Subchondral Bone Plate Thickness Research Articles

Thickening of subchondral bone is regionalised by loading of damaged articular cartilage and contra-lateral changes are linked to gait modification

Introduction: Thickening of subchondral bone (SCB) is an important hallmark of osteoarthritis (OA). The changes in subchondral bone that occur during OA have been investigated in animal models, including the mouse, however, their relationship to articular cartilage degeneration and the resultant modification in mechanical joint loading have yet to be fully determined. We have therefore used a non-surgical mouse model of mechanical knee joint trauma in which localised cartilage lesions develop in the lateral femur. In this study we defined changes in the SCB and epiphyseal trabecular bone in mouse knees loaded for different periods of time. In addition, changes in contra-lateral nonloaded joints were also analysed to determine whether they represent appropriate controls for such studies. Methods: Eight week-old male CBA mice were loaded non-invasively with different regimes: controls (n1⁄44), once loaded with 2weeks of habitual use (n1⁄47), 2weeks loaded (n1⁄48) or 5weeks loaded (n1⁄43). Joints were analysed with micro-CT (Skyscan, Belgium) and analysed using Dataviewer (for appropriate orientation) and CTAn (Skyscan). Hand-drawn regions of interest (ROIs) were defined including the lateral and medial compartments of femur and tibia, with further SCB plate ROIs central regions of the femoral condyles and cranial and caudal ROIs in the lateral femur. Percentage bone volume, trabecular thickness and SMI measurements were analysed. In addition, gait analysis was performed using Digigait system, consisting of videocapture of the paws of the mouse running on a transparent treadmill. Results: No significant differences between left and right limbs were seen in control non-loaded mice. SCB thickness was increased only after 5 weeks of loading when compared to control non-loaded mice, with greatest changes apparent in the lateral femur (control: 0.098 0.005mm, 5weeks: 0.129 0.006mm, p<0.0001). These increases were also significant when contra-lateral joints were used for comparison. Increases in SCB plate thickness were also evident in the lateral compartment of both the femur and tibia of the contralateral limb (left) in response to applied joint loading of the right limb in all loaded groups (vs control). Increases were also evident in the medial femur central regions of the contra-lateral left knee in all loaded groups. Gait analysis revealed that changes from normal gait were induced in the contra-lateral limb by joint loading from the second week after initiation of loading in both mice loaded once or repetitively for 2 weeks. Gait changes were not, however, found in the loaded limb. Discussion: Together these data indicate that prolonged applied joint loading is required to produce increases in the SCB thickness and that these are most marked in the lateral femur, sites of articular cartilage lesions. We also showed that SCB is sensitive to changes in gait particularly in the contralateral limb. These data support the hypotheses that concomitant articular cartilage damage aggravates focal SCB thickening induced by applied loading and, that changes in gait produce corresponding generalised, non-focal, increases in SCB thickness in contralateral joints. It is also tempting to conclude that contra-lateral joints do not necessarily provide a useful control in studies into bone changes in mechanicallyinduced models of OA.

Relationship between articular cartilage damage and subchondral bone properties and meniscal ossification in the Dunkin Hartley guinea pig model of osteoarthritis

Objectives: To describe the age-related changes of articular cartilage, subchondral bone morphology, and stiffness. Furthermore, to investigate whether subchondral bone histological and mechanical properties and meniscal histological properties are related to articular cartilage damage in the Dunkin Hartley guinea pig model of osteoarthritis (OA).Methods: Forty male Dunkin Hartley guinea pigs aged 2, 6, 9, and 12 months were studied. The right stifle joints and the left menisci were embedded undecalcified and the tibial articular cartilage and subchondral bone and the menisci were examined using histology. The stiffness of the left tibial subchondral bone was determined with indentation testing.Results: The Osteoarthritis Research Society International (OARSI) grade of the osteoarthritic cartilage lesions of the medial (p < 0.001) and lateral (p < 0.001) condyle and the ossification of the medial (p < 0.001) and lateral (p < 0.001) meniscus increased significantly with age and was significantly more pronounced at the medial condyle than at the lateral condyle. The grade of the osteoarthritic cartilage lesions was significantly correlated (r = 0.78, p < 0.001) with the meniscal ossification, weakly correlated (r = 0.34, p < 0.007) with the subchondral bone plate thickness, and not correlated with the subchondral bone density (r = −0.010, p = 0.94) and the subchondral bone stiffness (r = −0.13, p = 0.30).Conclusion: The meniscal ossification observed in Dunkin Hartley guinea pigs may play an important role in the pathogenesis of OA in these animals.

Cartilage, bone and synovial histomorphometry in animal models of osteoarthritis

This review focuses on histomorphometry for assessing the pathological changes in various compartments of the joint including cartilage, bone and synovium in animal models of osteoarthritis (OA). Different methodological approaches are presented concerning sampling, embedding, sectioning, staining, mounting of stained sections and measurement of histomorphometric parameters using automated and semi-automated methods. Notes are provided describing some methods in greater detail. Histomorphometry allows a significant gain of objectivity, accuracy and reproducibility in the quantification of the main histological parameters which best characterize OA in the affected joint (cartilage thickness (CT), chondrocyte size and density, cartilage fissure, proteoglycan (PG) content, subchondral bone plate thickness (SBPT), thickness of synovial living cell layer) in animal models. Use of histomorphometry could contribute to a better quantification of histological differences between control and OA animals. Contributing also to the introduction of normative data, it is a major advantage for therapeutic assessments in experimental OA and particularly for the analytical comparison of the efficacy of disease modifying OA drugs (DMOAD).

Is there a characteristic distal tarsal subchondral bone plate thickness pattern in horses with no history of hindlimb lameness?

Osteoarthritis (OA) is a common cause of distal tarsal pain, but disease development is poorly understood. Awareness of normal tarsal structure and function is important in order to understand the pathogenesis of OA. Thickening of the subchondral bone (SCB) plate has been related to the development of OA, but SCB plate patterns in the equine tarsus have not been documented. There is a repeatable pattern of SCB thickness across the distal tarsal joints, and specifically that thickness would be greatest dorsally and laterally. Twenty cadaver tarsi were collected from mature horses that had undertaken low-level exercise only with no history of hindlimb lameness. Magnetic resonance images were acquired using a high-resolution sagittal 3-dimensional T1-weighted spoiled gradient echo sequence. Subchondral bone thickness was measured on sagittal images at dorsal and plantar locations on the proximal and distal aspects of the central (CT) and third (T3) tarsal bones and proximal aspect of the third metatarsal bone (Mt3). On the proximal aspect of CT, medial and lateral SCB thickness were significantly greater than midline. On the distal aspect of CT and T3 and proximal Mt3, lateral SCB thickness was significantly greater than medial and midline sites. Dorsal SCB thickness was greatest on the proximal and distal aspects of CT and proximal Mt3. Subchondral bone accounted for a greater proportion of CT and T3 on the dorsal aspect than the plantar. There is a repeatable pattern of SCB thickness in the distal tarsal bones of horses with no history of hindlimb lameness. This reflects the pattern of loading across the joints. This study provides evidence of a consistent osteochondral pattern in the equine tarsus for reference in identification of osteoarticular pathologies.

Micro-CT Arthrographic Analysis of Monosodium Iodoacetate-Induced Osteoarthritis in Rat Knees

Purpose: To evaluate the arthrographic findings of MIA-induced osteoarthritis in rat knees using the micro-CT arthrography. Materials and Methods: Intra-articular monosodium iodoacetate (MIA) injection-induced arthritis was induced in the right knees of twelve rats; their left knees served as the control group. Eight weeks after MIA injection, micro-CT arthrography was performed on each knee. We measured the thickness of retro-patellar cartilages, the distances of tibio-femoral joint space, subchondral bone plate thickness, tibial epiphyseal height, and transverse patellar diameter. Subchondral trabecular bone indices were measured in the tibial lateral condylar epiphysis. The data were analyzed statistically using a paired t-test. Results: The retro-patellar articular cartilage showed thinning on the right side that had been induced to develop osteoarthritis. The right knees showed a significant reduction in the distance of the tibio-femoral joint space, prominent patellar osteophytes, and the resorption of subchondral bone. Among the subchondral trabecular bone indices, percent bone volume, and trabecular thickness was reduced on the right side. Conclusion: The articular cartilage thickness of MIA-induced arthritis model could be measured using micro-CT arthrography. It was possible to evaluate the osteoarthritic findings including the change in subchondral bone plate thickness, osteophyte formation, and subchondral bone resorption, as well as quantitatively analyze the trabecular bone indices.

Increased hydraulic conductance of human articular cartilage and subchondral bone plate with progression of osteoarthritis

Osteoarthritis (OA) is characterized by progressive degeneration of articular cartilage and remodeling of the subchondral bone plate, comprising calcified cartilage and underlying subchondral bone. Calcified cartilage remodeling due to upward invasion by vascular canals or to calcified cartilage erosion may contribute to biomechanical alteration of the osteochondral tissue and its subchondral bone plate component. The study hypothesis was that hydraulic conductance of osteochondral tissue and subchondral bone plate increases with structural changes indicative of increasing stages of OA. Osteochondral cores were harvested from the knees of cadaveric tissue donors and from discarded fragments from patients with OA undergoing knee surgery. The osteochondral cores from tissue donors were macroscopically normal, and the cores from patients with OA had partial-thickness or full-thickness erosion to bone. The cores were perfusion-tested to determine the hydraulic conductance, or ease of fluid flow, in their native state and after enzymatic removal of cartilage. Adjacent portions were analyzed by 3-dimensional histology for calcified cartilage, subchondral bone, and subchondral bone plate thickness and vascular canal density. Hydraulic conductance of native osteochondral tissue and subchondral bone plate was higher (2,700-fold and 3-fold, respectively) in fully eroded samples than in normal samples. The calcified cartilage layer was thicker (1.5-fold) in partially eroded samples than in normal samples but thinner and incomplete in fully eroded samples. Subchondral bone plate vascularity was altered with increasing stages of OA. During joint loading, increased hydraulic conductance of the osteochondral tissue and subchondral bone plate could have deleterious biomechanical consequences for cartilage. Increased fluid exudation from overlying and opposing cartilage, increased fluid depressurization, and increased cartilage tissue strains could lead to chondrocyte death and cartilage damage.

ADAMTS5−/− mice have less subchondral bone changes after induction of osteoarthritis through surgical instability: implications for a link between cartilage and subchondral bone changes

Osteoarthritis (OA) is characterized by damaged articular cartilage and changes in subchondral bone. Previous work demonstrated aggrecanase-2 deficient (ADAMTS5-/-) mice to be protected from cartilage damage induced by joint instability. This study analyzed whether this protective effect on cartilage is also reflected in the subchondral bone structure. Right knee joints from 10-week old male wild type (WT) and ADAMTS5-/- mice received transection of the medial meniscotibial ligament to induce OA, whereas left knees were left unoperated. After 8 weeks knee joints were scanned by micro-CT. The proximal tibia was selected for further analysis. Histology was performed to evaluate cartilage damage and osteoclast presence. ADAMTS5-/- joints had a significantly thinner subchondral plate and less epiphyseal trabecular bone compared to WT joints. Histology confirmed previous findings that ADAMTS5-/- mice have significantly less cartilage damage than WT in the instability-induced OA model. Although the subchondral bone plate became significantly thicker at the medial tibial plateau in operated joints of both genotypes, the percentage increase was significantly smaller in ADAMTS5-/- mice (WT: 20.7+/-4.7%, ADAMTS5-/-: 8.3+/-1.2% compared to the left unoperated control joint). In ADAMTS5-/- animals a significant decrease was found in both Oc.N./BS and Oc.S./BS. Finally, in WT but not in ADAMTS5-/- mice a significant correlation was found between medial subchondral bone plate thickness and cartilage damage at the medial tibial plateau. ADAMTS5-/- joints that were protected from cartilage damage showed minor changes in the subchondral bone structure, in contrast to WT mice where substantial changes were found. This finding suggests links between the process of cartilage damage and subchondral bone changes in instability-induced OA.

Role of subchondral bone in osteoarthritis development: A comparative study of two strains of guinea pigs with and without spontaneously occurring osteoarthritis

To evaluate the relationships among cartilage and subchondral bone before and after the onset of cartilage degeneration in the Hartley guinea pig model of spontaneous osteoarthritis (OA) as compared with those in Weiser-Maple guinea pigs, which do not develop OA. Mice from each strain were used at ages 2, 3, 5, and 8 months (n = 7 at each time point). The region observed was the medial tibial plateau. Cartilage degeneration was evaluated histologically. Subchondral bone structure was evaluated based on subchondral bone plate thickness and subchondral cancellous bone trabecular parameters calculated from the microfocal computed tomography 3-dimensional reconstruction image. The bone mineral density (BMD) of the subchondral cancellous bone as well as levels of urinary N-telopeptide of type I collagen (NTX) and serum osteocalcin (OC) were measured. In Hartley guinea pigs, the number of chondrocytes in the surface layer started to decrease at 3 months. At 8 months, fibrillation expanded to the radial zone. In Weiser-Maple guinea pigs, no cartilage degeneration was noted even at 8 months. Subchondral bone plate thickness was significantly lower in Hartley guinea pigs than in Weiser-Maple guinea pigs at 2 months. The subchondral bone had a rod-like and convex structure at 2 months in Hartley guinea pigs. BMD was significantly lower in Hartley guinea pigs than in Weiser-Maple guinea pigs at 2 months. The serum OC level was significantly higher in Hartley guinea pigs than in Weiser-Maple guinea pigs at 2 months and 3 months, whereas the urinary NTX level was significantly lower in Hartley guinea pigs at 3 months. Subchondral bone is fragile, and bone formation may be promoted in subchondral bone before the onset of cartilage degeneration in Hartley guinea pigs. Subchondral bone may be involved in the development of OA.

Cartilage damage pattern in relation to subchondral plate thickness in a collagenase-induced model of osteoarthritis

To see how initial differences in subchondral bone phenotype influence the development of cartilage damage and changes in subchondral bone architecture in an osteoarthritis (OA)-induced mouse model. Intra-articular collagenase injections (right knee joint) and saline controls (left knee joint) were applied in the knees of two mouse strains known to have either a low or a high bone mass phenotype: the low bone mass C57Bl/6 mice with a thin subchondral bone plate and high bone mass C3H/HeJ mice with a thick subchondral bone plate. The ages of the mice were 16 and 30 weeks, with n=8 per group. The collagenase injection induced an osteoarthritic phenotype that was evaluated 4 weeks later in the tibia using histological analyses and micro-computed tomography (micro-CT). Both strains developed cartilage damage in the collagenase-injected right knee joints to a comparable extent, however, the spatial distribution of cartilage damage differed significantly: C57Bl/6 mice had most damage at the postero-lateral side, whereas in C3H/HeJ mice the postero-medial region was the most affected. Spontaneous cartilage damage was found in the saline-injected left control knees of C57Bl/6 mice, but in C3H/HeJ mice spontaneous cartilage damage was virtually absent. In both strains the subchondral bone plate of collagenase-injected joints became thinner, independent of the site of cartilage damage. TRAP-positive osteoclasts were observed underneath the subchondral bone plate, in line with the observed decreased thickness. No link was found between subchondral bone plate thickness and cartilage damage in the collagenase-injected joints. The subchondral trabecular architecture only changed in the high bone mass C3H/HeJ mice, with thinning of trabeculae and increased trabecular spacing. Thinning of the subchondral bone plate was found as a common observation 4 weeks after OA had been induced in two strains of mice having either a high or low bone phenotype, but no relation was found with the amount of cartilage damage. In addition, this study shows that different strains of mice can react differently to instability-induced OA with respect to the spatial arrangement of cartilage damage and changes in subchondral trabecular structure.

Pulsed electromagnetic fields reduce knee osteoarthritic lesion progression in the aged Dunkin Hartley guinea pig

An experimental in vivo study was performed to test if the effect of Pulsed Electromagnetic Fields (PEMFs) on chondrocyte metabolism and adenosine A2a agonist activity could have a chondroprotective effect on the knee of Dunkin Hartley guinea-pigs of 12 months with spontaneously developed osteoarthritis (OA). After a pilot study, 10 animals were randomly divided into two groups: PEMF-treated group (6 h/day for 3 months) and Sham-treated group. Microradiography and histomorphometry were performed on the entire articular surface of knee joints used in evaluating chondropathy severity, cartilage thickness (CT), cartilage surface Fibrillation Index (FI), subchondral bone plate thickness (SBT) and histomorphometric characteristics of trabecular epiphyseal bone. The PEMF-treated animals showed a significant reduction of chondropathy progression in all knee examined areas ( p < 0.05). CT was significantly higher ( p < 0.001) in the medial tibia plateaus of the PEMF-treated group when compared to the Sham-treated group. The highest value of FI was observed in the medial tibia plateau of the Sham-treated group ( p < 0.05). Significant lower values were observed in SBT of PEMF-treated group in comparison to Sham-treated group in all knee examined areas ( p < 0.05). The present study results show that PEMFs preserve the morphology of articular cartilage and slower the progression of OA lesions in the knee of aged osteoarthritic guinea pigs. The chondroprotective effect of PEMFs was demonstrated not only in the medial tibial plateau but also on the entire articular surface of the knee.

Methods for cartilage and subchondral bone histomorphometry.

This chapter presents the histological assessment of cartilage and bone of tibial plateaus, by procedures that have been applied and validated in two animal models of osteoarthritis: meniscectomized rats and guinea pigs. It starts from bone sampling, followed by all the steps of sample preparation from embedding to sectioning (without prior decalcification), staining, and mounting. Depending on the cartilage or bone components to be visualized, two dyes are described: safranin O and Goldner's trichrome. On these stained sections, various histomorphometric parameters are then quantified using the dedicated programs of an image analyzer. The following parameters are evaluated at the medial side of the tibia and are described at the levels of both cartilage (cartilage thickness, fibrillation index, proteoglycan content ratio based on safranin-O staining intensities and chondrocyte density) and bone (subchondral bone plate thickness).

High-resolution imaging of osteoarthritis using microcomputed tomography.

Three-dimensional imaging of osteoarthritis is so far limited to late stages of the disease. In this chapter we introduce microcomputed tomography (microCT) as a new imaging tool that offers exciting features for diagnosis of earlier disease stages and for disease monitoring. microCT provides spatial resolution better than 100 microm, but the size of the objects that can be scanned is restricted to several centimeters. The strength of X-ray-based techniques like micro CT is the excellent visualization of bone. Therefore, the main application of microCT in osteoarthritis (OA) will be the analysis of bone in small-animal models or of human bone biopsies. As an example, we will exemplarily describe the application of microCT for the examination of knee joints of male STR1N mice. This inbred strain spontaneously develops OA that carries many characteristics of the human disease. With microCT it is possible to monitor the prominent bony alterations such as osteophyte formation, trabecular remodeling, subchondral bone plate thickening, and subchondral sclerosis. We discuss sample preparation, scanning procedures, data processing, and analysis as well as implications and restrictions for in vivo and in vitro applications.

Pathophysiology of osteoarthritis

Osteoarthritis (OA) is characterized by a degeneration of articular cartilage, in which the breakdown leads to matrix fibrillation, fissure appearance, gross ulceration, and fullthickness loss of the joint surface. This is accompanied by hypertrophic bone changes with osteophyte formation and subchondral bone plate thickening. At the clinical stage of the disease, change in the synovial membrane is also found together with an inflammatory reaction. The principal factors described are involved in two of the major tissues (these being the cartilage and the synovial membrane) implicated in the pathophysiology of this disease. Research has also shown that there is some continuity between bone and cartilage changes in OA, suggesting cross-talk between these tissues. Dr Lajeunesse provides a persuasive overview of this theory in his article, demonstrating that this tissue is more intimately related to the progression and/or the onset of OA, rather than being merely a consequence of this disease.

Quantitative assessment of articular cartilage and subchondral bone histology in the meniscectomized guinea pig model of osteoarthritis

Objective: A new image analysis system was employed to quantify the main histological parameters reflecting osteoarthritic features, at the cartilage and bone levels, in the meniscectomized guinea pig model of osteoarthritis (OA). Methods: Meniscectomized (MNX) and sham-operated (SH) guinea pigs were studied 1 and 3 months after partial meniscectomy at the medial side of the left knee ( n=10 to 12 animals/group). The left proximal tibias were included in methylmethacrylate. Sections were cut and stained with safranin O or Goldner trichrome. Parameters were quantified using special programs of a Biocom image analyser. The following parameters were evaluated at the medial side of the tibia: cartilage thickness (CT); fibrillation index (FI); proteoglycan content ratio based on safranin O staining intensities (PC); chondrocyte density (CD); bone volume (BV) and subchondral bone plate thickness (SBPT). The degree of user interaction varied from manually tracing objects to almost complete computer automation. Results: Meniscectomy resulted in significant variations of these reproducible histomorphometric parameters both after 1 month (FI: +522%, P<0.01) and 3 months (FI: +162%, P<0.001; PC: −36.7%, P<0.001; CD: −31.8%, P<0.001; SBPT: +8.7%, P<0.05) post-operation (results expressed as percentage variation of MNX vs SH). The linear correlation analysis including data from SH and/or MNX animals at the two grouped time points revealed significant r values, in particular between cartilage (CT) and subchondral bone parameters (SBPT) (r=−0.41, P<0.01). Conclusions: Contrary to scoring evaluation, this system allowed to show the time-dependent impact of the pathology with an early fibrillation of the medial tibial cartilage appearing as soon as 1 month post-surgery, and the close relationship between bone and cartilage parameters during the progression of OA.

Modification of articular cartilage and subchondral bone pathology in an ovine meniscectomy model of osteoarthritis by avocado and soya unsaponifiables (ASU)

Objective To examine the effect of an oral preparation of avocado and soya unsaponifiables (ASU) on the development of joint pathology in an ovine model of osteoarthritis (OA), using computer-assisted histomorphometric methods.Design OA was induced in ovine knee joints by bilateral lateral meniscectomy (N=32). ASU (900mg/weekday) was given orally to half the group (MenX+ASU), the remainder receiving placebo (MenX). Sixteen animals were used as non-operated controls (NOC). At 3 and 6 months post-meniscectomy, histological sections from the medial and lateral femoral condyles (MFC, LFC), tibial plateaux (MTP, LTP) and trochlear groove (TG) were prepared from all joints. Sections were scored using traditional histopathological scales, and computerized image analysis, measuring total cartilage area, uncalcified cartilage (UCC) and subchondral bone plate (SCP) thickness, and intensity of articular cartilage toluidine blue staining (mean greyscale intensity, black=255) as an index of proteoglycan (PG) content.Results Computerized image analysis showed significant histological differences not detectable by traditional scoring methods. ASU-treated animals at 6 months showed reduced loss of toluidine blue stain in the MTP (P=0.015) and LTP (P=0.001), and significantly greater staining in the TG than either placebo or NOC groups (P=0.011). UCC thickness increased after meniscectomy, but tended to be highest in ASU-treated animals, significantly so in the middle zone of the LFC (MenX+ASU: 1.03±0.21mm vs MenX: 0.79±0.14mm,P =0.018; NOC: 0.77±0.17mm). Lateral compartment SCP thickness increased post-meniscectomy but was increased significantly less in the inner zone of the LTP in ASU-treated sheep (MenX+ASU: 1.37±0.23mm vs MenX: 1.68±0.28mm, P=0.033; NOC=1.22±0.33mm).Conclusions In this model ASU treatment following meniscectomy appeared to confer a subtle but statistically significant protective effect on articular cartilage. Although the drug failed to prevent focal cartilage lesions, characteristic of this model, histomorphometric analysis demonstrated greater PG content and UCC thickness in adjacent joint regions of ASU-treated animals. In addition, a statistically significant reduction of subchondral bone sclerosis was noted in the LTP region of the drug-treated group. An anabolic effect on chondrocytes, resulting in the stimulation of matrix production in regions distant to the insult, was also suggested by the data. These findings support other studies which have proposed that ASU may exhibit disease-modifying anti-OA activity.

Carrageenan-induced arthritis in the rat.

This study documents a model of carrageenan-induced chronic inflammatory arthritis in the rat, using quantitative histomorphometric assessment. Ten Sprague-Dawley female rats were randomly assigned to one of two groups. Arthritis was induced in the right tibiofemoral joint by 7 intra-articular injections of 0.02 mL of 1% carrageenan in the arthritic group over 24 days. The control (normal) group was injected with 0.02 mL of saline in the right tibiofemoral joint. Sagittal sections of the right knee joint (distal femur and proximal tibia) were assessed by histomorphometry using the LECO 2001 image analysis system. Articular cartilage thickness, epiphyseal plate thickness, subchondral bone plate thickness, trabecular bone volume and thickness of the synovial lining cell layer were measured. Differences between normal and arthritic groups were statistically significant for articular cartilage thickness of the femur, epiphyseal plate thickness of both the femur and tibia, subchondral bone plate thickness of the tibia and the thickness of the synovial lining cell layer. These findings demonstrate that carrageenan-induced arthritic changes are similar to other, established models of arthritis in the rat.

Quantitative analysis of the bone-cartilage interface within the knee

Changes in cartilage thickness, calcified cartilage thickness, subchondral bone plate thickness and cartilage vascularity have been proposed as mediators or initiators of degenerative joint disease, but the changes seen in these parameters in normal ageing have not been determined. Image analysis techniques were used to examine these parameters. Cartilage condition deteriorated significantly with age. Cartilage thickness decreased with age, most rapidly in the patella. Subchondral plate thickness was greatest in the medial tibial plateau, and decreased in thickness with age. Calcified cartilage thickness appeared as a constant, showing no regional variation nor any changes with age. This was despite the significant increase in tidemark numbers with age. It is hypothesized that there is an optimum thickness of calcified cartilage, which allows the firm anchoring of collagen fibres within the cartilage matrix without adversely affecting the elasticity of hyaline cartilage.