Changes in Bone Mass,Bone Structure,Bone Biomechanical Properties,and Bone Metabolism after Spinal Cord Injury: A 6-Month Longitudinal Study in Growing Rats

Spinal cord injury (SCI) results in a great decline in bone mineral density (BMD) and deterioration of bone microarchitecture. The objective of this study was to investigate the time course of the changes in BMD, microarchitecture, biomechanical properties, and bone turnover in male growing rats following SCI. Sixty male growing Sprague-Dawley rats, 6 weeks of age, were randomly divided into SCI (lower thoracic cord transection) and sham-operated groups, and bone tissues and blood samples were examined at 3 weeks, 6 weeks, and 6 months after surgery. SCI rats had low bone weight (wet, dry, and ash weight) and BMD of the femora, tibiae, and third lumbar vertebrae at all time points compared to sham rats, while in forelimbs, there was a decrease of dry and ash weight compared to sham rats only at 3 weeks but not BMD. Bone microarchitecture and trabecular connectivity were deteriorated in SCI rats and remained so after. Bone formation rate and serum osteocalcin level in SCI rats were significantly increased 3 weeks after SCI surgery. However, eroded surface/bone surface and serum N-terminal telopeptide of type I collagen level remained elevated from 3 weeks to 6 months. In addition, SCI rats showed poor biomechanical properties in the proximal tibiae and femora but not in the humeri. In conclusion, SCI causes profound BMD loss, disturbances in bone microarchitecture, decreased mechanical strength in the lower extremity and lumbar spine, and high bone turnover. These findings will allow better understanding of osteoporosis following SCI.     

Bone substitutes

Summary Biocompatible calcium phosphate ceramics has been used for several years in orthopeadic surgery. We have been using two new synthetic biphasic calcium phosphate ceramics (BCP) since September 1996 for bone defect filling in any orthopaedic or trauma operation where autograft use was not possible or even wanted. The first, Eurocer 400® has 300 to 500 micron wide macropores with a totally interconnected porosity. This salt seed like product can be used in bone defect filling, when solidity is not a major concern. The second, Eurocer 200® has not totally interconnected 200 micron large pores. Its main characteristic is a mechanical resistance up to 30 Mpa. We use it in any case of weight-bearing surgery. Different sizes and presentation forms are available and will be chosen according to the recipient site shape. We report one hundred and fifty cases with a six to thirty month follow-up. In one third of the patients hip revision surgery was addressed. Another third concerned recent trauma or sequelae cases,.whereas the last third involved cold orthopaedic procedures. General principles are the need of a living and non-infected site after thorough debridement if necessary. Osteocompatibility of calcium phosphate ceramic is confirmed by our results. We report no mechanical failure. In all cases X-rays show a progressive integration, with new bone formation. Our substitutes have been histologically studied in nine cases, four to fifteen months after implantation. New bone formation around and in the substitute is impressive. Indeed, their good mechanical properties without loss of biological quality is the most relevant feature of these BCPs, leading to a wider indication field; therefore we have now abandoned the use of any bony auto, allo or xenograft.Paper presented at the 1998 meeting of GECO (Arc 1800, Bourg-Saint-Maurice, France)     

骨基质明胶复合自体红骨髓及同种异体骨修复骨缺损

目的:评价骨基质明胶复合自体红骨髓及同种异体骨联合移植修复骨缺损的疗效。方法:76例良性骨肿瘤和瘤样病损患者,彻底刮除病灶或作肿瘤骨段切除,并对瘤壁作灭活处理,以同种异体骨作支架,周围填充骨基质明胶和自体红骨髓复合物,术后观察机体反应及骨缺损修复情况。结果:术后机体无明显免疫排斥反应,无1例发生感染,所有病例随访时间为5～16个月,X线显示新骨形成时间为术后1.5～4月,完全骨化的时间为术后5～9月,骨缺损骨性愈合74例,并获得较好的关节功能,肿瘤复发2例。结论:骨基质明胶、自体红骨髓、同种异体骨复合物能有效修复骨缺损,有广泛的临床应用前景。     

Anthropometric,Bone Age,and Bone Mineral Density Changes after a Family-Based Treatment for Obese Children

Our objective was to identify anthropometric, bone age, and bone mineral density (BMD) changes after a family-based treatment program for obese children. We conducted a longitudinal prospective study of 50 obese children (body mass index percentage [BMI%] ≥120%) aged 9.12 ± 1.72 years (range 6–13) at baseline. A family-based treatment program, based on inadequate feeding style with progressive modification, aerobic physical exercise increase, active parental involvement, and the use of behavioural strategies (contracting, self-monitoring, social reinforcement), was developed during a 12-month period. Anthropometric data, lumbar spine (L2-L4) BMD by dual-energy X-ray absorptiometry, bone age (BA), bone age to chronological age ratio (BA/CA), and predicted adult height (PAH) were determined at baseline and 12 months. The statistical method used was analysis of variance and the paired Student t-test. Mean BMI standard deviation score (SDS) loss was –0.61 ± 0.76 and BMI% loss was –5.17 ± 9.73%. Height SDS significantly decreased, BA/CA ratio also decreased significantly, and PAH change was not significant. Lumbar spine BMD SDS and BMD% did not significantly change. A family-based treatment program was effective in obese children by reducing by 5% the BMI in 1 year and increasing the activity level. Treatment reduced growth velocity and delayed bone maturation rate without affecting PAH, reflecting a situation of previous early maturation. The treatment did not modify gaining bone mass.     

牛脱蛋白松质骨、胶原、BMP、RBM复合物修复骨缺损的实验研究

目的探讨牛脱蛋白松质骨、胶原、骨形态发生蛋白(BMP)、自体红骨髓(RBM)复合物修复骨缺损的能力及其作为自体骨移植替代材料的合理性、可行性.方法在42只家兔双侧桡骨中段制备骨缺损模型,分为4组牛脱蛋白松质骨、胶原、BMP、RBM复合物植入组(A1组20侧)、单纯牛脱蛋白松质骨植入组(A2组20侧)、自体骨植入组(B1组20侧)、空白对照(B2组20侧).在2、4、8、12周分别进行大体标本观察、X线检查、病理组织学检查及生物力学测试.结果 12周时,A1组、B1组骨缺损均已完全修复,而A2组、B2组骨缺损未修复;生物力学测试术后4周A1组的最大扭矩和抗扭刚度均高于B1组,而术后8周后则无显著性差异.结论牛脱蛋白松质骨、胶原、BMP、RBM复合物具有较强的成骨能力,可修复骨缺损,并能作为自体骨移植的一种替代材料.     

Bone Transport for Reconstruction in Benign Bone Tumors

Background

The aim of this study was to assess the results of using the Ilizarov apparatus to transport bones in the treatment of benign bone tumors.

Methods

Seven patients (six males and one female) with benign bone tumors were treated by bone transport with an Ilizarov apparatus at our institution. Their mean age at surgery was 14.4 years (range, 4.8 to 36.9 years). The histological diagnoses were osteofibrous dysplasia (4), giant-cell tumor (1), intraosseous cavernous hemangioma (1), and aneurysmal bone cyst (1). Three radiological indices were used for evaluating the results: an external fixation index, a distraction index, and a maturation index. The bone and functional results were evaluated according to the Association for the Study and Application of the Method of Ilizarov classification.

Results

Five patients had bone union at the reconstructed site, one patient had a local recurrence, and the other had a nonunion at the docking site. The mean length of distraction was 7.3 cm (range, 5.1 to 12.1 cm). The mean external fixation index was 26.0 day/cm (range, 19.8 to 32.5 day/cm), the distraction index was 9.6 day/cm (range, 6.8 to 12.0 day/cm), and the maturation index was 14.9 day/cm (range, 8.0 to 22.5 day/cm). Ultimately, the bone and the functional results were rated excellent in six cases and good in one case.

Conclusions

Bone transport using the Ilizarov apparatus is a good treatment option in patients with bone defects after the resection of an active or aggressive benign bone tumor.     

外固定架及重组合异种骨植骨治疗胫骨骨缺损与骨不连

目的：探讨外固定架和重组合异种骨(RBX)植骨治疗胫骨骨缺损、伴肢体短缩的胫骨骨不连及先天性胫骨假关节的临床疗效。方法：应用外固定架共治疗胫骨骨缺损、伴肢体短缩性骨不连及先天性胫骨假关节20例。胫骨断端清理后短缩长度2—9cm，平均4．8cm。断端应用RBX植骨12例。结果：20例病人随访8个月-7年，平均4年3个月，患肢功能恢复满意。12例应用RBX植骨治疗骨不连的平均愈合时间4．8个月。结论：本手术方法治疗胫骨骨缺损、伴肢体短缩的胫骨骨不连及先天性胫骨假关节，创伤小、操作简单，肢体功能恢复满意；RBX植骨治疗骨不连，安全，对促进骨愈合疗效可靠。     

Osteogenesis Imperfecta: Bone Turnover, Bone Density, and Ultrasound Parameters

We studied 21 patients (11 men and 10 women) with osteogenesis imperfecta (OI) and 21 age- and sex-matched controls. In all patients we measured serum levels of total alkaline phosphatase (ALP), type I procollagen carboxy-terminal propeptide (PICP), osteocalcin (BGP), urinary excretion of hydroxyproline (HOP/Cr), and pyridinoline crosslinks (Pyr/Cr). Bone mineral density was measured at the distal radius (BMD-R) and at the lumbar spine (BMD-LS) by dual X-ray absorptiometry (DXA). Ultrasound parameters were also performed at the calcaneous with the Achilles device and at the phalanxes with DBM Sonic 1200. A significant reduction (P < 0.001) in BMD and in ultrasound parameters was found in OI patients compared with normals. PICP was significantly reduced in the OI patients compared with controls (P < 0.001); other markers of bone turnover were higher in OI than in controls, but the difference did not reach the statistical significance. A significant correlation (P < 0.05) was found between PICP and BMD at the lumbar spine and between PICP and ultrasound parameters at the calcaneous. On the basis of our data, we conclude that patients with OI show low values of BMD and ultrasound parameters; therefore in these patients, not only is bone mass disturbed but also bone quality. The reduced levels of PICP in OI patients confirm that most OI patients have defects in collagen I biosynthesis. These defects may contribute to the fragility of OI bone by interfering with complete mineralization and/or normal tissue structure. PICP may be considered a useful marker in the clinical management of OI. Received: 26 March 1998 / Accepted: 15 January 1999     

Bone Quality and Bone Strength in BXH Recombinant Inbred Mice

The relationship between bone quality and strength was studied in 11 BXH recombinant inbred (RI) strains of mice. The bone quality parameters studied were bone mineralization, microhardness, architecture, and connectivity. Previous studies have demonstrated considerable variability in bone density, biomechanical properties, and microstructure among inbred strains of mice. In particular, C3H/HeJ (C3H) mice exhibit thicker femoral and vertebral cortices and fewer trabeculae in the vertebral body compared with C57BL/6J (B6) mice, despite having similar vertebral bone strength. A set of RI mouse strains has been generated from B6 and C3H (denoted BXH) in an attempt to isolate genetic regulation of numerous traits, including bone. The objective of this study was to investigate relationships among bone quality and bone strength in femurs and vertebrae among BXH RI mice. The study involved 11 BXH RI strains of female mice (n = 5−7) as well as the B6 and C3H progenitor strains. Parameters contributing to bone quality were evaluated, including BMD, bone mineralization, microhardness, architecture, and connectivity. There was a strong correlation between femoral and vertebral BMD in all strains (P < 0.001) except in BXH-9 and -10 (P < 0.001). Within the vertebrae, cortical bone was more mineralized than trabecular bone, and a strong correlation existed between the two (P < 0.001). However, cortical microhardness did not differ from trabecular microhardness. Cortical bone was more mineralized in the femur than in the vertebrae and significantly harder, by 30%. There was a wide range in trabecular connectivity, architecture, and femur geometry among BXH RI strains. BMD explained 43% of vertebral bone strength but only 11% of femoral bone strength. Trabecular connectivity explained an additional 8% of vertebral strength, while mineralization and femur geometry explained 7% and 50% of femoral strength, respectively. Different bone quality parameters had varying influences on bone mechanical properties, depending on bone site. BMD may play a larger role in explaining bone strength in the vertebrae than in the femur. Moreover, cortical bone in the femur is harder than in vertebrae. The control of cortical bone material properties may be site-dependent.     

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。     

Expression of Bone Microsomal Casein Kinase II, Bone Sialoprotein, and Osteopontin During the Repair of Calvarial Defects

The temporal expression of bone microsomal casein kinase II, osteopontin, bone sialoprotein, alkaline phosphatase, and the accumulation of a solid calcium–inorganic orthophosphate mineral phase, have been charted from day 2 to day 21 during the repair of calvarial defects in rats induced by the implantation of decalcified rat bone matrix. Unlike the sequence of events that occur when the same decalcified bone matrix is implanted subcutaneously or intramuscularly, in which cases the first tissue to form in response to the implant is cartilage that subsequently calcifies and is later resorbed and replaced by bone, the repair of cranial defects is quite different. In the latter case, the first cells induced are undifferentiated mesenchymal cells and early fibroblasts followed by osteoblastic direct bone formation. Somewhat later a few small islands of cartilage are formed, widely separated and spatially distinct from the newly formed bone matrix. All of the cartilage and most of the implanted decalcified bone matrix are later resorbed and replaced by new bone by day 21. This in vivo model of the repair of a bone defect by direct bone formation has provided an excellent system to follow specific biochemical and physicochemical events. The total accumulation and rate of accumulation of the mineral and the two noncollagenous phosphoproteins (bone sialoprotein and osteopontin), as well as the activities of alkaline phosphatase, and for the first time either in vivo or in cell culture, the activity of microsomal casein kinase II, the major enzyme that phosphorylates the bone phosphoproteins, have been determined as a function of healing time in vivo. The overall general pattern of accumulation of the phosphoproteins and calcium-phosphate mineral phase and their relationships are similar to those reported in osteoblast cell cultures also monitored as a function of time.     

骨段输送治疗下肢大段骨缺损

目的　总结骨段输送技术治疗大段骨缺损、骨感染及皮肤缺损的体会。方法　应用骨段输送治疗严重创伤或骨肿瘤术后大段骨缺损 9例 ,其中 6例伴有骨感染和皮肤缺损。结果　 9例骨缺损全部治愈 ,恢复了肢体持重功能。 1例儿童 2年后胫骨出现过生长。结论　骨段输送技术是治疗下肢大段骨缺损简单而有效的新方法。软组织创面可在骨段输送中逐渐缩小并闭合 ,骨骼感染可在骨段输送中逐渐被控制并伴随骨连接而愈合     

颗粒骨打压植骨技术在治疗髋臼骨缺损中的应用

目的介绍颗粒状松质骨打压植骨技术对髋臼骨缺损的重建方法。方法应用该技术对23例髋臼侧假体翻修患者及4例陈旧性髋臼骨折行人工全髋关节置换患者进行植骨,植骨块来源于深低温冰箱梯度降温后的冷冻干燥骨。术后进行临床评估及X线评估。结果术后平均随访3．1年,Harris评分平均提高36分,无1例假体需要再次翻修,有3例在X线上出现髋臼侧透亮带。结论打压植骨技术可以有效治疗髋臼骨缺损,应注重对颗粒松质骨的制备,植骨床的准备及对植骨块的紧密打压和固定。     

Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation

Background

Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction.

Methods

The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed.

Results

The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection.

Conclusions

DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the rabbit tibial DO model. These data suggest that percutaneous DBM administration at the end of the distraction period or in the early consolidation period may stimulate regenerate bone formation and consolidation in a clinical situation with delayed bone healing during DO.     

骨重建中的骨代谢指标

骨重建是破骨细胞和成骨细胞共同完成的旧骨退化,等量新骨取代的骨组织更新过程,在骨重建过程中,许多激素和细胞、体液因子以及细胞代谢产物影响骨的重建.目前国内外通过生物化学检测技术获得的骨代谢指标分为骨代谢调节激素、细胞与体液因子、骨吸收、骨形成标志物.笔者将影响骨重建生物化学指标的生理作用、临床意义进行综述.骨代谢指标虽不能作为骨质疏松诊断的金标准,但已广泛应用于临床,评价骨代谢状态、骨质疏松诊断分型、预测骨折风险、观察药物治疗的疗效,以及代谢性骨病的鉴别诊断.并且在抗骨质疏松药物的研究及流行病学研究方面具有重要应用价值.     

Changes in Osteoprotegerin/RANKL System, Bone Mineral Density, and Bone Biochemicals Markers in Patients with Recent Spinal Cord Injury

This study analyzed the temporal and regional variations in bone loss and explored bone cell activities via biochemical markers during an extended follow-up in patients with spinal cord injury (SCI). In parallel, the possible role of the osteoprotegerin (OPG)/RANKL system in disuse osteoporosis was investigated. Seven male patients with acute and complete SCI (31.3 ± 9.5 years) and 12 able-bodied (AB) men (26.9 ± 4.2 years) participated in the study. Measurements were performed 16, 24, 36, 48, and 71 weeks after injury. At week 16, marked calcium homeostasis disturbance and a concomitant increase in bone resorption markers were observed, reflecting an intense bone degradation process. Resorption activity decreased continuously with time. Contrasting with the great rise in the resorption markers, the bone formation markers showed little variation. During the period of investigation, a loss in bone mineral density (BMD) was demonstrated for the total body (−4.3%), pelvis (−15.7%) and lower limbs (−15.2%), whereas BMD did not change at the lumbar spine, upper limbs, or skull. At all stages, SCI patients had lower serum RANKL levels and higher serum OPG levels than did AB controls, but no significant variation with time was observed for either cytokine. These findings suggest that bone resorption persisted long after SCI and specifically affected BMD at sublesional sites. The marked modification of serum OPG/RANKL levels in SCI patients suggests that this system is affected, in disuse osteoporosis. However, the precise biologic role of the OPG/RANKL system in the bone tissue of SCI patients has yet to be determined.     

同种异体骨移植在骨肿瘤手术中的应用

目的：探讨同种异体骨移植在骨肿瘤手术中应用的范围、效果以及排异反应等问题.方法：1983年10月～2003年3月在骨肿瘤手术中使用异体骨移植120例。其中肿瘤刮除、异体松质骨移植102例；肿瘤刮除、异体大块皮质骨和松质骨移植12例；肿瘤段切除、异体股骨干移植2例；肿瘤段切除、异体半关节移植3例；肿瘤切除、大块异体骶骨移植l例：结果：120例中只有2例出现较轻的排异反应，表现为手术后切口渗出较多，3个月后停止渗出，切口愈合.其余病例均一期愈合.结论：同种异体骨在骨肿瘤手术中应用范围，一、效果好、很少出现排异反应,在骨缺损填充物中占有重要位置.     

Bone Density, Vitamin D Status, and Disordered Bone Remodeling in End-Stage Chronic Liver Disease

Hepatic osteodystrophy occurs in up to 50% of patients with chronic liver disease (CLD). The aim of this study was to determine the relative contribution of increased resorption and decreased formation to hepatic osteodystrophy by measuring biochemical markers. Twenty-seven patients with advanced CLD (14 female, 13 male) were enrolled. Bone mineral density (BMD), measured at the lumbar spine, and femoral neck, were measured by dual energy X-ray absorptiometry (DXA); bone turnover was assessed using biochemical markers of bone formation and resorption. Based on WHO criteria, osteoporosis and osteopenia were present in 41% and 18% of patients, respectively. All three markers of bone resorption (free deoxypyridinoline, pyridinoline, and hydroxyproline) were increased significantly in patients with CLD. There was a less marked change in the markers of bone formation (osteocalcin, procollagen type 1 peptide, and bone alkaline phosphatase), resulting in a negative uncoupling index in 23/27 (85%) of the patients. Only two (7%) patients had biochemical changes consistent with osteomalacia. The results suggest that increased bone resorption is the predominant cause of hepatic osteodystrophy and therapeutic strategies should be designed to suppress bone resorption, especially in preparation for liver transplantation. Bone biomarkers may be useful alternatives to bone biopsy in evaluating hepatic osteodystrophy. Received: 11 September 1997 / Accepted: 22 September 1998