Cartilage Thinning Research Articles

Articular cartilage with intra and extrafibrillar waters – Simulations of mechanical and chemical loadings by the finite element method

In line with previous constitutive developments, a three-phase multi-species electro-chemo-mechanical model of articular cartilage that accounts for the effect of two water compartments is pursued. Here, a finite element formulation is presented in order to solve initial and boundary value problems and to simulate the time and space heterogenous fields generated by mechanical and chemical loadings in laboratory samples. The formulation capitalizes upon (1) the chemo-mechanical model in Loret and Simões [B. Loret, F.M.F. Simões, Articular cartilage with intra- and extra-fibrillar waters. A chemo-mechanical model, Mech. Mater. 36 (5–6) (2004) 515–541; B. Loret, F.M.F. Simões, Mechanical effects of ionic replacements in articular cartilage. I. The constitutive model, Biomech. Model. Mechanobiol. 4 (2–3) (2005) 63–80; Mechanical effects of ionic replacements in articular cartilage. II. Simulations of successive substitutions of NaCl and CaCl 2 , Biomech. Model. Mechanobiol. 4 (2–3) (2005) 81–99] which was restricted to successive equilibria, and from which both time and space were excluded; and (2) the model in Loret and Simões [B. Loret, F.M.F. Simões, Articular cartilage with intra- and extra-fibrillar waters. Mass transfer and generalized diffusion, Eur. J. Mech.-A/Solids 26 (1995) 759–788], where the equations of mass transfer between the two fluid phases and the generalized diffusion equations in the extrafibrillar phase have been established. A thin cartilage layer, laterally confined, is loaded through time varying mechanical and chemical conditions applied on the lower and upper boundaries. Two types of chemical loadings are simulated. First the concentration of NaCl in the bath in contact with the cartilage is changed according to several time schemes, including in particular free swelling and cyclic changes. A more complex process consists in replacing NaCl by CaCl 2 . Chemical loading gives rise to heterogeneous fields during a transient period, whose extend depends on geometry and on a number of characteristic material properties, e.g. Darcy’s seepage time, Fick’s diffusion time, and typical times for intercompartmental mass transfer. Mechanical confined compression and swelling tests are simulated as well. Spatial profiles of the various chemical species and mechanical, chemical and electrical entities highlight the influences of the existence of two water compartments. At steady state, the strains, stresses, pressures and the distribution of water and ions in the two compartments obtained in Loret and Simões [B. Loret, F.M.F. Simões, Articular cartilage with intra- and extra-fibrillar waters. A chemo-mechanical model, Mech. Mater. 36 (5–6) (2004) 515–541; B. Loret, F.M.F. Simões, Mechanical effects of ionic replacements in articular cartilage. I. The constitutive model, Biomech. Model. Mechanobiol. 4 (2–3) (2005) 63–80; Mechanical effects of ionic replacements in articular cartilage. II. Simulations of successive substitutions of NaCl and CaCl 2 , Biomech. Model. Mechanobiol. 4 (2–3) (2005) 81–99] are recovered.

Large Osteochondral Fractures of the Lateral Femoral Condyle in the Adolescent: Outcome of Bioabsorbable Pin Fixation

Large osteochondral fractures of the lateral femoral condyle of the knee in adolescent patients can be diagnostically and therapeutically challenging. Historically, management has involved removal of the fragment, leaving a large area of bone devoid of articular cartilage on the weight-bearing surface of the lateral femoral condyle. This study assessed open reduction and internal fixation of the osteochondral fragments with use of multiple polyglycolic acid rods. Eight patients, between twelve and fifteen years old, with a large (>4 cm(2)) osteochondral fracture of the lateral femoral condyle were treated with open reduction and internal fixation with use of multiple polyglycolic acid rods. Each patient was evaluated at more than five years (a mean of nine years) after the index procedure with a clinical assessment, during which the knee was scored according to the International Knee Documentation Committee and Cincinnati knee rating systems, plain radiographs were made, and magnetic resonance imaging scans were acquired. The majority of patients scored well on both knee rating systems, with no poor results. Five of the eight patients had normal findings on knee radiographs, and three had radiographs that showed minor changes. Magnetic resonance imaging scans of all patients demonstrated intact articular cartilage in the lateral compartment with no area of full-thickness articular cartilage loss. No evidence of articular cartilage thinning was seen in two knees; a small area of <2 cm(2) of cartilage thinning, in four; a moderate area of 2.7 cm(2) of cartilage thinning, in one; and a large area of 11.2 cm(2) of abnormal cartilage signal, in one knee. Osteochondral fracture of the lateral femoral condyle is an injury to which adolescents with ligamentous laxity of the knee are prone. Our results show that internal fixation of these osteochondral fragments with bioabsorbable implants is possible and is a worthwhile option.

Cartilage ‘shoe’: a new technique for stabilisation of titanium total ossicular replacement prosthesis at centre of stapes footplate

After tympanoplasty using a total ossicular replacement prosthesis, many unsatisfactory hearing results are due to dislocation of the prosthesis. We developed a cartilage guide for stabilising the total ossicular replacement prosthesis in the oval window niche. An oval-shaped piece of cartilage measuring 2.5 x 3.5 mm with a central hole was precisely punched out of a thin cartilage plate. The cartilage was placed in the oval niche, and its hole centred the prosthesis on the stapes footplate. Hearing results in 52 patients confirmed acoustically the effectiveness of this method of total ossicular replacement prosthesis stabilisation on the stapes footplate. Subsequent 'second-look' surgery revealed stable ingrowth of the cartilage 'shoe' into the oval niche. Such a cartilage shoe might address one of the causes of unsatisfactory hearing following ossicular chain reconstruction with a total ossicular replacement prosthesis.

Experimental and clinical studies on the relevance of proton spin tomography in patients with coxarthrosis

We examined 2 in formalin fixed hip specimens from a corpse, 27 patients with coxarthrosis and 3 healthy young volunteers with MRT concerning the illustration of the hip joint and pathological changes by coxarthrosis. Specimen of the femoral head after endoprosthetic operation could be achieved in 18 cases for comparison with MRT. All pathological alterations as cartilage alterations, sclerosis, cysts, effusion, edema, fibrosis were figured with high sensitivity. Cartilage was figured much better by gradient echo sequence with short echo time than by spin echo sequence. Gradient echo sequence made it possible to figure and quantify thinning of cartilage with high sensitivity. Both sequences showed artefacts because of the chemical shift in the area of the cartilage-bone boundary, which impaired especially the judgement of cartilage by spin echo sequence. Gradient echo sequence allowed because of the phase-contrast effect the distinction of hematopoietic and fatty bone marrow and possibly the delineation of bone marrow edema.

Chondrolysis after partial lateral meniscectomy in athletes

Rapid chondrolysis after partial arthroscopic lateral meniscectomy has been seldom reported in literature. Considering the relatively high number of partial lateral meniscectomy performed, we cannot understand why this complication is so rare. The purpose of this paper is to report a series of athletes developing a chondrolysis associated with posterolateral corner laxity after a partial lateral meniscectomy and attempt to hypothesize the pathogenesis of this devastating complication. Five male professional soccer players of Italian championship with a mean age of 26.8 years underwent a partial lateral meniscectomy because of a traumatic lateral meniscus tear. Patients showed a slight varus knee and there were clinical signs compatible with a meniscal tear. No other pathological sign were found. An MRI scan confirmed these findings. After surgery patients were unable to resume sport activities because of swelling and knee pain during training sessions. At a mean time of 8 months (range 6-12 months) from surgery patients were re-examined and a new MRI scan was performed. Clinical examination revealed a slight swelling of the knee and signs of posterolateral corner laxity. MRI scan revealed intra-articular fluid and pathological findings of knee posterolateral corner associated with a thinning of the articular cartilage. Arthroscopy showed free cartilagineous debris floating into the knee and a high grade of cartilage damage on the lateral compartment. The evaluation of lateral compartment, ruled-out a new tear of the meniscal remnant and showed a positive drive-trough sign with knee in the Fig. 4 positioning. All patients had an open re-tensioning of the posterior meniscofemoral capsule, and in one case, an augmentation of the popliteal tendon using a free semi-tendinous graft was also done. This surgery gave a complete resolution of symptoms and patients resumed sports activities without any restriction after a period between 4 and 5 months. Based on this experience we hypothesize that partial lateral meniscectomy may have a role in causing a subtle rotatory instability that combined with high stress of sports activity can dramatically increase the susceptibility of joint to chondrolysis, Varus knee seems to be a possible predisposing factor. Open surgery addressing the insufficiency of lateral or posterolateral corner has been found to be effective in improving knee function and resolve patients symptoms at a short-term follow-up.

Fibular Collateral Ligament–Biceps Femoris Calcific Bursitis Causing Flexion Contracture in the Knee, External Rotation in the Leg, and Equinus Deformity in the Ankle

Objective The fibular collateral ligament (FCL)–biceps femoris (BF) bursa is not a commonly known location for calcific bursitis. A case of FCL-BF calcific bursitis is presented. Clinical Features An 18-year-old man had a blunt trauma on the lateral side of his right knee approximately 1 year before his examination. The pain and physical distortion developed in the trauma region over time. Physical examination revealed a 30° flexion contracture and slight valgus deformity in the right knee. There was 30° of external rotation in the leg and a 15° equinus deformity in the ankle. The patient had toe-toe gait. There was a tender swelling 3 × 4 cm in size on the posterolateral aspect of the right knee. Intervention and Outcome Plain radiography and computed tomography revealed a calcific mass, approximately 1.5 × 4 cm in size, between soft tissues adjacent to the posterolateral side of the right lateral femoral condyle. There were articular cartilage thinning and joint space narrowing at the lateral site of the knee joint, and magnetic resonance imaging showed bone marrow edema at the lateral condyles of the tibia and femur. The enlarged calcified bursa was excised. A segment of the contracted iliotibial tract was excised, and a fractional lengthening was performed on the BF tendon. Conclusion This case report revealed that calcific bursitis can occur in the FCL-BF bursa, which may lead to complications when neglected.

The effectiveness of diagnostic imaging methods for the assessment of soft tissue and articular disorders of the shoulder and elbow

There are no clear guidelines for diagnostic imaging of articular and soft tissue pathologies of the shoulder and elbow. Several methods are used, including magnetic resonance imaging (MRI), magnetic resonance arthrography (MRA) and ultrasound (US). Their cost-effectiveness is still unclear.We performed a meta-analysis of the relevant literature and discussed the role of MR imaging of the shoulder and elbow compared with other diagnostic imaging modalities.For the shoulder impingement syndrome and rotator cuff tears, MRI and US have a comparable accuracy for detection of full-thickness rotator cuff tears. MRA and US might be more accurate for the detection of partial-thickness tears than MRI. Given the large difference in cost of MR and US, ultrasound may be the most cost-effective diagnostic method for identification of full-thickness tears in a specialist hospital setting (Evidence level 3).Both MRA and CT arthrography (CTA) are effective methods for the detection of labrum tears. More recently, multidetector CTA has offered the advantages of thinner slices than with MRA in a shorter examination time. Still, MRA has the advantage towards CTA to directly visualize the affected structures with a better evaluation of extent and location and to detect associated capsuloligamentous injuries.For the elbow pathologies, plain MRI or MRA have the advantage towards CTA to detect occult bone injuries. CTA is better for the assessment of the thin cartilage of the elbow. Both US and MRI are reliable methods to detect chronic epicondylitis; US is more available and far more cost-effective (Evidence level 2). MRA can differentiate complete from partial tears of the medial collateral ligament. US or MRI can detect partial and complete biceps tendon tears and/or bursitis. MRI can provide important diagnostic information in lesions of the ulnar, radial, or median nerve.

Collagen IX-deficiency seriously compromises growth cartilage development in mice

For a large part, skeletal development, growth, and repair occur by endochondral ossification which comprises an orderly sequence of consecutive steps of proliferation and late differentiation of chondrocytes. After vascular invasion into hypertrophic cartilage, the tissue is remodelled into bone. At all stages, the process is under tight environmental control exerted by a combination of regulators, including nutritional supply and signalling through growth factors, hormones, and cell-matrix-interactions. Therefore, genetic elimination of collagen IX, a stabilizing component of the periphery of thin cartilage fibrils, is expected to compromise extracellular matrix properties and, hence, the chondrocyte environment required for normal cartilage development and homeostasis. Here, we have shown that growth plate cartilage morphology is markedly disturbed in mice lacking collagen IX. Abnormalities were most prominent in late proliferative, pre-hypertrophic, and hypertrophic zones whereas resting and early proliferative zones were less affected. In central epiphyseal regions of long bones, newborn animals show grossly abnormal areas with strongly reduced cell numbers, irregular distribution of glycosaminoglycans in the extracellular matrix, and a profoundly disturbed columnar arrangement of chondrocytes with an irregular β 1 integrin immunostaining. As a result, all long bones are shorter and broader in newborn Col9a1−/− mice. Remarkably, these abnormalities are attenuated in adult mice, but the number of cells per area still is too low due to reduced cell proliferation.

Premorbid knee osteoarthritis is not characterised by diffuse thinness: the Framingham Osteoarthritis Study

Objective:It is hypothesised that, like low bone density and fracture, thin cartilage predisposes to osteoarthritis (OA). Inferences about the effects of cartilage thickness on the development of OA can be...

Delayed gadolinium enhanced MRI of cartilage (dGEMRIC) of the first carpometacarpal (1CMC) joint: a feasibility study

The first carpometacarpal (1CMC) joint, at the base of the thumb, is a common site for symptomatic and radiographic osteoarthritis (OA) among the elderly 1–4. OA in the 1CMC joint can be particularly debilitating because it is associated with a decrease in pincer grip strength and limits activities such as writing and handling small objects 4. Currently, the diagnosis and staging of 1CMC OA is based on physical signs and symptoms and radiographic evidence of reactive bone changes 5. A deeper appreciation of OA etiology and progression in the 1CMC joint is currently limited by a lack of markers sensitive to early intraarticular degenerative changes, particularly those that are radiographically occult, that can be used to quantitatively assess disease status and therapeutic efficacy. The dGEMRIC (delayed Gadolinium Enhanced MRI of Cartilage) technique has previously been used in the knee and hip as a non-invasive method to evaluate one aspect of cartilage biochemical status, that of the spatial distribution of cartilage glycosaminoglycan (GAG) concentration 6–10, but has never been applied to the thin cartilage in the hand. This study found dGEMRIC evaluation of the 1CMC joint is technically feasible and demonstrates differences between cartilage in asymptomatic and OA joints, potentially providing an objective measure of disease progression and a means for better understanding biochemical changes which might precede cartilage destruction.

80 THERAPEUTIC EFFECTS OF FIBROBLAST GROWTH FACTOR-18 IN A RAT MODEL OF ESTABLISHED OSTEOARTHRITIS

79 – Knee cartilage morphology in various species and humans Species Number Cartilage surface area Cartilage thickness Cartilage volume Rat 16 6.2±0.9 mm2 0.14±0.12 mm 0.81±0.17 mm3 Rabbit 6 69±4.9 mm2 0.37±0.05 mm 23.5±3.9 mm3 Cat 3 85±9.1 mm2 0.67±0.05 mm 55.8±10.5 mm3 Dog 18 196±18 mm2 0.77±0.04 mm 142±15 mm3 Pig 1 1650 mm2 1.4 mm 2200 mm3 Horse 1 2390 mm2 1.4 mm 3290 mm3 Rhinoceros 1 5460 mm2 1.8 mm 9840 mm3 Human (Women) 45 1050±135 mm2 1.9±0.23 mm 1940±344 mm3 Human (Men) 72 1380±205 mm2 2.2±0.26 mm 2940±622 mm3 with those in a data base of young (18 to 35 years) healthy humans (45 women, weight 60 ± 7 kg, and 72 men, weight 77 ± 11 kg) who had been imaged at 1.5T. Sagittal spoiled gradient echo sequences with fat suppression or water excitations were acquired in all knees. The medial tibial cartilage was segmented by tracing the cartilage surface (AC) and subchondral bone area (tAB) throughout the entire medial tibia. The size of the cartilage surface areas (AC), the mean cartilage thickness (ThC) and the cartilage volume (VC) were computed using Chondrometrics software (Ainring, Germany). Results: The size of the cartilage surface areas in the rat (6.2 mm2) was approximately 200x smaller than that in humans (Table 1), whereas that in the rhinoceros was about 4.5 x larger than than in humans. The variability of cartilage thickness between the species, however, was substantially less than for cartilage surface areas. All species (including the rhinoceros: ThC = 1.8 mm) had thinner cartilage than humans (1.9 mm in women and 2.2 mm in men, respectively). The rat displayed the lowest mean cartialge thickness (0.14 mm) amongst the species investigated. Conclusions: To our knowledge these are the first quantitative data on the three-dimensional morphology of tibial cartilage in different species and humans. The data show that the interspecies differences in cartilage surface areas are much more prominent than those in cartilage thickness. This is likely due to the need to keep mechanical stresses (load/area) below a critical threshold at which the cartilage will undergo damage. These data can be used to estimate the appropriate dose of intra-articular medication with potentially beneficial structural or symptomatic effects on articular cartilage in animal models of OA.

The Pathophysiology and Clinical Management of Degenerative Joint Disease

Degenerative joint disease is a common and important disease that affects humans as well as domestic animals, especially dogs and cats. The etiological factors for the disease in humans and animals are similar. The disease is characterized by progressive deterioration of the joint, thinning of hyaline cartilage, joint effusion and periarticular osteophyte formation. Trauma, sepsis, prolonged immobilization, immune-mediated disease, congenital malarticulation (e.g. hip dysplasia or developmental diseases (e.g. osteochondrosis), may incite the development of degenerative joint disease. The insults stimulate the release of degenerative enzymes from chondrocytes and these destroy the articular cartilage matrix. Two distinct functional processes in injured chondrocytes are responsible for the positive feed-back cascade that ultimately results in joint destruction. The catabolic process is induced by proinflammatory stimuli and causes secretion of protease inhibitors and cell replication. In the recent past, a lot of basic and clinical research on degenerative joint disease has been conducted. Deeper understanding of the pathophysiology has resulted in the development of new treatment modalities for the disease. Practicing clinicians need to keep abreast with new knowledge and biomedical technology in order to manage their patients in the best way possible. This paper collates the current knowledge of the pathophysiology and clinical management of degenerative joint disease with special reference to the canine patient. The Kenya Veterinarian Vol. 28 2005: pp. 33-36

A quantitative study of humeral cartilage in individuals with spinal cord injury

Cross-sectional design. In this in vivo study, we investigated the influence of different load situations on humeral cartilage thickness in individuals with paraplegia and quadriplegia. ETH Zurich and Swiss Paraplegic Centre Nottwil, Switzerland. A previously validated three-dimensional (3D) gradient echo MRI-sequence with selective water excitation was used. Three groups were compared: individuals with paraplegia with high shoulder demand (n=11), individuals with quadriplegia with reduced load on the shoulder joint (n=8) and a control group (n=9). After 3D reconstruction, the mean cartilage thickness, local thicknesses (superior, medial, inferior) and the minimum joint space were calculated. The mean humeral cartilage thickness (1.40+/-0.14 mm) as well as the minimum joint space (2.57+/-0.50 mm) did not differ between groups. In individuals with paraplegia, the superior cartilage thickness was significantly greater than in individuals with quadriplegia (1.47 mm compared to 1.28 mm, P<0.05). In the control group, there was a significant negative correlation between mean cartilage thickness and age (r=-0.81). Neither higher shoulder demand nor reduced shoulder loading leads to thinning of humeral cartilage. It is hypothesized that higher local stresses prevent local cartilage degeneration, as in normal load situations humeral cartilage thinning is occurring with age. Furthermore, joint space narrowing was only associated with inferior cartilage thickness and cartilage thickness is not related to shoulder pain.

Characterisation of mineralisation of bone and cartilage: X-ray diffraction and Ca and Sr Kα X-ray fluorescence microscopy

Bone is a dynamic structure, constantly remodelling in response to changing mechanical and environmental factors. This is particularly evident in the mineral component encrusting the collagenous framework. The mineral is principally in the form of calcium apatite, but calcium can exchange with strontium, both during the cellular processes of mineralisation and resorption and by passive exchange with the deposited crystals. Mineralisation is generally characterized by densitometry, but because of the differences in absorption cross sections of calcium and strontium it can be misleading in studies of composition. In this work we have used X-ray diffraction to identify calcium and strontium apatite and X-ray fluorescence to quantify strontium and calcium distribution. With the beam characteristics available from synchrotron radiation, this has enabled us to obtain microscopic resolution on thin sections of bone and cartilage from the equine metacarpophalangeal joint. Two issues have been investigated; the first is the distribution of mineral in the bone–cartilage interface and within individual trabeculae. In trabecular bone the ratio of strontium to calcium concentration was typically 0.0035±0.0020, and higher by a factor of ∼3 at the periphery than in the centre of a trabeculum (possibly reflecting the more rapid turnover of mineral in the surface layer). In the dense subchondral bone the ratio was similar, approximately doubling in the calcified cartilage. The second objective was to explore the changes in mineralisation associated with development of osteoarthrosis. We analysed lesions showing cartilage thinning and changes in the trabecular organization and density of the underlying bone. At the centre of the lesion the ratio of strontium to calcium was much lower than that in normal tissue, although the calcified cartilage still showed a higher ratio than the underlying bone. In the superficially normal tissue around the lesion the calcified cartilage returned to a normal ratio much more rapidly than the underlying bone. These data demonstrate the complex relationship between changes in cartilage and the underlying bone.

Prevalence of labral tears and cartilage loss in patients with mechanical symptoms of the hip: evaluation using MR arthrography

To determine the prevalence of labral tears and cartilage lesions in patients with mechanical symptoms of the hip using magnetic resonance (MR) arthrography. A total of 100 patients with mechanical symptoms of the hip such as pain, clicking, locking and giving way underwent MR arthrography of the hip to rule out a labral tear. Hip joints were evaluated for labral alterations, bone marrow edema (BME), and other pathology using a novel semi-quantitative scoring system. Cartilage changes were graded separately for the acetabulum and femoral head in the anterior, posterior, central, medial, and lateral hip joint regions (10 locations) on a 6-point scale: 0=normal; 1=signal heterogeneity; 2=fissuring, 3=thinning <50% of the normal thickness; 4=thinning >50% of the normal thickness; 5=full thickness cartilage loss. Labral tears were categorized into normal, intrasubstance degeneration, simple tear or complex tear with two or more tear regions. Statistical methods were contingency tables, Fisher's exact test for discrete outcomes (based on grade scores), Spearman's rank correlation (r) and t tests for continuous outcomes, using pooled and stratified analyses. On MR arthrography, labral tears were found in 66 patients (66% prevalence) with 13 having more than one location involved. Locations were 19 lateral (13 simple, six complex), 54 anterior (39 simple, 15 complex), eight posterior (six simple, two complex). Cartilage lesions were found in 76 patients (76% prevalence) with 53 demonstrating involvement of more than one compartment. The most common finding was cartilage thinning <50% in 99 regions in 44 patients. Cartilage thinning >50% was shown in 34 patients in 67 areas. When we correlated the grade of cartilage abnormality with the grade of labral tear, we found a statistically significant correlation (r=0.29; P< or =0.01). The size of cartilage abnormality was correlated with the grade of labral tear in the lateral acetabulum (r=0.38; P<0.001), anterior acetabulum (r=0.22; P< or =0.002), and lateral femoral head (r=0.29; P< or =0.004). The grade of cartilage loss was correlated with the grade of BME (r=0.44; P< or =0.001). Labral tears and cartilage loss are common in patients with mechanical symptoms in the hip. Cartilage loss, labral tears and BME appear interrelated and may represent important risk factors that may affect the development and progression of osteoarthritis in the hip joint.

US findings of metacarpophalangeal joints in children with idiopathic juvenile arthritis

Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in children, with frequent involvement of the metacarpophalangeal joints (MCPJ). To compare US findings with those of radiography and clinical examination. All MCPJs in 20 children with JIA (17 females, median age 9.7 years, range 3.6 to 16.8 years) were evaluated clinically and imaged with gray-scale and color Doppler US, and 90 MCPJs were also imaged radiographically. Each MCPJ was graded on physical examination from 0 (normal) to 4 (severe) by the patient's rheumatologist. US demonstrated abnormalities in 64 of 200 MCPJs (32.0%), including pannus vascularity and/or tenosynovitis in 55 joints (27.5%) (pannus vascularity in 43, tenosynovitis in 40) and bone destruction in 25 joints (12.5%). Overall, US abnormalities and physical examination scores were significantly associated (P < 0.001). However, interobserver agreement between US and clinical evaluation was poor (kappa 0.1) and between US and radiography was only fair (kappa 0.4). US of the MCPJ in children with JIA can demonstrate cartilage thinning, bone erosions, and pannus vascularity. Abnormal US findings are significantly correlated with severity of disease as evaluated clinically.

Quantitative Analysis of Local Changes in Patellar Cartilage in Spinal Cord Injured Subjects

Most studies investigating articular cartilage changes use global parameters and neglect the large topological variation in the response of cartilage to immobilization and remobilization. We hypothesized a registration-based semi-automatic segmentation method would be highly reproducible to detect local changes in patellar articular cartilage thickness. We also hypothesized thinning of the cartilage is detectable in the smaller subregions of the patella in patients with a spinal cord injury (SCI) and the use of difference maps would allow us to detect early local thinning of the patellar cartilage. To determine the reproducibility, magnetic resonance images of the knee of seven healthy volunteers were acquired four times. Longitudinal changes were measured in the knees of seven patients with SCI as soon as possible, 6 months, and 12 months after the injury. Thickness maps and morphologic parameters for the cartilage of the patella and the four sub-regions were computed. The individual difference maps of 43% of the patients showed local areas of substantial thinning 6 and 12 months after injury.

Women have thinner cartilage and smaller joint surfaces than men after adjustment for body height and weight

Females have a higher incidence of knee osteoarthritis (OA) than males, but the reason for this is unclear. Here we examine the hypothesis that women have smaller joint surfaces than men, independent of weight and height, and thus encounter higher articular pressures that might contribute to the higher incidence of OA in the female knee. Forty healthy women and 57 men (21-39 years) with a body mass index of 16.8-32.8 were studied using magnetic resonance imaging. The right knee was scanned and proprietary software was used to determine the area of subchondral bone (cAB), mean cartilage thickness (ThC) and cartilage volume (VC) for all knee cartilage plates. Multilinear regression was used to correct the data for sex differences in height and weight. cAB, ThC, and VC were larger in men than in women in all knee cartilage plates. Correction for height and weight differences between the sexes reduced but did not eliminate sex differences in these parameters. The cAB was a strong predictor of VC independent of sex, height and weight, but did not predict ThC. Men have greater knee cABs, ThC and VC than females even after correction for height and weight. Nonetheless, estimated tibial and patellar pressures are similar between sexes and thus are unlikely to account for the sex differences in OA incidence.

Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: Increased expression of ATF-3 and pharmacological characterisation

Intra-articular injection of mono-iodoacetate (MIA) in the rat knee joint induces a histopathology with similarities to osteoarthritis (OA). Typically, a synovitis (days 1–3) is observed followed by thinning of articular cartilage and subsequent lesion of subchondral bone at days 8–14 onwards. Behaviourally, weight-bearing asymmetry is observed, which is sensitive to anti-inflammatory pharmacology at early but not later (days 14+) time points. As subchondral bone is densely innervated, an intriguing possibility is that focal bone pathology may cause neuropathy in this model. In male Wistar rats, activating transcription factor (ATF)-3-immunofluorescence was used as a marker of nerve injury in lumber (L)4 and L5 dorsal root ganglia of the ipsilateral knee. Significantly increased ATF-3-immunoreactivity following MIA treatment was measured in L5 on days 8 and 14 ( P < 0.05, Kruskal–Wallis and Mann–Whitney U-test), compared to saline controls. Furthermore, in an additional study animals were orally dosed vehicle (5 ml/kg), naproxen (0.3–10 mg/kg), celecoxib (1–10 mg/kg), amitriptyline (3–30 mg/kg) and gabapentin (10–100 mg/kg) and evaluated for weight-bearing asymmetry on days 14, 21 and 28 post-MIA. Significant resolution of weight-bearing was observed at high and intermediate doses of amitriptyline and gabapentin at all time points ( P < 0.05, ANOVA, post-hoc Bonferroni’s, vs pre-dose measurements). Transient and weak effects were observed with naproxen (10 mg/kg) on days 14 and 28, whereas celecoxib showed no significant effects. Collectively, these data suggest that this putative model of OA is associated with an early phase neuropathy in the L5 innervation territory of the knee.

Safety of, and biological and functional response to, a novel metallic implant for the management of focal full‐thickness cartilage defects: Preliminary assessment in an animal model out to 1 year

Focal full-thickness cartilage lesions of the human medial femoral condyle (MFC) can cause pain and functional impairment. Affected middle-aged patients respond unpredictably to existing treatments and knee arthroplasty may be required, prompting risk of revision. This study assesses the safety of, and biological and functional response to, a metallic resurfacing implant which may delay or obviate the need for traditional arthroplasty. The anatomic contour of the surgically exposed MFC of six adult goats was digitally mapped and an 11 mm diameter full-thickness osteochondral defect was created. An anchor-based Co-Cr resurfacing implant, matching the mapped articular contour, was implanted. Each goat's contralateral unoperated femorotibial joint was used as a control. Postoperative outcome was assessed by lameness examination, radiography, arthroscopy, synoviocentesis, necropsy, and histology up to 26 (n = 3) or 52 (n = 3) weeks. By postoperative week (POW) 4, goats demonstrated normal range of motion, no joint effusion, and only mild lameness in the operated limb. By POW 26 the animals were sound with only occasional very mild lameness. Arthroscopy at POW 14 revealed moderate synovial inflammation and a chondral membrane extending centrally across the implant surface. Radiographs at POWs 14 to 52 implied implant stability in the operated joints, as well as subchondral bone remodeling and mild exostosis formation in the operated and contralateral unoperated joints of some goats. By POW 26, histology revealed new trabecular bone abutting the implant. At POWs 26 and 52 MFC cartilage was metachromatic and intact in the operated and unoperated femorotibial joints. Proximal tibiae of some operated and unoperated limbs demonstrated limited subchondral bone remodeling and foci of articular cartilage fibrillation and thinning. The chondral membrane crossing the prosthesis possessed a metachromatic matrix containing singular and clustered chondrocytes. Our data imply the safety, biocompatibility, and functionality of the implant. Focal articular damage was documented in the operated joints at POWs 26 and 52, but lesions were much reduced over those previously reported in untreated defects. Expanded animal or preclinical human studies are justified.