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《Journal of orthopaedic research》2017,35(8):1653-1660
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Femke Intema Yvonne H Sniekers Harrie Weinans Marieke E Vianen Sue A Yocum Anne‐Marie M Zuurmond Jeroen DeGroot Floris P Lafeber Simon C Mastbergen 《Journal of bone and mineral research》2010,25(7):1650-1657
In osteoarthritis (OA), cartilage degradation is accompanied by subchondral bone changes. The pathogenesis and physiology of bone changes in OA are still unclear. The changes in subchondral bone architecture and cartilage damage were compared in differently induced experimental models of OA. Experimental OA was induced bilaterally by anterior cruciate ligament transection (ACLT) or by cartilage trauma (Groove model); bilateral sham surgery served as control. Lysylpyridinoline (LP, bone resorption) and C‐telopeptide of type II collagen (CTX‐II, cartilage breakdown) were measured over time. At 20 weeks after surgery, the subchondral cortical plate and trabecular bone of the tibia were analyzed by micro–computed tomography (µCT) and cartilage degeneration was analyzed histologically and biochemically. In both models, cartilage degeneration and cortical subchondral plate thinning were present. CTX‐II levels were elevated over time in both models. Subchondral trabecular bone changes were observed only in the ACLT model, not in the Groove model. Correspondingly, LP levels were elevated over time in the ACLT model and not in the Groove model. Interestingly, the trabecular bone changes in the ACLT model were extended to the metaphyseal area. The early decrease in plate thickness, present in both models, as was cartilage damage, suggests that plate thinning is a phenomenon that is intrinsic to the process of OA independent of the cause/induction of OA. On the other hand, trabecular changes in subchondral and metaphyseal bone are not part of a common pathway of OA development and may be induced biomechanically in the destabilized and less loaded ACLT joint. © 2010 American Society for Bone and Mineral Research 相似文献
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《Journal of orthopaedic research》2017,35(9):1982-1989
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Attenuation of cartilage degeneration by calcitonin gene‐related paptide receptor antagonist via inhibition of subchondral bone sclerosis in osteoarthritis mice 下载免费PDF全文
Tomoyuki Nakasa Masakazu Ishikawa Tsuyoshi Takada Shigeru Miyaki Mitsuo Ochi 《Journal of orthopaedic research》2016,34(7):1177-1184
Osteoarthritis (OA) is a progressive joint disorder which affects cartilage and subchondral bone. Calcitonin gene‐related peptide (CGRP) plays a role in bone metabolism. The purpose of this study is to examine the therapeutic effect of the blocking CGRP on OA progression in mice by inhibition of subchondral bone sclerosis. OA was induced by the resection of the medial meniscotibial ligament of the knee in C57/BL6 mice. An intraperitoneal injection of the CGRP receptor antagonist (BIBN4096) was administered after OA surgery. At 1, 4, and 8 weeks after injection, histological analysis were performed. In vitro, the effect of CGRP and BIBN4096 on osteogenesis and osteoclastogenesis was analyzed. BIBN4096 could prevent cartilage degeneration and subchondral bone sclerosis. The OARSI score in the BIBN4096 group was significantly lower than that in the control. In vitro, CGRP up regulated osteocalcin expression, but its expression was down regulated by BIBN4096. CGRP inhibited osteoclastogenesis of raw 267.4 cells, but its effect was reduced by the addition of BIBN4096.The current study showed that subchondral bone sclerosis and increasing expression of CGRP occurs in the early phase of OA in relation to cartilage degeneration, and that BIBN4096 could effectively attenuate OA progression. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1177–1184, 2016. 相似文献
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3‐D localization of non‐radioactive strontium in osteoarthritic bone: Role in the dynamic labeling of bone pathological changes 下载免费PDF全文
Arash Panahifar David M.L. Cooper Michael R. Doschak 《Journal of orthopaedic research》2015,33(11):1655-1662
The study objective was to visualize regions of bone that undergo pathological mineralization and/or remodeling during pathogenesis of osteoarthritis, by employing non‐radioactive strontium as a dynamic tracer of bone turnover. Post traumatic osteoarthritis was surgically induced in skeletally mature rats, followed by in vivo micro‐CT imaging for 12 weeks to assess bone micro‐structural changes. Rats either received strontium ranelate daily for the entire course of study or only last 10 days before euthanization. Distribution of strontium in bone was assessed in two and three dimensions, using electron probe micro‐analysis (EPMA) and synchrotron dual energy K‐edge subtraction micro‐CT (SRμCT), respectively. Considerable early formation of osteophytes around the collateral ligament attachments and margins of articulating surfaces were observed, followed by subchondral sclerosis at the later stages. Accordingly, strontium was heavily incorporated by mineralizing osteophytes at 4, 8, and 12 weeks post‐surgery, whereas subchondral bone only incorporated strontium between weeks 8–12.This study showed low dose stable strontium can effectively serve as a dynamic tracer of bone turnover to study pathological bone micro‐structural changes, at resolution higher than nuclear medicine. Co‐administration of strontium during therapeutic drug intervention may show enormous utility in assessing the efficacy of those compounds upon adaptive bone physiology. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1655–1662, 2015. 相似文献
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[目的]研究降钙素(calcitonin, CT)对骨性关节炎关节软骨退变和软骨下骨骨代谢的影响.[方法]30只3个月龄雌性日本大耳白兔随机分为三组,其中两组行右膝关节前交叉韧带切断术(anterior cruciate ligament transaction,ACLT),分为ACLT+CT组和ACLT+NS组,第3组为Sham组.ACLT+CT给予每日1次皮下注射降钙素5 IU/(kg·d),持续8周,ACLT+NS组给予同样剂量生理盐水.术后8周后处死所有动物.取股骨髁制成切片行MMP-13和Ⅱ型胶原免疫组化染色.取胫骨近端制成硬组织切片行骨形态计量学检测.体外实验中,取兔膝关节软骨,经消化、培养,将第3代软骨细胞分三组:向IL-1β组加入人重组IL-1β(10 ng/ml). IL-1β+CT组加入人重组IL-1β (10 ng/ml)2 d后,再向培养液中加入CT(50 ng/ml).正常组不加任何诱导剂和干扰剂培养.然后行MMP-13、Ⅱ型胶原免疫组化检测和Realtime RT-PCR法检测.[结果]Sham组和ACLT+CT组软骨下骨骨小梁相对体积和厚度等均显著高于ACLT+NS组.Sham组和ACLT+CT组的Ⅱ型胶原的光密度值均显著高于ACLT+NS组,而MMP-13的光密度值显著低于ACLT+NS组(P<0.05).正常组和IL-1β+CT组的Ⅱ型胶原光密度值均显著高于IL-1β组而MMP-13的光密度值都显著低于IL-1β组(P<0.05).在正常组和IL-1β+CT组中Ⅱ型胶原的mRNA含量均显著高于IL-1β组而MMP-13的mRNA含量均显著低于IL-1β组(P<0.05).[结论]降钙素5 IU/(kg·d)皮下注射能够增加ACLT兔膝关节软骨Ⅱ型胶原的分泌和抑制MMP-13的表达,并可能通过调节软骨下骨的骨代谢和微结构来保护关节软骨; CT(50 ng/ml)能增加体外培养的含有IL-1β(10 ng/ml)的软骨细胞中Ⅱ型胶原的含量和抑制MMP-13分泌. 相似文献
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Activated FGFR3 prevents subchondral bone sclerosis during the development of osteoarthritis in transgenic mice with achondroplasia 下载免费PDF全文
Toshiaki Okura Masaki Matsushita Kenichi Mishima Ryusaku Esaki Taisuke Seki Naoki Ishiguro Hiroshi Kitoh 《Journal of orthopaedic research》2018,36(1):300-308
The purpose of this study is to investigate the morphometric changes of the subchondral bone during the development of osteoarthritis (OA) in transgenic mice with achondroplasia (Fgfr3ach) carrying a heterozygous gain‐of‐function mutation in Fgfr3. Two OA models (spontaneously developed with age: The aging model, and surgically induced by destabilization of the medial meniscus: The DMM model) were established. Articular cartilage, epiphysis, and metaphysis of the knee joint were histologically and morphometrically compared between wild‐type mice, and Fgfr3ach mice in both OA models. Articular cartilage degeneration was scored according to the Osteoarthritis Research Society International (OARSI) scoring system. Several morphometric parameters including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and subchondral bone thickness in the medial tibial plateau (MTP) (Sb.Th med) were quantified by micro‐computed tomography (CT). In the aging model, although there were no significant differences in the OARSI score between wild‐type mice and Fgfr3ach mice, Sb.Th med and Tb.Th in the epiphysis significantly increased in wild‐type mice. In the DMM model, the OARSI score of the medial compartment was significantly lower in Fgfr3ach mice than in wild‐type mice. BMD, BV/TV, and Tb.Th in the epiphysis increased in wild‐type mice and unchanged in Fgfr3ach mice, and the Sb.Th med was significantly larger in wild‐type mice after surgery. Subchondral sclerosis, which preceded the cartilage degeneration, was inhibited in Fgfr3ach mice. Activated FGFR3 signaling prevented sclerotic changes of the subchondral bone and subsequent cartilage degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:300–308, 2018. 相似文献
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Assessment of cortical and trabecular bone changes in two models of post‐traumatic osteoarthritis 下载免费PDF全文
Hannah M. Pauly Blair E. Larson Garrett A. Coatney Keith D. Button Charlie E. DeCamp Ryan S. Fajardo Roger C. Haut Tammy L. Haut Donahue 《Journal of orthopaedic research》2015,33(12):1835-1845
Subchondral bone is thought to play a significant role in the initiation and progression of the post‐traumatic osteoarthritis. The goal of this study was to document changes in tibial and femoral subchondral bone that occur as a result of two lapine models of anterior cruciate ligament injury, a modified ACL transection model and a closed‐joint traumatic compressive impact model. Twelve weeks post‐injury bones were scanned via micro‐computed tomography. The subchondral bone of injured limbs from both models showed decreases in bone volume and bone mineral density. Surgical transection animals showed significant bone changes primarily in the medial hemijoint of femurs and tibias, while significant changes were noted in both the medial and lateral hemijoints of both bones for traumatic impact animals. It is believed that subchondral bone changes in the medial hemijoint were likely caused by compromised soft tissue structures seen in both models. Subchondral bone changes in the lateral hemijoint of traumatic impact animals are thought to be due to transmission of the compressive impact force through the joint. The joint‐wide bone changes shown in the traumatic impact model were similar to clinical findings from studies investigating the progression of osteoarthritis in humans. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1835–1845, 2015. 相似文献
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Nobuyuki Hiraoka Kenji A. Takahashi Yuji Arai Kei Sakao Osam Mazda Tsunao Kishida Kuniaki Honjo Sakae Tanaka Toshikazu Kubo 《Journal of orthopaedic research》2011,29(3):354-360
Subchondral bone is a candidate for treatment of osteoarthritis (OA). We investigated the effects of intra‐articular injection of hyaluronan (IAI‐HA) on subchondral bone in rabbit OA model. OA was induced by anterior cruciate ligament transection, with some rabbits receiving IAI‐HA. OA was graded morphologically, and expression of mRNA was assessed by real‐time RT‐PCR. Tissue sections were stained with hyaluronan‐binding protein, and penetration of fluorescent hyaluronan was assessed. The in vitro inhibitory effect of hyaluronan on MMP‐13 was analyzed in human osteoarthritic subchondral bone osteoblasts (OA Ob) by real‐time RT‐PCR and ELISA. Binding of hyaluronan to OA Ob via CD44 was assessed by immunofluorescence cytochemistry. Expression of MMP‐13 and IL‐6 mRNA in cartilage and subchondral bone, and morphological OA grade, increased over time. IAI‐HA ameliorated the OA grade and selectively suppressed MMP‐13 mRNA in subchondral bone. IAI‐HA enhanced the hyaluronan staining of subchondral bone marrow cells and osteocyte lacunae. Fluorescence was observed in the subchondral bone marrow space. In OA Ob, hyaluronan reduced the expression and production of MMP‐13, and anti‐CD44 antibody blocked hyaluronan binding to OA Ob. These findings indicate that regulation of MMP‐13 in subchondral bone may be a critical mechanism during IAI‐HA. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:354–360, 2011 相似文献
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Omri Lubovsky Michael Kreder David A. Wright Alex Kiss Aimee Gallant Hans J. Kreder Cari M. Whyne 《Journal of orthopaedic research》2013,31(12):1980-1985
Current analysis of displaced acetabular fractures is limited in its ability to predict functional outcome. This study aimed to (1) quantify initial acetabular damage following acetabular fracture through measurement of subchondral bone density and fracture lines, and (2) evaluate associations between acetabular damage and functional outcomes following fracture. Subchondral bone intensity maps were created for 24 patients with unilateral acetabular fractures. Measures of crack length and density differences between corresponding regions in the fractured acetabuli, normalized by the unfractured side, were generated from preoperative CT images. Damage measures were compared to quality of life survey data collected for each patient at least 2 years post‐injury (Musculoskeletal Functional Assessment [MFA] and Short Form‐36 [SF‐36], with specific focus on parameters that best describe patients' physical health). CT image quantification of initial damage to acetabular subchondral bone was associated with functional outcome post‐injury. In general, damage as quantified through differences in density in the superior dome region (zones 8 and 12) and the central anterior region of the acetabulum (zone 3) were found to be the strongest significant predictors of functional outcome (adjusted R2 = 0.3–0.45, p < 0.05). Damage to the superior dome was predictive of worse functional outcome whereas damage to the central anterior region indicated a better functional outcome. Once automated, this approach may form a basis to score acetabular fractures toward improving clinical prognoses. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1980–1985, 2013 相似文献
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目的探讨补肾活血方对大鼠膝骨性关节炎(knee osteoarthritis,KOA)软骨下骨骨重建中BMP-2及Smad-1/5的调节作用机制。方法将24只SPF级健康6月龄雌性SD大鼠随机分为治疗组、模型对照组及假手术组。治疗组、模型对照组参考改良Hulth造模法构建膝骨性关节炎模型,造模成功后4周模型对照组及假手术组灌予生理盐水,治疗组灌予等量补肾活血中药干预,并于灌胃第4、8周,测定软骨下骨BMP-2及Smad-1/5的表达水平。结果假手术组、治疗组在BV/TV、Tb.N上明显低于模型对照组(P0.05),在Tb.Th、Tb.Sp上明显高于模型对照组(P0.05)。假手术组与治疗组Tb.N、Tb.Th、Tb.Sp上比较,差异有统计学意义(P0.05),用药4周,治疗组BMP-2、Smad-1/5灰度值及阳性细胞个数较模型对照组增加(P0.05),较假手术组有所减少,差异无统计学意义(P0.05);用药8周后与用药4周比较,BMP-2、Smad-1/5灰度值及阳性细胞个数增加(P0.05)。结论补肾活血方通过提高BMP-2及Smad-1/5在KOA软骨下骨骨平衡分配,改善KOA软骨下骨异常代谢,从而起到治疗KOA的作用。 相似文献
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Alterations in microdamage morphology and accumulation are typically attributed to impaired remodeling, but may also result from changes in microdamage initiation and propagation. Such alterations are relevant for cancellous bone with high metabolic activity and numerous bone quality changes. This study investigates the role of trabecular microarchitecture on morphology and accumulation of microdamage in human cancellous bone. Trabecular bone cores from donors of varying ages and bone volume fraction (BV/TV) were separated into high and low BV/TV groups. Samples were subjected to no load or uniaxial compression to 0.6% (pre‐yield) or 1.1% (post‐yield) strain. Microdamage was stained with lead uranyl acetate and specimens were imaged via microcomputed tomography to quantify microdamage and determine its morphology in three‐dimensions (3D). Donors with high BV/TV had greater post‐yield strain and were tougher than low BV/TV donors. High BV/TV bone had less microdamage than low BV/TV bone under post‐ but not pre‐yield loading. Microdamage under both loading conditions showed significant correlations with microarchitecture and BV/TV, but the key predictor was structure model index (SMI). As SMI increased (more trabecular rods), microdamage morphology became crack‐like. Thus, low BV/TV and increased SMI have strong influences on microdamage accumulation in bone through altered initiation. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1739–1744, 2011 相似文献
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The Subchondral Bone in Osteoarthritis and Rheumatoid Arthritis of the Knee: A Histological and Microradiographical Study 总被引:2,自引:0,他引:2
Specimens of the joint surfaces of the tibia from patients with OA and RA were examined for bone mineralization, bone formation, osteoid tissue and bone resorption. Judging from the appearance of the osteoblasts in OA the sclerotic changes are mainly focal with relatively little osteogenesis. No osteoclasia was seen, in the sclerotic areas. Breakdown of the mineralized cartilage is followed by the development of cysts with highly cellular connective tissue with high osteoblastic activity and osteoclasia. Osteoid tissue is relatively sparse. The changes in RA are more diffuse with a more active osteoblastic activity and widespread zones of osteoid tissue as well as resorption by osteoclasts. It appears as if the increased uptake of 83Sr in OA is more dependent on the occurrence of relatively inert osteosclerosis than on a rapid turnover of the bone tissue. 相似文献
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Julien Wegrzyn Jean‐Paul Roux Monique E Arlot Stéphanie Boutroy Nicolas Vilayphiou Olivier Guyen Pierre D Delmas Roland Chapurlat Mary L Bouxsein 《Journal of bone and mineral research》2010,25(11):2324-2331
Low bone mineral density (BMD) is a strong risk factor for vertebral fracture risk in osteoporosis. However, many fractures occur in people with moderately decreased or normal BMD. Our aim was to assess the contributions of trabecular microarchitecture and its heterogeneity to the mechanical behavior of human lumbar vertebrae. Twenty‐one human L3 vertebrae were analyzed for BMD by dual‐energy X‐ray absorptiometry (DXA) and microarchitecture by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) and then tested in axial compression. Microarchitecture heterogeneity was assessed using two vertically oriented virtual biopsies—one anterior (Ant) and one posterior (Post)—each divided into three zones (superior, middle, and inferior) and using the whole vertebral trabecular volume for the intraindividual distribution of trabecular separation (Tb.Sp*SD). Heterogeneity parameters were defined as (1) ratios of anterior to posterior microarchitectural parameters and (2) the coefficient of variation of microarchitectural parameters from the superior, middle, and inferior zones. BMD alone explained up to 44% of the variability in vertebral mechanical behavior, bone volume fraction (BV/TV) up to 53%, and trabecular architecture up to 66%. Importantly, bone mass (BMD or BV/TV) in combination with microarchitecture and its heterogeneity improved the prediction of vertebral mechanical behavior, together explaining up to 86% of the variability in vertebral failure load. In conclusion, our data indicate that regional variation of microarchitecture assessment expressed by heterogeneity parameters may enhance prediction of vertebral fracture risk. © 2010 American Society for Bone and Mineral Research. 相似文献
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Stinus Hansen Jens‐Erik Beck Jensen Lars Rasmussen Ellen M Hauge Kim Brixen 《Journal of bone and mineral research》2010,25(9):1941-1947
Patients with primary hyperparathyroidism (PHPT) have continuously elevated parathyroid hormone (PTH) and consequently increased bone turnover with negative effects on cortical (Ct) bone with preservation of trabecular (Tb) bone. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a new technique for in vivo assessment of geometry, volumetric density, and microarchitecture at the radius and tibia. In this study we aimed to evaluate bone status in women with PHPT compared with controls using HR‐pQCT. The distal radius and tibia of 54 women—27 patients with PHPT (median age 60, range 44–75 years) and 27 randomly recruited age‐matched healthy controls (median age 60, range 44–76 years)—were imaged using HR‐pQCT along with areal bone mineral density (aBMD) by dual‐energy X‐ray absorptiomentry (DXA) of the ultradistal forearm, femoral neck, and spine (L1–L4). Groups were comparable regarding age, height, and weight. In the radius, patients had reduced Ct area (Ct.Ar) (p = .008), Ct thickness (Ct.th) (p = .01) along with reduced total (p = .002), Ct (p = .02), and Tb (p = .02) volumetric density and reduced Tb number (Tb.N) (p = .04) and increased Tb spacing (Tb.sp) (p = .05). Ct porosity did not differ. In the tibia, no differences in HR‐pQCT parameters were found. Moreover, patients had lower ultradistal forearm (p = .005), spine (p = .04), and femoral neck (p = 0.04) aBMD compared with controls. In conclusion, a negative bone effect of continuously elevated PTH with alteration of HR‐pQCT assessed geometry, volumetric density, and both trabecular and cortical microarchitecture in radius but not tibia was found along with reduced aBMD by DXA at all sites in female patients with PHPT. © 2010 American Society for Bone and Mineral Research 相似文献
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Christian Egloff Jochen Paul Geert Pagenstert Patrick Vavken Beat Hintermann Victor Valderrabano Magdalena Müller‐Gerbl 《Journal of orthopaedic research》2014,32(10):1356-1361
CT‐osteoabsorptiometry (CT‐OAM) has been used to visualize subchondral bone plate density distribution regarding to its mineralization. The purpose of this study was to display and analyze the density distribution of the subchondral bone plate before and after supramalleolar realignment osteotomies. We retrospectively analysed pre‐ and postoperative CT images of nine consecutive patients with post‐traumatic unilateral valgus ankle OA. The distribution charts of CT‐OAM scans were quantitatively analyzed for subchondral bone plate density distribution. VAS for pain and the Tegner activity scale were used to assess clinical outcome. At a mean follow‐up of 20 ± 5.6 months (range 13–27), we observed a significant pre‐ to postoperative decrease of the mean high‐density area ratio in tibia (lateral and posterior area) (p ≤ 0.05) and the talus (lateral area) (p ≤ 0.05). Pairwise comparison between the pre‐ and postoperative mineralization at the articular surface showed a significant decrease of the high‐density area ratio for the tibia and the talus. The VAS decreased from 6.2 ± 0.9 pre‐ to 2.8 ± 0.9 postoperatively (p = 0.027), and the Tegner score inclined from 4.5 ± 1.1 preoperatively to 5.3 ± 0.7 after surgery (p = 0.082). The tibial and talar subchondral bone plate density, regarding to its mineralization, decreased after supramalleolar medial closing wedge osteotomy in patients with valgus ankle OA. The results of this study suggest that realignment surgery may decrease peak bone density areas corresponding to the alignment correction and contribute to a homogenization of the subchondral bone plate mineralization. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1356–1361, 2014. Level of evidence Level IV, Case series. 相似文献