Extent Of Cartilage Damage Research Articles

Transtibial pullout repair of medial meniscus posterior root tears: effects on the meniscus healing score and ICRS grade among patients with mild osteoarthritis of the knee.

To assess the effects of transtibial pullout repair for medial meniscus posterior root tears (MMPRTs) among patients with early osteoarthritis of the knee as measured by the meniscus healing score and to determine whether the meniscus healing score correlates with the International Cartilage Repair Society (ICRS) grade progression. Forty-seven patients with mild osteoarthritic knees (Kellgren-Lawrence grade ≤ 2 and varus alignment < 5°) who underwent transtibial pullout repair less than 3months after MMPRT onset were assessed. The association between meniscus healing scores at 1year postoperatively and cartilage damage of the medial compartment (medial femoral condyle [MFC] and medial tibial plateau [MTP]) were evaluated. The MFC was divided into six zones (A to F) and the MTP into two zones (G and H). The mean ICRS grade for each zone was compared between the primary surgery and second-look arthroscopy. The correlation between cartilage damage and meniscus healing status at the time of second-look arthroscopy in each zone was analysed. The mean time interval from injury to surgery was 63days, and all clinical scores showed significant improvement. There were no significant differences in the extent of cartilage damage in areas B, C, E, or F (n.s.) for MFC or in areas G and H (n.s.) for MTP. The meniscus healing score and cartilage damage were correlated in the loading areas (B, C, E, and H; - 0.53, - 0.45, - 0.33, and - 0.38, respectively; p < 0.05). Transtibial pullout repair of MMPRTs among patients with mild osteoarthritic knees improved the clinical outcomes and showed a negative correlation between high meniscus healing scores and ICRS grades in the medial compartment loading area. This study suggests that early surgery should be undertaken for patients with mild osteoarthritic knee who develop MMPRTs. Level IV.

Bone marrow lesions in knee osteoarthritis: regional differences in tibial subchondral bone microstructure and their association with cartilage degeneration

The aim of this study was to investigate how bone microstructure within bone marrow lesions (BMLs) relates to the bone and cartilage across the whole human tibial plateau. Thirty-two tibial plateaus from patients with osteoarthritis (OA) at total knee arthroplasty and eleven age-matched non-OA controls, were scanned exvivo by MRI to identify BMLs and by micro CT to quantitate the subchondral (plate and trabecular) bone microstructure. For cartilage evaluation, specimens were processed histologically. BMLs were detected in 75% of the OA samples (OA-BML), located predominantly in the anterior-medial (AM) region. In contrast to non-OA control and OA-no BML, in OA-BML differences in microstructure were significantly more evident between subregions. In OA-BML, the AM region contained the most prominent structural alterations. Between-group comparisons showed that the AM region of the OA-BML group had significantly higher histological degeneration (OARSI grade) (P<.0001, P<.05), thicker subchondral plate (P<.05, P<.05), trabeculae that are more anisotropic (P<.0001, P<.05), well connected (P<.05, P=n.s), and more plate-like (P<0.05, P<0.05), compared to controls and OA-no BML at this site. Compared to controls, OA-no BML had significantly higher OARSI grade (P<.0001), and lower trabecular number (P<.05). In established knee OA, both the extent of cartilage damage and microstructural degeneration of the subchondral bone were dependent on the presence of a BML. In OA-no BML, bone microstructural alterations are consistent with a bone attrition phase of the disease. Thus, the use of BMLs as MRI image-based biomarkers appear to inform on the degenerative state within the osteochondral unit.

Outcomes of hip arthroscopy for femoroacetabular impingement: The effect of morphological type and chondrolabral damage.

Introduction: Hip arthroscopy for treatment of femoroacetabular impingement (FAI) has shown significant pain and functional improvement. However, the differential outcome of each of the FAI morphological types in contrast to one another remains largely unknown. This study was conducted to detect a possible difference in outcome among different FAI types treated using hip arthroscopy. Methods: In this prospective non randomized comparative study, after exclusion of non-FAI cases and cases with advanced arthritic changes, 90 hips in 85 patients that had hip arthroscopy for the treatment of FAI between 2011 and 2015 in our center were analyzed. The collected patient reported outcome measures (PROMs) included visual analog scale (VAS) of pain, the modified Harris hip score (mHHS), and the non arthritic hip score (NAHS) both preoperatively and at final follow-up. Patient satisfaction was collected at final follow-up. Postoperative PROMs were subjected to three main comparisons based on each of FAI type, labral procedure, and extent of cartilage damage. Repeat comparison based on FAI type after matching of exact chondrolabral condition was also attempted. Results: Mean follow-up was 32.8 months (five patients lost from follow-up). There was a significant improvement in the overall PROMs. This improvement was significantly higher in the cam group in contrast to the mixed group. After matching for chondrolabral condition, this difference was consistent and more evident. Discussion: The outcome of arthroscopic treatment of pure cam FAI is significantly better than that of mixed FAI. Matching of the same chondrolabral condition and repeating the comparison yields similar results.

Deletion of 12/15-lipoxygenase accelerates the development of aging-associated and instability-induced osteoarthritis.

12/15-Lipoxygenase (12/15-LOX) catalyzes the generation of various anti-inflammatory lipid mediators, and has been implicated in several inflammatory and degenerative diseases. However, there is currently no evidence that 12/15-LOX has a role in osteoarthritis (OA). The aim of this study was to investigate the role of 12/15-LOX in the pathogenesis of OA. The development of aging-associated and destabilization of the medial meniscus (DMM)-induced OA were compared in 12/15-LOX-deficient (12/15-LOX-/-) and wild-type (WT) mice. The extent of cartilage damage was evaluated by histology. The expression of OA markers was evaluated by immunohistochemistry and RT-PCR. Cartilage explants were stimulated with IL-1α in the absence or presence of the 12/15-LOX metabolites, 15-hydroxyeicosatetraenoic acids (15-HETE), 13-hydroxyoctadecadienoic acid (13-HODE) or lipoxin A4 (LXA4), and the levels of matrix metalloproteinases-13 (MMP-13), Nitric oxide (NO) and prostaglandin E2 (PGE2) were determined. The effect of LXA4 on the progression of OA was evaluated in wild type (WT) mice. The expression of 12/15-LOX in cartilage increased during the progression of DMM-induced OA and with aging in WT mice. Cartilage degeneration was more severe in 12/15-LOX-/- mice compared to WT mice in both models of OA, and this was associated with increased expression of MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs, aggrecanases (ADAMTS5), inducible NO synthases (iNOS), and mPGES-1. Treatment of cartilage explants with 12/15-LOX metabolites, suppressed IL-1α-induced production of MMP-13, NO and PGE2, with LXA4 being the most potent. Intra-peritoneal injection of LXA4 reduced the severity of DMM-induced cartilage degradation. These data suggest an important role of 12/15-LOX in the pathogenesis of OA. They also suggest that activation of this pathway may provide a novel strategy for prevention and treatment of OA.

Cartilage status in FAI patients - results from the Danish Hip Arthroscopy Registry (DHAR).

Introduction: The femoroacetabular impingement (FAI) morphology is associated with specific cartilage lesions, which are suspected to be early stages of the osteoarthritic development, which can be the end result of FAI. The cartilage status of FAI afflicted hip joints at the time of arthroscopic management is not fully elucidated. This study from the Danish Hip Arthroscopy Registry (DHAR) will try to show data on the cartilage status from a large cohort. Data from a national registry potentially represent large amounts of population-based epidemiological information from multiple centres and surgeons. Therefore, outcome data might be more reliable for a specific surgical intervention. Methods: This study includes patients operated for symptomatic FAI from January 2012 until December 31st 2013, with a minimum of two-year follow-up and being registered in DHAR. The extent of cartilage damage at the time of surgery is reported and the Patient Related Outcome Measures (PROM) outcome data are presented. Results: Data from a total of 686 FAI procedures in 1082 patients from January 2012 until December 31st 2013 were extracted from DHAR. Cartilage injuries were found in 88% of cases, mainly on the acetabular side. Overall PROM including pain scores improved significantly from preoperative status to follow-up one and two years postoperatively. The Copenhagen Hip and Groin Outcome Score (HAGOS), Hip Sports Activity Scale (HSAS) and global hip function showed less improvements in patients with more severe acetabular cartilage injury. Discussion: The majority of patients with femoroacetabular impingement (FAI) undergoing hip arthroscopy have significant cartilage changes at the time of surgery primarily at the acetabulum and to a lesser degree at the femoral head. During FAI surgery the majority of patients have cartilage debridement performed but rarely cartilage repair. The presence of severe cartilage injury at the time of arthroscopic FAI surgery results in reduced subjective outcome and hip function.

Cartilage damage and bone erosion are more prominent determinants of functional impairment in longstanding experimental arthritis than synovial inflammation.

ABSTRACTChronic inflammation of articular joints causing bone and cartilage destruction consequently leads to functional impairment or loss of mobility in affected joints from individuals affected by rheumatoid arthritis (RA). Even successful treatment with complete resolution of synovial inflammatory processes does not lead to full reversal of joint functionality, pointing to the crucial contribution of irreversibly damaged structural components, such as bone and cartilage, to restricted joint mobility. In this context, we investigated the impact of the distinct components, including synovial inflammation, bone erosion or cartilage damage, as well as the effect of blocking tumor necrosis factor (TNF) on functional impairment in human-TNF transgenic (hTNFtg) mice, a chronic inflammatory erosive animal model of RA. We determined CatWalk-assisted gait profiles as objective quantitative measurements of functional impairment. We first determined body-weight-independent gait parameters, including maximum intensity, print length, print width and print area in wild-type mice. We observed early changes in those gait parameters in hTNFtg mice at week 5 – the first clinical signs of arthritis. Moreover, we found further gait changes during chronic disease development, indicating progressive functional impairment in hTNFtg mice. By investigating the association of gait parameters with inflammation-mediated joint pathologies at different time points of the disease course, we found a relationship between gait parameters and the extent of cartilage damage and bone erosions, but not with the extent of synovitis in this chronic model. Next, we observed a significant improvement of functional impairment upon blocking TNF, even at progressed stages of disease. However, blocking TNF did not restore full functionality owing to remaining subclinical inflammation and structural microdamage. In conclusion, CatWalk gait analysis provides a useful tool for quantitative assessment of functional impairment in inflammatory destructive arthritis. Our findings indicate that cartilage damage and bone erosion, but not synovial inflammation, are the most important determinants for progressive functional impairment in this chronic erosive arthritis model.

Successful Total Meniscus Reconstruction Using a Novel Fiber-Reinforced Scaffold

Background: Meniscus injuries in the United States result in an estimated 850,000 surgical procedures each year. Although meniscectomies are the most commonly performed orthopaedic surgery, little advancement has been made in meniscus replacement and regeneration, and there is currently no total meniscus replacement device approved by the Food and Drug Administration. Hypothesis: A novel fiber-reinforced meniscus scaffold can be used as a functional total meniscus replacement. Study Design: Controlled laboratory study. Methods: A tyrosine-derived, polymer fiber–reinforced collagen sponge meniscus scaffold was evaluated mechanically (tensile and compressive testing) and histologically after 16 and 32 weeks of implantation in an ovine total meniscectomy model (N = 20; 16 implants plus 4 meniscectomies, divided equally over the 2 time periods). The extent of cartilage damage was also measured on tibial plateaus by use of toluidine blue surface staining and on femoral condyles by use of Mankin scores on histological slides. Results: Scaffolds induced formation of neomeniscus tissue that remained intact and functional, with breaking loads approximating 250 N at both 16 and 32 weeks compared with 552 N for native menisci. Tensile stiffness values (99 and 74 N/mm at 16 and 32 weeks, respectively) were also comparable with those of the native meniscus (147 N/mm). The compressive modulus of the neomeniscus tissue (0.33 MPa at both 16 and 32 weeks) was significantly increased compared with unimplanted (time 0) scaffolds (0.15 MPa). There was histological evidence of extensive tissue ingrowth and extracellular matrix deposition, with immunohistochemical evidence of types I and II collagen. Based on significantly decreased surface damage scores as well as Mankin scores, the scaffold implants provided greater protection of articular cartilage compared with the untreated total meniscectomy. Conclusion: This novel fiber-reinforced meniscus scaffold can act as a functional meniscus replacement, with mechanical properties similar to those of the native meniscus, while protecting the articular cartilage of the knee from the extensive damage after a total meniscectomy. Clinical Relevance: This meniscus replacement scaffold has the potential to improve surgical treatment and provide better long-term outcomes for those suffering from severe meniscus damage.

Attenuation of cartilage pathogenesis in post-traumatic osteoarthritis (PTOA) in mice by blocking the stromal derived factor 1 receptor (CXCR4) with the specific inhibitor, AMD3100.

SDF-1 was found to infiltrate cartilage, decrease proteoglycan content, and increase MMP-13 activity after joint trauma. In this study, we tested the hypothesis that interference of the SDF-1/CXCR4 signaling pathway via AMD3100 can attenuate pathogenesis in a mouse model of PTOA. We also tested the predictive and confirmatory power of fluorescence molecular tomography (FMT) for cartilage assessment. AMD3100 was continuously delivered via mini-osmotic pumps. The extent of cartilage damage after AMD3100 or PBS treatment was assessed by histological analysis 2 months after PTOA was induced by surgical destabilization of the medial meniscus (DMM). Biochemical markers of PTOA were assessed via immunohistochemistry and in vivo fluorescence molecular tomography (FMT). Regression analysis was used to validate the predictive power of FMT measurements. Safranin-O staining revealed significant PTOA damage in the DMM/PBS mice, while the DMM/AMD3100 treated mice showed a significantly reduced response with minimal pathology. Immunohistochemistry showed that AMD3100 treatment markedly reduced typical PTOA marker expression in chondrocytes. FMT measurements showed decreased cathepsins and MMP activity in knee joints after treatment. The results demonstrate that AMD3100 treatment attenuates PTOA. AMD3100 may provide a viable and expedient option for PTOA therapy given the drug's FDA approval and well-known safety profile.

Patellofemoral Osteochondral Allograft Transplantation

Patellofemoral (PF) cartilage defects are common. They may result from instability, incongruity between the patella and trochlea, repetitive overload (microtrauma), or direct impact (macrotrauma). If exhaustive conservative management fails to resolve symptoms of disabling anterior knee pain with activities of daily living, surgical treatment may be considered. There are 3 main indications for osteochondral allograft transplantation: cartilage defects that are associated with extensive abnormalities of the subchondral bone or frank bone loss that are expected to compromise surface procedures such as autologous chondrocyte implantation; cartilage defects that are associated with severe trochlear dysplasia; and PF osteoarthritis in young patients who are not candidates for arthroplasty. Osteochondral allograft transplantation is performed using 1 of the 2 following techniques, depending on the location and extent of cartilage damage being addressed. The dowel or press-fit technique utilizes a cylindrical reamer and coring reamer system to fashion a dowel and recipient site with a diameter ranging from 15-35 mm. The shell technique is an alternative, which addresses very large defects in which the chondral defect area is removed along with bone with a saw using the same plane(s) as for prosthetic resurfacing (total knee arthroplasty or PF arthroplasty). Careful assessment of PF kinematics and anatomy (or pathokinematics and pathoantatomy) are the key to optimizing success. In light of these factors, associated procedures (such as tibial tuberosity osteotomies, medial PF ligament reconstruction, or lateral retinacular lengthening) are very common in PF cartilage repair, especially with bipolar grafts. With attention to detail and technique, successful outcomes may be achieved in many patients.

Inhibition of asporin signaling is critical in the prevention of cartilage damage by physiotherapies

Purpose. Physiotherapies are the most frequently recommended non-invasive treatment options recommended for arthritic diseases. Here, we examined the signaling pathways responsible for the beneficial effects of exercise on various stages of monoiodoacetate-induced arthritis (MIA). We demonstrate that both success and failure of the physiotherapy is mediated via discrete signaling pathways involving Asporin, a susceptibility gene in osteoarthritis (OA). Asporin-mediated regulation of matrix synthesis in turn may regulate Transforming Growth Factor-β (TGF-β) networks essential for cartilage matrix synthesis. Methods. Treadmill walking (TW), used as a means of exposing MIA afflicted knees to physiotherapy, was initiated in rats at different stages of MIA induced cartilage damage and compared to unexercised MIA afflicted knees. TW started at 1 day post-MIA induction, or after cartilage damage had progressed to Grade I or Grade II. The cartilage specimens were analyzed by macroscopic, microscopic, μCT imaging, transcriptome-wide gene expression analysis and activation/suppression of signaling networks. Data was further analyzed by Ingenuity Pathways Analysis to construct molecular functional networks and signaling pathways to dissect pathways regulated by exercise. One-way ANOVA and a post hoc Tukey test were used for statistical analysis. Results. Treadmill walking immediately following initiation of MIA (1 day post-MIA induction) demonstrated a significant prevention of MIA progression. However, the efficacy of this intervention was significantly reduced when implemented on knees showing close to Grade I or greater cartilage damage. On the contrary, TW accelerated damage in the knees with close to Grade II cartilage pathologies. Transcriptome-wide gene expression analysis revealed that exercise intervention started 1-day post-MIA inception significantly suppressed signaling networks that inhibit matrix synthesis. In parallel, TW upregulated gene networks associated with matrix synthesis. However, TW intervention following Grade I damage was less effective in preventing cartilage damage and regulating matrix synthesis. Interestingly, Asporin and networks associated with TGF-β expression and signaling were the major gene products that were regulated by TW to control matrix synthesis (Aggrecan, Collagen type II, Matrilin, FRZB, Col 9A2 and Col9A3) and prevent cartilage damage as evident by microscopic grading of cartilage. Conclusions. The findings demonstrate that Asporin might be one of the critical genes controlled by TW, that in turn controls expression of TGF-β family of molecules, essential for cartilage matrix synthesis. The findings underscore the importance of physiotherapies by showing suppression of Asporin, an OA susceptibility gene by TW. Nevertheless, the extent of cartilage damage at the initiation of physiotherapy is an important determinant for the effectiveness of TW.

Assessment of treatment of Osteochondrosis dissecans (OCD) of shoulder joint in dogs-the results of two years of experience

Osteochondrosis is a common and clinically important joint disorder that occurs in human and many species of animals such as pigs, horses and dogs. The aim of this article is to present the results of conservative and surgical treatment of Osteochondrosis dissecans (OCD) and to compare the recovery time in relation to race, age and extent of cartilage damage. The study was performed on 36 dogs of both sexes, aged from 4 to 24 months, weighing 12-70 kg, of different breeds (predisposed and non-specific for this disease). All patients underwent clinical, orthopedic and radiological examination through which the location of OCD changes in the shoulder joint and the degree of this problem were established. Based on the examinations the patients were qualified for particular treatment procedures. Control tests were performed after 14, 30 and 60 days, which allowed for a precise evaluation of the progress of therapy. Achieved results indicate that dogs age and the lesions extent in the shoulder joint have an impact on the outcome of treatment. Studies showed that the best therapeutic effects were obtained in dogs aged 6-10 months, which underwent surgery. The study proved that the early diagnosis of OCD strongly influence the recovery rate and may inhibit the development of degenerative changes in the joint (DJD).

Transcriptome-wide gene regulation by gentle treadmill walking during the progression of monoiodoacetate-induced arthritis

Physiotherapies are the most widely recommended conservative treatment for arthritic diseases. The present study was undertaken to examine the molecular mechanisms underlying the effects of gentle treadmill walking (GTW) on various stages of monoiodoacetate-induced arthritis (MIA) to elucidate the basis for the success or failure of such therapies in joint damage. Knees were obtained from untreated control rats, rats with MIA that did not undergo GTW, rats with MIA in which GTW regimens were started 1 day post-MIA induction, and rats with MIA in which GTW regimens were started after cartilage damage had progressed to grade 1 or grade 2. The cartilage was examined macroscopically, microscopically, and by microfocal computed tomography imaging. Transcriptome-wide gene expression analysis was performed, and microarray data were assessed by Ingenuity Pathways Analysis to identify molecular functional networks regulated by GTW. GTW intervention started on day 1 post-MIA induction significantly prevented the progression of MIA, but its efficacy was reduced when implemented on knees exhibiting close to grade 1 cartilage damage. GTW accelerated cartilage damage in knees with close to grade 2 damage. Transcriptome-wide gene expression analysis revealed that GTW intervention started 1 day post-MIA inception significantly suppressed inflammation-associated genes and up-regulated matrix-associated gene networks. However, delayed GTW intervention after grade 1 damage had occurred was less effective in suppressing proinflammatory genes or up-regulating matrix synthesis. The present findings suggest that GTW suppresses proinflammatory gene networks and up-regulates matrix synthesis to prevent progression of cartilage damage in MIA-affected knees. However, the extent of cartilage damage at the initiation of GTW may be an important determinant of the success or failure of such therapies.

Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover

Traumatic osteoarthritis (OA) is possibly augmented by effects from loss of sex hormones. Salmon calcitonin is shown to reduce OA pathogenesis and bone resorption. We investigated the effects of oral salmon calcitonin treatment and ovariectomy on cartilage and bone pathology in a traumatic OA model. Six groups with 10 7-month-old female Sprague Dawley rats each were subjected to bilateral meniscectomy (MNX), ovariectomy (OVX) or Sham surgery and treated for 8 weeks with oral salmon calcitonin (CT) or vehicle (V) in the following way: (1) Sham+V; (2) MNX+V; (3) MNX+CT; (4) OVX+V; (5) MNX/OVX+V; (6) MNX/OVX+CT. Weights were recorded weekly and CTX-II was measured in serum. At termination 56 days post-surgery, the right tibia was analyzed for changes in articular cartilage thickness, extent of cartilage damage and subchondral bone changes in predefined zones, as recommended in the novel OARSI histopathology score. The combined MNX/OVX model produced a significantly reduced cartilage thickness (P=0.033) in the outer zone (Z1) of the tibial plateau and increased calcified cartilage damage (P=0.0004) and serum CTX-II (P=0.003). Addition of OVX to MNX significantly increased the width of matrix damage at the surface (P=0.025) and 50% cartilage depth (P=0.004). Treatment with oral salmon calcitonin counteracted the loss of cartilage thickness (P=0.055), significantly reduced subchondral bone damage score (P=0.019) and reduced the type II collagen degradation (P=0.009). Addition of ovariectomy augmented site-specific traumatic OA pathology, which was reduced by oral salmon calcitonin treatment. Treatments for OA might ideally affect both bone and cartilage.

Inverse relationship between matrix remodeling and lipid metabolism during osteoarthritis progression in the STR/ORT mouse

The biologic changes associated with osteoarthritis (OA) are incompletely understood. The aim of this study was to elucidate the molecular mechanisms underlying OA progression in an STR/Ort murine model of spontaneous disease. Global patterns of gene expression were assessed using microarray analysis of articular cartilage/subchondral bone from the tibial plateaus of STR/Ort mice at 3, 9, and 12 months of age. The age-dependent severity of osteophyte formation and extent of cartilage damage were determined in the corresponding femurs using microfocal computed tomography and the Mankin histologic scoring system. Pathway analysis was used to identify the functions of genes associated with OA progression, and changes in gene expression were confirmed using immunohistochemistry. Six hundred twenty-one genes were associated with both osteophyte formation and cartilage damage in the STR/Ort joints. Genes involved in the development/function of connective tissue and in lipid metabolism were most significantly enriched and regulated during disease progression. Genes directly interacting with peroxisome proliferator-activated receptor alpha (PPARalpha)/PPARgamma were down-regulated, whereas those genes involved with connective tissue remodeling were up-regulated during disease progression. Associations of down-regulation of myotubularin-related phosphatase 1 (a phosphoinositide 3-phosphatase involved in lipid signaling) and up-regulation of biglycan (a member of the small leucine-rich protein family known to modulate osteoblast differentiation and matrix mineralization) with OA progression were confirmed by immunohistochemistry. Since adipogenesis and osteogenesis are inversely related in the developing skeletal tissue, these results suggest that a shift in the differentiation of mesenchymal cells from adipogenesis toward osteogenesis is a component of the OA pathophysiologic processes occurring in the tibial plateau joints of STR/Ort mice.

Effects of knee injection on skeletal muscle metabolism and contractile force in rats

We tested the hypothesis that intrusion of the knee joint capsule alters quadriceps muscle metabolism and function independently from the damage induced to knee cartilage. Adult rats were separated into four groups: intraarticular injections of saline (SAL; n=9); intraarticular injections of papain, a model for osteoarthritis (PIA; n=7); sham injections (SHAM; n=8); and controls (CTL; n=5). 31P magnetic resonance spectroscopy (31P-MRS) was performed after 2 weeks. Spectra were obtained from the left quadriceps: two at baseline, eight during electrical stimulation with simultaneous measurement of contractile force, and 15 during recovery. 31P-MRS data were presented as the ratio of inorganic phosphate (Pi) to phosphocreatine (PCr), concentrations of PCr [PCr], intramuscular pH, and the rates and time constants of PCr breakdown during stimulation and PCr recovery. Intramuscular cytokine concentrations were measured within the quadriceps. Histologic slides of the knees were scored for severity of cartilage damage. The interventional groups produced values of Pi/PCr ratio, [PCr], contractile force and pH that were significantly different from CTL. These changes in muscle function were accompanied by higher concentrations of interleukin-1 observed with PIA and SAL. We did not observe any effect of cartilage damage on muscle function or metabolism. Knee joint intrusion alters quadriceps muscle metabolism with accelerated depletion of energy stores and fatigue during stimulation. This study demonstrates that needle intrusion into the knee joint results in muscle dysfunction, independently from the extent of cartilage damage.

Is pro-matrix metalloproteinase-3 a marker for posttraumatic cartilage degradation?

Objective: Since the development of posttraumatic osteoarthritis (OA) is a relatively slow process, estimation of OA risk would be of value with regard to chondroprotective measures and medication. In this study we investigated the significance of pro-matrixmetalloproteinase-3 (proMMP-3) for this purpose. Design: Synovial fluid (SF) and serum samples were collected from 259 patients of our trauma clinic at the time of arthroscopy. The extent of cartilage damage was assessed according to the Outerbridge-score. ProMMP-3 levels in SF and serum were determined by enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody. Additionally we determined SF and serum levels of total MMP-3 and COMP levels as well as TIMP-1 and -2 concentrations in 40 randomly selected patients by ELISA. Results: Serum proMMP-3 levels of the total cohort were markedly increased compared to healthy controls ( P<0.007). The comparison of serum and SF lavage proMMP-3 concentrations showed a significant correlation (r s=0.41, P<0.0001), however, only 26% of the investigated samples were increased above normal ranges. The grade of cartilage damage did not correlate with enzyme concentration neither in patients' serum nor in SF samples. ProMMP-3 SF concentration was increased early after trauma. Furthermore, proMMP-3 correlated significantly with total MMP-3 serum and SF levels as well as COMP SF levels. Conclusions: The measurement of proMMP-3 in serum or SF did not reflect the present cartilage damage and thus appears to have only minor potential for clinical use, but it should be considered for longitudinal studies, since it may reflect a risk for cartilage degradation in a subset of patients.

Intra-articular treatment of osteoarthritis of the knee: an arthroscopic and clinical comparison between sodium hyaluronate (500-730 kDa) and methylprednisolone acetate

Corticosteroids have long represented the drugs of choice for intra-articular treatment of osteoarthritis (OA), but their use has drawbacks, indicating the need for alternatives devoid of these effects. This comparative study examined the clinical efficacy and the structural effects of intra-articular injections of sodium hyaluronate (HA) of molecular weight (MW) 500–730 kDa (one injection weekly for 5 weeks) versus methylprednisolone acetate (MP) (one injection weekly for 3 weeks) in the treatment knee OA. We studied 99 patients with knee OA, primary or secondary to a traumatic event, classified according to criteria of the American College of Rheumatology. Pain assessments by VAS and arthroscopic examinations of synovial membrane and cartilage were performed at baseline and 180 days after the start of the treatment. Arthroscopic features were evaluated under blind conditions. Initially, MP showed a more immediate beneficial clinical effect in reducing pain than HA, but after 180 days the symptomatic effect of HA was more long lasting than that of MP. Arthroscopic findings at day 180, in comparison with baseline conditions, showed that both drugs were decreased synovial membrane inflammation but HA was superior to MP in reducing the grade and extent of cartilage damage. HA of 500–730 kDa represents a valid alternative to corticosteroids in the intra-articular treatment of OA with a beneficial effect on the structural alterations. This study supports previous data on a potential structure-modifying activity of HA in OA of the knee.