Histomorphometric analysis of subchondral bone of the femoral head in osteoarthritis and osteoporosis

There have been reports both supporting and refuting an inverse relationship between hip fracture and hip osteoarthritis (OA). We have investigated this relationship using histomorphometric study of femoral head subchondral bone. We studied 74 subjects with hip fracture (74% females) and 24 subjects with osteoarthritis (45% females). By histomorphometric analysis of parafined sections, we analysed followed subhondral trabecular bone parameters bone volume (BV), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th.), trabecular number (Tb.N.) and trabecular separation (Tb.S.). The subjects with osteoarthritis and subjects with hip fracture had BV/TV 31.3% and 19.6% respectively. BV/TV of osteoarthritis group was rather uniform whereas BV/TV of hip fracture group was greatly ranged and we divided it into three subgroups, 13.2%, 19.8% and 25.9% respectively. The OA group and hip fracture groups had Tb.Th. as followed 0.205 mm, 0.148 mm, 0.170 mm and 0.183 mm respectively. The OA group and hip fracture three subgroups had Tb.N. as followed 1.454/mm, 0.897/mm, 1.170/mm and 1.425/mm respectively. The OA group and hip fracture three subgroups had Tb.S. as followed 0.518 mm, 0.681 mm, 0.620 mm and 0.550 mm respectively. The results of our study support an inverse relationship between hip fracture and hip osteoarthritis.     

Effects of whole-body vibration on bone properties in aged rats

Objective:This study aimed to explore optimal conditions of whole-body vibration (WBV) for improving bone properties in aged rats.Methods:Eighty-week-old rats were divided into baseline control (BC), age-matched control (CON) and experimental groups, which underwent WBV (0.5 g) at various frequencies (15, 30, 45, 60 or 90 Hz) or WBV (45 Hz) with various magnitudes (0.3, 0.5, 0.7 or 1.0 g) for 7 weeks. After interventions, femur bone size, bone mechanical strength and circulating bone formation/resorption markers were measured, and trabecular bone microstructure (TBMS) and cortical bone geometry (CBG) of femurs were analyzed by micro-CT.Results:Several TBMS parameters and trabecular bone mineral content were significantly lower in the 15 Hz WBV (0.5 g) group than in the CON group, suggesting damage to trabecular bone. On the other hand, although frequency/magnitude of WBV did not influence any CBG parameters, the 0.7 g and 1.0 g WBV (45 Hz) group showed an increase in tissue mineral density of cortical bone compared with the BC and CON groups, suggesting the possibility of improving cortical bone properties.Conclusion:Based on these findings, it should be noted that WBV conditions are carefully considered when applied to elderly people.     

Effect of Low-Magnitude Whole-Body Vibration Combined with Alendronate in Ovariectomized Rats: A Random Controlled Osteoporosis Prevention Study

Background

Alendronate (ALE) is a conventional drug used to treat osteoporosis. Low-magnitude whole-body vibration (WBV) exercise has been developed as a potential treatment for osteoporosis. The aim of this study was to investigate whether low-magnitude WBV could enhance the protective effect of ALE on bone properties in ovariectomized rats.

Methods

A total of 128 Sprague-Dawley rats were randomly divided into five groups (SHAM, OVX+VEH, OVX+WBV, OVX + ALE, OVX+WBV+ALE). The level of WBV applied was 0.3 g at 45–55 Hz for 20 min/day, 5 day/week and for 3 months. ALE was administered in dose of 1 mg/Kg once a week. Every four weeks eight rats from each group were sacrificed and their blood and both tibiae were harvested. The expression of osteocalcin and CTX in serum was measured by enzyme-linked immunosorbent assay (ELISA) and the tibiae were subjected to metaphyseal three-point bending and μCT analysis.

Results

Osteocalcin rose after ovariectomy and was not appreciably changed by either alendronate or WBV alone or in combination. Alendronate treatment significantly prevented an increase in CTX. WBV alone treatment did not alter this effect. Compared with the OVX+WBV group, nearly all tested indices such as the BV/TV, TV apparent, Tb.N, Tb.Th, and Conn.D were higher in the OVX+ALE group at week 12.Compared with the OVX+WBV group, certain tested indices such as BV/TV, TV apparent, Tb.N, and Con.D, were higher in the OVX+WBV+ALE group at week 12. At week 12, tibiae treated with WBV+ALE exhibited a significantly higher F_max compared to the OVX+VEH group, and a significant difference was also found in energy absorption between the OVX+WBV+ALE and OVX+VEH groups.

Conclusions

Compared with the WBV, ALE was more effective at preventing bone loss and improved the trabecular architecture. However, WBV enhanced the effect of alendronate in ovariectomized rats by inducing further improvements in trabecular architecture.     

去卵巢大鼠腰椎骨微结构变化的动态观察

目的:动态观察去卵巢大鼠腰椎骨微结构的变化。方法:将90只3月龄雌性SD大鼠按体重进行分层随机抽样分组,分为基础组(10只)、假手术组(40只)和去卵巢组(40只)。手术前(0周)处死基础组大鼠,手术后3、6、12、24周时,分批处死假手术和去卵巢组大鼠各8-10只。从每组随机取6只大鼠的第5腰椎行micro-CT扫描及三维结构重建,选取椎体1 mm处,2.0 mm×3.5mm,厚0.9 mm的骨组织为感兴趣区域(interesting area),进行骨形态计量学分析。结果:与同一时间点假手术组大鼠比较,去卵巢3周时,第5腰椎体积骨密度(v BMD)、骨体积分数(BV/TV)、骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)、骨小梁间隙(Tb.Sp)和结构模型指数(SMI)均无显著变化;去卵巢6周时,Tb.Th显著下降(P0.05),而其他指标均无显著变化;从去卵巢12周到24周时,不仅Tb.Th显著下降(P0.05),而且v BMD、BV/TV和Tb.N也显著下降(P0.05),同时Tb.Sp和SMI显著增加(P0.05)。结论:3月龄大鼠在去卵巢后的6周时骨小梁厚度变薄,12周以后,体积骨密度和骨体积分数下降,骨小梁数目减少。     

阿司匹林对去势大鼠腰椎骨密度及微观结构的影响

目的:研究阿司匹林对去势(卵巢切除)大鼠腰椎骨密度及微观结构的影响。方法:取48只3月龄SD雌性大鼠随机分为6组:去势组(OVX组)、对照组(Sham组)及4个阿司匹林治疗组(Aspirin组),每组8只。OVX组及Aspirin组采用卵巢切除法建立骨质疏松模型。去势后1周,阿司匹林治疗组剂量分别为2.25、4.46、8.92及26.75 mg/kg(A1、A2、A3及A4组),每天灌胃一次,OVX组及Sham组予同等量生理盐水灌胃。灌胃3个月后处死,剖取腰椎椎体,以双能X线吸收骨密度测量仪(DXA)和Micro-CT进行测量分析。结果:DXA分析结果显示:阿司匹林各剂量组BMD值较OVX组有统计学差异(P<0.01)。Micro-CT分析表明:与OVX组比较,阿司匹林各剂量组BV/TV、Tb.Th、Tb.N、BMD均显著性提高(P<0.01),BS/BV、Tb.Sp显著性降低(P<0.01),阿司匹林各剂量组BV/TV、BS/BV、Tb.Th、Tb.N、Tb.Sp、BMD与Sham组相比有统计学差异(P<0.01)。结论:阿司匹林可以改善去势大鼠骨小梁结构,增加骨质密度,对去势大鼠骨质疏松具有防治作用,其作用途径可能包括抑制骨吸收和刺激骨形成两方面。     

Gender-related changes in three-dimensional microstructure of trabecular bone at the human proximal tibia with aging

Despite increasing interest in age- and gender-related bone alterations, data on trabecular microstructure at the proximal tibia are scarce. The aim of this study was to identify trabecular microstructural change at the human proximal tibia with age and gender, using micro-computed tomography (micro-CT) and scanning electron microscopy (SEM). Fifty-six proximal tibias from 28 Japanese men and women (57-98 years of age) were used in this study. The subjects were chosen to give an even age and gender distribution. Both women and men were divided into three age groups, middle (57-68 years), old (72-82 years) and elderly (87-98 years) groups. The trabecular bone specimens from the medial compartment of the proximal tibial metaphysis were examined. Trabecular bone mineral density (BMD), bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) decreased between the middle-aged and elderly groups similarly in women and men. However, trabecular number (Tb.N) decreased by 13% between the middle-aged and elderly groups in women and nearly double that in men. As compared with women, men had higher BV/TV and lower trabecular separation (Tb.Sp) in the old age and elderly groups, and higher Tb.N and connectivity density (Conn.D) in the elderly group. Increased trabecular resorbing surfaces, perforated or disconnected trabeculae and microcallus formations were observed with age. These findings indicate that both BMD and BV/TV decreased at the proximal tibia with age similarly for women and men, but significant differences between women and men were observed for some microstructural parameters. These findings illustrate potential mechanisms underlying osteoporotic proximal tibial fracture.     

A micro-computed tomography study of the trabecular bone structure in the femoral head

The goal of this study was to characterize the trabecular microarchitecture of the femoral head using micro-computed tomography (ICT). Femoral head specimens were obtained from subjects following total hip replacement. Cylindrical cores from the specimens were scanned to obtain 3-D images with an isotropic resolution of 26 Im. Bone structural parameters were evaluated on a per millimeter basis: relative bone volume (BV/TV), trabecular number (Tb.N), thickness (Tb.Th) and separation (Tb.Sp), structure model index (SMI), and connectivity (Conn.D). The ICT data show that the first two millimeters, starting at the joint surface, are characterized by more plate-like trabeculae, and are significantly denser than the underlying trabecular bone. Regional differences in the trabecular architecture reveal that the superior pole has significantly higher BV/TV, Tb.N and Tb.Th values, with lower Tb.Sp compared to the inferior and side poles. Because subchondral bone is essential in the load attenuation of joints, the difference in bone structure between the subchondral and trabecular bone might arise from the different functions each have within joint-forming bones. The denser trabecular structure of the superior pole as compared to the inferior pole can be interpreted as a functional adaptation to higher loading in this area.     

Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis

Mesenchymal stem cells (MSCs) have shown chondroprotective effects in clinical models of osteoarthritis (OA). However, effects of MSC-derived exosomes on OA remain unclear. The study aimed to investigate the therapeutic potential of exosomes from human bone marrow MSCs (BM-MSCs) in alleviating OA. The anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgery were performed on the knee joints of a rat OA model, followed by intra-articular injection of BM-MSCs or their exosomes. In addition, BM-MSC-derived exosomes were administrated to primary human chondrocytes to observe the functional and molecular alterations. Both of BM-MSCs and BM-MSC-derived exosomes alleviated cartilage destruction and subchondral bone remodelling in OA rat model. Administration of BM-MSCs and exosomes could reduce joint damage and restore the trabecular bone volume fraction, trabecular number and connectivity density of OA rats. In addition, in vitro assays showed that BM-MSCs-exosomes could maintain the chondrocyte phenotype by increasing collagen type II synthesis and inhibiting IL-1β–induced senescence and apoptosis. Furthermore, exosomal lncRNA MEG-3 also reduced the senescence and apoptosis of chondrocytes induced by IL-1β, indicating that lncRNA MEG-3 might partially account the anti-OA effects of BM-MSC exosomes. The exosomes from BM-MSCs exerted beneficial therapeutic effects on OA by reducing the senescence and apoptosis of chondrocytes, suggesting that MSC-derived exosomes might provide a candidate therapy for OA treatment.     

Pulsed Electromagnetic Fields Improve Bone Microstructure and Strength in Ovariectomized Rats through a Wnt/Lrp5/β-Catenin Signaling-Associated Mechanism

Growing evidence has demonstrated that pulsed electromagnetic field (PEMF), as an alternative noninvasive method, could promote remarkable in vivo and in vitro osteogenesis. However, the exact mechanism of PEMF on osteopenia/osteoporosis is still poorly understood, which further limits the extensive clinical application of PEMF. In the present study, the efficiency of PEMF on osteoporotic bone microarchitecture and bone quality together with its associated signaling pathway mechanisms was systematically investigated in ovariectomized (OVX) rats. Thirty rats were equally assigned to the Control, OVX and OVX+PEMF groups. The OVX+PEMF group was subjected to daily 8-hour PEMF exposure with 15 Hz, 2.4 mT (peak value). After 10 weeks, the OVX+PEMF group exhibited significantly improved bone mass and bone architecture, evidenced by increased BMD, Tb.N, Tb.Th and BV/TV, and suppressed Tb.Sp and SMI levels in the MicroCT analysis. Three-point bending test suggests that PEMF attenuated the biomechanical strength deterioration of the OVX rat femora, evidenced by increased maximum load and elastic modulus. RT-PCR analysis demonstrated that PEMF exposure significantly promoted the overall gene expressions of Wnt1, LRP5 and β-catenin in the canonical Wnt signaling, but did not exhibit obvious impact on either RANKL or RANK gene expressions. Together, our present findings highlight that PEMF attenuated OVX-induced deterioration of bone microarchitecture and strength in rats by promoting the activation of Wnt/LRP5/β-catenin signaling rather than by inhibiting RANKL-RANK signaling. This study enriches our basic knowledge to the osteogenetic activity of PEMF, and may lead to more efficient and scientific clinical application of PEMF in inhibiting osteopenia/osteoporosis.     

Preventive Effects of Supplemental Selenium and Selenium Plus Iodine on Bone and Cartilage Development in Rats Fed with Diet from Kashin–Beck Disease Endemic Area

The purpose of this study was to investigate the effects of supplemental selenium and selenium plus iodine on bone and growth plate cartilage histology and serum biochemistic parameters in rats. Ninety-six Wistar rats were randomly divided into the following four groups: group A, the rats fed with normal diet; group B, fed with diet from Kashin–Beck disease (KBD) endemic area; group C, fed with diet from KBD endemic area supplemented with selenium; and group D, fed with diet from KBD endemic area supplemented with selenium and iodine. After 4, 8, and 12 weeks, bone and cartilage samples were collected from the rats and were examined for morphological changes in the tibial growth zone and for changes in the plate cartilage and metaphysic. Compared to the rats fed with diet from the KBD endemic area, the rats fed with the supplemental selenium or selenium plus iodine exhibited diminished necrosis of the chondrocytes in the growth plate. In the groups of rats receiving supplemental selenium and selenium plus iodine, the bone volume/tissue volume ratio (BV/TV), the trabecular thickness (Tb.Th), and the trabecular number were increased, while the trabecular separation was decreased. In the 12th week of the experiment, BV/TV and Tb.Th were significantly increased in the selenium plus iodine group compared to the selenium group. It is concluded that feeding the diet from the KBD endemic area caused necrosis of chondrocytes and dysfunctions of bone development similar to the pathological changes that are seen in KBD. Selenium and iodine protected chondrocytes in growth plate and promoted the formation of trabecular bone. The effects of selenium plus iodine on bone formation were more obvious than those of selenium alone     

Extracorporeal shockwave therapy in osteoporotic osteoarthritis of the knee in rats: an experiment in animals

Introduction

This study investigated the effectiveness of extracorporeal shockwave therapy (ESWT) in osteoporotic (OP) osteoarthritis (OA) of rat knee.

Methods

Fifty-six rats were divided into seven groups including sham, OA, OP, OA + OP, OA + ESWT, OP + ESWT, and OA + OP + ESWT groups. The evaluations included gross pathology, bone mineral density (BMD), micro-computed tomography (micro-CT) scan, bone-strength test, histopathologic examination, and immunohistochemical analysis.

Results

On gross pathology, group OA + OP showed larger areas of osteoarthritic changes than did groups OA and OP, as compared with the sham group. BMD and bone strength significantly decreased in groups OA, OP, and OA + OP relative to the sham group, and ESWT significantly improved BMD and bone-strength changes. On micro-CT scan, the subchondral plate thickness significantly decreased, and the bone porosity increased in groups OA, OP, and OA + OP, and ESWT significantly improved the changes in subchondral-plate thickness and bone porosity. In histopathologic examination, Mankin score and safranin O score significantly increased in groups OA and group OA + OP, but not in group OP relative to the sham group, and ESWT significantly improved the changes. In immunohistochemical analysis, Dickkopf-1 (DKK-1) significantly increased, but vessel endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), and bone morphogenetic protein 2 (BMP-2) decreased in groups OA, OP, and OA + OP relative to the sham group, and ESWT significantly reversed the changes.

Conclusions

Osteoporosis increased the severity of cartilage damage in osteoarthritis of the knee. ESWT showed effectiveness in the reduction of osteoporotic osteoarthritis of the knee in rats.     

Doxycycline effects on mechanical and morphometrical properties of early- and late-stage osteoarthritic bone following anterior cruciate ligament injury.

As posttraumatic osteoarthritis (OA) progresses, the mechanical and morphometrical properties of the subchondral bone change and may be linked to damage of the articular cartilage. Potentially to slow that progression, doxycycline was administered orally twice daily (4 mg.kg(-1).day(-1)) in skeletally mature canines after anterior cruciate ligament transection (ACLX). To test if doxycycline significantly altered the structure and function of OA bone, we tested cancellous bone mechanical properties, measured bone mineral content, and analyzed bone structure by microcomputed tomography. Our investigation focused on subchondral trabecular bone changes in the medial femoral condyle at 36 and 72 wk after ACLX. Significant mechanical changes discovered at 36 wk post-ACLX were less obvious at 72 wk in both treated and ACLX groups. Doxycycline treatment conserved bone strain energy density at 72 wk. Doxycycline had little effect on the degradation of superficial osseous tissue at 36 wk post-ACLX; by 72 wk, doxycycline in an ACLX model limited subchondral bone loss within the first 3 mm of periarticular bone with established OA. Significant bone loss occurred in the deeper trabecular bone for all groups. Substantial architectural adaptation within deeper trabecular bone accompanied changes in mechanics in early and established OA.     

Quantification of subchondral bone changes in a murine osteoarthritis model using micro-CT

In the past few years there has been a considerable interest in the role of bone in osteoarthritis. Despite the increasing evidence of the involvement of bone in osteoarthritis, it remains very difficult to attribute the cause or effect of changes in subchondral bone to the process of osteoarthritis. Although osteoarthritis in mice provides a useful model to study changes in the subchondral bone, detailed quantification of these changes is lacking. Therefore, the goal of this study was to quantify subchondral bone changes in a murine osteoarthritis model by use of micro-computed tomography (micro-CT). We induced osteoarthritis-like characteristics in the knee joints of mice using collagenase injections, and after four weeks we calculated various 3D morphometric parameters in the epiphysis of the proximal tibia. The collagenase injections caused cartilage damage, visible in histological sections, particularly on the medial tibial plateau. Micro-CT analysis revealed that the thickness of the subchondral bone plate was decreased both at the lateral and the medial side. The trabecular compartment demonstrated a small but significant reduction in bone volume fraction compared to the contralateral control joints. Trabeculae in the collagenase-injected joints were thinner but their shape remained rod-like. Furthermore, the connectivity between trabeculae was reduced and the trabecular spacing was increased. In conclusion, four weeks after induction of osteoarthritis in the murine knee subtle but significant changes in subchondral bone architecture could be detected and quantified in 3D with micro-CT analysis.     

Skeletal Characterization of Smurf2-Deficient Mice and In Vitro Analysis of Smurf2-Deficient Chondrocytes

Overexpression of Smad ubiquitin regulatory factor 2 (Smurf2) in chondrocytes was reported to cause spontaneous osteoarthritis (OA) in mice. However, it is unclear whether Smurf2 is involved in bone and cartilage homeostasis and if it is required for OA pathogenesis. Here we characterized age-related changes in the bone and articular cartilage of Smurf2-deficient (MT) mice by microCT and histology, and examined whether reduced Smurf2 expression affected the severity of OA upon surgical destabilization of the medial meniscus (DMM). Using immature articular chondrocytes (iMAC) from MT and wild-type (WT) mice, we also examined how Smurf2 deficiency affects chondrogenic and catabolic gene expressions and Smurf2 and Smurf1 proteins upon TGF-β3 or IL-1β treatment in culture. We found no differences in cortical, subchondral and trabecular bone between WT and MT in young (4 months) and old mice (16–24 months). The articular cartilage and age-related alterations between WT and MT were also similar. However, 2 months following DMM, young MT showed milder OA compared to WT (~70% vs ~30% normal or exhibiting only mild OA cartilage phenotype). The majority of the older WT and MT mice developed moderate/severe OA 2 months after DMM, but a higher subset of aged MT cartilage (27% vs. 9% WT) remained largely normal. Chondrogenic gene expression (Sox9, Col2, Acan) trended higher in MT iMACs than WT with/without TGF-β3 treatment. IL-1β treatment suppressed chondrgenic gene expression, but Sox9 expression in MT remained significantly higher than WT. Smurf2 protein in WT iMACs increased upon TGF-β3 treatment and decreased upon IL-1β treatment in a dose-dependent manner. Smurf1 protein elevated more in MT than WT upon TGF-β3 treatment, suggesting a potential, but very mild compensatory effect. Overall, our data support a role of Smurf2 in regulating OA development but suggest that inhibiting Smurf2 alone may not be sufficient to prevent or consistently mitigate post-traumatic OA across a broad age range.     

Multipotential stromal cells in the talus and distal tibia in ankle osteoarthritis – Presence,potency and relationships to subchondral bone changes

A large proportion of ankle osteoarthritis (OA) has an early onset and is post-traumatic. Surgical interventions have low patient satisfaction and relatively poor clinical outcome, whereas joint-preserving treatments, which rely on endogenous multipotential stromal cells (MSCs), result in suboptimal repair. This study investigates MSC presence and potency in OA-affected talocrural osteochondral tissue. Bone volume fraction (BV/TV) changes for the loading region trabecular volume and subchondral bone plate (SBP) thickness in OA compared with healthy tissue were investigated using microcomputed tomography. CD271-positive MSC topography was related to bone and cartilage damage in OA tissue, and in vitro MSC potency was compared with control healthy iliac crest (IC) MSCs. A 1.3- to 2.5-fold SBP thickening was found in both OA talus and tibia, whereas BV/TV changes were depth-dependent. MSCs were abundant in OA talus and tibia, with similar colony characteristics. Tibial and talar MSCs were tripotential, but talar MSCs had 10-fold lower adipogenesis and twofold higher chondrogenesis than IC MSCs (P = .01 for both). Cartilage damage in both OA tibia and talus correlated with SBP thickening and CD271+ MSCs was 1.4- to twofold more concentrated near the SBP. This work shows multipotential MSCs are present in OA talocrural subchondral bone, with their topography suggesting ongoing involvement in SBP thickening. Potentially, biomechanical stimulation could augment the chondrogenic differentiation of MSCs for joint-preserving treatments.     

Subchondral bone response to injected adipose-derived stromal cells for treating osteoarthritis using an experimental rabbit model

Although articular cartilage is the target of osteoarthritis (OA), its deterioration is not always clearly associated with patient symptoms. Because a functional interaction between cartilage and bone is crucial, the pathophysiology of OA and its treatment strategy must focus also on subchondral bone. We investigated whether adipose-derived stromal cells (ASCs) injected into a joint at two different concentrations could prevent subchondral bone damage after the onset of mild OA in a rabbit model. We measured both volumetric and densitometric aspects of bone remodeling. Although OA can stimulate bone remodeling either catabolically or anabolically over time, the accelerated turnover does not allow complete mineralization of new bone and therefore gradually reduces its density. We measured changes in morphometric and densitometric bone parameters using micro-CT analysis and correlated them with the corresponding parameters in cartilage and meniscus. We found that ASCs promoted cartilage repair and helped counteract the accelerated bone turnover that occurs with OA.     

动态观察去卵巢骨质疏松大鼠股骨骨微结构的变化

目的:绝经后骨质疏松是好发于中老年女性人群中的骨代谢疾病,去卵巢骨质疏松大鼠模型是国内外通用的模拟绝经后骨质疏松发生的经典动物模型,本研究通过观察去卵巢骨质疏松大鼠股骨骨微结构的动态变化,为骨质疏松大鼠模型的临床应用提供理论参考依据。方法:将90只3月龄雌性SD大鼠按体重分层后随机分为基础组(10只)、假手术组(40只)和去卵巢组(40只)。分别在手术前(基础组)和后的3、6、12、24周,腹主动脉取血处死基础组以及假手术组和去卵巢组大鼠,每组各8-10只。每组中随机取6只大鼠,对其左股骨行micro-CT扫描及三维结构重建。选择股骨远端距生长板远端1 mm处,2.0 mm×3.5 mm,厚0.9 mm的骨组织为感兴趣区域,对感兴趣区域进行骨形态计量学分析。结果:与0周组比较,从去卵巢3周开始一直持续到24周,去卵巢组大鼠股骨vBMD、BV/TV和Tb.N显著降低,Tb.Sp和SMI显著升高,而Tb.Th无显著变化;与0周组比较,从假手术后3周开始一直到24周,假手术组所有检测指标均无显著变化。与同周龄假手术组比较,从去卵巢3周开始一直持续到24周,去卵巢组大鼠股骨Tb.N、BV/TV和vBMD显著降低,Tb.Sp显著升高,而Tb.Th没有显著变化。从去卵巢6周开始一直到24周,去卵巢组大鼠SMI显著增加。结论:3月龄大鼠股骨远端的骨微结构在去卵巢3周时就出现显著变化。提示,采用3月龄大鼠进行抗骨质疏松药物筛选时,去卵巢3周后就可以进行药物处理。     

Sequential Change in T2* Values of Cartilage,Meniscus, and Subchondral Bone Marrow in a Rat Model of Knee Osteoarthritis

Background

There is an emerging interest in using magnetic resonance imaging (MRI) T2* measurement for the evaluation of degenerative cartilage in osteoarthritis (OA). However, relatively few studies have addressed OA-related changes in adjacent knee structures. This study used MRI T2* measurement to investigate sequential changes in knee cartilage, meniscus, and subchondral bone marrow in a rat OA model induced by anterior cruciate ligament transection (ACLX).

Materials and Methods

Eighteen male Sprague Dawley rats were randomly separated into three groups (n = 6 each group). Group 1 was the normal control group. Groups 2 and 3 received ACLX and sham-ACLX, respectively, of the right knee. T2* values were measured in the knee cartilage, the meniscus, and femoral subchondral bone marrow of all rats at 0, 4, 13, and 18 weeks after surgery.

Results

Cartilage T2* values were significantly higher at 4, 13, and 18 weeks postoperatively in rats of the ACLX group than in rats of the control and sham groups (p<0.001). In the ACLX group (compared to the sham and control groups), T2* values increased significantly first in the posterior horn of the medial meniscus at 4 weeks (p = 0.001), then in the anterior horn of the medial meniscus at 13 weeks (p<0.001), and began to increase significantly in the femoral subchondral bone marrow at 13 weeks (p = 0.043).

Conclusion

Quantitative MR T2* measurements of OA-related tissues are feasible. Sequential change in T2* over time in cartilage, meniscus, and subchondral bone marrow were documented. This information could be potentially useful for in vivo monitoring of disease progression.