体外冲击波治疗骨折延迟愈合和骨不连研究进展

骨折后延迟愈合及骨不连的发生率高达5%~10%，目前手术是治疗骨不连的“黄金标准”，主要包括清理骨折断端、再通髓腔、自体骨移植及更换固定方式，但骨不连的手术治疗存在创伤大、感染以及二次手术取出内固定的问题。近年来，体外冲击波疗法（ESWT）因其无创、高效、低廉等优势在骨肌疾病的治疗中得到广泛应用，尤其在治疗骨折延迟愈合和骨不连方面取得良好疗效，本文就体外冲击波疗法在治疗骨折骨不连的进展做一综述，期望能够对临床工作有所帮助。     

体外冲击波治疗骨折延迟愈合和骨不连研究进展

骨折后延迟愈合及骨不连的发生率高达5%~10%，目前手术是治疗骨不连的“黄金标准”，主要包括清理骨折断端、再通髓腔、自体骨移植及更换固定方式，但骨不连的手术治疗存在创伤大、感染以及二次手术取出内固定的问题。近年来，体外冲击波疗法（ESWT）因其无创、高效、低廉等优势在骨肌疾病的治疗中得到广泛应用，尤其在治疗骨折延迟愈合和骨不连方面取得良好疗效，本文就体外冲击波疗法在治疗骨折骨不连的进展做一综述，期望能够对临床工作有所帮助。     

体外冲击波在促进骨愈合中的应用

目的:观察体外冲击波促进骨折愈合、治疗骨不连的疗效。方法:选取22例外伤性骨折愈合延迟、骨不连患者进行体外冲击波冲击治疗,治疗后每4～6周进行X线片复查,观察骨折愈合情况。首次冲击波治疗12周后如骨折处无明显骨痂形成,则进行第2次冲击波治疗。冲击波能量为0.4mJ/mm2,每次脉冲总数为1600～2400次。结果:22例下肢外伤性骨折愈合延迟及骨不连经体外冲击波治疗后,骨性骨痂形成的时间为4～12周,20例有明显骨痂形成,其中17例在治疗后3～6个月内骨折完全愈合。2例胫骨下段骨折冲击波治疗无效。结论:体外冲击波在治疗骨不连,促进骨折愈合方面效果满意,有广阔的应用前景。     

脱钙骨基质治疗长骨骨折延迟愈合及骨不连

目的探讨脱钙骨基质(decalcifiedbonematrix,DBM)治疗长骨骨折延迟愈合和骨不连的疗效。方法长骨延迟愈合、骨不连共57例,男45例,女12例;年龄21~65岁,平均42岁。开放性骨折17例,闭合骨折40例。骨折延迟愈合32例中,肱骨4例,股骨10例,胫骨18例;骨不连25例中,肱骨5例,股骨4例,胫骨16例。全部采用DBM于骨断端处和骨缺损区植入治疗。结果57例患者均获随访,随访时间4~37个月,平均7.8个月。骨折延迟愈合32例中骨折愈合31例,1例胫骨骨折未愈合;骨不连25例中骨折愈合23例,2例未愈合,其中胫骨1例、肱骨1例。愈合时间3~6.6个月,平均4.7个月。结论DBM治疗长骨骨折延迟愈合及骨不连,其疗效满意、并发症少。     

骨折延迟愈合和不愈合的治疗进展

骨折最主要并发症之一是骨折不愈合或延迟愈合。为了最终恢复骨的完整性和生物力学性能，骨折治疗包括手术或内固定方式、骨移植、外固定、电刺激、超声检查、高能量体外冲击波等。骨不愈合及延迟愈合的最佳治疗方法是自体骨移植。然而，合适的移植骨是有限的，且移植后会增加供骨部位的发病率。目前，骨不愈合或延迟愈合的治疗原则已有进步，目标是提供无损伤、并发症少及安全的治疗。本文介绍了骨不愈合或延迟愈合的一些有效而安全的治疗方法的进展。     

有限手术治疗四肢长骨骨折术后延迟愈合或骨不连

四肢长骨骨折术后出现延迟愈合或骨不连,适时进行干预,可有效防止骨折固定物变形、断裂,骨折畸形愈合或假关节形成。我科自2002年2月~2009年12月采用保留原骨折固定方式、小切口处理骨折处游离间隙、个体化植骨等有限手术方法,治疗四肢长骨骨折术后延迟愈合或骨不连48     

手术治疗腕舟状骨骨折不愈合的研究进展

舟状骨骨折是腕骨最常见的骨折之一,在临床诊断中由于常被延误或未被诊断,进而直接或间接地影响舟状骨骨折的愈合效果,导致延迟愈合和骨不连的发生率较高。国内外学者通过临床实验探索多种可治疗和减少舟状骨骨折延迟愈合和不愈合的手术方法,其中有些手术方法为目前研究的热点。本文就其具体手术治疗方式进行详细阐述,以期探索手术治疗腕舟状骨骨折不愈合的最佳途径,以期对临床有指导意义。     

叩击式骨应力刺激仪治疗创伤性股骨骨髓炎后遗骨延迟愈合及骨不连

目的探讨叩击式骨应力刺激仪对创伤性股骨骨髓炎后遗骨延迟愈合、骨不连的治疗效果。方法1998年2月～2006年9月,对16例创伤性股骨骨髓炎后遗骨延迟愈合或骨不连采取叩击式骨应力刺激仪治疗。其中男11例,女5例,年龄35～50岁;感染性骨不连13例,感染性骨延迟愈合3例。将小腿置于骨应力刺激仪托架上,对跟骨进行纵向冲击。每天治疗3次,每次30min,每次间隔3h,记录疗效评价指标。结果3例骨延迟愈合及11例骨不连均愈合,骨愈合时间12～35周,平均(20.45±2.56)周;2例不愈合改开放手术治疗。疗效评价指标显效率87.5%,无效率12.5%。无一例感染复发或再骨折。结论叩击式骨应力刺激仪对创伤性股骨骨髓炎后遗骨延迟愈合及骨不连具有一定治疗效果,能促进骨折愈合。     

骨折不愈合与延迟愈合的成因与治疗

目的探讨骨折不愈合与延迟愈合的成因、报肯治疗的方法与设果。方法对1990年7月～2004年12月间收治的107例骨折不愈台、54例骨折延迟愈合2例先天性胫骨骨不连进行回顾性研究，分析原因，随访治疗结果。18例延迟愈合行保守治疗，本组其他145例行手术治疗，结果除2例先天性胫骨骨不连外，其余161例的成因中均有医源性因素。10例失去随访，153例平均随访17（6-28）个月，骨折均获骨性连接，愈合时间平均10（6-14）个月，肢体功能恢复良好，结论医源性技术缺陷是骨折不愈合与延迟愈合的主要原因，针对各种不同因素进行合理治疗可获得满意效果。     

自体骨髓经皮注射移植治疗骨延迟愈合和骨不连

目的：应用自体骨髓经皮注射治疗骨延迟愈合、骨不连22例。方法：3例肱骨、3例尺桡骨、2例股骨、13例胫骨，均为创伤后骨延迟愈合和骨不连；1例右侧先天性胫骨假关节术后再骨折；年龄10—67岁，平均30岁；骨折后至接受骨髓移植时间为4—18个月，平均12个月。手术时患者取俯卧位，从髂骨后翼穿刺，缓侵抽取骨髓液3—5ml，每个穿刺点间隔2cm，总量40—120ml，平均7ml；经皮注入到X线定位的骨折处。术后石膏固定4—12周，定期摄片检查。结果：2例骨延迟愈合、骨不连在术后2—9个月骨愈合，平均6个月；逐渐负重和恢复肢体活动。1例先天性胚骨假关节失败，再次手术。结论：自体骨鹤移植治疗骨延迟愈合和骨不连有效；该方法创伤小、简便有效。     

Role of mechanical loading in the progressive ossification of a fracture callus

The progressive ossification pattern in a fracture callus was predicted based on a theory that relates the local stimulus for ossification to the tissue mechanical loading history. Two-dimensional finite element analyses of a fracture callus were considered at three different stages of ossification. The sites of callus ossification represented in the initial model were predicted by previous analyses relating mechanical stress and vascularity to the differentiation of mesenchymal tissue in the early callus. The zones of further ossification, bone bridging, and bone consolidation predicted in the present study were found to be similar to the ossification patterns that have been documented by other researchers. The approach used to predict fracture healing is identical to that of previous studies predicting joint morphogenesis, with the exception that fracture healing requires continuous, attached skeletal elements, whereas joint morphogenesis requires discontinuous, articulating skeletal elements.     

Expression and localization of ossification-related factors in fracture healing: Comparative study of experimental union and non-union models

The immunohistochemical expression and localization of some ossification-related factors, including a bone growth factor (bone morphogenetic protein, BMP), non-collagenous proteins (osteocalcin, BGP; bone sialoprotein, BSP), and type II collagen, were compared in union and non-union models of fracture healing in rats. In the union model, fracture healing was seen by day 25, whereas the non-union model did not show healing even on day 32. In both models, BMP, BGP, BSP, and type II collagen were expressed mainly in chondrocytes, with proliferating cell nuclear antigen (PCNA)-positive reaction in the soft callus. In the non-union model, the expression of BMP, BGP, BSP, type II collagen, and PCNA disappeared earlier than in the union model. In fracture healing, PCNA-positive cells expressed the ossification-related factors, these being essential for ossification.     

The role of oxygen during fracture healing

Oxygen affects the activity of multiple skeletogenic cells and is involved in many processes that are important for fracture healing. However, the role of oxygen in fracture healing has not been fully studied. Here we systematically examine the effects of oxygen tension on fracture healing and test the ability of hyperoxia to rescue healing defects in a mouse model of ischemic fracture healing. Mice with tibia fracture were housed in custom-built gas chambers and groups breathed a constant atmosphere of 13% oxygen (hypoxia), 21% oxygen (normoxia), or 50% oxygen (hyperoxia). The influx of inflammatory cells to the fracture site, stem cell differentiation, tissue vascularization, and fracture healing were analyzed. In addition, the efficacy of hyperoxia (50% oxygen) as a treatment regimen for fracture nonunion was tested. Hypoxic animals had decreased tissue vascularity, decreased bone formation, and delayed callus remodeling. Hyperoxia increased tissue vascularization, altered fracture healing in un-complicated fractures, and improved bone repair in ischemia-induced delayed fracture union. However, neither hypoxia nor hyperoxia significantly altered chondrogenesis or osteogenesis during early stages of fracture healing, and infiltration of macrophages and neutrophils was not affected by environmental oxygen after bone injury. In conclusion, our results indicate that environmental oxygen levels affect tissue vascularization and fracture healing, and that providing oxygen when fractures are accompanied by ischemia may be beneficial.     

骨内膜成骨的动物模型

目的 为了解骨内膜在骨折愈合不同阶段的功能变化及其调节机制。设计一个骨折愈合过程中骨内膜成骨的动物模型。方法 将３月龄雌性ＳＤ大鼠４０只随机分成４组,每组１０只,在左胫骨造成长５ｍｍ的环形骨膜缺损,用骨锉在骨膜缺损区造成长５ｍｍ的骨缺损,深达髓腔,约显露髓腔的１／６。结果 １４天时裸露的贿腔已开始出现骨性关闭的征象,２８天时髓腔完全由坚质骨关闭,而各时间点组的骨缺损处填充物均为颜痕样结缔组织。结论     

TGF-β1 als pathophysiologischer Faktor bei der Frakturheilung

AIM: TGF-beta1 is an important local and systemic regulatory molecule during fracture healing. Various authors have shown differences in the systemic levels of TGF-beta1 over the time taken for bone healing in distraction osteogenesis and osteotomies. Previous studies have shown characteristic differences in the physiological levels of growth factors between normal fracture healing and delayed fracture union. The aim of the present study was to evaluate possible differences in sera levels of patients with normal and delayed union fracture healing. METHODS: Patients with long bone shaft fractures were recruited prospectively. Peripheral blood samples were collected over a period of 1 year using a standardized time schedule. At the end of the individual's investigation period, TGF-beta1 levels were determined. To achieve a homogeneous collective of patients, only those with a maximum of two fractures were included in the study. After matching for four criteria, we compared patients with normal fracture healing to patients with delayed unions. The fact of delayed union was accepted in case of failed consolidation 4 months after trauma. RESULTS: During a prospective study period of 1 year, 15 patients with normal fracture healing could be compared to 15 patients suffering from delayed union. By determining the absolute sera levels we found a typical increase of TGF-beta1 up to 2 weeks after fracture in both groups, with a subsequent decrease up to the sixth week after fracture. However, a decline in serum concentration occurred earlier in patients with delayed union, causing significantly lower TGF-beta1 levels in the non-union group 4 weeks after trauma (P=0.00006). CONCLUSION: Even with a relatively small number of patients, we could show a significant difference in serum concentrations of TGF-beta1 between the investigated groups. If these results can be verified within a larger collective, TGF-beta1 could be used as a predictive cytokine for delayed fracture healing.     

Molecular basis for affected cartilage formation and bone union in fracture healing of the streptozotocin-induced diabetic rat

Most studies have focused on the association between diabetes mellitus (DM) and impaired osseous healing, but there is also evidence that diabetes impairs cartilage formation during fracture healing. To investigate the molecular mechanisms by which diabetes affects endochondral ossification, experiments were performed in a model of rat closed fracture healing complicated with diabetes. Diabetic rats were created by a single intravenous injection of streptozotocin (STZ), while controls were treated with vehicle alone. Fractures were made 2 weeks after STZ injection. Animals were killed at 4, 7, 10, 14, 21, 28 and 42 days following fracture, and samples were subject to radiographic, histological and molecular analyses. In the DM group, a significantly smaller cartilaginous callus was formed compared with controls throughout healing, with the cartilage area being reduced rapidly after day 14. When the bone union rate was evaluated radiographically on day 28, DM calluses exhibited a lower rate than controls. However, when evaluated on day 42, both groups showed an equivalent union rate. Cellular proliferation of chondroprogenitor cells and proliferating chondrocytes in soft calluses of the DM group was significantly reduced during early stages of healing (days 4 and 7), but no longer reduced thereafter. Moreover, expression levels of collagen type II, type X and osteopontin (OPN) were constantly low in the DM group. These results show the molecular basis for diminished cartilage formation and delayed union in fracture healing of the STZ-induced diabetic rats.     

The influence of parathyroid hormone on the process of fracture healing

The influence of parathyroid hormone (PTH) on the process of fracture healing was examined using the fractured rats which were parathyroidectomized or given synthetic PTH. The biochemical and histological changes were studied. The results were as follows: I) Parathyroidectomized rats (PTX rats) showed decreased serum Ca, increased serum P and decreased serum PTH as observed in hypoparathyroidism. The fracture healing was impaired due to delay of both chondroclasis at the phase of endochondral ossification and secondary remodeling of primary cancellous bone. II) In rats treated with PTH (PTH rats) both serum Ca and P levels were increased at the early stage. Bone resorption as well as formation was also promoted at the early stage. At the late stage only bone formation remained good with poor bone resorption, indicating that secondary bone remodeling is decreased. The union of callus was impaired. Fracture healing was consequently delayed in both PTX and PTH rats. It is therefore suggested that PTH may be one of the important factors in fracture healing.     

The role of morphogens in endochondral ossification

Summary The formation of bone occurs normally by one of two developmental processes: intramembranous or endochondral ossification. Endochondral ossification occurs in the morphogenesis of the limb buds and growth plates, and in the regeneration of bone following injury (fracture callus). Two classes of diffusible morphogen-like molecules (MLMs) involved in limb development are the bone morphogenetic proteins (BMPs) and retinoic acid (RA). These MLMs are associated, respectively, with the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) of the primitive limb bud. They function as potent regulators of pattern formation and are involved in tissue proliferation and differentiation. The presence of endochondral ossification in fracture callus suggests a role for MLMs in that process as well. To date, virtually nothing is known about the role of morphogens in the regeneration of bone (fracture healing). In this article, we review the current knowledge of MLMs in bone formation and propose a theory on their role in fracture healing. We hypothesize that MLMs involved in fracture healing may also express spatial and temporal information. A more complete understanding of the role of morphogens in both limb development and fracture healing is of major importance to practicing orthopedists and their patients.