). In the BG group at 3 years, the filled cavity appeared, however, dense on X-rays, and glass granules on CT scans were observed. During the follow-up period, the cortical thickness seemed to increase more in the BG group than in the AB group (p < 0.0001).     

自体骨及重组人骨形态发生蛋白2复合骨在腰椎中融合的效果：与异体骨比较

BACKGROUND: Recombinant human bone morphogenetic protein 2 (rhBMP2) can effectively promote new  bone formation and fracture healing, but its specific application in the lumbar spinal fusion remains controversial. OBJECTIVE: To study the effect of autogenous bone, rhBMP2 composite bone or allogeneic bone on the lumbar spinal fusion of rabbits.  METHODS: Forty-five New Zealand white rabbits were enrolled to make intertransverse lumbar interbody fusion models and then randomly subjected to autogenous iliac bone, rhBMP2 composite bone or allogeneic iliac bone via L5-L6 intertransverse process, respectively. Then, the rats were sacrificed under anesthesia at 8 weeks after operation to observe the lumbar fusion. RESULTS AND CONCLUSION: Compared with the allogeneic iliac bone group, the fusion rates, tensile strength ratio of L5-6/L4-5, and percentage of new bone tissues were increased more significantly in the other two groups  (P < 0.05), and moreover, there was no difference between the autogenous iliac bone and rhBMP2 composite bone groups. These findings indicate that the autogenous iliac bone and rhBMP2 composite bone have similar fusion effects, both of which are superior to the allogeneic bone.   中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

医用硫酸钙人工骨与同种异体骨修复良性骨肿瘤骨缺损的对比分析

背景：探讨医用硫酸钙人工骨可替代同种异体骨作为骨缺损的修复材料的可行性。 目的：观察医用硫酸钙人工骨材料治疗良性骨肿瘤骨缺损的临床疗效。 方法：纳入应用医用硫酸钙人工骨材料于临床修复良性骨肿瘤刮除术后骨缺损病例31例和同种异体骨材料修复病例36例。观察植入材料后4,8,12周摄X射线片植骨吸收情况及植骨材料降解率。 结果与结论：全部病例均获随访3个月以上。两组病例在随访期间植骨材料降解率差异无显著性意义。良性骨肿瘤植骨区无复发。患者植入材料后3个月X射线片示骨缺损部位有新骨生成。结果表明医用硫酸钙人工骨材料临床疗效和同种异体骨接近。     

Screw insertion in trabecular bone causes peri-implant bone damage

Secure fracture fixation is still a major challenge in orthopedic surgery, especially in osteoporotic bone. While numerous studies have investigated the effect of implant loading on the peri-implant bone after screw insertion, less focus has been put on bone damage that may occur due to the screw insertion process itself. Therefore, the aim of this study was to localize and quantify peri-implant bone damage caused by screw insertion.We used non-invasive three-dimensional micro-computed tomography to scan twenty human femoral bone cores before and after screw insertion. After image registration of the pre- and post-insertion scans, changes in the bone micro-architecture were identified and quantified. This procedure was performed for screws with a small thread size of 0.3 mm (STS, N = 10) and large thread size of 0.6 mm (LTS, N = 10).Most bone damage occurred within a 0.3 mm radial distance of the screws. Further bone damage was observed up to 0.6 mm and 0.9 mm radial distance from the screw, for the STS and LTS groups, respectively. While a similar amount of bone damage was found within a 0.3 mm radial distance for the two screw groups, there was significantly more bone damage for the LTS group than the STS group in volumes of interest between 0.3–0.6 mm and 0.6–0.9 mm.In conclusion, this is the first study to localize and quantify peri-implant bone damage caused by screw insertion based on a non-invasive, three-dimensional, micro-CT imaging technique. We demonstrated that peri-implant bone damage already occurs during screw insertion. This should be taken into consideration to further improve primary implant stability, especially in low quality osteoporotic bone. We believe that this technique could be a promising method to assess more systematically the effect of peri-implant bone damage on primary implant stability. Furthermore, including peri-implant bone damage due to screw insertion into patient-specific in silico models of implant-bone systems could improve the accuracy of these models.     

Long-term reaction to bone cement in osteoporotic bone: new bone formation in vertebral bodies after vertebroplasty

Elderly patients frequently suffer from osteoporotic vertebral fractures resulting in the need of vertebroplasty or kyphoplasty. Nevertheless, no data are available about the long-term consequences of cement injection into osteoporotic bone. Therefore, the aim of the present study was to evaluate the long-term tissue reaction on bone cement injected to osteoporotic bone during vertebroplasty. The thoracic spine of an 80-year-old female was explanted 3.5 years after vertebroplasty with polymethylmethacrylate. The treatment had been performed due to painful osteoporotic compression fractures. Individual vertebral bodies were cut in axial or sagittal sections after embedding. The sections were analysed using contact radiography and staining with toluidine blue. Furthermore, selected samples were evaluated with scanning electron microscopy and micro-compted tomography (in-plane resolution 6 microm). Large amounts of newly formed callus surrounding the injected polymethylmethacrylate were detected with all imaging techniques. The callus formation almost completely filled the spaces between the vertebral endplate, the cancellous bone, and the injected polymethylmethacrylate. In trabecular bone microfractures and osteoclast lacuna were bridged or filled with newly formed bone. Nevertheless, the majority of the callus formation was found in the immediate vicinity of the polymethylmethacrylate without any obvious relationship to trabecular fractures. The results indicate for the first time that, contrary to established knowledge, even in osteoporosis the formation of large amounts of new bone is possible.     

同种异体骨移植中的骨形成相关因子表达研究

目的:从分子水平研究骨形态发生蛋白2(bone morphogenetic protein-2,BMP-2)及其相关因子—转化生长因子-β(transforming growth factor-β,TGF-β)和血管内皮生长因子(vascular endothelial cell growth factor,VEGF)在同种异体骨移植中的表达。方法:以移植兔桡骨为研究对象,分别于同种异体骨和自体骨植入后4、6、8、10和12周取各组节段骨痂,提取总RNA,采用逆转录聚合酶链式反应(reverse trans cription-polymerase chain reaction,RT-PCR)检测BMP-2、TGF-β和VEGF的mRNA表达和变化趋势,比较同种异体骨和自体骨移植的多因子表达情况。结果:RT-PCR结果经半定量分析显示,BMP-2、TGF-β和VEGF在4～12周的变化均呈非线性曲线,在第8周时BMP-2及TGF-β、VEGF的表达量均为最高。结论:同种异体骨和自体骨移植后骨组织内存在BMP-2、TGF-β和VEGF的持续分泌表达,其表达趋势与成骨细胞骨形成的活跃程度呈正相关,并且同种异体骨和自体骨移植后多因子表达无明显差异。     

Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes

Previous investigations have shown that both the early biological response and the mechanical properties of a porous hydroxyapatite bone graft substitute are highly sensitive to its pore structure. The objective of this study was to evaluate whether the pore structure continued to influence bone integration in the medium to long term. Two screened batches of porous hydroxyapatite (PHA) designated as batch A and batch B, with porosities of approximately 60 and 80%, respectively, were selected for this study and implanted for periods of 5, 13, and 26 weeks into the lower femur of New Zealand White rabbits. Histomorphometric analysis of the absolute volume of bone ingrowth within batch A and B implants from 5 to 26 weeks showed that the absolute volume of bone ingrowth was consistently lower in batch A (10-21%), compared to batch B implants (24-31%). However, when the volume of bone ingrowth was normalised for the available pore space, this difference was reduced (23-47% and 32-42% for batches A and B, respectively). These observations suggest that differences in the volume of bone ingrowth initially depended on pore interconnectivity rather than pore size, whereas the volume or morphology of the PHA influenced the volume and morphology of bone ingrowth at later time points. Compression testing showed that bone ingrowth had a strong reinforcing effect on PHA bone graft substitutes, and a strong correlation was identified between mechanical properties and the absolute volume of ingrowth for both batches A and B. Furthermore, at 13 and 26 weeks, there was no significant variation in the ultimate compressive strength of integrated batch A and B implants. This similarity in ultimate mechanical properties indicated that the absolute volume of ingrowth may be mediated by the PHA structure through its impact on the dynamics of the local biomechanical environment. The results of push-out testing showed that fixation of PHA bone graft substitutes was independent of density within the range studied, with no significant difference in the interfacial shear stress between batches A and B at each time point throughout the study.     

骨微损伤、骨重建与代谢性骨病

骨微损伤能启动骨重建,骨重建障碍而导致微损伤积累可引发骨折。扫描电镜、同步加速器射线μ-CT和高分辨磁共振显像是研究骨微损伤的新方法,骨理化构成和年龄对微损伤发生和发展有重要影响,骨细胞在微损伤修复中起重要作用,骨微损伤研究有利于代谢性骨病防治。     

血管化在骨组织工程中的应用

随着骨缺损修复治疗方法的不断完善发展,组织工程化人工骨被逐渐应用于此治疗,但随着组织工程技术的提高,血管化应用于人工骨将代替单纯应用人工骨,并被认为是将来较理想的修复方法。本文将对骨组织血管化的机理,血管化在骨组织工程中的作用和具体应用进行综述。     

磷酸钙人工骨修复骨缺损的研究进展

继发于各类病因的大段骨缺损通常需要人工骨材料进行修复,目前常用的人工骨材料包括磷酸钙和硫酸钙基人工骨、生物活性玻璃等,以磷酸钙为主要成分的人工骨,复合其他一种或多种材料以期改善人工骨的性能是目前的研究热点。本文将总结以磷酸钙为基质的各类复合材料,包括与聚合物复合的磷酸钙材料、以磷酸钙为基质的合金材料、药物缓释材料以及骨组织工程材料在骨缺损修复中的研究进展,为以磷酸钙为基质新材料的研究奠定基础。     

Advances in bone biology and new treatments for bone loss

Recent advances in bone biology have led to a more detailed understanding of bone remodeling which is a process that leads to resorption of old bone and replacement by formation of new bone. The most important discoveries in this process of bone remodeling were those of the RANK Ligand/RANK/OPG system which is now recognized the dominant pathway regulating bone resorption. RANK Ligand (RANKL) is a cytokine belonging to the tumor necrosis factor family and is expressed by osteoblasts; it binds to membrane bound receptor RANK on osteoclasts and promotes differentiation of marrow cells through various stages to multinucleated osteoclasts which resorb bone. Several hormones such as parathyroid hormone, calcitriol and prostaglandins stimulate RANK Ligand expression by osteoblasts. Osteoblasts also secrete osteoprotegerin (OPG) which is a soluble receptor that is a potent antagonist of osteoclast formation by binding and inactivating RANKL and OPG is therefore an important regulator of bone resorption. OPG is stimulated by estrogen. OPG has been genetically engineered and in human subjects is a potent inhibitor of bone resorption. Another method for preventing bone resorption is to develope antibodies against RANKL and this has been shown to be a successful strategy. A single subcutaneous injection of this antibody (Denosumab) every 6 months proved to be a potent inhibitor of bone resorption and clinical fracture trials using this agent are now underway. These are novel developments that have risen from basic research in bone biology and other discoveries in the bone remodeling process can be expected to lead to further treatment options for various bone diseases.     

硫酸钙人工骨修复骨缺损的研究进展

硫酸钙（CS）材料由于其具有生物相容性好、生物可吸收降解性高、制备成本相对低廉、原材料来源丰富等特点,常用于大段骨缺损修复的治疗。然而,其材料存在着降解速度快、骨诱导活性差等问题。因此硫酸钙材料与不同材料的复合,使其相关性能得到改进与加强成为了目前研究的热点,近年来研究人员通过将硫酸钙与不同的材料相结合,负载各种抗生素、药剂、生长因子等无机、有机分子,制备出新型复合硫酸钙材料,并经体外细胞实验和体内动物实验探究评价新型材料的机械和生物性能,为进一步硫酸钙人工骨材料的研究和开发提供了理论与实践支持。本文将通过对近年来以硫酸钙材料为载体的新型复合材料在骨缺损修复方面的研究进展进行综述总结,以期为后续的研究提供参考。     

骨搬移治疗感染性骨缺损大鼠骨生长因子的表达

文题释义：感染性骨缺损：多由高能量损伤引起并伴有感染性病变的骨缺损，若治疗不及时或处理不当会出现肢体功能障碍和败血症等一系列严重的并发症。 骨搬移：应用张力-应力法则，通过外固定架向组织施加牵拉力来促进骨、软组织及神经的生长并加速周围血液循环以达到控制感染、促进损伤修复的目的。 背景：研究表明骨愈合是在多种生长因子参与下完成修复、再生与重建的病理生理性过程，其中碱性成纤维细胞生长因子和胰岛素样生长因子1在骨愈合的过程中发挥重要作用。 目的：探讨胰岛素样生长因子1和碱性成纤维细胞生长因子2种骨生长因子在骨搬移术治疗大鼠感染性骨缺损前后的表达情况。方法：取SD大鼠36只，在每只大鼠胫骨下端造约4 mm的感染性骨缺损，2周后随机分为手术组和对照组。对照组做清创后安装支架不进行搬移；手术组清创后进行骨搬移手术治疗。于安装支架后第2周通过X射线摄片；第2，3，4周通过苏木精-伊红染色和ELISA检测2组感染性骨缺损的愈合情况及胰岛素样生长因子1和碱性成纤维细胞生长因子的表达情况。实验方案经广西医科大学动物实验伦理委员会批准(批准号为201903036)。 结果与结论：①X射线片显示：手术组2周后缺损区有骨痂形成，周围软组织未见肿胀，愈合效果良好；②苏木精-伊红染色显示：与对照组相比，手术组纤维组织有所减少，成骨细胞增多，骨小梁趋于致密并有较多间充质细胞和新生毛细血管生成；③ELISA结果显示：相比于对照组，手术组胰岛素样生长因子1表达量在第2，3周显著增多(P < 0.05)；碱性成纤维细胞生长因子在第2周表达量显著增多(P < 0.05)；④结论：骨搬移手术治疗后大鼠的胰岛素样生长因子1和碱性成纤维细胞生长因子表达上调，提示胰岛素样生长因子1和碱性成纤维细胞生长因子表达上调可能是促进感染性骨缺损愈合的原因之一。 ORCID: 0000-0002-2695-2232(郭彦德) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程     

Osteoclast formation in vitro from bone marrow mononuclear cells in osteoclast-free bone

Recent evidence points to the fact that osteoclasts are derived from mononuclear cells of hematopoietic bone marrow. In this study we have examined the formation of osteoclasts from mononuclear cells in vitro. The mononuclear cells were isolated after 7 days from cultures of mouse bone marrow cells. The isolated cells were co-cultured with osteoclast-free, fetal-mouse calvaria. After 10 to 14 days of co-culture, multinucleated cells which have all the characteristics of osteoclasts were found in juxtaposition to seams of woven bone. These data strongly suggest that bone marrow mononuclear cells, when suitably induced, can give rise to osteoclasts in vitro.     

Crystallization pathways in bone

Many biomineralization processes involve the sequestering of ions by cells and their translocation through the cells to the final deposition site. In many invertebrate crystallization pathways the cells deposit an initial highly disordered mineral phase with intracellular vesicles, and this mineral is subsequently transported into the final deposition site outside the cell. As this initial mineral phase is metastable, it can easily dissolve or crystallize during sample preparation and examination. A cryogenic electron microscopy study of the forming fin bone of a zebra fish strain with continuously growing fins shows that the cells responsible for bone tissue formation do have mineral-bearing intracellular vesicles and that the mineral phase is a highly disordered calcium phosphate. We also show that globules of disordered calcium phosphate are present in the extracellular collageneous matrix and that they are not membrane bound. Close to the mineralization front these globules appear to penetrate into the collagen fibrils where they crystallize to form mature bone. This crystallization pathway is similar to pathways observed in invertebrates, and it differs from the matrix vesicle pathway documented for a variety of vertebrate mineralizing tissues as the extracellular mineral globules are not membrane bound.