Einheilung von autologen Spongiosatransplantaten und Hydroxylapatitkeramiken im Tibiasegmentdefekt Wert der sonographischen Verlaufskontrolle

The aim of this study was to develop and test a scoring system based on real-time ultrasonography (US), which is able to predict the healing of a bone defect filled with a bone graft substitute or cancellous bone graft. We implanted porous hydroxy-apatite (HA) ceramic blocks into a segmental defect in the tibia of 51 sheep; 14 sheep received autologous bone graft from the iliac crest. Follow-up times were 3, 6 and 12 months. With the exception of the 12-month animals, there was a minimum of 6 animals in each group. At the end of follow-up the tibiae were tested in torsion to failure. These results were correlated with radiographic and ultrasound scores measured on the same specimens. With the scoring system it was possible to describe the osseous integration of the HA ceramic or mineralisation of the cancellous bone graft. Sheep with ceramic implant that developed non-unions showed a significantly lower score than sheep with a sufficient implant integration. A significant correlation between these scores and the biomechanical results was found. We were able to define a cut-off within the scoring system which made the prediction of instability/non-union possible. In our model we were able to predict the osseous integration of HA ceramics and autologous cancellous bone grafts with the use of real-time ultrasound.     

New segmental long bone defect model in sheep: quantitative analysis of healing with dual energy x-ray absorptiometry.

An appropriate animal model is required for the study of treatments that enhance bone healing. A new segmental long bone defect model was developed for this purpose, and dual energy x-ray absorptiometry was used to quantify healing of this bone defect. In 15 sheep, a 3-cm segmental defect was created in the left tibia and fixed with an interlocking intramedullary nail. In seven animals, the defect was left empty for the assessment of the spontaneous healing response. In eight animals serving as a positive control, autologous bone grafting was performed. After 12 weeks, healing was evaluated with radiographs, a torsional test to failure, and dual energy x-ray absorptiometry. The mechanical test results were used for the assessment of unions and nonunions. Radiographic determination of nonunion was not reliably accomplished in this model. By means of dual energy x-ray absorptiometry, bone mineral density and content were measured in the middle of the defect. Bone mineral density was 91+/-7% (mean +/- SEM) and 72+/-6% that of the contralateral intact tibia in, respectively, the autologous bone-grafting and empty defect groups (p = 0.04). For bone mineral content, the values were, respectively, 117+/-18 and 82+/-9% (p = 0.07). Torsional strength and stiffness were also higher, although not significantly, in the group with autologous bone grafting than in that with the empty defect. Bone mineral density and content were closely related to the torsional properties (r2 ranged from 0.76 to 0.85, p < or = 0.0001). Because interlocking intramedullary nailing is a very common fixation method in patients, the newly developed segmental defect model has clinical relevance. The interlocking intramedullary nail provided adequate stability without implant failure. This model may be useful for the study of treatments that affect bone healing, and dual energy x-ray absorptiometry may be somewhat helpful in the analysis of healing of this bone defect.     

Mechanical and radiological assessment of the influence of rhTGFbeta-3 on bone regeneration in a segmental defect in the ovine tibia: pilot study.

Limitations in the use of autologous bone graft, which is the gold standard therapy in bone defect healing, drive the search for alternative treatments. In this study the influence of rhTGFbeta-3 on mechanical and radiological parameters of a healing bone defect in the sheep tibia was assessed. In the sheep, an 18-mm long osteoperiosteal defect in the tibia was treated by rhTGFbeta-3 seeded on a poly(L/DL-lactide) carrier (n = 4). In a second group (n = 4), the defect was treated by the carrier only, in a third group (n = 4) by autologous cancellous bone graft, and in a fourth group (n = 2) the defect remained blank. The healing process of the defect was assessed by weekly in vivo stiffness measurements and radiology as well as by quantitative computed tomographic assessment of bone mineral density (BMD) every 4 weeks. The duration of the experiment was 12 weeks under loading conditions. In the bone graft group, a marginally significant higher increase in stiffness was observed than in the PLA/rhTGFbeta-3 group (p = 0.06) and a significantly higher increase than in the PLA-only group (p = 0.03). The radiographic as well as the computed tomographic evaluation yielded significant differences between the groups (p = 0.03), indicating the bone graft treatment (bone/per area, 83%; BMD, 0.57 g/cm(3)) performing better than the PLA/rhTGFbeta-3 (38%; 0.23 g/cm(3)) and the PLA-only treatment (2.5%; 0.09 g/cm(3)), respectively. Regarding the mechanical and radiological parameters assessed in this study, we conclude that rhTGFbeta-3 has a promoting effect on bone regeneration. However, under the conditions of this study, this effect does not reach the potential of autologous cancellous bone graft transplantation.     

椎间盘镜下异体松质骨复合自体红骨髓植骨治疗骨不连及骨缺损

目的探讨椎间盘镜下异体松质骨复合自体红骨髓植骨治疗四肢长骨干骨不连及骨缺损的临床疗效。方法2003年9月～2006年9月,选择25例创伤后骨不连、骨缺损患者,其中胫骨9例,股骨13例,肱骨3例。骨不连、骨缺损引起须植骨长度1～6 cm,平均2.7 cm,均在椎间盘镜下行瘢痕清除,然后在骨缺损部位植入异体松质骨,再于髂骨取自体红骨髓15～20 ml注入植骨处。结果25例随访12～36个月,平均25个月,切口均一期愈合,无一例发生神经血管损伤症状。除2例术后内固定失败外,余23例骨不连、骨缺损均获骨性愈合,植骨生长良好,骨愈合时间4～9个月,平均5.1月,无感染及再出现骨不连。结论椎间盘镜下异体松质骨复合自体红骨髓植骨治疗骨不连和骨缺损,无须自体髂骨取骨,局部创伤小,血运破坏小,并发症少,骨愈合率高,是一种微创有效的治疗方法。     

Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow.

Hydroxyapatite is a synthetic bone graft, which is used for the treatment of bone defects and nonunions. However, it is a rather inert material with no or little intrinsic osteoinductive activity. Recombinant human osteogenic protein-1 (rhOP-1) is a very potent biological agent, that enhances osteogenesis during bone repair. Bone marrow contains mesenchymal stem cells, which are capable of new bone formation. Biosynthetic bone grafts were created by the addition of rhOP-1 or bone marrow to granular porous hydroxyapatite. The performance of these grafts was tested in a sheep model and compared to the results of autograft, which is clinically the standard treatment of bone defects and nonunions. A 3 cm segmental bone defect was made in the tibia and fixed with an interlocking intramedullary nail. There were five treatment groups: no implant (n=6), autograft (n=8), hydroxyapatite alone (n=8), hydroxyapatite loaded with rhOP-1 (n=8), and hydroxyapatite loaded with autologous bone marrow (n=8). At 12 weeks, healing of the defect was evaluated with radiographs, a torsional test to failure, and histological examination of longitudinal sections through the defect. Torsional strength and stiffness of the healing tibiae were about two to three times higher for autograft and hydroxyapatite plus rhOP-1 or bone marrow compared to hydroxyapatite alone and empty defects. The mean values of both combination groups were comparable to those of autograft. There were more unions in defects with hydroxyapatite plus rhOP-1 than in defects with hydroxyapatite alone. Although the differences were not significant, histological examination revealed that there was more often bony bridging of the defect in both combination groups and the autograft group than in the group with hydroxyapatite alone. Healing of bone defects, treated with porous hydroxyapatite, can be enhanced by the addition of rhOP-1 or autologous bone marrow. The results of these composite biosynthetic grafts are equivalent to those of autograft.     

自体红骨髓注射治疗骨不连术后局灶性骨缺损

目的：观察自体红骨髓注射治疗骨不连术后局灶性骨缺损的临床疗效。方法：13例骨不连术后局灶性骨缺损患者,男8例,女5例;年龄15-60岁,平均32．5岁。骨缺损部位：胫骨7例,股骨2例,肱骨4例。采用自体红骨髓注射至骨折断端治疗,自体红骨髓经皮注射每2周1次,共5次,每月复查肢体正侧位X线片。结果：13例全部获得随访,时间6～12个月,平均7．5个月。13例骨缺损完全修复,平均愈合时间4个月。无严重并发症发生。结论：自体红骨髓注射创伤小,疗效明确,并能缩短骨缺损修复时间,有利于促进肢体功能恢复,是治疗骨不连术后局灶性骨缺损的一种好方法。     

New-bone formation by osteogenic protein-1 and autogenic bone marrow in a critical tibial defect model in sheep

AIM: Osteogenic Protein-1 (OP-1) is known to be a very potent osteoinductive growth factor. However, experimental studies using critical-size defect models in the weight-bearing lower extremity show non-uniform results. Therefore, we studied the osteoinductivity of OP-1 in a tibial worst-case defect model in sheep. Potential improvement of OP-1 induced new bone formation using a composite graft with autogenous bone marrow was to be investigated. METHOD: In 19 sheep a 5 cm segmental defect of the tibial diaphysis was treated by intramedullary nailing and filled with the following implants: 5 mg OP-1 + inactivated demineralized bone matrix (group 1; n = 6); 5 mg OP-1 + inactivated demineralized bone matrix + 5 ml autogenous bone marrow (group 2; n = 5); autogenous cancellous bone (group 3; n = 4), or inactivated demineralized bone matrix + 5 ml autogenous bone marrow (group 4; n = 4). RESULTS: In total, 3 out of 10 defect sites treated with OP-1 were completely bridged radiographically by 12 weeks. Initially, x-rays showed accelerated new bone formation by use of the composite grafts containing OP-1 and autogenous bone marrow. However, 12 weeks post surgery 3D-CT-volumetry could not detect significant differences of new bone formation within the defect sites treated by OP-1 with or without bone marrow, while new bone formation by autogenous cancellous bone was better than by OP-1. CONCLUSION: In our worst case defect model, the osteoinductive potential of OP-1 is initially accelerated but 12 weeks post surgery not increased when combined with autogenous bone marrow transplantation. So far, critical segmental bone defects of the weight-bearing lower extremity can not be bridged regularly in our model by use of OP-1. Therefore, for the treatment of such critical defects with rotational instability the examined application device of OP-1 can not yet be recommended.     

自体松质骨加骨髓移植治疗陈旧性腕舟骨骨折不连的临床研究

目的观察自体松质骨加骨髓移植治疗陈旧性腕舟骨骨折不连及近端坏死型腕舟骨骨折的临床效果。方法随机选择14例陈旧性腕舟骨骨折不连患者，搔刮舟骨远、近两端死骨，保留皮质骨壳，取自体松质骨（桡骨远端或髂骨）移植至舟骨远、近两端，舟骨复位后交叉克氏针固定。髂骨内抽取自体红骨髓5ml，快速、加压注入舟骨骨折部位。术后6周开始，每周拍摄计算机X线片（CR-X）一次，至骨折愈合，并记录骨折愈合及恢复工作时间。结果术后随访10周～5年，14例陈旧性腕舟骨全部愈合，骨折愈合时间为8～12周，平均9．3周。13例腕关节活动度达到健侧腕部标准，活动时无疼痛，恢复了原来工作；1例较术前有改善，但腕关节活动未达健侧标准，且活动时疼痛。结论自体松质骨加自体骨髓移植治疗陈旧性腕舟骨骨折不连，较传统治疗方法，缩短了骨折愈合时间，提高了治愈率，保留了原解剖结构和生物力学特性，是一种有效的治疗方法。     

Preliminary experience with a novel model assessing In vivo mechanical strength of bone grafts and substitute materials

A novel canine tibia model was used to evaluate four bone graft materials: autologous cortical bone, allograft cortical bone, hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic granules, and a HA/TCP and collagen composite. Mechanical material properties were assessed using custom-designed stainless steel plugs for control of graft volume and interface surface area. These plugs held the bone graft materials in the cortex of the tibia shaft and allowed in vivo mechanical testing. After 6 months of ad lib weight bearing, the grafts were harvested and tested in torsion. The samples in each animal were compared with the test plugs into which new bone had grown without the addition of graft. Control bone peak shear strength averaged 47 (±8.3) MPa (6.78±1.2 kpsi). Compared on the basis of peak torque, stiffness, and energy to peak torque, no significant differences were found among any of the graft materials or control bone. Histologic examination revealed the materials to be osteoconductive with the extensive formation of dense, compact cancellous bone. The new bone in the autograft and allograft samples completely filled the available space, whereas gaps persisted in the synthetic ceramics.     

Reconstruction of Large Diaphyseal Defects of the Femur and the Tibia with Autologous Bone

Abstract   Post-traumatic segmental bone defects of the femur and the tibia above the critical size require special attention because conventional bone grafts result in high rates of nonunion. The biological and biomechanical aspects of this challenging surgery, as well as ongoing refinements to achieve mechanically stable bone healing with correct bone alignment are reviewed. Choosing the best appropriate method is mainly dependent on both the location and etiology of the bone defect. Three patients with successful bone reconstruction using two-stage reconstruction with cancellous bone graft, double-barrel free vascularized fibula transfer and distraction osteogenesis are described. Advantages and disadvantages of these methods are discussed in accordance with recent literature.     

In vivo effects of modification of hydroxyapatite/collagen composites with and without chondroitin sulphate on bone remodeling in the sheep tibia

The addition of chondroitin sulphate (CS) to bone cements with calcium phosphate has lead to an enhancement of bone remodeling and an increase in new bone formation in small animals. The goal of this study was to verify the effect of CS in bone cements in a large animal model simulating a clinically relevant situation of a segmental cortical defect of a critical size on bone–implant interaction and bone remodeling. The influence of adding CS to hydroxyapatite/collagen (HA/Col) composites on host response was assessed in a standard sheep tibia model. A midshaft defect of 3 cm was created in the tibiae of 14 adult female sheep. The defect was filled with a HA/Col cement cylinder in seven animals and with a CS‐modified hydroxyapatite/collagen (HA/Col/CS) cement cylinder in seven animals. In all cases the tibia was stabilized with an interlocked universal tibial nail. The animals in each group were analyzed with X‐rays, CT scans, histology, immunohistochemistry, and enzymehistochemistry, as well as histomorphometric measurements. The X‐ray investigation showed a significantly earlier callus reaction around the HA/Col/CS implants compared to HA/Col alone. The amount of newly formed bone at the end point of the experiment was significantly larger around HA/Col/CS cylinders both in the CT scan and in the histomorphometric analysis. There were still TRAP‐positive osteoclasts around the HA/Col implants after 3 months. The number of osteopontin‐positive osteoblasts and the direct bone contact were significantly higher around HA/Col/CS implants. We conclude that addition of CS enhances bone remodeling and new bone formation around HA/Col composites. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:15–21, 2009     

Treatment of nonunion by percutaneous injection of bone marrow and demineralized bone matrix. An experimental study in dogs

Successful treatment of nonunited fractures remains a major clinical challenge. Because bone marrow and demineralized bone matrix (DBM) are capable of stimulating osteogenesis, experiments were designed to test the effectiveness of bone marrow or DBM or both when injected percutaneously into a canine nonunion model. Six-millimeter segmental defects were created in the midtibial diaphysis of 24 adult mongrel dogs and held distracted by external fixation. For comparative purposes, a 0.5-mm osteotomy was created in five dogs. Five weeks later, the 6-mm defects were injected with either saline, autogeneic marrow, DBM powder, a composite of bone marrow and DBM, or treated by open grafting techniques with autogenic cancellous bone. Healing of the defect was evaluated roentgenographically, biomechanically (three-point bending), histologically, and biochemically 13 weeks postsurgery. Marrow and DBM stimulated defect healing. However, the combination of bone marrow with DBM produced a synergistic response in the defect, which was greater than the sum of either marrow or DBM alone. Healing in the composite-grafted dogs was comparable to those treated by standard cancellous bone grafting. These data suggest that percutaneous injection of bone marrow and DBM may be a potential alternative that offers numerous advantages over standard open grafting techniques in the treatment of fractures with nonunited defects.     

四肢难治性骨不连的三种治疗策略疗效分析

[目的] 比较分析3种方法治疗四肢难治性骨不连的临床疗效.[方法] 2003年4月-2008年2月,共收治四肢难治性骨不连36例39肢,男22例,女14例;年龄15～71岁,平均51.5岁;胫骨19肢,肱骨9肢,股骨7肢,尺、桡骨4肢;治疗骨不连手术次数1～4次,平均2.5次;术前X线片骨不连骨断端距离:4.5～36 mm,平均16.5 mm;下肢短缩距离:5～40 mm,平均21 mm.自体骨髓复合人工骨联合髂骨骨膜移植19肢(联合组),自体骨髓移植联合人工骨9肢(骨髓组),自体髂骨移植治疗11肢(髂骨组).[结果] 39肢最终均达骨性愈合,均获随访12～28个月,平均18.5个月.骨愈合时间、固定物取出1个月患肢功能评分和术后X线片评分,联合组疗效优越(P＜0.05).联合组骨愈合时间(5.5±1.5)个月,骨髓组骨愈合时间(6.6±1.8)个月,髂骨组骨愈合时间(7.4±2.1)个月.[结论] 自体骨髓复合人工骨联合髂骨骨膜移植治疗四肢难治性骨不连临床疗效优越.     

Membrane-guided bone regeneration: Segmental radius defects studied in the rabbit

We tested the principle of guided tissue regeneration (GTR) for healing segmental long-bone defects. 7 mm (3 animals) or 10 mm (5 animals) long segmental defects were created in the diaphyses of both radii in 8 rabbits. The defect on one side was covered with a barrier membrane of expanded polytetrafluoroethylene membrane shaped as a tube, while the contralateral side with no membrane served as the control. Healing was followed with radiographs obtained repeatedly during a 13- (n 3) or 27- (n 5) week period. Thereafter, the animals were killed and ground sections of the defect sites were prepared for histologic examination.

Radiographically, the control sites showed some early subperiosteal callus formation and nonunion of the defects after 6 weeks. The bone ends were rounded off and sealed with cortical bone. No major changes were noted after 6 weeks.

At the test sites, subperiosteal bone formation at the bone ends was first observed radiographically at 2 weeks. At 9 weeks, a thin cortical bone bridged the defect along the inner surface of the membrane. Histologically, an interrupted line of thin, cortical bone was observed along the inner surface of the barrier membrane. Fatty bone marrow occupied the central and largest volume of the defect.

We conclude that it seems possible to use the principle of GTR to accomplish bone union of segmental long-bone defects.     

自体深筋膜复合自体红骨髓移植治疗骨不连

目的：根据膜引导性骨再生与骨诱导再生的理论,将自体深筋膜复合自体红骨髓移植治疗骨不连,为临床寻找一种简便有效的治疗骨不连的方法。方法：自2006年3月至2009年3月,采用自体深筋膜复合自体红骨髓移植的方法对17例骨不连患者进行治疗,男10例,女7例;年龄7～52岁,平均32岁;胫骨10例,桡骨5例,锁骨2例。受伤至入院时间7～36个月,平均12个月。入院前已手术1次者10例,2次者5例,3次者2例。骨不连部位均位于骨干,皮肤软组织条件较好。X线片显示增生性骨不连11例,萎缩性骨不连6例。均拆除原有内固定物,重新用髓内钉或钢板内固定,并用自体深筋膜密闭缝合骨折端,内注入自体红骨髓。结果：17例患者均获得随访,时间5个月～2年,平均1年。骨折临床愈合时间12～20周,平均16周。术后根据骨折愈合标准对疗效进行评估：优14例,良2例,差1例。结论：自体深筋膜复合自体红骨髓移植治疗骨不连,骨折愈合时间短,适合于骨不连位于骨干,皮肤软组织条件较好的患者。     

Technique to prepare the bed for autologous bone grafting in nonunion surgery

This article describes a technique for preparing the bed for autologous bone grafting in nonunion surgery. The procedure is divided into 2 steps. First, both ends of the fracture fragments are chipped into small pieces using an osteotome and hammer without peeling off the periosteum, creating pathways into the bone marrow. Second, cancellous bone harvested from the iliac crest is grafted into the aperture created by the previous bone chipping treatment. The technique is easy to perform and is a promising approach for enhancing bone healing in nonunion and delayed union.     

Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation

Gastrectomy often results in increased likelihood of osteoporosis, metabolic aberration, and risk of fracture, and there is a need for a gastric peptide with osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound and fracture healing in rats in addition to having an angiogenic effect. Therefore, in the present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157 was further studied (either percutaneously given locally [10 microg/kg body weight] into the bone defect, or applied intramuscularly [intermittently, at postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]). For comparison, rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. Moreover, a comparison of the number of animals with unhealed defects (all controls) or healed defects (complete bony continuity across the defect site) showed that besides pentadecapeptide intramuscular application for 14 days (i.e., local application of bone marrow or autologous cortical graft), also following other pentadecapeptide BPC-157 regimens (local application, or intermittent intramuscular administration), the number of animals with healed defect was increased. Hopefully, in the light of the suggested stomach significance for bone homeostasis, the possible relevance of this pentadecapeptide BPC-157 effect (local or intramuscular effectiveness, lack of unwanted effects) could be a basis for methods of choice in the future management of healing impairment in humans, and requires further investigation.     

Notwendigkeit von „bone morphogenetic proteins“ in der Frakturbehandlung

Bone morphogenetic proteins (BMP) are bone growth factors. They are released locally following a fracture event and stimulate the healing process right through to bone remodelling. Since 2001 it has been possible to use BMP2 and BMP7 as medications for genetic engineering; BMP2 is indicated for open fractures of the lower leg and BMP7, for nonunion in the tibia. Delayed fracture healing and nonunion are common, being observed in up to 10% of all cases (up to 30% in risk groups). Quite apart from the personal, sometimes disastrous, consequences for the individual patient, they also represent a considerable loss to the national economy. The conventional treatments for nonunion (including autologous and allogeneic bone transplantation, dynamisation of the nail or a strained plate fixation) are not always successful. The success rate of initial cancellous bone transplantation in the lower leg for delayed fracture healing is only 60–70%. In our patient population (26 tibial fractures treated with BMP7; average of 3 previous operations) healing was achieved with no further surgery in 89% of cases. In view of the high economic costs of delayed healing and the decidedly higher success rate of BMP implantation, this medication should be used at an early stage despite its high cost.     

Bone grafts prepared with selective cell retention technology heal canine segmental defects as effectively as autograft.

Using a canine critical-size segmental defect model, a two-phased study was undertaken to evaluate the healing efficacy of demineralized bone and cancellous chips (DBM-CC) enriched with osteoprogenitor cells using a Selective Cell Retention (SCR) technology. The goals of this study were: 1) to determine the bone-healing efficacy of SCR-enriched grafts versus autograft, and 2) to assess the value of clotting SCR-enriched grafts with platelet-rich plasma (PRP). Thirty dogs were included in Phase I: 18 dogs were treated with an SCR-enriched DBM-CC graft clotted with autologous bone marrow, and were compared to 12 autograft controls. In Phase II, 24 animals were divided into 4 groups of 6 animals, each treated with a different bone graft material: 1) iliac crest autograft, 2) DBM-CC alone, 3) DBM-CC saturated with marrow, and 4) SCR-enriched DBM-CC clotted with PRP. All grafts were placed unilaterally in a 21-mm long osteoperiosteal femoral, instrumented, critical-size defect. Radiographs were obtained for all animals postoperatively and every 4-16 weeks; animals were then sacrificed. All femurs were prepared for histology. Femurs in the Phase II study were also analyzed by micro-CT. At 16 weeks, healing--defined by bridging bone across the defects--was observed in 50% of the DBM-CC alone group and 67% of the DBM-CC saturated with marrow group; 100% of the autograft and SCR-enriched DBM-CC groups were healed. Histologically, grafts clotted with PRP showed more mature bone than those implanted with autologous bone, which in turn were similar to those implanted with bone marrow clotted SCR-enriched grafts. These results demonstrated that: 1) SCR-enriched DBM-CC was equivalent to autograft to repair critical-size defects, and 2) while not statistically significant, PRP may have accelerated bone maturation when used to clot osteoprogenitor-enriched DBM-CC grafts--as compared to cell-enriched, DBM-CC grafts without PRP--in large animal models.     

Inhibition of cortical and cancellous bone formation in glucocorticoid-treated OVX sheep

INTRODUCTION: Little is known about the effects of steroids on cortical bone. The purpose of this study was to explore the effects of glucocorticoid treatment on cortical bone density, strength, and formation of new bone in ovariectomized sheep and to compare it to cancellous bone. MATERIALS AND METHODS: Sixteen ovariectomized merino sheep either received a 6-month glucocorticoid treatment (GLU; 0.45 mg/kg/day Methylprednisolone s.c.) or were left untreated (control). After 2 and 4 months, newly formed bone was labeled by the administration of calceingreen and Tetracycline-hydrochloride. After 12 months, the animals were sacrificed and cortical specimens were obtained from the tibial diaphysis. Cancellous bone specimens were harvested from the proximal tibia. All specimens were scanned for apparent BMD by pQCT and tested mechanically. Formation of new bone was analyzed using histological slices of the femoral condyles and cross-sections of the mid-diaphysis of the tibia. RESULTS: The intracortical formation of new bone in glucocorticoid-treated sheep was 70% lower after 2 months and 80% lower after 4 months. Six months after the termination of the steroid administration, the active bone area was 20% lower than in the control group. Cortical width and cortical bone area were reduced by 7-8% and marrow area increased by 8% in steroid-treated animals compared to control animals. Neither cortical apparent bone mineral density nor biomechanical parameters of cortical bone specimens differed between the groups. Cancellous bone formation in steroid-treated animals declined by 68% after 2 months and by 90% after 4 months. After 1 year, cancellous bone formation was reduced by 38% compared to control. The apparent cancellous bone mineral density and cancellous bone compressive stiffness were reduced by 34% and 55%, respectively. CONCLUSION: A six-month glucocorticoid treatment of ovariectomized sheep resulted in a substantial reduction of bone formation both in cortical and in cancellous bone and reduced cortical width by increased endosteal resorption. Beyond changes in cancellous bone, impaired cortical bone remodeling may add to the increased fracture risk at the hip or the distal radius in patients treated with steroids.