Change In Cartilage Volume Research Articles

External Focus of Attention Reduces Cartilage Load During Drop Landings.

The aim of the present study was to examine the effects of attentional focus instructions on acute changes in the transverse relaxation time (T2) of the femorotibial cartilage and in cartilage volume during repeated drop-jump landings. Ten healthy females (Mage = 20.4 ± 0.8 years) performed a drop landing task from a 50 cm high box over the course of 3 days (50 repetitions each day) across three attentional focus conditions: external focus (EF: focus on landing as soft as possible), internal focus (IF: focus on bending your knees when you land), and control (CON: no-focus instruction), which was counterbalanced across focus conditions. T2 mapping and the volume of femorotibial cartilage were determined from magnetic resonance imaging scans at 1.5 T for the dominant knee before and after completing the drop landings in each attentional focus condition per day. Results indicated a smaller change in cartilage T2 relaxation time and volumetry in the central load-bearing lateral cartilage under the EF, compared to IF and CON. Moreover, the change in T2 and cartilage volume was greater for lateral tibial cartilage as compared to femoral cartilage and was independent of attentional focus instructions. No significant acute quantitative changes were observed in the medial compartment. The peak vertical ground reaction force was found to be the lowest under the EF, compared to IF and CON. These findings suggest that external focus of attention may reduce cartilage load, potentially aiding in the control or management of cartilage injuries during landing in female athletes.

Phosphotungstic acid-enhanced micro-computed tomography and RNA sequencing provide a new perspective on temporomandibular joint arthritis induced by complete Freund's adjuvant and collagen-induced arthritis in rat models

Background/PurposeTemporomandibular joint (TMJ) arthritis causes inflammation and degradation of the mandibular condylar cartilage and subchondral bone. Complete Freund's adjuvant (CFA) and collagen-induced arthritis (CIA) are models for studying TMJ arthritis. While micro-computed tomography (micro-CT) is crucial for three-dimensional (3D) bone analysis, it has limitations in imaging nonmineralized tissues. Phosphotungstic acid (PTA) enhances soft tissue contrast. However, research on the 3D imaging of mandibular condylar cartilage and the molecular mechanisms of CFA- and CIA-induced arthritis remains unclear. This study aimed to investigate the bone and PTA-stained cartilage in the mandibular condyle using 3D reconstruction and explore the characteristics of enriched gene ontology terms underlying CFA- and CIA-induced TMJ arthritis in rat models. Materials and methodsRat mandibular condyles were collected from control, CFA, and CIA groups. Live micro-CT created 3D bone structures, and PTA-enhanced micro-CT constructed 3D mandibular condylar cartilage. Gene ontology enrichment analysis identified enriched gene ontology terms from differentially expressed genes through RNA sequencing. ResultsMajor deformities in cartilage volume and bone morphology were observed in the arthritis-induced groups. The CIA group exhibited significant correlations between cartilage volume and bone parameters changes. Gene ontology enrichment analysis indicated fewer terms with upregulated differentially expressed genes related to inflammation and immune response in the CIA group than in the CFA group. ConclusionThis study reveals distinct responses between CFA- and CIA-induced TMJ arthritis models. The CIA group exhibited strong correlations between cartilage volume and bone parameter changes and had less pronounced inflammation and immune response than the CFA group.

Gender differences in patterns of cartilage loss: Data from the Osteoarthritis Initiative

OBJECTIVEUnderstanding gender-specific differences in patterns of cartilage loss can improve our knowledge of the pathogenesis of knee osteoarthritis (KOA) development and progression and may inform clinical trials of treatments for KOA. The goal of our observational study was to examine gender differences in patterns of cartilage loss in the central weight-bearing regions of the femur. METHODSWe measured cartilage volume change in the indexed knee of 700 subjects with Kellgren-Lawrence (KL) 1, 2, or 3 from the OAI for four follow-up periods (BL to 24mo, BL to 48mo, BL to 72mo, and BL to 96mo) using the local area cartilage segmentation (LACS) method. Briefly, the LACS method uses robust coordinate systems fixed to anatomical landmarks to measure patterns of change in cartilage volume in sub-regions using responsiveness heat maps. RESULTSWe observed a statistically significant gender difference in cartilage change in the medial femur (MF), lateral femur (LF), and medial tibia (MT). The heat maps, showed loss was primarily in the posterior central weight-bearing portion of the LF and more general in the LT and MF. Similar patterns were observed for each of the four follow-up periods. CONCLUSIONSThe LACS method was capable of illustrating gender-specific differences in patterns of cartilage loss that may offer insight into the variation of gender differences in the natural history of KOA and may be useful in evaluating the benefit of interventions for KOA.

Association of smoking with cartilage loss of knee osteoarthritis: data from two longitudinal cohorts

BackgroundPrevious studies have been inconsistent concerning the association between smoking and risk of osteoarthritis (OA). This study aimed to explore the associations of smoking status and change in cartilage volume of OA in two longitudinal cohorts.MethodsSubjects from the Osteoarthritis Initiative cohort (OAI, n = 593) and the Tasmanian Older Adult Cohort (TASOAC, n = 394) were included in this study. For both cohorts, participants were classified into three groups based on their smoking status, namely ‘never’, ‘former’, and ‘current’ smokers. The outcome measures were the annual rate of change of tibiofemoral cartilage volume over 2 years in OAI and of tibial cartilage volume over 2.6 years in TASOAC. Potential confounders were balanced using the inverse probability of treatment weighting (IPTW) method.ResultsOverall, 42.3% and 37.4% of participants were former smokers, and 5.7% and 9.3% were current smokers in the OAI and TASOAC cohorts, respectively. Compared to never smokers, neither former nor current smoking was associated with risk of the annual rate of change of tibiofemoral cartilage volume in OAI (former smoker: β=-0.068%/year, 95% confidence interval [CI] -0.824 to 0.688, p = 0.860; current smoker: β=-0.222%/year, 95% CI -0.565 to 0.120, p = 0.204) and tibial cartilage volume in TASOAC (former smoker: β = 0.001%/year, 95% CI -0.986 to 0.989, p = 0.998; current smoker: β=-0.839%/year, 95% CI -2.520 to 0.844, p = 0.329).ConclusionsOur findings from two independent cohorts consistently showed that smoking was not associated with knee cartilage loss in older adults.

Knee Cartilage Change within 5 Years after Aclr Using Hamstring Tendons with Preserved Tibial-Insertion: A Prospective Randomized Controlled Study Based on Magnetic Resonance Imaging.

Background: Comparing to anterior cruciate ligament reconstructions (ACLR) with free hamstring tendon (FHT), ACLR with preserved tibial-insertion hamstring tendon (HT-PTI) could ensure the blood supply of the graft and avoid graft necrosis. Yet, whether HT-PTI could protect the cartilage and clinical outcomes in mid-long period after ACLR was still unclear. Purpose: To compare the cartilage change and clinical results between the HT-PTI and FHT in 5 years after ACLR. Study design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 45 patients who underwent isolated ACLR with the autograft of hamstring tendons were enrolled and randomized into 2 groups. The study group undertook ACLR with HT-PTI, whereas the control group had FHT. At pre-operation, and 6, 12, 24, and 60 months post-operation, all cases underwent evaluation with Knee Injury and Osteoarthritis Outcome Score (KOOS), and MR examination. The knee cartilage was divided into 8 sub-regions of which the T2 value and cartilage volume on MRI were measured and documented. The data of two groups were compared and their correlations were analyzed. Results: A total of 18 patients in the HT-PTI group and 19 patients in the FHT group completed the follow-up. The KOOS scores were improved at each follow-up time point (p < 0.001), reached the most superior at 12 months and maintained until 60 months but had no significant difference between the two groups. At 60 months, the cartilage in most subregions in FHT group had higher T2 values than those of pre-operation (p < 0.05) and also higher than HT-PTI group; The cartilage volume changes (CV%) are positive at 6 months and negative from 12 to 60 months in the FHT group, while being negative at all time points in the HT-PTI group. The values of absolute CV% in most subregions in FHT group were significantly higher than those in the HT-PTI group at 6 and 60 months (p < 0.05). Conclusion: The improvement of KOOS score peaked at 12 months in all cases and had no difference between the two groups. The cartilage in the FHT group had more volume loss, earlier and wider damage than that in the HT-PTI group within 5 years. No significant correlation was found among KOOS score, CV%, and T2 value.

Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults.

Osteoarthritis (OA) is the most prevalent joint disorder characterized by joint structural pathological changes with the loss of articular cartilage as its hallmark. Tools that can predict cartilage loss would help identify people at high risk, thus preventing OA development. The recent advance of the metabolomics provides a new avenue to systematically investigate metabolic alterations in disease and identify biomarkers for early diagnosis. Using a metabolomics approach, the current study aimed to identify serum metabolomic signatures for predicting knee cartilage volume loss over 10 years in the Tasmania Older Adult Cohort (TASOAC). Cartilage volume was measured in the medial, lateral, and patellar compartments of the knee by MRI at baseline and follow-up. Changes in cartilage volume over 10 years were calculated as percentage change per year. Fasting serum samples collected at 2.6-year follow-up were metabolomically profiled using the TMIC Prime Metabolomics Profiling Assay and pairwise metabolite ratios as the proxies of enzymatic reaction were calculated. Linear regression was used to identify metabolite ratio(s) associated with change in cartilage volume in each of the knee compartments with adjustment for age, sex, and BMI. The significance level was defined at α = 3.0 × 10−6 to control multiple testing. A total of 344 participants (51% females) were included in the study. The mean age was 62.83 ± 6.13 years and the mean BMI was 27.48 ± 4.41 kg/m2 at baseline. The average follow-up time was 10.84 ± 0.66 years. Cartilage volume was reduced by 1.34 ± 0.72%, 1.06 ± 0.58%, and 0.98 ± 0.46% per year in the medial, lateral, and patellar compartments, respectively. Our data showed that the increased ratios of hexadecenoylcarnitine (C16:1) to tetradecanoylcarnitine (C14) and C16:1 to dodecanoylcarnitine (C12) were associated with 0.12 ± 0.02% reduction per year in patellar cartilage volume (both p < 3.03 × 10−6). In conclusion, our data suggested that alteration of long chain fatty acid β-oxidation was involved in patellar cartilage loss. While confirmation is needed, the ratios of C16:1 to C14 and C12 might be used to predict long-term cartilage loss.

Can metformin relieve tibiofemoral cartilage volume loss and knee symptoms in overweight knee osteoarthritis patients? Study protocol for a randomized, double-blind, and placebo-controlled trial

BackgroundOsteoarthritis (OA) is the most common joint disease, and is most frequently seen in the knees. However, there is no effective therapy to relieve the progression of knee OA. Metformin is a safe, well-tolerated oral medication that is extensively used as first-line therapy for type 2 diabetes. Previous observational studies and basic researches suggested that metformin may have protective effects on knee OA, which needs to be verified by clinical trials. This study, therefore, aims to examine the effects of metformin versus placebo on knee cartilage volume loss and knee symptoms in overweight knee OA patients by a randomized controlled trial over 24 months.MethodsThis protocol describes a multicenter, randomized, double-blind, and placebo-controlled clinical trial aiming to recruit 262 overweight knee OA patients. Participants will be randomly allocated to the two arms of the study, receiving metformin hydrochloride sustained-release tablets or identical inert placebo for 24 months (start from 0.5 g/day for the first 2 weeks, and increase to 1 g/day for the second 2 weeks, and further increase to 2 g/day for the remaining period if tolerated). Primary outcomes will be changes in tibiofemoral cartilage volume and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score over 24 months. Secondary outcomes will be changes in visual analogue scale (VAS) knee pain, tibiofemoral cartilage defects, effusion-synovitis volume, and tibiofemoral bone marrow lesions maximum size over 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per-protocol analyses will be performed as the secondary analyses.DiscussionIf metformin is proved to slow knee cartilage volume loss and to relieve knee symptoms among overweight knee OA patients, it will have the potential to become a disease modifying drug for knee OA. Metformin is a convenient intervention with low cost, and its potential effects on slowing down the structural progression and relieving the symptoms of knee OA would effectively reduce the disease burden worldwide.Trial registrationClinicalTrials. gov NCT05034029. Registered on 30 Sept 2021.

Safety and Efficacy of Injecting Mesenchymal Stem Cells Into a Human Knee Joint To Treat Osteoarthritis: A Systematic Review.

Intraarticular stem cell therapy has become increasingly used to treat knee osteoarthritis (KOA) with minimal high-quality evidence to support its use. This study aims to see how well intra-articular injections of mesenchymal stem cells (MSCs) worked and how safe they were for individuals with KOA. A total of 10 studies were extracted using PubMed, Cochrane Library, and PMC from 2017 to 2021 in the English language. An assessment of the risk of bias was applied via the Cochrane Collaborative Bias Risk Tool and Newcastle-Ottawa Quality. Changes in pain and functional outcomes in patients with KOA were measured by a Knee injury and Osteoarthritis Outcome Score (KOOS) scores, Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at baseline, and follow-up evaluation criteria. The magnetic resonance imaging (MRI) was evaluated using the whole-organ magnetic resonance imaging score (WORMS) and cartilage volume changes. A total of six randomized controlled trials (RCTs), three prospective retrospective clinical trials, and one retrospective clinical trial included 723 patients. They were diagnosed with unilateral or bilateral KOA with Kellgren-Lawrence (KL) grade 1-4 KOA and followed up for six, 12, and 24 months. The experimental groups received multipotent MSCs, mesenchymal progenitor cells (MPCs), adipose tissue progenitor stem cells (AD-MPCs), adipose tissue mesenchymal stem cells (AD-MSCs), bone marrow mesenchymal stem cells (BM-MSCs), bone marrow aspiration (BMA), bone marrow aspiration concentration (BMAC), or micro fragmented adipose tissue (MFAT) while the controlled groups received normal saline (NS), hyaluronic acid (HA), placebo, or went through conservative management.In conclusion, significant improvements were noticed in the MSCs groups via different outcome measuring tools like KOOS, VAS, WOMAC, and MRI. Furthermore, no significant adverse events (AEs) have been observed. Therefore, intra-articular injections of MSCs are effective and safe in relieving pain and improving motor function in individuals with KOA in the short term, contrary to earlier research findings.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Associations between the morphological parameters of proximal tibiofibular joint (PTFJ) and changes in tibiofemoral joint structures in patients with knee osteoarthritis

BackgroundTo describe the longitudinal associations between the morphological parameters of proximal tibiofibular joint (PTFJ) and joint structural changes in tibiofemoral compartments in patients with knee osteoarthritis (OA).MethodsThe participants were selected from the Vitamin D Effects on Osteoarthritis (VIDEO) study. PTFJ morphological parameters were measured on coronal and sagittal MRI. The contacting area (S) of PTFJ and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ), and coronal plane (posterior stress-bolstering area, Sυ) were assessed. Knee structural abnormalities, including cartilage defects, bone marrow lesions (BMLs), and cartilage volume, were evaluated at baseline and after 2 years. Log binominal regression models and linear regression models were used to assess the associations between PTFJ morphological parameters and osteoarthritic structural changes.ResultsIn the longitudinal analyses, the S (RR: 1.45) and Sτ (RR: 1.55) of PTFJ were significantly and positively associated with an increase in medial tibial (MT) cartilage defects. The Sτ (β: − 0.07), Sυ (β: − 0.07), and S (β: − 0.06) of PTFJ were significantly and negatively associated with changes in MT cartilage volume. The Sτ (RR: 1.55) of PTFJ was positively associated with an increase in MT BMLs, and Sφ (RR: 0.35) was negatively associated with an increase in medial femoral BMLs.ConclusionsThis longitudinal study suggests that higher load-bearing area of PTFJ could be a risk factor for structural changes in medial tibiofemoral (MTF) compartment in knee OA.Trial registrationClinicaltrials.gov Identifier: NCT01176344Anzctr.org.au Identifier: ACTRN12610000495022Date of registration: 7 May 2010

Intra-articular injection of culture-expanded adipose tissue-derived stem cells for knee osteoarthritis: Assessments with clinical symptoms and quantitative measurements of articular cartilage volume

BackgroundIntra-articular administration of adipose tissue-derived stem cells (ADSC) is an alternative treatment option for knee osteoarthritis (OA) after conventional treatment fails; however, the clinical results related to the severity of OA grade and changes of cartilage volumes after the administration of ADSC is unknown. This study aimed to determine 1) clinical outcomes after the ADSC administration in knee OA with consideration of radiographic OA grades and 2) changes in cartilage volumes after ADSC administration. MethodsThis observational study included 86 knees from 51 patients who underwent intra-articular administration of cultured ADSC; 47 patients (80 knees) completed follow-up for 6 months (follow-up rate: 93%). The Knee injury and Osteoarthritis Outcome Scores (KOOS) were reported at baseline and 1, 3, and 6 months after the administration. The efficacy rate in the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) was evaluated using the KOOS. Cartilage volume of the knee joint was measured using quantitative 3-dimensional magnetic resonance imaging (3D-MRI) software at baseline and 6 months in 52 knees in 31 patients (follow-up rate: 61%). ResultsAll items on the KOOS except “sports/recreation” improved significantly at 6 months with more significance in knees with a Kellgren–Lawrence (KL) grade 2 or 3 compared with KL grade 4 knees. The OMERACT-OARSI responder at 6 months was significantly greater in knees with KL grade 2 or 3 (64%) than in knees with KL grade 4 (42%, p = 0.045). Cartilage volume changes varied among patients and were not related to the changes in KOOS after ADSC administration. ConclusionsIntra-articular administration of ADSC in knee OA improved KOOS at 6 months. The effects were more significant in knees with KL grade 2 or 3 than with KL grade 4. Changes in KOOS were not related to change in cartilage volumes after ADSC administration.

Clinical validation of the use of prototype software for automatic cartilage segmentation to quantify knee cartilage in volunteers

BackgroundThe cartilage segmentation algorithms make it possible to accurately evaluate the morphology and degeneration of cartilage. There are some factors (location of cartilage subregions, hydrarthrosis and cartilage degeneration) that may influence the accuracy of segmentation. It is valuable to evaluate and compare the accuracy and clinical value of volume and mean T2* values generated directly from automatic knee cartilage segmentation with those from manually corrected results using prototype software.MethodThirty-two volunteers were recruited, all of whom underwent right knee magnetic resonance imaging examinations. Morphological images were obtained using a three-dimensional (3D) high-resolution Double-Echo in Steady-State (DESS) sequence, and biochemical images were obtained using a two-dimensional T2* mapping sequence. Cartilage score criteria ranged from 0 to 2 and were obtained using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). The femoral, patellar, and tibial cartilages were automatically segmented and divided into subregions using the post-processing prototype software. Afterwards, all the subregions were carefully checked and manual corrections were done where needed. The dice coefficient correlations for each subregion by the automatic segmentation were calculated.ResultsCartilage volume after applying the manual correction was significantly lower than automatic segmentation (P < 0.05). The percentages of the cartilage volume change for each subregion after manual correction were all smaller than 5%. In all the subregions, the mean T2* relaxation time within manual corrected subregions was significantly lower than in regions after automatic segmentation (P < 0.05). The average time for the automatic segmentation of the whole knee was around 6 min, while the average time for manual correction of the whole knee was around 27 min.ConclusionsAutomatic segmentation of cartilage volume has a high dice coefficient correlation and it can provide accurate quantitative information about cartilage efficiently without individual bias.Advances in knowledge: Magnetic resonance imaging is the most promising method to detect structural changes in cartilage tissue. Unfortunately, due to the structure and morphology of the cartilages obtaining accurate segmentations can be problematic. There are some factors (location of cartilage subregions, hydrarthrosis and cartilage degeneration) that may influence segmentation accuracy. We therefore assessed the factors that influence segmentations error.

EXPLORING GENDER‐DEPENDENT DIFFERENCES IN PATTERNS OF CARTILAGE LOSS USING RESPONSIVENESS HEAT MAPS: DATA FROM THE OAI

Understanding gender-specific differences in patterns of cartilage loss can improve our knowledge of the pathogenesis of knee osteoarthritis (KOA) development and progression and may inform clinical trials of treatments for KOA. Quantitative cartilage assessment using segmentation software offers an ideal method for appreciating these patterns. The goal of our study was to examine gender differences in patterns of cartilage loss in the central weight-bearing regions of the medial femur (MF), lateral femur (LF), medial tibia (MT), and lateral tibia (LT) using cartilage segmentation software. We measured cartilage volume change in the indexed knee of 480 subjects with Kellgren-Lawrence (KL) 2 and 3 from the OAI at the baseline (BL) and 96-month (mo) time points using the local area cartilage segmentation (LACS) method. Briefly, the LACS method uses robust coordinate systems fixed to anatomical landmarks to find the cartilage volume or thickness in consistent sub-regions on each cartilage plate. (See Figure 1.) Using the coordinate systems, LACS permits assessment of change in much smaller sub-regions through the use of responsiveness heat maps. The average age, BMI, and KL score were 59.5years, 28.7kg/m 2 , 2.03 (males) and 60.5years, 28.8kg/m 2 , 1.99 (females). Figure 2 shows heat map images of the change in cartilage volume from BL to 96mo for males and females. The intensity of the colors (red for loss, blue for gain) represents the standardized response mean (SRM) value at each location. We observed more focused thinning for females in the lateral/posterior portion of the MF and the medial side of the LT. An increase in cartilage thickness in the posterior side of the LF sub-region was also observed for females, as shown with the blue area. Similar patterns were observed for other follow-up time points (i.e., BL to 24mo, BL to 48mo, and BL to 72mo) and when stratifying by age, BMI and KL score. Heat maps of smaller subregions were capable of illustrating gender-specific differences in patterns of cartilage loss, differences that may offer insight into the variation of gender differences in the natural history of KOA. Heat maps of cartilage thickness changes may be useful in evaluating the benefit of interventions for KOA. NIH AR071409 none CORRESPONDENCE ADDRESS: jduryea@bwh.harvard.edu .

Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis

Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing. To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA. This randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020. Interventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants). The 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up. Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of -2.1 vs -1.8 points, respectively (difference, -0.4 [95% CI, -0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was -1.4% vs -1.2%, respectively (difference, -0.2% [95% CI, -1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences. Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617000853347.

Effect of Atorvastatin on Knee Cartilage Volume in Patients With Symptomatic Knee Osteoarthritis: Results From a Randomized Placebo-Controlled Trial.

To determine whether atorvastatin slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis (OA) in a multicenter, randomized, double-blind, placebo-controlled trial. Participants ages 40-70 years were randomized to receive oral atorvastatin (40 mg once daily) (n = 151) or matching placebo (n = 153). The primary end point was annual percentage change in tibial cartilage volume over 2years, assessed using magnetic resonance imaging (MRI). The prespecified secondary end points were progression of cartilage defects and bone marrow lesions over 2 years, which were assessed using MRI and change in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index pain, stiffness, and function scores. A total of 248 of 304 participants (81.6%) completed the trial (mean age 55.7 years; 55.6% women). The annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups (mean change -1.66% versus -2.17%, between-group difference 0.50% [95% confidence interval (95% CI) -0.17%, 1.17%]). There were no significant differences in the progression of cartilage defects (odds ratio [OR] 0.86 [95% CI 0.52, 1.41]) or progression of bone marrow lesions (OR 1.00 [95% CI 0.62, 1.63]). Moreover, there were no significant differences in change in WOMAC pain, stiffness, or function scores over 2 years between the atorvastatin and placebo groups (mean change in pain score -36.0 versus -29.5, adjusted difference -2.7 [95% CI -27.1, 21.7]; mean change in stiffness score -14.2 versus -11.8, adjusted difference -0.2 [95% CI -12.2, 11.8]; mean change in function score -89.4 versus -87.5, adjusted difference 0.3 [95% CI -83.1, 83.6]). The incidence of adverse events (AEs) was similar between the atorvastatin and placebo groups (57 [37.7%] versus 52 [34.0%] experiencing AEs). Treatment with oral atorvastatin (40 mg once daily), compared to placebo, did not significantly reduce cartilage volume loss over 2 years in patients with symptomatic knee OA. These findings do not support the use of atorvastatin for the treatment of knee OA.

Association of Machine Learning-Based Predictions of Medial Knee Contact Force With Cartilage Loss Over 2.5 Years in Knee Osteoarthritis.

The relationship between in vivo knee load predictions and longitudinal cartilage changes has not been investigated. We undertook this study to develop an equation to predict the medial tibiofemoral contact force (MCF) peak during walking in persons with instrumented knee implants, and to apply this equation to determine the relationship between the predicted MCF peak and cartilage loss in patients with knee osteoarthritis (OA). In adults with knee OA (39 women, 8 men; mean ± SD age 61.1 ± 6.8 years), baseline biomechanical gait analyses were performed, and annualized change in medial tibial cartilage volume (mm3 /year) over 2.5 years was determined using magnetic resonance imaging. In a separate sample of patients with force-measuring tibial prostheses (3 women, 6 men; mean ± SD age 70.3 ± 5.2 years), gait data plus in vivo knee loads were used to develop an equation to predict the MCF peak using machine learning. This equation was then applied to the knee OA group, and the relationship between the predicted MCF peak and annualized cartilage volume change was determined. The MCF peak was best predicted using gait speed, the knee adduction moment peak, and the vertical knee reaction force peak (root mean square error 132.88N; R2 = 0.81, P < 0.001). In participants with knee OA, the predicted MCF peak was related to cartilage volume change (R2 = 0.35, β = -0.119, P < 0.001). Machine learning was used to develop a novel equation for predicting the MCF peak from external biomechanical parameters. The predicted MCF peak was positively related to medial tibial cartilage volume loss in patients with knee OA.

Gait risk factors for disease progression differ between non-traumatic and post-traumatic knee osteoarthritis

To examine if relationships between knee osteoarthritis (OA) progression with knee moments and muscle activation during gait vary between patients with non-traumatic and post-traumatic knee OA. This longitudinal study included participants with non-traumatic (n=17) and post-traumatic (n=18) knee OA; the latter group had a previous anterior cruciate ligament rupture. Motion capture cameras, force plates, and surface electromyography measured knee moments and lower extremity muscle activation during gait. Cartilage volume change were determined over 2 years using magnetic resonance imaging in four regions: medial and lateral plateau and condyle. Linear regression analysis examined relationships between cartilage change with gait metrics (moments, muscle activation), group, and their interaction. Measures from knee adduction and rotation moments were related to lateral condyle cartilage loss in both groups, and knee adduction moment to lateral plateau cartilage loss in the non-traumatic group only [β=-1.336, 95% confidence intervals (CI)=-2.653 to-0.019]. Generally, lower levels of stance phase muscle activation were related to greater cartilage loss. The relationship between cartilage loss in some regions with muscle activation characteristics varied between non-traumatic and post-traumatic groups including for: lateral hamstring (lateral condyle β=0.128, 95%CI=0.003 to 0.253; medial plateau β=0.199, 95%CI=0.059 to 0.339), rectus femoris (medial condyle β=-0.267, 95%CI=-0.460 to-0.073), and medial hamstrings (medial plateau; β=-0.146, 95%CI=-0.244 to-0.048). Findings indicate that gait risk factors for OA progression may vary between patients with non-traumatic and post-traumatic knee OA. These OA subtypes should be considered in studies that investigate gait metrics as risk factors for OA progression.

Daily cumulative load and body mass index alter knee cartilage response to running in women.

It is unknown whether a greater accumulation of knee load over a typical day is related to how cartilage responds to an acute bout of loading. This information may clarify the role of habitual activity on cartilage function. Is there a relationship between change in tibial and femoral cartilage thickness, volume, and T2 relaxation time following running with daily cumulative knee load in women? Secondarily, is there a relationship between cartilage change following running and the statistical interaction of body mass index (BMI) and daily steps? Participants (n = 15) completed gait analyses and wore an accelerometer over a week. Daily cumulative knee load was the statistical interaction between tibial compressive joint reaction force (JRF) impulse with the average number of daily steps measured using accelerometry. Magnetic resonance imaging scans were acquired before and immediately after 15-min of treadmill running. Changes in tibial and femoral cartilage thickness, volume, and T2 relaxation time were calculated. Multiple linear regressions tested the associations of cartilage change outcomes with: baseline (thickness, volume, T2), JRF impulse, steps, and the interaction JRF impulse*steps. Secondarily, BMI was substituted for JRF impulse. Tibial volume change was explained by baseline volume, JRF impulse, steps, and JRF impulse*steps (R2 = 0.50, p = 0.013). Additionally, tibial volume change was explained by baseline volume, BMI, steps, and BMI*steps (R2 = 0.43, p = 0.002). Those who were more physically active with lower JRF impulse (or lower BMI) showed less change in tibial cartilage after a running exposure. This may suggest cartilage conditioning.

Efficacy and safety of intra-articular injection of mesenchymal stem cells in the treatment of knee osteoarthritis: A systematic review and meta-analysis.

Objective:To evaluate the effects and safety of intra-articular injection of mesenchymal stem cells on patients with knee osteoarthritis by a systematic review and meta-analysis.Methods:PubMed, EMBASE, and Cochrane Library were retrieved. An assessment of the risk of bias was done through the Cochrane Collaborative Bias Risk Tool, publication bias was assessed by plotting funnel plots and Egger tests. Pain and functional improvements in patients with knee osteoarthritis were determined by changes in VAS scores and WOMAC scores at baseline and follow-up endpoints. For the evaluation of MRI, the WORMS score and changes in cartilage volume were used. In addition, the number of adverse events in the intervention group and the control group were counted to explore the safety.Results:A total of 10 randomized controlled trials involving 335 patients were included. In the pooled analysis, compared with the control groups, the VAS scores of MSC groups decreased significantly (MD,−19.24; 95% CI: −26.31 to −12.18, P < .00001. All of the WOMAC scores also improved significantly: the total scores (SMD, − 0.66; 95% CI: − 1.09 to −0.23, P = .003), pain scores (SMD, − 0.46; 95% CI: − 0.75 to −0.17, P = .002), stiffness scores (SMD, −0.32; 95% CI: −0.64 to 0.00 P = 0.05), and functional scores (SMD, −0.36; 95% CI: −0.69 to −0.04, P = .03). Two studies with non-double-blind designs were the main source of heterogeneity. In terms of cartilage repair, there was no significant difference in the WORMS score, but there was a significant increase in cartilage volume in the MSC group (SMD, 0.69; 95% CI: 0.25 to 1.13, P = .002). The proportion of patients with adverse events in the MSCs treatment group was significantly higher than that in the control group (OR, 3.20; 95% CI: 1.50 to 6.83, P = .003).Conclusions:Intra-articular injection of mesenchymal stem cells is effective and safety to relieve pain and improve motor function of patients with knee osteoarthritis in a short term which is different to conclusions of previous study.

The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms.

To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA. In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months. Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: -53.0mm3, 95% CI: -100.0, -6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: -8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals. In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms.