复合材料置入软骨下骨诱发兔膝骨关节炎的实验研究

[目的]通过增加软骨下骨硬度模拟软骨下骨硬化,诱发骨关节炎的发生,探讨骨关节炎发病机制.[方法]调整聚甲基丙烯酸甲酯粉剂(polymethylmethacrylate,PMMA)、甲基丙烯酸甲酯液剂(methylmethacrylate,MMA)、羟基磷灰石(hydroxyapatite,HA)和蒸馏水的比例,使反应温度低于40℃,测量该比例下聚合后的极限强度和刚度并与软骨下骨比较,制得PMMA/HA复合材料.刮除兔胫骨平台内侧软骨下骨后置入复合材料,对术后3、6、9、12周的关节软骨进行组织学观察,免疫组化法榆测Ⅱ型胶原和基质会属蛋白酶-1(matrix metallo proteinase-1,MMP-1)在软骨中的表达和分布,并与空白、对照组比较.透射电镜观察空白、6、12周组软骨细胞改变.[结果]该复合材料置入软骨下骨后,随观察时间延长实验组逐渐出现退变,Mankin分级逐渐升高,电镜也显示实验组软骨细胞退变表现.免疫组化显示Ⅱ型胶原表达增加主要在移行层和深层上部,MMP-1表达以软骨表层及中上层居多,随观察时间延长二者染色强度均逐渐升高.[结论]增加软骨下骨硬度后,诱发了兔膝骨关节炎.提示软骨下骨硬化可引起软骨退变,其可能是骨关节炎的病因之一.     

Interspecies comparison of subchondral bone properties important for cartilage repair

Microfracture repair tissue in young adult humans and in rabbit trochlea is frequently of higher quality than in corresponding ovine or horse models or in the rabbit medial femoral condyle (MFC). This may be related to differences in subchondral properties since repair is initiated from the bone. We tested the hypothesis that subchondral bone from rabbit trochlea and the human MFC are structurally similar. Trochlea and MFC samples from rabbit, sheep, and horse were micro‐CT scanned and histoprocessed. Samples were also collected from normal and lesional areas of human MFC. The subchondral bone of the rabbit trochlea was the most similar to human MFC, where both had a relatively thin bone plate and a more porous and less dense character of subchondral bone. MFC from animals all displayed thicker bone plates, denser and less porous bone and thicker trabeculae, which may be more representative of older or osteoarthritic patients, while both sheep trochlear ridges and the horse lateral trochlea shared some structural features with human MFC. Since several cartilage repair procedures rely on subchondral bone for repair, subchondral properties should be accounted for when choosing animal models to study and test procedures that are intended for human cartilage repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:63–70, 2015.

     

碘乙酸钠大鼠骨关节炎模型骨微结构研究

目的 探讨碘乙酸钠（monosodium iodoacetate, MIA）大鼠骨关节炎（osteoarthritis,OA）模型在不同时段的病理及软骨下骨微结构的变化特点。方法 选取SPF级8周龄雄性Wistar大鼠36只,通过随机数字法分成空白对照组（Sham组）、OA造模2周组（OA-2W组）、OA造模4周组（OA-4W组）,分别进行MIA造模2周和4周后,获取膝关节胫骨标本并行组织切片染色及Micro-CT扫描,计算软骨组织OOCHAS评分及软骨下骨骨微结构参数。结果 MIA造模后可见软骨表面缺损,关节周缘骨赘增生,软骨下骨密度(bone mineral density, BMD)减低,骨小梁变薄稀疏,组织切片见软骨结构形态紊乱,局部簇集现象,染色变浅甚至消失。Sham组软骨下BMD平均为（1 367.97±37.43）mg/cc,OA-2W组BMD下降至（1 330.66±38.99）mg/cc,OA-4W组BMD下降至（1 285.5±47.08）mg/cc。软骨组织切片OOCHAS评分,Sham组平均为0（0,1）分,OA-2W组平均为12（9.75,15）分,OA-4W组平均为24（20,24）分。结论 MIA造模2周时达到OA中期阶段,造模4周时为OA晚期阶段,OA会造成软骨下骨密度减低、骨小梁稀疏等骨质疏松表现,并且随着病情进展会逐渐加重。     

BMI‐related microstructural changes in the tibial subchondral trabecular bone of patients with knee osteoarthritis

Overweight is a risk factor for osteoarthritis on the knees. Subchondral trabecular bone (SCTB) densification has been shown to be associated with cartilage degeneration. This study analyzed the microarchitectural changes in the SCTB of tibial plateaus to validate the hypothesis that the degree of remodeling is correlated with a patient's body weight. Twenty‐one tibial plateaus were collected during total knee arthroplasty from 21 patients (15 women and 6 men). These patients had a mean age of 70.4 years (49–81), mean weight of 74.7 kg (57–93) and mean body mass index (BMI) of 28.4 kg/m² (21.3–40.8). One cylindrical plug was harvested in the center of each tibial plateau (medial and lateral). Micro‐CT parameters (7.4 μm resolution) were determined to describe the SCTB structure. On the medial plateau, there were significant correlations between BMI and bone volume fraction BV/TV (r = 0.595, p = 0.004), structure model index SMI (r = −0.704 p = 0.0002), trabecular space Tb.Sp (r = 0.600, p = 0.04) and trabecular number Tb.N (r = 0.549, p = 0.01). SCTB densification during osteoarthritis is associated with a reduction in its elastic modulus, which could increase cartilage stress, and accelerate cartilage loss. SCTB densification has been shown to precede cartilage degeneration. The correlation of SCTB microarchitecture and body weight may explain why knee osteoarthritis is more common in overweight or obese patients. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1653–1660, 2017.

     

Elevated marrow inflammatory cells and osteoclasts in subchondral osteosclerosis in human knee osteoarthritis

Subchondral osteosclerosis, characterized by an increase of hypomineralized bone material, is a pathological hallmark of osteoarthritis. The cellular components in the subchondral marrow compartment that participate in this aberrant bone remodeling process remain to be elucidated. This study assessed the presence of marrow inflammatory cells and their relative abundance between nonsclerotic and sclerotic tissues in knee osteoarthritis. Bone samples from osteoarthritic knee tibial plateaus were stratified for histological analyses using computed tomography osteoabsorptiometry. Immunohistological analysis revealed the presence of CD20 (B‐lymphocyte) and CD68 (macrophage), but not CD3 (T‐lymphocyte) immunoreactive mononuclear cells in subchondral marrow tissues and their relative abundance was significantly increased in sclerotic compared with nonsclerotic bone samples. Multinucleated osteoclasts that stained positive for CD68 and tartrate‐resistant acid phosphatase, predominantly associated with CD34‐positive blood vessels and their abundance was strongly increased in sclerotic samples. Bone‐specific alkaline phosphatase activity in outgrowth osteoblasts was induced by conditioned medium from nonsclerotic, but not sclerotic, bone pieces. These results suggest that an interaction between bone‐resident cells and marrow inflammatory cells might play a role in aberrant bone remodeling leading to subchondral osteosclerosis. Elevated osteoclast activity in sclerotic bone suggests that bone formation and resorption activities are increased, yet uncoupled, in human knee osteoarthritis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:262–269, 2016.     

Association between subchondral bone structure and osteoarthritis histopathological grade

Despite increasing evidence that subchondral bone contributes to osteoarthritis (OA) pathogenesis, little is known about local changes in bone structure compared to cartilage degeneration. This study linked structural adaptation of subchondral bone with histological OA grade. Twenty‐five osteochondral samples of macroscopically different degeneration were prepared from tibiae of 14 patients. Samples were scanned with micro‐computed tomography (μCT) and both conventional structural parameters and novel 3D parameters based on local patterns were analyzed from the subchondral plate and trabecular bone. Subsequently, samples were processed for histology and evaluated for OARSI grade. Each bone parameter and OARSI grade was compared to assess structural adaptation of bone with OA severity. In addition, thicknesses of cartilage, calcified cartilage, and subchondral plate were analyzed from histological sections and compared with subchondral bone plate thickness from μCT. With increasing OARSI grade, the subchondral plate became thicker along with decreased specific bone surface, while there was no change in tissue mineral density. Histological analysis showed that subchondral plate thickness from μCT also includes calcified cartilage. Entropy of local patterns increased with OA severity, reflecting higher tissue heterogeneity. In the trabecular compartment, bone volume fraction and both trabecular thickness and number increased with OARSI grade while trabecular separation and structure model index decreased. Also, elevation of local patterns became longitudinal in the subchondral plate and axial transverse in trabecular bone with increasing OARSI grade. This study demonstrates the possibility of radiological assessment of OA severity by structural analysis of bone. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 35:785–792, 2017.

     

Systematic mapping of the subchondral bone 3D microarchitecture in the human tibial plateau: Variations with joint alignment

Tibial subchondral bone plays an important role in knee osteoarthritis (OA). Microarchitectural characterization of subchondral bone plate (SBP), underlying subchondral trabecular bone (STB) and relationships between these compartments, however, is limited. The aim of this study was to characterize the spatial distribution of SBP thickness, SBP porosity and STB microarchitecture, and relationships among them, in OA tibiae of varying joint alignment. Twenty‐five tibial plateaus from end‐stage knee‐OA patients, with varus (n = 17) or non‐varus (n = 8) alignment were micro‐CT scanned (17 μm/voxel). SBP and STB microarchitecture was quantified via a systematic mapping in 22 volumes of interest per knee (11 medial, 11 lateral). Significant within‐condylar and between‐condylar (medial vs. lateral) differences (p < 0.05) were found. In varus, STB bone volume fraction (BV/TV) was consistently high throughout the medial condyle, whereas in non‐varus, medially, it was more heterogeneously distributed. Regions of high SBP thickness were co‐located with regions of high STB BV/TV underneath. In varus, BV/TV was significantly higher medially than laterally, however, not so in non‐varus. Moreover, region‐specific significant associations between the SBP thickness and SBP porosity and the underlying STB microarchitecture were detected, which in general were not captured when considering the values averaged for each condyle. As subchondral bone changes reflect responses to local mechanical and biochemical factors within the joint, our results suggest that joint alignment influences both the medial‐to‐lateral and the within‐condyle distribution of force across the tibia, generating corresponding local bony responses (adaptation) of both the subchondral bone plate and underlying subchondral trabecular bone microarchitecture. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1927–1941, 2017.

     

Attenuation of cartilage degeneration by calcitonin gene‐related paptide receptor antagonist via inhibition of subchondral bone sclerosis in osteoarthritis mice

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.     

降钙素在体内体外实验中对兔关节炎关节软骨退变及软骨下骨骨代谢的影响

[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.     

Activated FGFR3 prevents subchondral bone sclerosis during the development of osteoarthritis in transgenic mice with achondroplasia

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 (Fgfr3^ach) 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 Fgfr3^ach 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 Fgfr3^ach 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 Fgfr3^ach mice than in wild‐type mice. BMD, BV/TV, and Tb.Th in the epiphysis increased in wild‐type mice and unchanged in Fgfr3^ach 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 Fgfr3^ach 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.     

补肾活血方调控膝骨性关节炎大鼠软骨下骨的作用机制研究

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。     

Osteoarthritic versus osteoporotic bone and intra‐skeletal variations in normal bone: Evaluation with µCT and bone histomorphometry

Several studies have shown that in contrast to osteoporosis (OP), osteoarthritis (OA) is characterized by high bone mineral density (BMD). Bone strength not only depends on mineral content as determined by dual X‐ray absorptiometry (DXA), but also on bone microarchitecture. We studied intertrochanteric bone from normal controls and OA and OP patients by bone histomorphometry (BHM) and microcomputed tomography (µCT) as well as DXA in order to first, test the differences between OA and OP comparing both groups to healthy controls, second, to assess variations between three different skeletal sites in controls and third, to determine the level of agreement between µCT, BHM, and DXA. Analysis was performed on 115 samples from OA and OP patients, and controls. We found significant differences between OA and OP samples in structural parameters and in the osteoid fraction (p < 0.05). The majority of the intra‐skeletal differences were shown between lumbar spine and femoral head samples (p < 0.05). Significant agreements were found between µCT and BHM and DXA (r = 0.32–0.45, p < 0.05). Our findings suggest differences in intertrochanteric bone between OA and OP, the age‐related intra‐skeletal variations and a correlation between microscopic and macroscopic bone evaluation methods. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1059–1066, 2013     

Assessment of cortical and trabecular bone changes in two models of post‐traumatic osteoarthritis

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.     

Chondroprotective effect of high‐dose zoledronic acid: An experimental study in a rabbit model of osteoarthritis

To address the need to impact the subchondral bone‐articular cartilage interaction for the treatment of degenerative osteoarthritis (OA), bisphosphonates may be used as a means to inhibit the subchondral bone resorption. The purpose of the present study is to evaluate the chondroprotective effect of zoledronic acid (ZOL) in a model of OA. Eighteen adult male rabbits underwent an anterior cruciate ligament transection and were separated into two groups: ZOL group (n = 10) received 0.6 mg/kg intravenous injection of ZOL on day 1, 15, and 29 and placebo group (n = 8) received saline. The animals were euthanized at 8 weeks. Macroscopically, the ZOL group had significantly milder ulcerations, cartilage softening and fibrillation compared to the placebo group. Microscopically, morphology of the articular cartilage was better in the ZOL treated group compared with the placebo group, without complete disorganization in any section of the ZOL group. Furthermore, the chondrocytes in the ZOL treated group were mainly cloning, indicating cartilage repairing and regeneration process, while in the placebo group hypocellularity predominated. Additionally, subchondral necrosis was evident in some specimens of the placebo group. Zoledronic acid, in a high‐dose regimen, proved to be chondroprotective in a well‐established animal model of OA. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1646–1651, 2014.     

兔骨关节炎两种动物模型的比较

[目的]探讨建立两种骨关节炎动物模型的效果及其适用条件。[方法]17只新西兰大白兔分为Hulth模型组、韧带切除模型组及空白对照组：在手术建模后第1、3、6周取双侧股骨髁部，比较各组骨关节大体形态及病理变化。[结果]两模型组Mankin’s评分显著高于对照组（P〈0．05），关节软骨退变进行性加重。Hulth模型组关节炎程度较严重，类似骨关节炎中晚期，韧带切除模型组类似骨关节炎早期或中期。[结论]Hulth模型组和韧带切除模型组均能建立标准的骨关节炎动物模型。Hulth模型组适用于外科手术治疗方面研究，韧带切除模型适合发病机理、药物治疗方面研究，     

绝经后女性膝关节骨性关节炎与胫骨软骨下骨骨密度的相关性研究

目的评价绝经后女性膝关节骨性关节炎与胫骨软骨下骨骨密度的相关性。方法选取2017年7月至2017年10月就诊于新疆医科大学第一附属医院的绝经后膝关节骨性关节炎女性80例,年龄45~92(65.2±10.9)岁。按照KellgrenLawrence诊断标准将Ⅰ、Ⅱ、Ⅲ、Ⅳ级KOA分为A、B、C、D等4个组。将胫骨内侧及外侧选为感兴趣区(regions of interest,ROI)分别标记为ROI 1,ROI 2。采用GE Lunar Prodigy型双能X线骨密度仪分别测量两个ROI骨密度,同时测量股骨颈及腰椎骨密度。结果共纳入骨性关节炎患者80例。ROI 1平均骨密度值0.66±0.24 g/cm~2,ROI 2平均骨密度值0.46±0.19 g/cm~2,腰椎平均骨密度值0.76±0.15 g/cm~2,股骨颈平均骨密度值0.75±0.14 g/cm~2。ROI 1、ROI 2、股骨颈及腰椎骨密度值与KOA分级比较后发现,ROI 1、ROI 2、股骨颈骨密度值在4组间差异有统计学意义(P0.05),腰椎骨密度差异没有统计学意义(P0.05)。胫骨软骨下骨骨密度与KOA分级、年龄、腰椎骨密度、股骨颈骨密度进行相关性分析后发现,胫骨软骨下骨骨密度与KOA分级、年龄呈负相关,与腰椎及股骨颈骨密度呈正相关。结论随KOA的进展,胫骨软骨下骨皮质终板硬化,但其下方的松质骨骨密度减低。     

Subchondral bone fragility with meniscal tear accelerates and parathyroid hormone decelerates articular cartilage degeneration in rat osteoarthritis model

The aims of this study were to investigate the influence of subchondral bone fragility (SBF) on the progression of the knee osteoarthritis by using a novel rat model, and to examine the preventive effect of parathyroid hormone (PTH) on cartilage degeneration. First, 40 rats were assigned to the following four groups: Sham, SBF, Medial meniscal tear (MMT), and MMT + SBF groups. In SBF and MMT + SBF groups, we induced SBF by microdrilling the subchondral bone. Second, 10 additional rats were randomly assigned to the following two groups: MMT + SBF + saline and MMT + SBF + PTH groups. Osteoarthritic changes in the articular cartilage and subchondral bone were evaluated using safranin‐O/fast green staining, matrix metalloproteinase‐13 (MMP‐13), and type X collagen immunohistochemistry, toluidine blue staining, and micro‐CT scanning. The combination of SBF and meniscal tear increased the number of mast cells in the subchondral bone, and led to the abnormal subchondral bone microarchitecture, such as abnormally decreased trabecular number and increased trabecular thickness, compared with meniscal tear alone. Moreover, SBF with meniscal tear enhanced articular cartilage degeneration and increased the expression of MMP‐13 and type X collagen, compared with meniscal tear alone. The administration of PTH decreased the number of mast cells in the subchondral bone and improved the microstructural parameters of the subchondral bone, and delayed the progression of articular cartilage degeneration. These results suggest that SBF is one of the factors underlying the osteoarthritis development, especially in knees with traumatic osteoarthritis, and that the administration of PTH is a potential therapeutic treatment for preventing OA progression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1959–1968, 2018.

     

Chondroprotective effect of alendronate in a rabbit model of osteoarthritis

The aim of this study was to determine how alendronate (ALN) alters cartilage degeneration and periarticular bone quality in a rabbit anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA). Thirty rabbits underwent an ACLT on the left knee and a sham operation on the right knee. Fifteen rabbits received weekly subcutaneous injections of ALN (0.14 mg/kg) and 15 rabbits (the control [cont] group) received saline. Animal knees were divided into four groups: cont/sham, cont/ACLT, ALN/sham, and ALN/ACLT. Histological, radiological, and immunohistochemical indices were evaluated for each group. Bone volume ratios by micro‐computed tomography showed that ALN prevented periarticular bone loss. Histologically, the cont/ACLT group had significantly worse cartilage damage than the cont/sham group 12 weeks after the surgery. However, the ALN/ACLT group had mild cartilage degeneration compared with that of the ALN/sham group. Immunohistochemical analysis showed that ALN suppressed the expression of matrix metalloproteinase‐13, interleukin‐1β, type‐X collagen, vascular endothelial growth factor, and receptor activator of nuclear factor κB ligand in OA cartilage. ALN had a chondroprotective effect in an experimental rabbit model of OA. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1572–1577, 2011     

Quantitative measures of damage to subchondral bone are associated with functional outcome following treatment of displaced acetabular fractures

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