Cell-free biomimetic osteochondral scaffold for the treatment of knee articular surface lesions: Clinical outcomes differ based on patient and lesion characteristics.

PURPOSE: A cell-free biomimetic osteochondral scaffold was developed to treat cartilage knee lesions, with positive clinical results documented in small case series. However, clear evidence on patient and lesion characteristics that might affect the outcome is still lacking. The aim of this study is to analyse a large cohort of patients treated with this scaffold to investigate factors that could influence the clinical outcome. METHODS: Two hundred and three patients (mean age 30.7 ± 10.9 years) treated with this scaffold were prospectively evaluated at baseline, 6-, 12- and 24-month follow-up. The clinical outcome was analysed using the International Knee Documentation Committee (IKDC) score, and the activity level was assessed with the Tegner score. The influence of patient and lesion characteristics on clinical outcomes was analysed. RESULTS: Mild and severe adverse reactions were found in 39.0% and 1.5% of patients, respectively. The failure rate was 2.0%, increasing to 12.3% when including also clinical failures. The IKDC subjective score increased from 43.3 ± 15.9 to 61.0 ± 16.2 at 6 months, 68.3 ± 18.5 at 12 months and 73.8 ± 18.3 at 24 months (p < 0.0005). The Tegner improved from 2.5 ± 1.7 to 4.2 ± 1.7 at 24 months (p < 0.0005), without reaching the pre-injury level (6.0 ± 2.2) (p < 0.0005). The IKDC objective score changed from 68.5% normal and nearly normal knees before the treatment to 90.1% at 24 months. At 24 months, age showed a correlation with the IKDC subjective score (ρ = -0.247; p < 0.0005), women had a lower score (p < 0.0005), as well as patients with patellar lesions (p = 0.002). Previous surgery correlated with lower results (p = 0.003), while better results were found in osteochondritis dissecans (OCD) compared to degenerative lesions (p = 0.001). CONCLUSION: This cell-free biomimetic scaffold is a safe and effective treatment for cartilage knee lesions, offering positive clinical results at 2 years with a low failure rate. Better outcomes were observed in younger patients, in lesions of the femoral condyles and in OCD, while joints affected by patellar lesions, patients who underwent previous knee surgery, and women may expect lower results. LEVEL OF EVIDENCE: III, Cohort study.

Previous cartilage surgery is associated with inferior patient-reported outcomes after knee arthroplasty.

PURPOSE: The hypothesis of the present study assumed that a history of focal cartilage lesions would not affect Knee Injury and Osteoarthritis Outcome scores (KOOSs) following knee arthroplasty compared to a matched national cohort of knee arthroplasty patients. METHODS: Fifty-eight knee arthroplasty patients with previous surgery for focal cartilage lesions (cartilage cohort) were compared to a matched cohort of 116 knee arthroplasty patients from the Norwegian Arthroplasty Register (control group). Age, sex, primary or revision arthroplasty, type of arthroplasty (total, unicondylar or patellofemoral), year of arthroplasty surgery and arthroplasty brand were used as matching criteria. Demographic data and KOOS were obtained through questionnaires. Regression models were employed to adjust for confounding factors. RESULTS: Mean follow-up post knee arthroplasty surgery was 7.6 years (range 1.2-20.3) in the cartilage cohort and 8.1 (range 1.0-20.9) in the control group. The responding patients were at the time of surgery 54.3 versus 59.0 years in the cartilage and control group, respectively. At follow-up the control group demonstrated higher adjusted Knee Injury and Osteoarthritis Outcome subscores than the previous focal cartilage patients with a mean adjusted difference (95% confidence interval in parentheses): Symptoms 8.4 (0.3, 16.4), Pain 11.8 (2.2, 21.4), Activities of daily living (ADL) 9.3 (-1.2, 18.6), Sport and recreation 8.9 (-1.6, 19.4) and Quality of Life (QoL) 10.6 (0.2, 21.1). The control group also demonstrated higher odds of reaching the patient-acceptable symptom state threshold for the Knee Injury and Osteoarthritis Outcome subscores with odds ratio: Symptoms 2.7 (1.2, 6.4), Pain 3.0 (1.3, 7.0), ADL 2.1 (0.9, 4.6) and QoL 2.4 (1.0, 5.5). CONCLUSION: Previous cartilage surgery was associated with inferior patient-reported outcomes after knee arthroplasty. These patients also exhibited significantly lower odds of reaching the patient-acceptable symptom state threshold for the Knee Injury and Osteoarthritis Outcome subscores. LEVEL OF EVIDENCE: Level III.

Postoperative quadriceps weakness and male sex are risk factors for patellofemoral articular cartilage lesions after anatomical anterior cruciate ligament reconstruction.

PURPOSE: Patellofemoral (PF) compartment cartilage lesions are a frequent problem after anterior cruciate ligament (ACL) reconstruction. This study aimed to determine the factors that influence PF cartilage lesions after anatomical ACL reconstruction. METHODS: This study enrolled a total of 114 patients who did not manifest PF compartment cartilage lesions during anatomical ACL reconstruction and underwent second-look arthroscopy 18 months postoperatively. Arthroscopy using the International Cartilage Repair Society (ICRS) classification was used to assess cartilage lesions. The correlation between surgical findings, radiographic factors, and clinical factors and change of ICRS grade was analysed. Multivariate regression analysis was conducted to reveal the independent risk factors for PF cartilage lesions among patients' demographic data and parameters that correlated with the change of ICRS grade in the correlation analyses. RESULTS: ICRS grade changes in PF cartilage were significantly correlated with age, sex, quadriceps strength at 1 year postoperatively, hamstrings strength at pre- and 1 year postoperatively, and single leg hop test at 1 year postoperatively. However, no significant correlation was found between the time between injury and surgery, posterior tibial slope angle, pre- and postoperative Tegner activity scale, graft type, initial graft tension, meniscus injury, meniscus injury treatment, pre- and postoperative range of motion, anteroposterior laxity and preoperative quadriceps strength, and the change in ICRS grade. Multivariate regression analysis revealed male (P = 0.019) and quadriceps strength weakness at 1 year postoperatively (P = 0.009) as independent risk factors for PF cartilage lesions. CONCLUSIONS: Quadriceps strength weakness 1 year after ACL reconstruction and males were correlated with a new PF cartilage lesion after anatomical ACL reconstruction, with no significant correlation between bone-patellar tendon-bone autograft, initial graft tension, or extension deficit and new PF cartilage lesion. Rehabilitation that focuses on quadriceps strength after ACL reconstruction is recommended to prevent new PF cartilage lesions. LEVEL OF EVIDENCE: Level IV.

Development of new cartilage lesions after ACL reconstruction is associated with abnormal knee rotation.

PURPOSE: The purpose of this study is to examine the association between the development of articular cartilage pathology and knee rotation after single-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: Seventeen patients that underwent single-bundle ACL reconstruction and did not have any cartilage lesions at the time of surgery based on the Outerbridge classification or meniscal injury that required meniscectomy > 20% were examined by MRI and in the biomechanics laboratory at a 6-year minimum follow-up. Cartilage lesions that occurred after reconstruction were graded on MRI according to a modified Noyes scale. For cartilage evaluation, the lateral and medial femoral condyles were divided into 9 segments each (lateral, central, and medial third and each third was divided into anterior, central, and posterior segment). Tibial rotation during a pivoting task was measured with optoelectronic motion analysis system and side-to-side differences of tibial rotation between the reconstructed and contralateral intact knees were calculated. The association between the total modified Noyes scale score (outcome variable) and side-to-side differences of tibial rotation after controlling for meniscectomy and meniscal repair was investigated with hierarchical regression models. RESULTS: Side-to-side difference of tibial rotation was associated with total modified Noyes scale score (p = 0.015, ß = 0.667, adjusted R2 = 42.1%). All patients developed new cartilage lesions in MRI located mainly at the central region of the lateral femoral condyle and less frequently in the central and anterior regions of the medial femoral condyle. CONCLUSION: Abnormally increased tibial rotation that persists after ACL-R is significantly associated with the development of new articular cartilage lesions at mean 8.4 years after reconstruction which were located mainly at the central region of the LFC and secondarily in the central and anterior regions of the MFC (more superficial lesions). These findings suggest that there is emerging evidence that abnormal rotational kinematics is a potential risk factor for the pathogenesis and onset of posttraumatic articular cartilage degeneration after ACLR. LEVEL OF EVIDENCE: IV.

Pathological mechanism of joint destruction in haemophilic arthropathy.

Haemophilic arthropathy (HA), caused by intra-articular haemorrhage, is one of the most common complications in patients with haemophilia. Factor replacement therapy provides missing coagulation factors to prevent children with haemophilia from joint bleeding and decreases their risk for HA. However, haemophilia patients in developing countries are still suffering from HA due to insufficient replacement therapy. Symptoms such as pain and activity limitations caused by HA seriously affect the functional abilities and quality of life of patients with HA, causing a high disability rate in the haemophilia cohort. The pathological mechanism of HA is complicated because the whole pathological mainly involves hypertrophic synovitis, osteopenia, cartilage and bone destruction, and these pathological changes occur in parallel and interact with each other. Inflammation plays an important role in the whole complex pathological process, and iron, cytokines, growth factors and other factors are involved. This review summarizes the pathological mechanism of HA to provide background for clinical and basic research.

Intraosseous injections of platelet rich plasma for knee bone marrow lesions treatment: one year follow-up.

PURPOSE: Cartilage lesions are usually accompanied by subchondral bone alterations or bone marrow lesions (BMLs). BML associated with joint degeneration and cartilage lesions are considered to be predictors of rapidly progressing OA. Currently no existing treatment can fully halt OA progression. One of the approaches is an autologous, biological treatment based on the use of platelet rich plasma (PRP) injections. The purpose of this study is to assess the short-term effectiveness of intraosseous PRP injections, within the BML of individuals affected by OA, in ameliorating pain and improving knee functionality. MATERIALS AND METHODS: The study involved 17 patients with an average age of 41.7 ± 14.3 years old. OA stage was determined using the Kellgren-Lawrence grading system by performing radiographic scanning of the knee joint before surgical intervention. Patients with K-L grade 3 knee joint OA prevailed. Patient OA history varied between one and nine years (average 5.2 ± 4.5 years). Clinical and functional state of the knee were assessed by pain visual analogue scale (VAS) score, the Western Ontario and McMaster Universities Score (WOMAC), and the Knee Injury and Osteoarthritis Outcome Score (KOOS) which were filled out by patients previous to the surgical procedure at one, three, six and 12 months post-operatively. Before surgery, in addition to standard blood tests, serum cartilage oligomeric matrix protein (COMP) levels were tested for all patients. RESULTS: Evaluation of preliminary results revealed a statistically significant reduction of pain based on the VAS score. A significant improvement was also observed in the patients' WOMAC score and in the overall KOOS score. Serum marker levels were initially elevated in our experimental patient group compared to the same marker in healthy control respondents, and continued to rise one month and three months following surgery, at six and 12 month the level was similar as at three months. CONCLUSIONS: In our opinion, first COMP increasing can be caused by injection of platelet rich plasma. It is not adequate to interpret this growth in COMP levels as increased osteochondral degeneration. One year follow-up period showed good quality of life improvement, significant pain reduction, and essential MRI changes. The long-term observation of these cohort of patients combined with an analysis of MRI images is still ongoing.

Osteoarthritis-related nociceptive behaviour following mechanical joint loading correlates with cartilage damage.

OBJECTIVE: In osteoarthritis (OA), the pain-structure relationship remains complex and poorly understood. Here, we used the mechanical joint loading (MJL) model of OA to investigate both knee pathology and nociceptive behaviour. DESIGN: MJL was used to induce OA in the right knees of 12-week-old male C57BL/6 mice (40 cycles, 9N, 3x/week for 2 weeks). Mechanical sensitivity thresholds and weight-bearing ratios were measured before loading and at weeks one, three and six post-loading. At these time points, separate groups of loaded and non-loaded mice (n = 12/group) were sacrificed, joints collected, and fur corticosterone levels measured. µCT analyses of subchondral bone integrity was performed before joint sections were prepared for nerve quantification, cartilage or synovium grading (scoring system from 0 to 6). RESULTS: Loaded mice showed increased mechanical hypersensitivity paired with altered weight-bearing. Initial ipsilateral cartilage lesions 1-week post-loading (1.8 ± 0.4) had worsened at weeks three (3.0 ± 0.6, CI = -1.8-0.6) and six (2.8 ± 0.4, CI = -1.6-0.4). This increase in lesion severity correlated with mechanical hypersensitivity development (correlation; 0.729, P = 0.0071). Loaded mice displayed increased synovitis (3.6 ± 0.5) compared to non-loaded mice (1.5 ± 0.5, CI = -2.2-0.3) 1-week post-loading which returned to normal by weeks three and six. Similarly, corticosterone levels were only increased at week one post-loading (0.21 ± 0.04 ng/mg) compared to non-loaded controls (0.14 ± 0.01 ng/mg, CI = -1.8-0.1). Subchondral bone integrity and nerve volume remained unchanged. CONCLUSIONS: Our data indicates that although the loading induces an initial stress reaction and local inflammation, these processes are not directly responsible for the nociceptive phenotype observed. Instead, MJL-induced allodynia is mainly associated with OA-like progression of cartilage lesions.

Cost-effectiveness analysis of Coblation versus mechanical shaver debridement in patients following knee chondroplasty.

BACKGROUND: To compare costs and outcomes following knee chondroplasty with Coblation versus mechanical shaver debridement (MSD) in patients with grade III articular cartilage lesions of the knee. METHODS: A decision-analytic model was developed to compare costs and outcomes of the two methods from a US payer perspective. We used published clinical data from a single-center randomized clinical trial (RCT) designed to compare outcomes between Coblation and MSD in patients with grade III articular cartilage lesions of the medial femoral condyle. Following primary knee chondroplasty, patients experienced either treatment success (no additional surgery required) or required a revision over the 4 year follow-up period. Costs associated with the initial chondroplasty, physical therapy sessions through the 6 week postoperative period, and revision rates at 4 years post-surgery were estimated using 2018 US Medicare Physician Fee Schedule. Sensitivity analyses including a 10 year time horizon and threshold analyses were performed to test the robustness of the model. RESULTS: The estimated total cost per patient was $4614 and $7886 for Coblation and MSD, respectively, resulting in cost-savings of $3272 in favor of Coblation, making it a dominant strategy because of lower costs and improved clinical outcomes. Threshold analysis showed that Coblation remained dominant even when revision rates were assumed to increase from the base case rate of 14-66%. Sensitivity analyses showed that cost-saving results were insensitive to variations in revision rates, number of physical therapy sessions and the time horizon used. CONCLUSION: Coblation chondroplasty is a cost-saving procedure compared with MSD in the treatment of patients with grade III articular cartilage lesions of the knee.

Post-traumatic Articular Cartilage Lesions Increase at Second-look Arthroscopy Following Primary Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament (ACL) reconstruction (ACLR) after ACL rupture improves the instability of the knee joint and decreases mechanical stress to the meniscus and articular cartilage. However, there are reports that post-traumatic osteoarthritis (PTOA) is observed over time following ACLR. In this study, we assessed changes in cartilage lesions by arthroscopic findings following anatomical double-bundle ACLR and at post-operative second-look arthroscopy about 14 months later. We retrospectively evaluated 37 knees in cases with patients <40 years of age who had undergone an anatomical double-bundle ACL reconstruction <1 year after ACL rupture injury from March 2012 to December 2016. Clinical results and arthroscopic cartilage/meniscal lesion were evaluated and compared between a cartilage lesion-detected group and intact-cartilage group. Surgery improved anteroposterior laxity and other clinical measures; however, cartilage lesions were detected at 11 sites during ACLR and at 54 sites at second-look arthroscopy. The periods from injury to second-look arthroscopy and from ACLR to second-look arthroscopy were significantly longer in the cartilage-lesion group (n=23) than in the intact-cartilage group (n=14). Conversely, 96% of meniscal damage observed during ACLR was cured at the time of second-look arthroscopy. Knee articular cartilage lesions after ACL rupture cannot be completely suppressed, even using the anatomical ACL reconstruction technique. This study suggested that articular cartilage lesions can progress to a level that can be confirmed arthroscopically at approximately 17 months after ACL injury. Therefore, in ACLR patients, the possibility of developing knee articular cartilage lesions and PTOA should be considered.

Anterior cruciate ligament reconstruction performed within 12 months of the index injury is associated with a lower rate of medial meniscus tears.

PURPOSE: To verify the correlation of time to surgery with the prevalence of concomitant intra-articular injuries detected on arthroscopy during anterior cruciate ligament (ACL) reconstruction. METHODS: The medical records of 653 patients who underwent ACL reconstruction surgery were retrospectively analyzed. Univariate and multivariate logistic regression analysis was performed to identify factors that were associated with the presence of at least one intra-articular injury, medial meniscus tears, lateral meniscus tears and chondral injuries at the time of surgery. Further univariate analysis was conducted to determine the earliest time-point for surgery, after which the rate of concomitant injuries was significantly higher. RESULTS: Longer time to surgery (OR 1.019 95% CI 1.010, 1.028, p = 0.000), male sex (OR 1.695 95% CI 1.074, 2.675 p = 0.023), and higher BMI (OR 1.050 95% CI 1.006, 1.097 p = 0.025) were correlated with a higher prevalence of medial meniscus tears. There was an increased prevalence of medial meniscus tears when surgery was carried out more than 12 months after the index injury (OR 2.274 95% CI 1.469, 3.522, p = 0.000). The correlation between longer time to surgery and chondral injuries approached statistical significance (OR 1.006 95% CI 0.999, 1.012, p = 0.073). However, a longer time to surgery was not associated with an increased prevalence of lateral meniscus tears (OR 1.003 95% CI 0.998, 1.009, p = n.s.). CONCLUSIONS: Longer time to surgery is associated with an increased prevalence of medial meniscus tears in ACL reconstruction. Surgery performed within 12 months of the index injury reduces the prevalence of medial meniscus tears. Prioritizing males and overweight patients for counselling and early intervention can be considered. LEVEL OF EVIDENCE: Therapeutic level III retrospective cohort study.

UniCAP offers a long term treatment for middle-aged patients, who are not revised within the first 9 years.

PURPOSE: The aim of this study was to investigate the long-term outcome of the unicompartmental knee resurfacing prosthesis (UniCAP) using clinical and radiographic assessments, and to evaluate the revision and survival rates. METHODS: This was a prospective cohort study of patients with UniCAP prostheses with 6-9 years of follow-up. The clinical examination included the Knee Society Score (KSS) and Visual Analogue Scale (VAS) score. The radiographic examination included the Kellgren-Lawrence (KL) grading scale. A comparison analysis of the clinical preoperative and follow-up data and a Kaplan-Meier survival analysis were performed. RESULTS: Of the 64 UniCAP patients, 36 (56%) were revised and one died. Examinations were performed on 23 (85%) of them. When compared with the preoperative data, the examinations showed a significant increase in the KSS objective [mean = 47.4, standard deviation (SD) = 5.8 vs. mean = 90.0, SD = 6.9] and function (mean = 46.7, SD = 6.8 vs. mean = 91.1, SD = 6.9) scores, a decrease in the VAS-score (mean = 7.3, SD = 0.5 vs. mean = 3.4, SD = 1.4) and a significant increase in the KL medial score (mean = 1.7, SD = 0.6 vs. mean = 2.1, SD = 0.5). The Kaplan-Meier survival rate after 5 years indicated good long-term outcomes. CONCLUSIONS: There was a survival rate of approximately 40% after 9 years of follow-up, but in the group of patients (35-65 years old) not eligible for a final total arthroplasty. These patients were often left with pain and disability. This implant can be a temporary or even long-term treatment because it improved the disability and function over the long-term without a major progression in the osteoarthritis, function or pain. Long term results of this mini-prosthesis have not been previously reported. LEVEL OF EVIDENCE: IV.

No evidence for the most appropriate postoperative rehabilitation protocol following anterior cruciate ligament reconstruction with concomitant articular cartilage lesions: a systematic review.

PURPOSE: Anterior cruciate ligament (ACL) rupture commonly occurs in conjunction with articular cartilage injury. However, there is no consensus on the most appropriate rehabilitation which should be carried out for ACL reconstruction (ACLR) and the surgical management of articular cartilage lesions of the knee. The purpose of this study was to systematically review the literature to investigate the recommended rehabilitation protocol for patients undergoing ACLR with concomitant articular cartilage injury with a view to develop guidelines on the most appropriate treatment. METHODS: Two reviewers independently searched five database for randomised controlled trials (RCTs), non-randomised comparative and retrospective cohort studies (CS) describing the management of concomitant ACL rupture and articular cartilage injury and the postoperative rehabilitation regimen. Risk of bias was performed using a modified Downs & Black's checklist. The primary outcome was specific rehabilitation protocols including weight-bearing status, immobilisation, continuous passive motion (CPM), and return to play criteria. Secondary outcomes included patient-reported outcomes. A best evidence synthesis was performed. RESULTS: The review yielded six studies which reported on rehabilitation techniques. All studies were of low methodological quality. There was considerable variability in not only the chondral lesion reported but also the treatment techniques utilised and especially the rehabilitation regimes. No consensus was found on weight-bearing status, postoperative immobilisation, the use of CPM, or return to play criteria. Given the quality of the papers, there was no evidence to recommend any specific rehabilitation regime in the postoperative management of concomitant ACLR and articular cartilage lesions. CONCLUSION: This systematic review revealed that despite how common concomitant ACL rupture and articular cartilage injury is, there is no evidence to support one, most appropriate rehabilitation protocol. From a clinical perspective, decisions on postoperative rehabilitation for patients undergoing ACLR and treatment of articular cartilage lesions should be made on a case-by-case basis with criteria-based progression until more robust evidence becomes available. A list of specific rehabilitation protocols based on the cartilage restoration technique is provided. LEVEL OF EVIDENCE: IV.

Intraoperative validation of quantitative T2 mapping in patients with articular cartilage lesions of the knee.

OBJECTIVE: The aim of this study was to compare T2 relaxation times of knee cartilage with intraoperative results for the assessment of early osteoarthritis (OA) and to define T2 values for the differentiation between healthy and degenerated cartilage. DESIGN: Twenty-one patients with cartilage lesions or moderate OA were examined using 3T magnetic resonance imaging (MRI). In this prospective study, a total of 882 regions of interest (ROIs) were examined by a sagittal, multi-echo, spin-echo T2 sequence and a morphological high-resolution three-dimensional, fat-saturated proton-density space sequence. Cartilage lesions were identified arthroscopically, graded by the International Cartilage Repair Society (ICRS) score in 42 defined ROIs per patient and consecutively compared with mean T2 values using analysis of variance and Spearman's rank correlation test. Receiver operating characteristics (ROC) curves were developed to identify threshold T2 values to differentiate between the ICRS grades. RESULTS: A total of 882 ROIs were examined and graduated in ICRS score 0 (67.3%), 1 (25.2%), 2 (6.2%) and the merged ICRS 3 and 4 (1.0%). T2 values increased with increasing grade of cartilage damage with a statistically significant positive correlation between T2 values and ICRS scores. A T2 value threshold of 47.6 ms was identified to differentiate between ICRS score 0 (normal) and all other grades (ROC curve analysis). CONCLUSION: T2 mapping might provide a diagnostic tool for the detection of early knee-joint cartilage damage and for the non-invasive differentiation between ICRS grades by MRI in clinical practice.

Identifying Hidden Zones of the Far Posterior Cartilage of the Femoral Condyles Not Visible During Knee Arthroscopy.

OBJECTIVE: The purpose of this study was to compare standard knee arthroscopic and MRI findings and measurements for visualization of the femoral condyle articular cartilage. The hypothesis was that certain posterior cartilage defects identified with MRI may not be accessible with routine arthroscopy. MATERIALS AND METHODS: Six cadaveric knees were examined by routine arthroscopy through standard inferomedial and inferolateral portals. Suture anchors were inserted into the femoral condyles at 30°, 60°, 90°, and 120° of flexion as markers of the cartilage surface at the most posterior aspect of the condyle that could be accessed at each degree of flexion. Each specimen was then examined with 3-T MRI and gross dissection. Measurements were obtained and compared. RESULTS: During arthroscopy at 90° of knee flexion, only 5.83 mm of the medial femoral condyle and 6.83 mm of the lateral femoral condyle were visualized posterior to the anchor placed at 90° of flexion. These arthroscopic measurements were statistically significant underestimates of the actual amount of cartilage identified posterior to the 90° anchor at gross dissection (medial condyle, 44.20 mm; lateral condyle, 37.50 mm) and MRI (medial, 41.33 mm; lateral, 38.87 mm). This indicates that 85.9% of the medial and 81.8% of the lateral posterior articular cartilage of the femoral condyle seen at MRI were not visualized during arthroscopy. CONCLUSION: More than 80% of the articular cartilage proximal to the menisci seen at MRI is not visible during routine arthroscopy. This far posterior articular cartilage should be called the hidden zone.

Celastrol, an NF-κB inhibitor, ameliorates hypercalciuria and articular cartilage lesions in a mouse model of secondary osteoporosis.

Notwithstanding compelling contribution of NF-κB to the progression of osteoporosis has been reported, little is known regarding direct inhibition of NF-κB benefiting osteoporosis. In this study, therefore, we evaluated the role of celastrol, an NF-κB inhibitor, in a mouse model of secondary osteoporosis. Animals were divided into three groups as Sham (control), SO (secondary osteoporosis) and SO + CA (secondary osteoporosis treated with celastrol). Significant decreases in body weight and body fat were observed following celastrol treatment in SO group, but leptin levels were much higher. Celastrol also exhibited a significant decrease in urinary calcium excretion. Moreover, other important events were observed after celastrol treatment, covering substantial decrements in serum concentrations of PTH, TRAP-5b, CTX and DPD, improved structure of articular cartilage and cancellous bone (revealed by H&E and safranin-O staining), and significant decline in levels of NF-κB (P65), MMP-1, and MMP-9. These findings demonstrated that celastrol treatment not only improved abnormal lipid metabolism and hypercalciuria in mice subjected to secondary osteoporosis, but also ameliorated articular cartilage lesions. Our results provided evidence of targeted therapy for NF-κB in the clinical treatment of secondary osteoporosis.

Osteoarthritis in morbidly obese children and adolescents, an age-matched controlled study.

PURPOSE: Main objective of this study was to investigate the association of pain and early cartilage lesions in morbidly obese children and adolescents. METHODS: A total of 57 subjects were included in the study. Morbidly obese patients (n = 39) were subdivided into two groups: Group A: (11 males and 9 females, 14.2 ± 2.7 years) with permanent knee pain; and Group B: (10 males and 9 females, 14.4 ± 2.2 years) without permanent or without any knee pain. Group C (8 males and 10 females, 15.0 ± 2.9 years) included age-matched children and adolescents of normal weight. MRI examinations were performed in all subjects, and an extensive analysis of the images was conducted according to the condition of the cartilage surface and the meniscus. Patients' subjective health was assessed by means of four well-known knee scores (IKDC, KOOS, Tegner/Lysholm, and VAS). Nonparametric Jonckheere-Terpstra test was used to test the trend of the natural order between the three groups. RESULTS: In 38 of 39 morbidly obese children and adolescents, in at least one region of the knee, a marked cartilage lesion could be shown by MRI. Group A showed significantly (p < 0.001) more cartilage lesions (mean 3.7) compared to Group B (mean 2.8) and Group C (mean 0.8). IKDC, and all the KOOS subunits, showed significantly (p < 0.001, p Bonferroni < 0.001) increasing scores from Group A to B to C, in addition to KOOS symptoms. CONCLUSIONS: Morbid obesity causes early lesions of the knee cartilage, even in young patients. Significantly, more patients with reported pain show more severe damages.

Treatment of full-thickness cartilage lesions and early OA using large condyle resurfacing prosthesis: UniCAP(®).

PURPOSE: The UniCAP (®) implant for femoral resurfacing treatment of large cartilage lesions and early OA was introduced in 2006. The outcome of the present study is from a prospective cohort study of 64 patients, followed 2 years clinically and 7 years for revisions. METHODS: From 2009 to 2013, 64 patients were treated with femoral resurfacing using the UniCAP implant. Indication for treatment with UniCAP implant was symptomatic huge cartilage lesion or early OA at the femoral condyle demonstrated by MRI or arthroscopy, which was ICRS grades 3-4 and more than 4 cm(2). There were 28 males and 36 females with a median age of 51 (range 35-65) years. Patients were followed for 2 years clinically with Knee Society subjective outcome scores (KSS), pain scores and radiographic evaluations and for 7 years with complications and reoperations. RESULTS: At 2 years, the follow-up mean KSS improved from 49 (6.9) to 88 (17.1), the mean KSS function score improved from 46 (8.0) to 90 (17.1), and the mean Pain score improved from 7.4 (0.5) to 2.3 (1.4). 47 % of the implants were revised within 7 years to arthroplasty due to the progression of cartilage lesions, progressing of osteoarthritis or increased knee pain. The reoperation rate did not show any significant difference between females and males. The Kaplan-Meier survival rate was 50 % at 7 years, no difference among females and males. CONCLUSION: The present study demonstrated an improved subjective outcome and reduced pain after femoral resurfacing using the UniCAP (®) implant in a relatively large cohort of patients with symptomatic large cartilage lesions or early OA. A 47 % reoperation rate with conversion to arthroplasty was found. The femoral resurfacing implantation can be a temporary treatment for large cartilage lesions or early OA that is expected to develop into osteoarthritis. For younger patients who are ineligible for arthroplasty treatment, this implant can offer a temporary solution. LEVEL OF EVIDENCE: IV.

Joint Arthroplasty With Osteochondral Grafting From the Knee for Posttraumatic or Degenerative Hand Joint Disorders.

PURPOSE: To describe the operative procedure and report the clinical outcomes of articular surface reconstruction for various hand joint disorders using autologous osteochondral grafts from the knee. METHODS: Ten patients underwent articular surface reconstruction for hand joint disorders with autologous osteochondral grafts from the patellofemoral joint. Mean patient age was 35 years (range, 15-52 y). The patients were followed for an average of 48 months (range, 16-89 mo). Arthroplasty was performed on the metacarpophalangeal joint in 4 cases, and on the proximal interphalangeal joint in 6 cases. The patients' clinical outcomes were evaluated with joint range of motion, visual analog scale (0-10 points), and Disabilities of the Arm, Shoulder, and Hand (DASH) score. Histological examination was performed in 3 cases after surgery. RESULTS: Graft union was confirmed in all cases without radiographic evidence of resorption or necrosis. Follow-up radiographic examinations showed good graft incorporation without signs of osteoarthritis such as joint space narrowing. The finger flexion-extension arc improved significantly from an average of 21° to 61°. The mean visual analog scale also improved significantly from 7.0 to 1.5. The mean total active motion showed a significant improvement from 151° before surgery to 201° after surgery, and the mean DASH score improved significantly from 33 to 12. There were no significant differences for the arc of finger motion and DASH score between metacarpophalangeal and proximal interphalangeal joint disorders or between hemiarthroplasty and total joint arthroplasty. Histological examination revealed viable chondrocytes in the implanted cartilage. CONCLUSIONS: Autologous osteochondral grafting from the patellofemoral joint provided satisfactory outcomes and may be a useful option for joint surface reconstruction of traumatic or degenerative hand joint disorders. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Cartilage Injuries: Basic Science Update.

The last several decades have brought about substantial development in our understanding of the biomolecular pathways associated with chondral disease and progression to arthritis. Within domains relevant to foot and ankle, genetic modification of stem cells, augmentation of bone marrow stimulation techniques, and improvement on existing scaffolds for delivery of orthobiologic agents hold promise in improving treatment of chondral injuries. This review summarizes novel developments in the understanding of the molecular pathways underlying chondral damage and some of the recent advancements within related therapeutics.

Individualized metal implants for focal cartilage lesions in the knee can be cost-effective: A simulation on 47-year-old in a Swedish setting.

OBJECTIVES: In the aging population, the knee is the joint most commonly causing impaired function and incapacity. While definite treatment by prosthetic replacement is often performed late, symptomatic knee cartilage lesions cause much suffering also in younger ages. Early intervention could, therefore, be instituted at an early stage to the benefit of both patients and society. Small, metal surface, resurfacing implants have been tested with promising results. A system that features patient-specific implants and surgical instruments shows good clinical results and favorable survival rates. This study aims to assess the cost utility of this metal device compared with microfracture (MFX), being the standard procedure in Sweden. METHODS: We constructed a simulation model in Excel. In the model, a cohort of 47-year-old patients (which is the mean age of patients treated with the metal implant) with symptomatic knee cartilage lesions received either MFX or metal implantation. Outcomes for the cohort were simulated over 40 years, such as in a previously published model based on MFX, and sensitivity analyses (deterministic and probabilistic) of the results were undertaken. Data on transition probabilities, costs, and quality of life were taken from clinical data, published literature, and official price lists. Only direct medical costs were included. RESULTS: Results from the analysis showed that the metal device is a cost-effective treatment strategy compared with MFX. The incremental cost-effectiveness ratio (ICER) reached acceptable levels at ∼5 years postoperatively. Over the full-time horizon of 40 years, the metal device was cost saving with concomitant gains in quality-adjusted life years (QALYs), translating to a dominant treatment strategy. Results were robust according to sensitivity analysis with the initial success rate of up to three years for both metal and MFX having the largest impact. CONCLUSIONS: A metal implant may be a cost-effective treatment alternative for patients in their 40's when compared to MFX in a Swedish setting. LEVEL OF EVIDENCE: 5 [1].