The vascular repair of an experimental osteotomy held in an external fixator

The vascular repair of a lower tibial transverse osteotomy in the New Zealand white rabbit held in an external fixator was studied in three groups. In the first group, composed of 18 animals, the osteotomy gap was maintained throughout repair. Three animals were killed every two weeks up to 12 weeks postoperatively. In the second group, composed of three animals killed at six weeks, the fragments were brought into contact. In a third and similar group, the osteotomy was compressed. Plain roentgenograms were taken weekly, and intraarterial perfusion with Micropaque was performed when the animals were killed. Roentgenography using fine-grain film, microradiography, and histology were carried out on a midsagittal tibial slice. The results showed that following transverse osteotomy in which the gap was maintained, vascular union of the proximal and distal cortices and associated external callus masses had usually occurred by ten weeks postoperatively. However, an occasional hypovascular zone at the osteotomy site at 12 weeks was associated with fibrous delayed union. In contrast, when apposition or compression of the fragments was used, repair was accelerated, and cortical bone union was established at six weeks. Vascular union of the fragments occurred predominantly through the medullary vessels. The results emphasize the overriding clinical importance of abolition of a fracture gap to achieve rapid revascularization of a fracture and its union by bone.     

Prediction of the healing potential of closed adult tibial shaft fractures by bone scintigraphy

Fifty unilateral closed adult tibial shaft fractures treated by closed methods were studied prospectively using bone scintigraphy to predict the healing potential of individual fractures. Dynamic and static scintigrams, using 99mtechnetium methylene diphosphonate, were obtained at zero, six, and 12 weeks after fracture. The data were analyzed according to the methods of recent workers in this field. Forty-one fractures united normally at 20 weeks and nine fractures developed delayed union. Analysis of results showed significant differences in uptake ratios, mean net counts, and an osteogenesis index between fractures with normal and delayed union. Of particular value was a ratio of uptake over the fracture site to an adjacent site in the same bone obtained at six weeks. A ratio greater than 2 indicated the potential to heal normally. The findings suggest that a single static scintigram at six weeks is strongly predictive of subsequent healing.     

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。     

Low-intensity pulsed ultrasound increases bone volume, osteoid thickness and mineral apposition rate in the area of fracture healing in patients with a delayed union of the osteotomized fibula

INTRODUCTION: Low-intensity pulsed ultrasound (LIPUS) accelerates impaired fracture healing, but the exact mechanism is unknown. The aim of this study was to investigate how LIPUS affects bone healing at the tissue level in patients with a delayed union of the osteotomized fibula, by using histology and histomorphometric analysis to determine bone formation and bone resorption parameters. MATERIALS AND METHODS: Biopsies were obtained from 13 patients (9 female, 4 male; age 42-63) with a delayed union of the osteotomized fibula after a high tibial osteotomy, treated for 2-4 months with or without LIPUS in a randomized prospective double-blind placebo-controlled trial. In the histological sections of the delayed union biopsies, 3 areas of interest were distinguished, i.e. 1) area of new bone formation at the fracture ends, 2) area of cancellous bone, and 3) area of cortical bone. Histomorphometrical analysis was performed to determine bone formation and bone resorption parameters (as well as angiogenesis). RESULTS: In LIPUS-treated delayed unions, endosteal callus formation by direct bone formation without a cartilage intermediate as well as indirect bone formation was observed, while in untreated controls only indirect bone formation was observed. In the area of new bone formation, LIPUS significantly increased osteoid thickness by 47%, mineral apposition rate by 27%, and bone volume by 33%. No increase in the number of blood vessels was seen in the newly formed bony callus. In the area of cancellous bone, bone volume was significantly increased by 17% whereas no effect on osteoid thickness and mineral apposition rate was seen. LIPUS did not affect osteoid volume, osteoid maturation time, number of osteocytes, osteocyte lacunae, or osteoclast-like cells in any of the areas of interest. CONCLUSIONS: Our results suggest that LIPUS accelerates clinical fracture healing of delayed unions of the fibula by increasing osteoid thickness, mineral apposition rate, and bone volume, indicating increased osteoblast activity, at the front of new bony callus formation. Improved stability and/or increased blood flow, but probably not increased angiogenesis, might explain the differences in ossification modes between LIPUS-treated delayed unions and untreated controls.     

Serum bone markers after intramedullary fixed tibial fractures

Serum levels of bone markers were measured prospectively for 1 year in 30 adult patients with an intramedullary fixed tibial fracture. In a double blinded design, half of the patients received low intensity ultrasound. All fractures healed, although in seven of 30 the healing was delayed more than 6 months. There was no significant difference in radiologic healing time between the ultrasound group (median, 113 days) and the placebo group (median, 112 days). The marker for bone resorption, crosslinked telopeptide, peaked at 1 to 4 weeks, whereas markers for bone formation peaked at 10 to 16 weeks for bone specific alkaline phosphatase and osteocalcin. Crosslinked telopeptide was lower at 1 week in patients treated with ultrasound than in those receiving placebo. Patients with delayed healing did not differ in crosslinked telopeptide compared with patients with normal healing. There were no differences in bone formation markers between patients who received ultrasound or placebo. Patients with delayed healing had lower levels of bone specific alkaline phosphatase between 4 and 7 weeks than did patients with normal healing, although no such differences were seen for osteocalcin. The results indicate that low intensity ultrasound might slow bone resorption, although there is no visible effect on bone formation. Patients with delayed healing had adequate bone resorption but slower early bone formation than did patients with normal healing.     

Effect of recombinant human osteogenic protein-1 on the healing of a freshly closed diaphyseal fracture

Osteogenic protein-1 (OP-1), or bone morphogenetic protein-7, is an osteoinductive morphogen that is involved in embryonic skeletogenesis and in bone repair. In bone defect models without spontaneous healing, local administration of recombinant human OP-1 (rhOP-1) induces complete healing. To investigate the ability of rhOP-1 to accelerate normal physiologic fracture healing, an experimental study was performed. In 40 adult female goats a closed tibial fracture was made, stabilized with an external fixator, and treated as follows: (1) no injection; (2) injection of 1 mg rhOP-1 dissolved in aqueous buffer; (3) injection of collagen matrix; and (4) injection of 1 mg rhOP-1 bound to collagen matrix. The test substances were injected in the fracture gap under fluoroscopic control. At 2 and 4 weeks, fracture healing was evaluated with radiographs, three-dimensional computed tomography (CT), dual-energy X-ray absorptiometry, biomechanical tests, and histology. At 2 weeks, callus diameter, callus volume, and bone mineral content at the fracture site were significantly increased in both rhOP-1 groups compared with the no-injection group. As signs of accelerated callus maturation, bending and torsional stiffness were higher and bony bridging of the fracture gap was observed more often in the group with rhOP-1 dissolved in aqueous buffer than in uninjected fractures. Treatment with rhOP-1 plus collagen matrix did not result in improved biomechanical properties or bony bridging of the fracture gap at 2 weeks. At 4 weeks there were no differences between groups, except for a larger callus volume in the rhOP-1 plus collagen matrix group compared with the control groups. All fractures showed an advanced stage of healing at 4 weeks. In conclusion, the healing of a closed fracture in a goat model can be accelerated by a single local administration of rhOP-1. The use of a carrier material does not seem to be crucial in this application of rhOP-1.     

组织隔离法与机械活动法在兔胫骨骨不连模型建立中的作用

目的 评价组织隔离法与机械活动法在建立兔胫骨萎缩型与肥大型骨不连模型中的作用方法将l2只体重为3～4．5kg的新西兰大白兔随机分成A、B两组，A组于胫骨中段截骨，两断端套接1cm硅胶管，单侧外固定器固定，保持两断端间距2mm，8周取出硅胶管，观察组织隔离法构建萎缩型骨不连模型的效果。B组于胫骨中段截骨后采用2枚1mm克氏针行髓内松动固定，被动活动断端200次／天，持续1个月，观察机械活动法构建肥大型骨不连模型的效果。结果 A组中所有动物在硅胶管取出后4周，无1例断端出现骨愈合表脱，X线片显示良好萎缩型骨不连的复制。B组中所有动物存6周内截骨端出现延迟愈合，部分伴有畸形．骨断端有人量肥大骨痂形成。结论 硅胶管组织隔离法是复制兔胫骨萎缩型骨不连模型的有效方法，而采用被动机械活动复制兔胫骨肥大型骨不连模型的方法尚需进一步研究。     

Percutaneous autologus bone marrow injection in the treatment of delayed or nonunion

Background:

Bone marrow is a source of osteoprogenitor cells that are key elements in the process of bone formation and fracture healing. The purpose of the study was to ascertain the osteogenic potential of autologous bone marrow grafting and its effectiveness in the management of delayed union and nonunion.

Materials and Methods:

Twenty-eight patients with delayed union and three with nonunion of fracture of the long bones were treated with this procedure. Of these 28 cases, two patients had fracture shaft femur, one had fracture shaft ulna and 25 patients had tibial shaft fractures. The average time duration between procedure and injury was 25 weeks (range 14-53 weeks). The bone marrow was aspirated from the anterior iliac crest and injected percutaneously at the fracture site. The procedure was carried out as an outpatient procedure. All but five cases required one injection of bone marrow.

Results:

Union was observed in 23 cases. The average time of healing after the procedure was 12 weeks (range 7-18 weeks).

Conclusion:

The technique of percutaneous autologous bone marrow injection provides a very safe, easy and reliable alternative to open bone grafting, especially for early intervention in fracture healing process.     

A single systemic dose of pamidronate improves bone mineral content and accelerates restoration of strength in a rat model of fracture repair.

Complications in fracture repair that lead to a delay in union remain clinically problematic. We believe that unwanted pre-mature catabolism of the healing callus, for example, in stress shielded situations, diminishes the rate at which strength is restored in bone repair and possibly leads to delayed union. We hypothesized that a single systemic dose of a nitrogen-containing bisphosphonate (N-BP) would increase bone mineral content (BMC), volume, and mechanical strength of union in fracture repair. We also set out to investigate local delivery to assess whether systemic exposure could be eliminated, due to concerns of bisphosphonate dosing of non-target organs. After an open osteotomy fixed with a K wire, 40 12-week old Wistar male rats were divided into four groups of 10: saline control, bolus systemic subcutaneous injection of pamidronate (3 mg/kg), local low dose of pamidronate (0.1 mg), and a local high dose of pamidronate (1.0 mg). Rats were sacrificed 6 weeks post-operatively. Operated and non-operated femora underwent radiographic evaluation, quantitative computer tomography, and biomechanical testing in torsion. The growth plates and metaphyses of the tibia of the non-operated side were assessed for evidence of systemic exposure in the local groups. Significant increases in callus BMC and volume of the bolus systemic dose group were found compared to the saline control (p< or =0.05). Further, the strength of the systemic dose callus was increased by 60% from 0.35 Nm (+/-0.11) for the saline control callus to 0.56 Nm (+/-0.25) for the systemic group (p=0.05). Local treatment did not result in increased strength. The contralateral tibial growth plates of the local groups showed evidence of systemic exposure by the presence of retained primary spongiosa. This study confirms that a single perioperative systemic dose of pamidronate leads to significant increases in the BMC, volume, and strength of healing fractures in rats, making single dose N-BP therapy an appealing candidate for further examination in fracture repair.     

The influence of fracture etiology and type on fracture healing: a review of 104 consecutive tibial shaft fractures

This study was conducted to determine retrospectively the factors which influence fracture healing and risk for nonunion in patients with tibial shaft fractures. One hundred consecutive patients with 104 tibial shaft fractures and a mean age of 40 (14-85) years were reviewed. Fractures were classified according to the AO classification system. There were 22 open fractures and 52 comminuted fractures. Thirty-eight fractures were caused by high-energy trauma. Fracture pattern, soft-tissue condition, level of energy of the trauma, malalignment, and treatment methods were identified. The influence of these factors on the time of hospital stay and sick-leave, delayed union, and nonunion were calculated. Normal healing occurred in 61 fractures with a mean healing time of 17 weeks, delayed union in 27 with a mean of 35 weeks, and nonunion in 16 with a mean of 69 weeks. The relative risk of developing nonunion in open fractures was 8.2 (CI = 2.9-10.5) and 2.9 (CI = 1.2-3.2) in fractures exposed to high-energy trauma. This study showed that the soft-tissue condition and level of trauma energy are good predictors for the development of complications. Considering these risk factors at an early stage in the planning of treatment might reduce the risk of nonunion. ergy level of the trauma, fracture comminution, initial fracture displacement, treatment method, contamination, and associated injuries will influence fracture healing. Conservative treatment has in general been recommended for undisplaced closed or grade I open fractures caused by low-energy trauma [15, 18, 21]. However, conservative treatment of a tibial shaft fracture means immobilization of the lower leg for a long period of time, especially if healing is delayed. Thus, it is important to consider the risk of healing complications when planning the appropriate treatment method in the early stage after the injury. The purpose of this study was to analyze complications such as delayed union and nonunion and to identify factors which affect the healing of tibial shaft fractures.     

Repair of bone allograft fracture using bone morphogenetic protein-2

Long-term clinical data have shown that reconstruction using bone allografts provide adequate function after extensive tumor surgery. Complications such as nonunion of allograft-host interface, infection, and allograft fracture often require major revision surgeries. Allograft fractures usually do not induce the same repair process that is seen in normal fracture healing. The authors did an experimental study to test whether bone morphogenetic protein-2 can induce and achieve osseous repair in an allograft osteotomy model. Recombinant human bone morphogenetic protein-2 was applied at femoral intercalary allograft osteotomy sites in 20 rats. Forty additional rats served as controls (carrier alone and sham). Specimens in all groups were examined histologically and radiographically at 4 and 8 weeks. Specimens in the control groups showed only fibrosis by 8 weeks. In contrast, none of 10 specimens in the experimental group showed radiographic union at 8 weeks. New bone formation and integration with underlying allografts were seen in the experimental group as early as 4 weeks. These data suggest that fracture repair in the allograft bone can be triggered by a biologic regulator that is expressed during normal fracture healing.     

Magnetic resonance imaging of tibial shaft fracture repair

Summary Magnetic resonance imaging (MRI) of normal fracture repair was evaluated in six randomly chosen adult patients with solitary, closed fractures of the tibial shaft by obtaining serial MRI scans until union of the fracture. The mean time to union was 14.3 weeks. Ultralow-field 0.02-Tesla magnet equipment was used. The MRI scans showed a characteristic pattern of events common for all the patients studied and compatible with the recognized histomorphology of fracture repair. The intramedullary cavity demonstrated a marked decrease in the signal intensity. In the soft tissues surrounding the fracture the initially evenly high signal intensity gradually developed a granular appearance with embedded low-intensity nodules. These nodules corresponded to the first areas to become mineralized, as could be seen on plain radiographs several weeks later. The question of whether MRI renders it possible to predict delayed union calls for continued investigations.     

内侧钢板与外侧钢板治疗胫骨远端闭合骨折的疗效比较

目的比较内侧钢板与外侧钢板内固定治疗胫骨远端闭合骨折的临床疗效。方法对56例胫骨远端闭合骨折患者应用钢板内固定治疗,根据钢板置于胫骨内侧或前外侧的不同分为内侧组(35例)和外侧组(21例)。比较两组患者手术时间、住院时间、骨折愈合时间、感染率、畸形愈合、延缓愈合等并发症情况。应用Johnner-Wruhs评分系统评价术后患肢功能,比较两组患者的疗效。结果骨折愈合时间:内侧组(17.57±3.27)周,外侧组(21.14±4.54)周,差异有统计学意义(P0.05);内侧组中23例经皮微创锁定钢板内固定的骨折愈合时间为(15.22±4.67)周。骨折延缓愈合:内侧组1例,外侧组5例;畸形愈合:内侧组无,外侧组3例;Johnner-Wruhs评分优良率:内侧组88.57%(31/35),外侧组66.67%(14/21);以上3项两组比较差异均有统计学意义(P0.05)。两组患者在手术时间、住院时间、感染率比较差异无统计学意义(P0.05)。结论内侧钢板和外侧钢板用于治疗胫骨远端闭合骨折均能取得较好的疗效,内侧钢板尤其是经皮微创锁定钢板内固定术在缩短骨折愈合时间和减少骨折畸形愈合、延缓愈合方面相对于外侧钢板有一定的优势。     

Influence of stable fixation on trabecular bone healing: a morphologic assessment in dogs

The healing patterns of trabecular bone are different from those of compact bone. In order to investigate further this observation, a histomorphometric assessment was undertaken. The influence of internal fixation devices on trabecular bone healing was also studied. Intercondylar osteotomies were produced in 19 dogs and fixed with screws. All dogs were killed between 1 and 14 weeks; eight of them had the screws removed 4 weeks after osteotomy and were killed 4 or 10 weeks later. The results of morphometry were compared to the histologic and radiologic pictures. Anatomic reduction with stable fixation led to contact healing characterized by a narrow endosteal bone formation at the osteotomy site that disappeared only after union was complete (4 weeks). In gap healing, the endosteal bone formation was greater. Internal fixation devices appeared to cause a diffuse osteopenia once union was complete. Their removal just after completion of union seems to prevent the bone loss. Screws induced bone formation around their threads; after they were removed, the reaction disappeared but the screw holes were not filled with normal trabeculae 10 weeks later. Union of fractures through trabecular bone can be assessed radiologically. A decrease of band-like bone density at the fracture site indicates completion of union. This is the optimal time for implant removal. It prevents the osteopenia observed in cases of continuous presence of screws.     

Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model

Osteoporosis (OP) is one of the most prevalent bone diseases worldwide with bone fracture the major clinical consequence. The effect of OP on fracture repair is disputed and although it might be expected for fracture repair to be delayed in osteoporotic individuals, a definitive answer to this question still eludes us. The aim of this study was to clarify the effect of osteoporosis in a rodent fracture model. OP was induced in 3‐month‐old rats (n = 53) by ovariectomy (OVX) followed by an externally fixated, mid‐diaphyseal femoral osteotomy at 6 months (OVX group). A further 40 animals underwent a fracture at 6 months (control group). Animals were sacrificed at 1, 2, 4, 6, and 8 weeks postfracture with outcome measures of histology, biomechanical strength testing, pQCT, relative BMD, and motion detection. OVX animals had significantly lower BMD, slower fracture repair (histologically), reduced stiffness in the fractured femora (8 weeks) and strength in the contralateral femora (6 and 8 weeks), increased body weight, and decreased motion. This study has demonstrated that OVX is associated with decrease in BMD (particularly in trabecular bone) and a reduction in the mechanical properties of intact bone and healing fractures. The histological, biomechanical, and radiological measures of union suggest that OVX delayed fracture healing. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:384–393, 2008     

兔骨折延迟愈合动物模型的建立

目的为骨折延迟愈合的实验研究建立一种客观的动物实验模型。方法选取纯种新西兰大白兔,在后肢胫骨中下段截断,切除远近端各1 cm内外骨膜及黄骨髓,保留断端约1 mm间隙,并且钢板固定。术后4、8、12周后经大体标本、病理组织学及X线检查确定骨折愈合情况。结果大体标本肉眼观察、放射学检查及病理组织学检查均显示术后8周仍未见骨性连接,术后12周才达骨性愈合。结论本实验所建立的动物模型,具有骨折延迟愈合的表现,又未出现骨不连,符合骨折延迟愈合的要求,可以认为是一种可靠而实用的实验性骨折延迟愈合动物模型。     

Low-intensity pulsed ultrasound affects RUNX2 immunopositive osteogenic cells in delayed clinical fracture healing

IntroductionOsteogenic cell proliferation and differentiation play an important role in adequate fracture healing, and is target for osteoinductive therapies in delayed fracture healing. The aim of this study was to investigate whether low-intensity pulsed ultrasound enhances fracture healing at the tissue level in patients with a delayed union of the osteotomized fibula through an effect on the presence of RUNX2 immunopositive osteogenic cells. The effect was studied in both atrophic and hypertrophic delayed unions.Materials and methodsBiopsies were obtained from 6 female and 1 male patient (age 43–63) with a delayed union of the osteotomized fibula after a high tibial osteotomy treated for 2–4 months with or without low-intensity pulsed ultrasound in a randomized prospective double-blind placebo-controlled trial. Immunolocalization of RUNX2 protein was performed to identify osteogenic cells. Histomorphometrical analysis was performed to determine the number of cells expressing RUNX2 located within and around the newly formed woven bone at the fracture end (area of new bone formation), and up to 3 mm distant from the fracture end.ResultsCells expressing RUNX2 were present in all histological sections of control and low-intensity pulsed ultrasound-treated bone evaluated. Within the area of new bone formation, RUNX2 immunopositive cells were found in the undifferentiated soft connective tissue, at the bone surface (presumably osteoblasts), and within the newly formed woven bone. Low-intensity pulsed ultrasound treatment of fibula delayed unions significantly reduced the number of RUNX2 immunopositive cells within the soft connective tissue at the fracture ends, whereas the number of RUNX2 immunopositive cells at the bone surface was not affected. The number of RUNX2 immunopositive cells was similar for the atrophic and hypertrophic delayed unions.ConclusionsImmunolocalization of RUNX2 positive cells in delayed unions of the fibula reveals that delayed clinical fracture healing does not result in impairment of osteogenic cell proliferation and/or differentiation at the tissue level, even if delayed unions are clinically regarded as atrophic. Reduced number of osteogenic RUNX2 immunopositive cells within the soft connective tissue, and unchanged number of RUNX2 immunopositive cells at the bone surface, implicate that low-intensity pulsed ultrasound does not increase osteogenic cell presence, but likely affects osteogenic cell differentiation.     

固骼生促进新鲜骨折愈合的临床观察

目的 探讨骨缺损修复材料——固骼生(Nova．Bone)应用于四肢骨折内固定手术的临床效果。方法 对四肢骨折实施内固定手术时，在骨折线内及周围均匀植入固骼生材料2～5mm3，共治疗64例，同时选择32例未应用固骼生组作为对照组随访观察。结果 全部病例经12～20周随访，应用固骼生组骨折愈合时间12～16周，无骨折延迟愈合及不愈合。对照组(未应用固骼生组)骨折愈合时间16。20周，2例发生骨折延迟愈合。结论 固骼生是一种新型的骨缺损修复材料，在四肢骨折内固定术时植入骨骼生能明显加速骨折愈合过程。