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1.
The demographic changes in the human population continue to lead to an increasing incidence of osteoporosis. The main clinical symptom of osteoporosis is fracture. Fracture fixation in osteoporosis is frequently complicated by failure of fixation. There is a great need for a large-animal model of osteoporosis for controlled studies, which allows the investigation of fracture healing and fracture treatment in weak bone. Eight swiss mountain sheep, 7–9 years old, were divided into four treatment groups of two animals each. Group 1 was ovariectomized and fed a calcium/vitamin D-restricted diet (O+D). Group 2 was ovariectomized and given a daily intramuscular injection of 25 mg methylprednisolone (O+S). Group 3 was ovariectomized, fed a calcium/vitamin D-restricted diet and injected with 25 mg intramuscular methylprednisolone per day (O+D+S). Group 4 was used as an untreated, not sham operated control group. At the beginning of the study and every 2 months for 6 months the bone mineral density (BMD) was determined using quantitative computed tomography (pQCT) at the distal radius. Biopsies were taken after 6 months from vertebral bodies and femoral heads and the bone structure, i.e. trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), bone surface fraction (BS/BV) and bone volume fraction (BV/TV), was determined by micro-CT. In vitro compression testing of the biopsies was performed to determine failure load and stiffness. The control group showed no changes in BMD. The greatest decrease in BMD was seen in group 3 (O+D+S), which had a decline of 58% in cancellous bone and 22% in cortical bone. In the vertebral body biopsies a prominent change in structural parameters was observed (Tb.N, –53%; Tb.Th, –63%, Tb.Sp, +150%). The changes were less pronounced in the femoral head biopsies. In the compression test the vertebral body biopsies of group 3 (O+D+S) had stiffness values 40% lower failure load 70% lower compared with the control group. The most effective method of inducing osteoporosis in sheep was found to be the combined treatment. These results need to be confirmed in a larger number of animals. Received: 4 May 2001 / Accepted: 13 December 2001  相似文献
2.
We examined the effects of one-year high-dose bisphosphonates (risedronate 0.5 mg/kg/day or alendronate 1.0 mg/kg/day) on the three-dimensional (3-D) microstructural and mechanical properties of canine cancellous bone. A high-resolution micro-CT scanner was used to scan cubic specimens produced from the first lumbar vertebrae. Microstructural properties of the specimens were calculated directly from the 3-D datasets and the mechanical properties of the specimens were determined. Our data demonstrate significant microarchitectural changes in the bisphosphonate-treated cancellous bone that was typically plate-like, denser, with thicker and more trabeculae compared with those of the controls. Consistent with architectural changes, the Youngs moduli of cancellous bone increased in all three directions with the greatest increase in primary axial loading (cephalo-caudal) direction after treatment. Our results suggest a bone remodeling-adaptation mechanism stimulated by bisphosphonates that increases bone volume fraction, thickens trabeculae, changes trabeculae towards more plate-like, and increases mechanical properties. The secondary degree of anisotropy contributed significantly to the explained variance in bone strength, and the primary or tertiary degree of anisotropy improved the explanation of variances for Youngs moduli, i.e., 79% of strength variances or 74–83% of modulus variances could be explained by the combined anisotropy and bone volume fraction. These significant improvements of cancellous bone architecture provide a rationale for the clinical observation that fracture risk decreased by 50% in the first year of bisphosphonate therapy with only a 5% increase in bone mineral density. We conclude that bisphosphonates enhance mechanical properties and reduce fracture risk by improving architectural anisotropy of cancellous bone 3-D microarchitecture.  相似文献
3.
In a pilot experiment comparing four different modalities for inducing osteoporosis in the sheep, a combination of ovariectomy, calcium/vitamin D-restricted diet and steroid administration was found to generate the highest decrease in bone mineral density (BMD). The aim of the present study was to quantify the outcome of this triple treatment in an animal model of osteoporosis in terms of alteration in bone mass, bone structure and bone mechanics. A total of 32 sheep were divided into two equal groups. Group 1 (age 3–5 years) was used as a normal control. Group 2 (age 7–9 years) was ovariectomized, fed a calcium/vitamin D-restricted diet and injected with methylprednisolone (MP) over 7 months (22 weeks MP solution, 6 weeks MP suspension). The BMD at the distal radius and tibia was determined preoperatively and at repeated intervals bilaterally using quantitative computed tomography. Steroid blood levels were determined 4 and 24 h after selected injections. BMD was measured at L3 and L4 after 7 months. Biopsies were taken from iliac crests, vertebral bodies and femoral heads, and bone structure parameters investigated by three-dimensional micro-CT. Compressive mechanical properties of cancellous bone were determined from biopsies of vertebral bodies and femoral heads. After 7 months of osteoporosis induction the BMD of cancellous bone decreased 36 ± 3% in the radius and 39 ± 4% in the tibia. Steroid blood levels 24 h after injection of MP suspension were significantly higher than after injection of MP solution. Changes in structural parameters of cancellous bone from the iliac crest, lumbar spine and femoral head in group 2 indicated osteoporosis-associated changes. In group 2 there was a significant reduction in BMD of the lumbar spine and a significant reduction in stiffness and failure load in compression testing of biopsies of lumbar vertebrae. In sheep, changes in the structural parameters of bone such as trabecular number and separation during osteoporosis induction are comparable to the human situation. The sheep model presented seems to meet the criteria for an osteoporosis model for fracture treatment with respect to mechanical and morphometric bone properties. Received: 4 May 2001 / Accepted: 6 December 2001  相似文献
4.
Zhang G  Qin L  Hung WY  Shi YY  Leung PC  Yeung HY  Leung KS 《BONE》2006,38(6):818-825
AIM: Factorial design was used to test our hypothesis whether a group of flavonoids (FE) derived from herbal Epimedium Brevicornum Maxim exerted its preventive effects on estrogen-deficiency-induced osteoporosis mainly through an enhancement in intestinal calcium absorption. MATERIALS AND METHODS: Forty-five 12-month-old female Wistar rats were used and randomly assigned into sham-operated group and four ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX group), OVX with FE (FE group), OVX with calcium supplement (CS group), and OVX with FE and CS (FE + CS group). Daily oral administration of FE (10 mg/kg/day) and/or CS (56 mg/kg/day) started on day 4 after OVX for 12 weeks. Before sacrificing the animals, urine and serum samples were collected for assaying indicators related to intestinal calcium absorption, regulator for calcium homeostasis, and markers of bone turnover. The left proximal femur was dissected for evaluation of the primary end-point (failure force), the second end-points (pQCT-quantified densitometry, geometry, and micro-CT-quantified 3-D trabecula micro-architecture), and pQCT-defined cross-sectional envelope. RESULTS: FE was found to be able to prevent OVX-induced reduction in failure force as well as the above second end-points, without resulting in an increased uterus weight. CS had no preventive effect on OVX-induced reduction in failure force. Two-way factorial interaction analysis between FE and CS showed that the un-enhanced suppression of parathyroid hormone for calcium homeostasis did not provide link between the enhanced intestinal calcium absorption and the enhanced inhibition of bone resorption in the present study. Furthermore, the discrepancies between the enhanced intestinal calcium absorption and the un-enhanced end-point measures as well as anabolic effect were also revealed by the interaction analysis. CONCLUSION: The present study suggested that FE inhibited bone resorption, stimulated bone formation, and accordingly prevented osteoporosis without hyperplastic effect on uterus in the OVX rat model, which was however independent of an enhancement in intestinal calcium absorption.  相似文献
5.
目的测量三足负重酒精灭活性股骨头坏死犬模型的股骨头松质骨的矿物质密度和骨小梁的三维结构变化,初步探讨局部注射酒精和负重对股骨头力学强度的影响。方法取健康成年Beagle犬24只,体重18~23kg。随机取12只犬建立三足负重犬动物模型,余12只不作任何处理,为四足犬。所有动物随机取一侧后肢为实验侧,于股骨头内局部注射无水酒精,建立股骨头坏死犬动物模型;对侧为对照侧,股骨头内注入等量生理盐水。将三足和四足犬对照侧作为对照组,三足犬实验侧为三足犬组,四足犬实验侧作为四足犬组。于髋部注射酒精后1、3、6及12周处死动物,取双后肢股骨头行Micro-CT扫描。以股骨头内钻孔针道为中心,自针道边缘由中心向外各选取相互连接的直径为1mm的圆柱形区域,依次命名为Ⅰ、Ⅱ和Ⅲ区。对各区的骨矿密度(bone mineral density,BMD)、骨体积分数(bone volume fraction,BVF)、骨矿容量(bone mineral content,BMC)、骨表面积与骨骼体积比(bone surface to bone volume ratio,BS/BV)、结构模型指数(structure model index,SMI)、骨小梁厚度(trabecular plate thickness,Tb.Th)、骨小梁数目(trabecular plate number,Tb.N)、骨小梁间隙(trabecular spacing,Tb.Sp)进行测量和比较;对股骨头软骨下骨区行三维重建,观察其三维结构变化。结果注射酒精后1周各组各项参数差异均无统计学意义(P〉0.05)。3周,三足犬和四足犬组Ⅰ、Ⅱ和Ⅲ区的BMC、BMD、BVF及BS/BV自针道向外逐渐递增,各区间差异有统计学意义(P〈0.05)。6周,三足犬组和四足犬组Ⅰ、Ⅱ区的BMC、BMD、BVF和Tb.N较Ⅲ区明显下降,Tb.Sp较Ⅲ区增加,差异有统计学意义(P〈0.05)。12周,对照组、三足犬组和四足犬组3区的各项参数差异无统计学意义(P〉0.05)。注射酒精后3周,BMC、BMD和BVF在三足犬组和四足犬组开始下降,与1周比较差异有统计学意义(P〈0.05);6周,下降最明显,BMC与1、3周比较,差异有统计学意义(P〈0.05),BMD与BVF差异无统计学意义(P〉0.05),12周与6周比较,差异无统计学意义(P〉0.05)。三足犬组股骨头内注射酒精后,随时间延长,骨小梁结构逐渐变细、密度降低、间隙增宽、12周时可观察到局部骨小梁的连续性破坏和骨小梁的断裂。结论局部注射酒精致犬股骨头坏死后,坏死骨质的吸收将导致骨小梁力学强度的下降。持续的生物应力将阻碍坏死后的修复反应,使坏死骨小梁的力学强度更为降低,是致坏死股骨头塌陷的重要原因。  相似文献
6.
The purpose of this study was to determine the relationship between three-dimensional (3D) trabecular structure and two-dimensional plain radiographic patterns. An in vitro cylinder of human calcaneal trabecular bone was three-dimensionally imaged by micro-CT using synchrotron radiation, at 33.4 μm resolution. The original 3D image was processed using 14 distinct sequences of morphologic operations, i.e., of dilations and erosions, to obtain a total of 15 3D models or images of calcaneal trabecular bone. These 15 models had distinct densities (volume fractions) and architectures. The 3D structure of each calcaneal model was assessed using mean intercept length (fabric), by averaging individual fabric measurements associated with each medial-lateral image slice, and determining the relative anisotropy, R3D, of the structure. A summated pattern or plain radiograph was also computed from the 3D image data for each calcaneal model. Each summated pattern was then locally thresholded, and the resulting two-dimensional (2D) binary image analyzed using the same fabric analysis as used for the 3D data. The anisotropy of the 2D summated pattern was denoted by Rx-ray. The volume fractions of the 15 models ranged from 0.08 to 0.19 with a mean of 0.14. The medial-lateral anisotropies, R3D, ranged from 1.38 to 2.54 with a mean of 1.88. The anisotropy of the 2D summated patterns, Rx-ray, ranged from 1.35 to 2.18 with a mean of 1.71. The linear correlation of the 3D trabecular architecture, R3D, with the radiographic trabecular architecture, Rx-ray, was 0.99 (p<0.0001). This study shows that the plain radiograph contains architectural information directly related to the underlying 3D structure. A well-controlled sequential reproducible plain radiograph may prove useful for monitoring changes in trabecular architecture in vivo and in identifying those individuals at increased risk of osteoporotic fracture. Received: 9 December 1997 / Accepted: 3 September 1998  相似文献
7.
Glucocorticoids are potent anti-inflammatory molecules used in the treatment of asthma, rheumatoid arthritis, inflammatory bowel disease, and other inflammatory and dermatological diseases, as well as in posttransplantation immunotherapy. Although glucocorticoids have been prescribed for many years, their potential side effects, when administered orally, can prevent their long-term use. The most serious side effect observed in the clinic is glucocorticoid-induced osteoporosis (GIOP). To develop a small animal model to characterize glucocorticoid-induced bone loss, we carried out a series of experiments using BALB/c mice given daily intraperitoneal doses of the synthetic glucocorticoid, dexamethasone. Following dexamethasone treatment, the mice became osteopenic, with highly significant decreases in bone formation rate and mineral apposition rate, as assessed by standard histomorphometry. Moreover, 3 week treatment with dexamethasone resulted in a decrease in trabecular thickness and trabecular number with an increase in surface-to-volume ratio of trabeculae in the distal femur, as measured using microcomputed tomography (micro-CT). The serum bone formation marker, osteocalcin, was dose-dependently decreased in all mice treated with dexamethasone and showed a parallel extent of regulation to the bone formation rate changes. In addition, serum levels of leptin, recently identified as playing a role in the regulation of bone mass, increased following dexamethasone treatment. BALB/c mice therefore represent a useful model system in which the detrimental effects of glucocorticoids on bone can be studied.  相似文献
8.
股骨颈骨折病人的股骨头样本结构的Micro-CT评估   总被引:2,自引:0,他引:2  
[目的]利用Micro-CT(Micro-computed Tomography)对正常人和老年股骨颈骨折病人的股骨头松质骨样本进行三维评价和比较。[方法]对6位正常人(正常组,27~36岁)和9位老年股骨颈骨折病人(骨折组,70~78岁)的股骨头松质骨样本进行DEXA检查,获取骨矿物密度数据。行Micro-CT扫描,得到松质骨小梁空间结构的计算机三维图形,并进行三维计量。[结果]与正常组相比,股骨颈骨折病人股骨头负重区样本的骨小梁结构在骨体积分数BV/TV、骨表面积体积比BS/TV、骨小梁厚度Tb.Th、骨小梁间隙Tb.Sp存在显著差异(P〈0.01),而骨小梁数目Tb.N、结构模型指数SMI和骨小梁模型因子Tb.Pf之间无统计学差别。骨密度检测两组没有显著性差异(P〉0.05)。[结论]股骨头松质骨的空间结构会因年龄增大而发生改变。  相似文献
9.
IL-6 is a pleiotropic cytokine involved in cell signaling in the musculoskeletal system, but its role in bone healing remains uncertain. The purpose of this study was to examine the role of IL-6 in fracture healing. Eight-week-old male C57BL/6 and IL-6 −/− mice were subjected to transverse, mid-diaphyseal osteotomies on the right femora. Sacrifice time points were 1, 2, 4, or 6 weeks post-fracture (N = 14 per group). Callus tissue properties was analyzed by microcomputed tomography (micro-CT) and Fourier transform infrared imaging spectroscopy (FT-IRIS). Cartilage and collagen content, and osteoclast density were measured histologically. In intact unfractured bone, IL-6 −/− mice had reduced crystallinity, mineral/matrix ratio, tissue mineral density (TMD), and bone volume fraction (BVF) compared to wildtype mice. This suggests that there was an underlying deficit in baseline bone quality in IL-6 −/− mice. At 2 weeks post-fracture, the callus of IL-6 −/− mice had reduced crystallinity and mineral/matrix ratio. These changes were less evident at 4 weeks. At 2 weeks, the callus of the IL-6 −/− mice had an increased tissue mineral density (TMD), an increased cartilage and collagen content, and reduced osteoclast density compared to these parameters in wildtype mice. By 4 and 6 weeks, these parameters were no longer different between the two strains of mice. In conclusion, IL-6 −/− mice had delayed callus maturity, mineralization, and remodeling compared with the callus of the wildtype mice. These effects were transient indicating that the role of IL-6 appears to be most important in the early stages of fracture healing.  相似文献
10.
取向性仿生双相磷酸钙支架的制备、结构评价和初步应用   总被引:2,自引:0,他引:2  
目的利用三维凝胶叠层成型法(3DGellamination)制备出取向性仿生双相磷酸钙生物陶瓷支架,并在体外对支架的结构进行三维重建和相关评价。方法2003年11月至2005年3月,以犬股骨头的松质骨样本显微CT(MicroCT)图像为基础,提取其中的图像信息,利用三维凝胶叠层成型法制备出具有仿骨小梁结构的双相磷酸钙(BCP)仿生生物陶瓷支架。随后对支架进行MicroCT扫描,用三维结构参数对支架和松质骨样本进行三维评价和比较。并利用体外细胞培养技术观察细胞在支架表面的生长情况。同时将复合骨髓间充质细胞的支架植入股骨头负重区的骨缺损内,初步观察其治疗效果。结果本方法制备出的股骨头仿生支架具有良好的三维空间结构,支架小梁具有一定的方向性,呈板状模型,其轴向方向的弹性模量和强度分别达到(464.0±36.0)MPa和(5.6±0.8)MPa。细胞在支架表面大量生长。动物实验结果表明,支架与周围骨床结合紧密,骨质沿支架小梁表面生长。结论本研究制备的BCP多孔支架的小梁具有一定的取向性,支架具有良好的生物相容性、一定的力学强度和良好的适于血管长入的空间结构。  相似文献
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