Knee Structural Changes Research Articles

Long-term Prognosis of Patellar Tendinopathy (Jumper's Knee) in Young, Elite Volleyball Players: Tendon Changes 11 Years After Baseline.

The long-term prognosis of jumper's knee and whether structural changes in the patellar tendon persist is unknown. To investigate whether limitations in knee function and structural changes persisted beyond the athletic career of young elite volleyball players. Cohort study; Level of evidence, 2. Volleyball players (mean ± SD age, 18 ± 0.8 years) enrolled in 2006-2011 in a prospective cohort study were invited in 2020-2022 to a follow-up study. Participants rated their knee function with the Victorian Institute of Sport Assessment-Patellar Tendon (VISA-P) score (baseline and follow-up) and the International Knee Documentation Committee (IKDC) score (follow-up) and reported if jumper's knee had influenced their decision to retire from sport. Tendon thickness and structural changes were assessed with ultrasound (baseline) and magnetic resonance imaging (MRI) (follow-up) of both patellar tendons. We included 138 of 143 former athletes (97%) 11.4 ± 1.6 years after their baseline examination. At baseline, 37 persons (52 knees) had developed jumper's knee. At follow-up, participants reported lower knee function scores in knees diagnosed with jumper's knee at baseline than healthy knees (VISA-P scores: jumper's knee, 81 [95% CI, 70-92]; healthy, 90 [95% CI, 86-94]; P < .001; IKDC scores: jumper's knee, 82 [95% CI, 75-89]; healthy, 92 [95% CI, 91-95]; P < .001). Jumper's knee problems directly caused 7 of the 37 athletes (19%) with jumper's knee at baseline to retire from competitive volleyball. Of the 138 players included, 97 (70%) completed a bilateral MRI examination (194 knees). At follow-up, 38 of the 54 abnormal tendons (70%) had no structural changes (P < .001 vs baseline) while 22 of the 140 normal tendons (16%) had developed structural changes. Clinical symptoms were not correlated with tendon structure at follow-up (VISA-P scores for normal tendons: 85 [95% CI, 73-87]; abnormal: 89 [95% CI, 85-92]; P = .48). Jumper's knee is not a self-limiting condition; volleyball players who had developed jumper's knee during adolescence reported persistent reductions in knee function 11 years later, leading one-fifth to retire from competitive volleyball. Although approximately 70% of tendons with structural changes at baseline were normal at follow-up, there was no clear relationship between structure and function.

Effect of umbilical cord blood-mononuclear cells on knee osteoarthritis in rabbits

BackgroundTo investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits.MethodsA rabbit KOA model was prepared by anterior cruciate ligament transection (ACLT). Fifty New Zealand white rabbits were randomly divided into the control group, model group, sodium hyaluronate (SH) group, platelet-rich plasma (PRP) group and UCB-MNC group. Knee injections were performed once a week for five consecutive weeks. The gross view of the knee joint, morphology of knee cartilage and structural changes in the knee joint were observed on CT scans, and graded by the Lequesne MG behavioral score and the Mankin score. TNF-α and IL-1β levels in the synovial fluid of the knee were measured by the enzyme-linked immunosorbent assay (ELISA). Expression levels of MMP-13 and COL-II in the knee cartilage were detected by Western blotting and qRT-PCR.ResultsThe Lequesne MG behavioral score and the Mankin score were significantly higher in the model group than those in the control group (P < 0.05). Rabbits in the SH, PRP and UCB-MNC groups had sequentially lower scores than those in the model group. Imaging features of KOA were more pronounced in the model group than in the remaining groups. CB-MNC significantly relieved KOA, compared to SH and PRP. Significantly higher levels of TNF-α and IL-1β in the synovial fluid of the knee, and up-regulated MMP-13 and down-regulated COL-II in the knee cartilage were detected in the model group than in the control group. These changes were significantly reversed by the treatment with SH, PRP and UCB-MNCs, especially UCB-MNCs.ConclusionInjections of UCB-MNCs into knees protect the articular cartilage and hinder the progression of KOA in rabbits by improving the local microenvironment at knee joints.

Dietary Inflammatory Index and Magnetic Resonance Imaging-Detected Knee Structural Change and Pain: A 10.7-Year Follow-up Study.

To determine whether the dietary inflammatory index (DII) scores were associated with knee structural changes and pain over a 10.7-year follow-up. This study used data from a prospective population-based cohort study (mean age 63 years, 51% female) in which 1,099, 875, 768, and 566 participants completed assessments at baseline, 2.6, 5.1, and 10.7 years, respectively. T1-weighted and T2-weighted magnetic resonance imaging was performed to measure cartilage volume (CV) and bone marrow lesions (BMLs) at baseline and 10.7 years. The Western Ontario and McMaster Universities Osteoarthritis Index pain questionnaire was used to measure knee pain at each visit. Pain trajectories ("minimal pain," "mild pain," and "moderate pain") were previously identified. Baseline energy-adjusted DII (E-DII) scores were calculated. Linear, log-binomial regression, linear mixed-effects modeling, and multi-nominal logistic regression were used for analyses. The mean ± SD E-DII score at baseline was -0.48 ± 1.39. In multivariable analyses, higher E-DII scores were not associated with tibial CV loss or BML size increase except for medial tibial BML size increase. Higher E-DII scores were associated with a higher pain score (β=0.21; 95% confidence interval [CI] 0.004-0.43) and an increased risk of belonging to the "moderate pain" compared to the "minimal pain" trajectory group (relative risk ratio 1.19; 95% CI 1.02-1.39). A proinflammatory diet, as indicated by a higher DII score, may be associated with a greater pain score and higher risk of more severe pain trajectory over 10 years. However, inconsistent findings related to structural changes suggest a discordance between the potential impact of diet on structural damage and pain in knee OA.

Knee- and Overall Health-Related Quality of Life Following Anterior Cruciate Ligament Injury: A Cross-sectional Analysis of Australian and Canadian Cohorts.

OBJECTIVE: To describe the knee- and overall health-related quality of life (QOL) 3 to 12 years after anterior cruciate ligament (ACL) tear, and to assess the association of clinical and structural features with QOL after ACL tear. DESIGN: Cross-sectional analysis of combined data from Australian (n = 76, 5.4 years postinjury) and Canadian (n = 50, 6.6 years postinjury) prospective cohort studies. METHODS: We conducted a secondary analysis of patient-reported outcomes and index knee magnetic resonance imaging (MRI) acquired in 126 patients (median 5.5 [range: 4-12] years postinjury), all treated with ACL reconstruction. Outcomes included knee (ACL Quality of Life questionnaire [ACL-QOL]) and overall health-related QOL (EQ-5D-3L). Explanatory variables were self-reported knee pain (Knee Injury and Osteoarthritis Outcome Score [KOOS-Pain subscale]) and function (KOOS-Sport subscale), and any knee cartilage lesion (MRI Osteoarthritis Knee Score). Generalized linear models were adjusted for clustering between sites. Covariates were age, sex, time since injury, injury type, subsequent knee injuries, and body mass index. RESULTS: The median [range] ACL-QOL score was 82 [24-100] and EQ-5D-3L was 1.0 [-0.2 to 1.0]. For every 10-point higher KOOS-Sport score, the ACL-QOL score increased by 3.7 points (95% confidence interval [CI]: 1.7, 5.7), whereas there was no evidence of an association with the EQ-5D-3L (0.00 points, 95% CI: -0.02, 0.02). There were no significant association between KOOS-Pain and ACL-QOL (4.9 points, 95% CI: -0.1, 9.9) or EQ-5D-3L (0.05 points, 95% CI: -0.01, 0.11), respectively. Cartilage lesions were not associated with ACL-QOL (-1.2, 95% CI: -5.1, 2.7) or EQ-5D-3L (0.01, 95% CI: -0.01, 0.04). CONCLUSION: Self-reported function was more relevant for knee-related QOL than knee pain or cartilage lesions after ACL tear. Self-reported function, pain, and knee structural changes were not associated with overall health-related QOL. J Orthop Sports Phys Ther 2023;53(7):1-12. Epub: 8 June 2023. doi:10.2519/jospt.2023.11838.

The protective effects and mechanism of Ruyi Zhenbao Pill, a Tibetan medicinal compound, in a rat model of osteoarthritis.

Ruyi Zhenbao Pill (RZP) is a prescribed Tibetan formulation for the treatment of white-pulse-disease, yellow-water-disease as well as pain-related disease. RZP is composed of 30 medicinal materials including herbal medicine, animal medicine and mineral medicine. They are widely used in the Tibetan area to treat cerebrovascular disease, hemiplegia, rheumatism, and pain diseases for centuries. The aim of the present study was to evaluate the anti-osteoarthritis function of RZP and to clarify the underlying mechanisms. The active components in RZP were identified using HPLC methods. Osteoarthritis (OA) animal model was established via intra-articular injection of papain in rat knees. After the administration of RZP (0.45, 0.9g/kg) for 28 days, the clinical observation was conducted, and pathological changes as well as serum biochemical indexes were detected. Moreover, therapeutic targets and pathways of RZP were discussed. The results showed that RZP could suppress knee joint swelling and arthralgia, thus relieving joint pain and inflammation in OA rats. Microcomputed tomography (μCT)-based physiological imaging and staining pictures confirmed the therapeutic effects of RZP on OA symptoms including knee joint swelling and structural changes with progressive inflammation in OA rats. RZP could promote the synthesis or inhibit the degradation of COLⅡ, attenuate OA-induced OPN up-regulation and thus relieve the OA symptom. Furthermore, RZP (0.45-0.9g/kg) could all ameliorate the imbalance of biomarkers related to OA such as MMP1, TNF-α, COX2, IL-1β and iNOS in knee joints or serum. In conclusion, RZP could effectively relieve inflammatory reaction induced by OA injury and the formulation could be applied to the treatment of OA therapy.

Associations Between Dietary Intake of Vitamin K and Changes in Symptomatic and Structural Changes in Patients With Knee Osteoarthritis.

To investigate associations of dietary vitamin K intake with changes in knee symptoms and structures in patients with knee osteoarthritis (OA). Participants with symptomatic knee OA were enrolled (n=259) and followed up for 2 years (n=212). Baseline dietary vitamin K intake was calculated from a validated food frequency questionnaire. Knee symptoms were assessed by using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Knee cartilage defects, bone marrow lesions, and effusion-synovitis volume were measured from magnetic resonance imaging (MRI) scans. Univariable and multivariable linear regressions were used for analyses. A higher vitamin K intake quartile was significantly associated with a greater decrease in the total WOMAC score and dysfunction score over 24 months. The subgroup analyses showed in patients with severe baseline visual analog scale (VAS) pain that a higher vitamin K intake quartile was associated with more improvement in all WOMAC scores. There were no overall significant associations between vitamin K intake and changes in MRI features. In subgroup analysis, vitamin K intake was negatively associated with changes in tibiofemoral, patellar, and total cartilage defects in participants with a severe baseline radiographic grade and was negatively associated with change in total and patellar cartilage defects in participants with severe baseline VAS pain and in female patients. The association of higher vitamin K intake with decreased knee symptoms over 24 months in patients with knee OA suggests that clinical trials examining the effect of vitamin K supplementation for knee OA symptoms are warranted. Whether there is an effect on knee structure is unclear.

The Efficacy of Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis Symptoms and Structural Changes: A Systematic Review and Meta-Analysis

BackgroundPlatelet-rich plasma (PRP) usage in orthopedics continues to rise, despite guidelines suggesting non-superiority to comparative cohorts. Therefore, we performed a systematic review and meta-analysis on PRP efficacy using two clinical assessments: (1) Visual Analog Scale and (2) Western Ontario and McMaster Universities Osteoarthritis Index. We assessed consistency and clinical relevancy by determining study heterogeneity (eg, sample sizes, ages, body mass index, arthritic severities, etc.). Comparative cohorts were: (A) hyaluronic acid (HA); (B) corticosteroid (CS); (C) normal saline (NS); and (D) exercise therapy. We performed sub-analyses of structural changes assessed on ultrasound, radiograph, or magnetic resonance imaging . MethodsWe utilized PubMed, Cochrane Library, and Embase databases up to December 1, 2021, according to Preferred Reporting Items for Systematic-Reviews and Meta-Analyses guidelines. Twenty-four studies met criteria, with comparisons to: HA (n = 11); CS (n = 6); NS (n = 5); and exercise therapy (n = 3). Seven studies assessed structural changes. Evaluations utilized a methodological scoring system. I2 statistics and forest plots pooled analyses and delineated study results. ResultsPRP led to Visual Analog Scale and Western Ontario and McMaster Universities Osteoarthritis Index improvements in most studies when compared to HA, CS, and NS (P ≤ .05). Comparison to exercise therapy resulted in inconclusive findings (P ≥ .05). However, substantial heterogeneity (I2 ≥ 76%) was reported due to study variability. No differences were found when assessing structural changes or cartilage thickness by magnetic resonance imaging (standardized mean difference −0.01 [−0.19, 0.18], P = .91). ConclusionsPRP may be associated with pain and functional improvements but was not clinically relevant (inconsistent study- and patient-metrics). In addition, PRP did not confer superiority when assessing knee-related structural changes.

The association of meniscal body height with knee structural changes in middle-aged and elderly patients with symptomatic knee osteoarthritis.

To investigate whether and how meniscal height is associated with osteoarthritis (OA)-related knee structural changes in symptomatic knee OA. We studied 106 patients (61 female, aged 40-73 years) with symptomatic knee OA. X-ray was used for Kellgren-Lawrence score. Meniscal body heights and extrusion were measured on coronal sections of intermediate-weighted MRI sequence. Knee structural changes were assessed using the modified whole-organ magnetic resonance imaging score (WORMS). Associations between meniscal body height and knee structural changes were assessed using linear regression analysis. Higher medial meniscal body height was significantly associated with severe medial meniscal lesions (p = 0.001-0.023), medial compartmental cartilage lesions (p = 0.045), patellofemoral compartmental and medial compartmental bone marrow edema patterns (p = 0.001-0.037), anterior cruciate ligament and patellar ligament abnormalities (p = 0.020-0.023), and loose bodies (p = 0.017). However, lateral meniscal body height was negatively correlated with WORMS scores for lateral meniscal lesions (p ≤ 0.018), lateral compartmental cartilage lesions (p ≤ 0.011), and lateral compartmental bone marrow edema patterns (p = 0.038). Higher medial meniscal body height was associated with more severe medial compartment structural abnormalities and patellofemoral bone marrow edema patterns, while lateral meniscal body height was inversely correlated with the severity of lateral compartment structural abnormalities. Our study revealed that meniscal body height was associated with multiple OA-related knee structural changes, which would be beneficial in identifying patients with or at risks for knee OA.

Opioid users show worse baseline knee osteoarthritis and faster progression of degenerative changes: a retrospective case-control study based on data from the Osteoarthritis Initiative (OAI)

BackgroundOpioids are frequently prescribed for pain control in knee osteoarthritis patients, despite recommendations by current guidelines. Previous studies have investigated the chondrotoxicity of different opioid subtypes. However, the impact opioids may have on progression of osteoarthritis in vivo remains unknown. The aim of this study was thus to describe the associations between opioid use and knee structural changes and clinical outcomes, over 4 years.MethodsParticipants with baseline opioid use (n=181) and who continued use for ≥1 year between baseline and 4-year follow-up (n=79) were included from the Osteoarthritis Initiative cohort and frequency matched with non-users (controls) (1:2). Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained, including a total summation score (WORMS total, range 0–96) and subscores for cartilage (0–36), menisci (0–24), and bone marrow abnormalities and subchondral cyst-like lesions (0–18, respectively). Knee Injury Osteoarthritis Outcomes score (KOOS) symptoms, quality of life (QOL), and pain were also obtained at baseline and follow-up (range 0–100; lower scores indicate worse outcomes). Using linear regression models, associations between baseline and longitudinal findings were investigated. As pain may modify observations, a sensitivity analysis was performed for longitudinal findings. All analyses were adjusted for sex, BMI, age, race, and Kellgren-Lawrence grade.ResultsOpioid users had greater structural degeneration at baseline (WORMS total: Coef. [95% CI], P; 7.1 [5.5, 8.8], <0.001) and a greater increase over 4 years (4.7 [2.9, 6.5], <0.001), compared to controls. Cartilage and meniscus scores increased greater in opioid users, compared to controls (P≤0.001), and findings withstood the adjustment for baseline pain (P≤0.002). All baseline KOOS scores were lower in opioid users compared to controls (P<0.001). QOL loss was greater, when adjusted for baseline KOOS pain (QOL −6.9 [−11.6, −2.1], 0.005).ConclusionsOpioid users had worse baseline knee structural degeneration and faster progression. Opioid use was also associated with worse symptoms, pain, and QOL. Furthermore, QOL loss was greater in opioid users compared to controls, when adjusted for baseline KOOS pain, indicating that opioids may not be suited to prevent subjective disease progression in KOA patients.

Association between popliteal artery wall thickness and structural progression in individuals with symptomatic knee osteoarthritis

Purpose: Osteoarthritis is the most prevalent chronic joint disorder with multifactorial aetiologies. There has been evidence for the involvement of vascular pathology in the progression and development of knee osteoarthritis. Increased popliteal artery wall thickness has been shown to be a risk factor for cardiovascular disease, being used as a surrogate marker of atherosclerosis. Previous studies have shown associations between increased popliteal artery wall thickness and adverse knee structural changes in community-based adults without clinical knee osteoarthritis.

Meta-analysis on the association between knee extensor strength and structural changes of knee osteoarthritis.

This study aimed to perform a meta-analysis to evaluate whether knee extensor (KE) strength weakness was associated with increased structural worsening in knee osteoarthritis (KOA) including joint space narrowing (JSN) and cartilage loss. PubMed, Embase, Scopus, ScienceDirect, Web of Science, and Cochrane library were searched from their inception to May 2020, to identify eligible studies. Odds ratios (ORs) accompanied by 95% confidence intervals (CIs) were calculated for the relationship between KE strength and outcomes. Totally eleven longitudinal studies were included. The pooled crude OR indicated no significant association between KE strength weakness and KOA progression of JSN (OR: 1.13, 95% CI: 0.90, 1.42), and this result duplicated after confounders were adjusted (OR: 1.10, 95% CI: 0.87, 1.39). Subgroup analysis showed the association remained non-significant in sex-specific outcomes and subsets of neutral and malaligned knees, but there was a trend toward increased risk of JSN progression in female knees with low strength (OR: 1.24, 95% CI: 0.87, 1.76, I2 = 82%). The pooled crude OR showed that KE strength weakness was associated with increased risk of cartilage loss (OR:1.43, 95% CI: 1.05, 1.95). After adjustment, we found a non-significant trend that low KE strength could increase the risk of cartilage loss (OR: 1.25, 95% CI: 0.95, 1.64), and this trend was separately observed in tibiofemoral or patellofemoral compartments. This meta-analysis suggested that KE strength weakness was not significantly associated with an increased risk of radiographic structural KOA progression in patients with KOA or known risk factors for KOA. However, there was a trend that women with weaker KE strength displayed a higher risk of JSN worsening and that KE strength weakness had an association with an increased risk of cartilage damage. Key points • Knee extensor strength weakness is not significantly associated with an increased risk of radiographic structural KOA progression in patients with or at risk of knee osteoarthritis. • There is a non-significant trend toward an increased risk of JSN progression in female knees with low knee extensor strength. • There is a trend that low KE strength can increase the risk of cartilage loss no matter in tibiofemoral or patellofemoral compartments, but it's not significant.

Dynamic changes in the infrapatellar knee structures with quadriceps muscle contraction. An in vivo study

ObjectiveTo determine the effect of knee flexion and submaximal isometric quadriceps muscle (Q) contraction on the patellar tendon (PT), the infrapatellar fat pad (IPFP), and the deep infrapatellar bursa (IPB) from extension to full flexion. MethodsIn Study 1, the dominant knee of seven healthy subjects was studied in full extension and at 60° flexion during relaxation and Q contraction. Each knee was inspected and palpated, the transverse infrapatellar diameter was measured by plicometry, and measurements of the anteroposterior (AP) thickness of the IPFP were made by ultrasound (US). In Study 2, the dominant knee of seven healthy subjects was studied by US in full flexion, and then, at 15° decrements, down to 60° flexion during relaxation and Q contraction. Both studies had IRB approval. Results were analyzed with the Wilcoxon test and descriptive statistics. ResultsIn Study 1, Q contraction caused straightening of the patellar tendon (PT), a statistically significant widening of the IPFP by plicometry, and an increased AP thickness of the IPFP by US, in both knee positions. In Study 2, in full knee flexion, the PT contacted the tibial cortex in all seven subjects. Upon increasing extension, the PT-tibial cortex contact was lost in all subjects nearing 90° flexion. The contraction of the Q made the concave PT straight, grew the width of the underlying IPFP, and the apron of the IPFP moved distally within the IPB in all knee positions. A small amount of bursal fluid was present in all seven subjects. ConclusionQ contraction makes the IPFP bulge anteriorly, on both sides of the PT, and distally into the IPB, with possible biomechanical implications. In full knee flexion, the PT contacted the tibia, confirming a fulcrum at this site.

Intra-articular corticosteroid knee injection induces a reduction in meniscal thickness with no treatment effect on cartilage volume: a case\u2013control study

Although intra-articular corticosteroid injections (IACI) are commonly used for the treatment of knee osteoarthritis (OA), there is controversy regarding possible deleterious effects on joint structure. In this line, this study investigates the effects of IACI on the evolution of knee OA structural changes and pain. Participants for this nested case–control study were from the Osteoarthritis Initiative. Knees of participants who had received an IACI and had magnetic resonance images (MRI) were named cases (n = 93), and each matched with one control (n = 93). Features assessed at the yearly visits and their changes within the follow-up period were from MRI (cartilage volume, meniscal thickness, bone marrow lesions, bone curvature, and synovial effusion size), X-ray (joint space width), and clinical (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain score) data. Participants who received IACI experienced a transient and significantly greater rate of loss of the meniscal thickness (p = 0.006) and joint space width (p = 0.011) in the knee medial compartment in the year they received the injection, compared to controls. No significant effect of the IACI was found on the rate of cartilage loss nor on any other knee structural changes or WOMAC pain post-treatment. In conclusion, a single IACI in knee OA was shown to be safe with no negative impact on structural changes, but there was a transient meniscal thickness reduction, a phenomenon for which the clinical relevance is at present unknown.

Threshold for lateral meniscal body extrusion on MRI in middle-aged and elderly patients with symptomatic knee osteoarthritis

PurposeTo determine the MRI-based threshold of lateral meniscal body extrusion (LMBE) that are associated with meniscal damage, cartilage damage and radiological knee osteoarthritis (OA). Materials and methodsA total of 142 patients (59 men and 83 women) with a mean age of 57.2±7.9 (SD) years (range: 41–77 years) with symptomatic knee OA were included. Radiological assessment was performed using the Kellgren-Lawrence scoring system. Meniscus and cartilage damage were assessed using the whole-organ magnetic resonance imaging score. Meniscal extrusion was quantified on coronal sections of intermediate-weighted MRI sequences. Differences between medial and lateral compartments in meniscal extrusion and incidence of tibiofemoral OA-related structural changes were assessed using Wilcoxon signed rank test and Bowker test. Receiver operating characteristic curves and Youden index were used for determining thresholds for meniscal extrusion. ResultsA total of 142 knees were assessed. Meniscal body extrusion distances between medial and lateral compartments were significantly different in the entire sample, and in subjects with and without radiological knee OA (P<0.05 for all). The incidence of structural changes between medial and lateral compartments were significantly different (P=0.003 for meniscal damage; P=0.001 for femoral cartilage damage). Three mm and 2mm were determined to be the optimal thresholds for medial and lateral meniscal body extrusion, respectively. ConclusionMedial and lateral meniscal body extrusion were associated with the incidence of OA-related knee structural changes in symptomatic patients with knee OA. A threshold of 2mm for LMBE with respect to meniscal damage, cartilage damage and radiological knee OA was determined.

Natural history of new horizontal meniscal tears in individuals at risk for and with mild to moderate osteoarthritis: data from osteoarthritis initiative.

To study the natural history of new horizontal meniscal tears and their association with progression of cartilage degeneration in individuals at risk for or with mild to moderate knee osteoarthritis over 4years. Individuals who developed a new meniscal tear in the right knee over 2years were selected from the Osteoarthritis Initiative 3T MRI studies. Knee structural changes were analyzed at the time of tear appearance (baseline), and after 4years using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Meniscal tears were classified as either horizontal tears or non-horizontal tears. Individuals without a meniscal tear were 1:3 frequency matched according to BMI, gender, race, and age and served as the control group. Linear regression analysis was used to compare cross-sectional and longitudinal changes in cartilage WORMS scores. Forty-one subjects developed horizontal tears, including one indiviudal who developed a tear in both menisci, and 34 developed non-horizonal tears. We found that (29/41 (70.7%)) of horizontal and (20/34 (58.8%)) of non-horizonatal tears were stable during follow-up (p = 0.281). Although knees with an incident tear had higher than controls WORMS MAX total knee scores at baseline (coef. = 0.47, p = 0.044, 95% CI = 0.01 to 0.93), there were no significant differences between the horizontal subgroup and knees without tears in overall cartilage scores at baseline and in progression over 4years of follow-up. New horizontal meniscal tears tended to be stable over 4years and presented no significant differences in progression of cartilage degeneration when compared with knees without tears. • Most of horizonal meniscal tears were stable over 4years. • There were no statistically significant differences in overall progression of cartilage degenerative changes between knees with horizonal meniscal tears and control knees without tears • Horizontal tears most often occurred at the posterior horn of the medial meniscus and at the body of the lateral meniscus.

Associations of serum citrate levels with knee structural changes and cartilage enzymes in patients with knee osteoarthritis.

The aim of this study was to investigate cross-sectional associations between serum levels of citrate and knee structural changes and cartilage enzymes in patients with knee osteoarthritis (OA). A total of 137 subjects with symptomatic knee OA (mean age 55.0years, range 34-74, 84% female) were included. Knee radiography was used to assess knee osteophytes, joint space narrowing (JSN) and radiographic OA assessed by Kellgren-Lawrence (K-L) grading system. T2-weighted fat-suppressed fast spin echo magnetic resonance imaging (MRI) was used to determine knee cartilage defects, bone marrow lesions (BMLs) and infrapatellar fat pad (IPFP) signal intensity alternations. Colorimetric fluorescence was used to measure the serum levels of citrate. Enzyme-linked immunosorbent assay was used to measure the serum cartilage enzymes including matrix metalloproteinase (MMP)-3 and MMP-13. After adjustment for potential confounders (age, sex, body mass index), serum citrate was negatively associated with knee osteophytes at the femoral site, cartilage defects at medial femoral site, total cartilage defects, and total BMLs (odds ratio [OR] 0.17-0.30, all P<.05). Meanwhile, serum citrate was negatively associated with IPFP signal intensity alteration (OR 0.30, P=.05) in multivariable analyses. Serum citrate was significantly and negatively associated with MMP-13 (β -3106.37, P<.05) after adjustment for potential confounders. However, citrate was not significantly associated with MMP-3 in patients with knee OA. Serum citrate was negatively associated with knee structural changes including femoral osteophytes, cartilage defects, and BMLs and also serum MMP-13 in patients with knee OA, suggesting that low serum citrate may be a potential indicator for advanced knee OA.

Human adipose-derived Mesenchymal stem cells, low-intensity pulsed ultrasound, or their combination for the treatment of knee osteoarthritis: study protocol for a first-in-man randomized controlled trial

BackgroundHuman adipose-derived Mesenchymal stem cells (HADMSCs) have proven their efficacy in treating osteoarthritis (OA), in earlier preclinical and clinical studies. As the tissue repairers are under the control of mechanical and biochemical signals, improving regeneration outcomes using such signals has of late been the focus of attention. Among mechanical stimuli, low-intensity pulsed ultrasound (LIPUS) has recently shown promise both in vitro and in vivo. This study will investigate the potential of LIPUS in enhancing the regeneration process of an osteoarthritic knee joint.MethodsThis study involves a prospective, randomized, placebo-controlled, and single-blind trial based on the SPIRIT guidelines, and aims to recruit 96 patients initially diagnosed with knee osteoarthritis, following American College of Rheumatology criteria. Patients will be randomized in a 1:1:1 ratio to receive Intraarticular HADMSCs injection with LIPUS, Intraarticular HADMSCs injection with shame LIPUS, or Normal saline with LIPUS. The primary outcome is Western Ontario and McMaster Universities Index of OA (WOMAC) score, while the secondary outcomes will be other knee structural changes, and lower limb muscle strength such as the knee cartilage thickness measured by MRI. Blinded assessments will be performed at baseline (1 month prior to treatment), 1 month, 3 months, and 6 months following the interventions.DiscussionThis trial will be the first clinical study to comprehensively investigate the safety and efficacy of LIPUS on stem cell therapy in OA patients. The results may provide evidence of the effectiveness of LIPUS in improving stem cell therapy and deliver valuable information for the design of subsequent trials.Trial registrationThis study had been prospectively registered with the Chinese Clinical Trials Registry. registration number: ChiCTR1900025907 at September 14, 2019.

Association between metabolic syndrome and knee structural change on MRI.

To examine the association of metabolic syndrome (MetS) and its components with knee cartilage volume loss and bone marrow lesion (BML) change. Longitudinal data on 435 participants from a population-based cohort study were analysed. Blood pressure, glucose, triglycerides and high-density lipoprotein (HDL) were collected. MetS was defined based on the National Cholesterol Education Program-Adult Treatment Panel III criteria. MRI of the right knee was performed to measure cartilage volume and BML. Radiographic knee OA was assessed by X-ray and graded using the Altman atlas for osteophytes and joint space narrowing. Thirty-two percent of participants had MetS and 60% had radiographic knee OA. In multivariable analysis, the following were independently associated with medial tibial cartilage volume loss: MetS, β = -0.30%; central obesity, β = -0.26%; and low HDL, β = -0.25% per annum. MetS, hypertriglyceridaemia and low HDL were also associated with higher risk of BML size increase in the medial compartment (MetS: relative risk 1.72, 95% CI 1.22, 2.43; hypertriglyceridaemia: relative risk 1.43, 95% CI 1.01, 2.02; low HDL: relative risk 1.67, 95% CI 1.18, 2.36). After further adjustment for central obesity or BMI, MetS and low HDL remained statistically significant for medial tibial cartilage volume loss and BML size increase. The number of components of MetS correlated with greater cartilage volume loss and BML size increase (both P for trend <0.05). There were no statistically significant associations in the lateral compartment. MetS and low HDL are associated with medial compartment cartilage volume loss and BML size increase, suggesting that targeting these factors has the potential to prevent or slow knee structural change.

The ratio adipsin/MCP-1 is strongly associated with structural changes and CRP/MCP-1 with symptoms in obese knee osteoarthritis subjects: data from the Osteoarthritis Initiative

There is a need to identify reliable biomarkers that can predict knee osteoarthritis (OA) progression. We investigated a panel of adipokines and some related inflammatory factors alone and their ratios for their associative value at assessing cartilage volume loss over time and symptoms in obese [High body mass index (BMI)] and non-obese (Low BMI) OA subjects. Human OA serum was from the Osteoarthritis Initiative Progression subcohort. Baseline levels of adiponectin (high and low molecular weight forms), adipsin, chemerin, leptin, visfatin, C-reactive protein (CRP), interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were evaluated with specific assays. Cartilage volume was assessed at baseline and 48 months by quantitative magnetic resonance imaging (MRI), and symptoms using baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Data were analysed by linear regression with confounding factors at baseline, followed by multiple comparison adjustment. The levels of the nine biomarkers and their ratios (36) were studied. Among High BMI subjects, only the ratio adipsin/MCP-1 was associated with cartilage volume loss over time in the lateral compartment [β,-2.95; 95% confidence interval (CI),-4.42,-1.49; P=0.010], whereas MCP-1 was associated with WOMAC pain (-1.74;-2.75,-0.73; P=0.030) and the ratio CRP/MCP-1 with WOMAC pain (0.76; 0.37, 1.14; P=0.023), function (2.43; 1.20, 3.67; P=0.020) and total (3.29; 1.58, 5.00; P=0.027). No associations were found for biomarkers or ratios in Low BMI OA. In this study, the ratio adipsin/MCP-1 was found to be associated with the knee structural changes and that of CRP/MCP-1 with symptoms in obese OA subjects. Our data further underline the relevance of ratios as biomarkers to a stronger association to OA progression and symptoms.

Is treated HIV infection associated with knee cartilage degeneration and structural changes? A longitudinal study using data from the osteoarthritis initiative

BackgroundMetabolic disorders presenting in HIV-infected patients on antiretroviral therapy (ART) may increase the risk of osteoarthritis. However, structural changes of the knee in HIV infected subjects are understudied. The aim of this study is to investigate knee cartilage degeneration and knee structural changes over 8 years in subjects with and without HIV infection determined based on the use of ART.MethodsWe studied 10 participants from the Osteoarthritis Initiative who received ART at baseline and 20 controls without ART, frequency matched for age, sex, race, baseline body mass index (BMI) and Kellgren & Lawrence grade. Knee abnormalities were assessed using the whole-organ magnetic resonance imaging score (WORMS) and cartilage T2 including laminar and texture analyses were analyzed using a multislice-multiecho spin-echo sequence. Signal abnormalities of the infrapatellar fat pad (IPFP) and suprapatellar fat pad (SPFP) were assessed separately using a semi-quantitative scoring system. Linear regression models were used in the cross-sectional analysis to compare the differences between ART/HIV subjects and controls in T2 (regular and laminar T2 values, texture parameters) and morphologic parameters (subscores of WORMS, scores for signal alterations of IPFP and SPFP). Mixed effects models were used in the longitudinal analysis to compare the rate of change in T2 and morphological parameters between groups over 8 years.ResultsAt baseline, individuals on ART had significantly greater size of IPFP signal abnormalities (P = 0.008), higher signal intensities of SPFP (P = 0.015), higher effusion scores (P = 0.009), and lower subchondral cysts sum scores (P = 0.003) compared to the controls. No significant differences were found between the groups in T2-based cartilage parameters and WORMS scores for cartilage, meniscus, bone marrow edema patterns and ligaments (P > 0.05). Longitudinally, the HIV cohort had significantly higher global knee T2 entropy values (P = 0.047), more severe effusion (P = 0.001) but less severe subchondral cysts (P = 0.002) on average over 8 years.ConclusionsKnees of individuals with HIV on ART had a more heterogeneous cartilage matrix, more severe synovitis and abnormalities of the IPFP and SPFP, which may increase the risk of incident knee osteoarthritis.