Cartilage Thickness Loss Research Articles

Radiographic severity, extent and pattern of cartilage loss are not associated with patient reported outcomes before or after total knee arthroplasty in end-stage knee osteoarthritis

BackgroundThe aim of this study was to determine if radiographic severity, extent or pattern of knee osteoarthritis was associated with pain and function before total knee arthroplasty (TKA) or improvement therein one year after TKA. MethodsA prospective study of 259 patients undergoing unilateral TKA for Kellgren-Lawrence (KL) grade ≥ 3 knee osteoarthritis was conducted: mean age 69.8 ± 9.7 (44–91); mean BMI 31.0 ± 5.8 (17–52); 152/259 (58.7%) female. Preoperative radiographs were assessed using the KL and Ahlback systems. Preoperatively and 1 year postoperatively patients completed Oxford Knee Scores, VAS-Pain and EQ-5D scores. Full thickness cartilage loss was recorded intraoperatively. ResultsMedian radiographic severity was Ahlback 2, KL 4: 51/259 (19.7%) hypertrophic; 23/259 (8.8%) atrophic. Neither Ahlback nor Kellgren-Lawrence OA grade was associated with OKS, VAS Pain or EQ-5D prior to TKA (p > 0.05). The extent and pattern of cartilage loss did not affect preoperative PROMs. Radiographic OA severity, compartment involvement, and pattern of cartilage loss were not significantly associated with PROMs or improvements therein following TKA (p > 0.05). Hypertrophic OA was associated with less pain before TKA (difference 6.8, 0.23–13.9 95%CI, p = 0.044), and worse improvement in OKS following TKA (difference −3.41, −6.8 to −0.05 95%CI, p = 0.047). Better preoperative OKS and hypertrophic OA were independently associated with poorer improvement in OKS 1 year following TKA (R2 = 0.208). ConclusionProvided at least one compartment has KL grade ≥ 3 changes, further radiographic severity, pattern or extent of cartilage loss did not affect PROMs before or after TKA: multicompartmental was no worse than unicompartmental disease.

Immunosuppressive regulatory T cells are unable to suppress T helper 17 cells in post-traumatic osteoarthritis

Immunosuppressive regulatory T cells are unable to suppress T helper 17 cells in post-traumatic osteoarthritis

Does cartilage loss cause pain in osteoarthritis and if so, how much?

ObjectivesAlthough treatment development in osteoarthritis (OA) focuses on chondroprotection, it is unclear how much preventing cartilage loss reduces joint pain. It is also unclear how nociceptive tissues may be involved.MethodsUsing...

Characterization of OA development between sexes in the rat medial meniscal transection model

Osteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage degradation. While clear sex differences exist in human OA development, most pre-clinical research has been conducted solely in male animals, limiting generalizability of findings to both sexes. The objective of this study was to determine if sex impacts the progression and severity of OA in the rat medial meniscal tear (MMT) preclinical model used to surgically induce OA. It was hypothesized that differences would be observed between males and females following MMT surgery. An MMT model was employed in male and female Lewis rats to induce OA. Animals were euthanized 3 weeks post-surgery and EPIC-μCT was used to quantitatively evaluate articular cartilage structure and composition, osteophyte volumes and subchondral bone structure. Analysis of medial 1/3 articular cartilage, showed increased cartilage thickness and proteoglycan loss in the MMT of both sexes, when compared to sham. Both male and female MMT groups also saw increased subchondral bone mineral density and larger osteophyte volumes. Significant interactions between sex and OA development were seen in normalized cartilage volume (larger in females), and normalized total osteophyte volumes (larger in males). This study demonstrates the viability of both sexes in the rat MMT preclinical OA model. Though clear differences exist, this model can be used to model OA development and evaluate sex as a factor in the efficacy of OA therapeutics.

Predicting knee replacement in participants eligible for disease-modifying osteoarthritis drug treatment with structural endpoints

Evaluate associations between 2-year change in radiographic or quantitative magnetic resonance imaging (qMRI) structural measures, and knee replacement (KR), within a subsequent 7-year follow-up period. Participants from the Osteoarthritis Initiative were selected based on potential eligibility criteria for a disease-modifying osteoarthritis (OA) drug trial: Kellgren-Lawrence grade 2 or 3; medial minimum joint space width (mJSW) ≥2.5mm; knee pain at worst 4-9 in the past 30 days on an 11-point scale, or 0-3 if medication was taken for joint pain; and availability of structural measures over 2 years. Mean 2-year change in structural measures was estimated and compared with two-sample independent t-tests for KR and no KR. Area under the receiver operating characteristic curve (AUC) was estimated using 2-year change in structural measures for prediction of future KR outcomes. Among 627 participants, 107 knees underwent KR during a median follow-up of 6.7 years after the 2-year imaging period. Knees that received KR during follow-up had a greater mean loss of cartilage thickness in the total femorotibial joint and medial femorotibial compartment on qMRI, as well as decline in medial fixed joint space width on radiographs, compared with knees that did not receive KR. These imaging measures had similar, although modest discrimination for future KR (AUC 0.62, 0.60, and 0.61, respectively). 2-year changes in qMRI femorotibial cartilage thickness and radiographic JSW measures had similar ability to discriminate future KR in participants with knee OA, suggesting that these measures are comparable biomarkers/surrogate endpoints of structural progression.

A simple combination criteria increase the likelihood to observe cartilage loss in patients with osteoarthritis

Purpose: Knee osteoarthritis (OA) is a chronic disease with slow evolution. Kellgren and Lawrence (KL) classification is used to identify the radiographic stages of the disease, but has limited predictive validity of structural disease progression. We hypothesized that, in combination with KL, Osteoarthritis Research Society International (OARSI) Joint Space Narrowing (JSN) grades, permit a superior identification of structural progressors, i.e. patients with subsequent cartilage thickness loss.

Patients with anteromedial osteoarthritis achieve the greatest improvement in patient reported outcome after total knee arthroplasty.

472 patients with pre- and 1-year postoperative patient reported outcome measures (PROMs) undergoing TKA surgery were retrospectively identified and classification of the OA disease pattern was made on preoperative radiographs. Measured resection was the universal technical approach. The key findings showed greater improvement in mean PROMs for anteromedial OA (AMOA) compared with other OA disease patterns; 3.1 points (95% CI 1.4-4.7, p < 0.001) in Oxford Knee score, 11.7 points (95% CI 0.9-22.5, p = 0.034) in Forgotten Joint score and 0.08 points (95% CI 0.02-0.14, p = 0.007) in EQ5D score. Similar results were observed when comparing AMOA with AMOA that had only partial thickness cartilage loss (AMOA-PTCL). Patients with AMOA achieve greater improvement in PROMs after TKA surgery when using measured resection compared with other OA disease patterns. This finding has important implications for reporting, risk stratification and interpretation in TKA outcome studies, including randomized trials, why further investigation of the topic is of highly relevance.

Longitudinal changes in location-specific cartilage thickness and T2 relaxation-times after posterior cruciate ligament reconstruction for isolated and multiligament injury

BackgroundKnee cartilage undergoes pathological changes after anterior cruciate ligament rupture. However, little is known about the development and progression of structural pathology after posterior cruciate ligament (PCL) injury. This study aimed to determine the location-specific longitudinal changes in knee cartilage morphology (thickness) and composition (T2 relaxation-times) after PCL rupture and reconstruction (PCLR) and compare these to uninjured controls. MethodsFifteen adults (mean age 39 years (standard deviation 10), 12 men) with PCLR for isolated and multiligment injury had MRIs acquired at a minimum 5 years post-PCLR and 1 year later. Location-specific changes in knee cartilage thickness and T2 relaxation-times were determined quantitatively after segmentation, and compared with annualised cartilage changes in 13 active controls (mean age 45 years (standard deviation 4), 6 men). FindingsFollowing PCLR, the annual loss of cartilage thickness was greatest in the medial femoral condyle (mean −4.0%, 95% confidence interval [95% CI] −6.7, −1.4), medial tibia (mean −3.7%, 95% CI −6.1, −1.3), and patella (mean −3.2%, 95% CI −4.7, −1.6). In the medial femoral condyle and trochlea, the PCLR group lost significantly more cartilage thickness than uninjured controls (mean difference −3.7%, 95% CI −0.9, −6.5; and −1.8%, 95% CI −0.1, −3.6, respectively). Deep and superficial zone T2 relaxation-times were relatively constant over time, without longitudinal differences between PCLR and control knees. InterpretationPCL reconstructed knees displayed substantially greater rates of cartilage loss in the medial tibiofemoral and patellofemoral compartments compared to uninjured controls, highlighting that the process of degeneration remains active many years after injury.

Loss of patellofemoral cartilage thickness over 5 years following ACL injury depends on the initial treatment strategy: results from the KANON trial

ObjectivesTo evaluate changes in patellofemoral cartilage thickness over 5 years after anterior cruciate ligament (ACL) injury and to determine the impact of treatment strategy.Methods121 adults (ages 18–35 years, 26% women)...

Protective Effect of Alendronate on Lumbar Facet Degeneration in Ovariectomized Rats.

BackgroundFacet joint degeneration (FJD) is a potential source of lower back pain, and estrogen deficiency can accelerate FJD. The present study aimed to investigate the effects of alendronate (ALN) on FJD induced by ovariectomy (OVX) in rats.Material/MethodsThirty female Sprague-Dawley rats underwent either bilateral OVX (n=20) or sham surgery (n=10). The OVX rats subsequently received either subcutaneous ALN (70 μg/kg/week) or vehicle for 12 weeks. Subchondral bone mass and microarchitecture were evaluated by micro-computed tomography. Cartilage degradation was evaluated by toluidine blue staining and histological scoring.ResultsCompared with the Sham group, the OVX group had significantly decreased bone mineral density, bone volume/trabecular volume, and trabecular thickness, significantly increased trabecular separation in subchondral bone, and significantly higher histological score for cartilage degeneration, particularly loss of cartilage thickness. ALN treatment significantly reversed the changes in subchondral bone, preserved cartilage thickness, and reduced the histological score. Immunohistochemical analyses showed significantly decreased expression of ADAMTS-4, MMP-13, and caspase-3 in the OVX+ALN group compared with the OVX group.ConclusionsTreatment with ALN suppressed bone loss, subchondral bone architecture deterioration, and cartilage degeneration in OVX rats, which can be explained by roles of ALN in preservation of subchondral bone mass and microarchitecture, and counteraction of catabolism and chondrocyte apoptosis in cartilage.

Association between changes in molecular biomarkers of cartilage matrix turnover and changes in knee articular cartilage: a longitudinal pilot study

BackgroundAn early detection of Osteoarthritis is urgently needed and still not possible until today. The aim of the study was to assess whether molecular biomarkers of cartilage turnover are associated with longitudinal change in knee cartilage thickness during a 2 year period in individuals with increased risk of developing knee osteoarthritis. A secondary aim was to assess whether prior knee injury or subjective patient-reported outcomes at baseline (BL) were associated with articular cartilage changes. Nineteen volleyball players (mean age 46.5 ± 4.9 years, 47% male) with a 30-year history of regular high impact training were recruited. The serum biomarkers Cpropeptide of type II procollagen (CPII), cartilage oligomeric matrix protein (COMP), collagenase generated carboxy-terminal neoepitope of type II collagen (sC2C), cartilage intermediate layer protein 2 (CILP-2), and the urine biomarkers C-telopeptide of type II collagen (CTX-II) and collagenase-generated peptide(s) of type II collagen (C2C-HUSA) were assessed at BL and at 2 year follow up (FU). Femorotibial cartilage thinning, thickening and absolute thickness change between BL and FU was evaluated from magnetic resonance imaging. Subjective clinical status at BL was evaluated by the International Knee Documentation Committee Subjective Knee Form and the Short-Form 36 Physical Component Score.ResultsCILP-2 was significantly higher at FU and linearly associated with the absolute cartilage thickness change during the experimental period. Prior injury was a predictor of increased absolute cartilage thickness change.ConclusionMeasuring the change in the cartilage biomarker CILP-2 might be a valid and sensitive method to detect early development of knee osteoarthritis as CILP-2 appears to be related to cartilage thickness loss in certain individuals with increased risk of developing knee osteoarthritis. Prior knee injury may be predictive of increased articular cartilage thickness change.

Meniscus position and size in knees with versus without structural knee osteoarthritis progression - data from the osteoarthritis initiative

To explore whether and which quantitative 3D measures of medial and/or lateral meniscus position and size are associated with subsequent medial femorotibial structural progression of knee osteoarthritis and to determine the correlation between central slice and total meniscus measures. Knees with radiographic osteoarthritis from Osteoarthritis Initiative participants with longitudinal medial MRI-based cartilage thickness and radiographic joint space width (JSW) loss over 12 months were selected. These 37 structural progressor knees (64.7 ± 8.0y, 30.2 ± 4.6 kg/m2, 35% men) were matched 1:1 to 37 non-progressor knees (64.6 ± 9.8y, 30.2 ± 4.4 kg/m2, 35% men) without cartilage thickness or JSW loss. Quantitative measures of meniscus position and size were computed from manual segmentations of coronal baseline MRIs. Cohen’s D was used as measure of effect size. Maximum extrusion distance of the total medial meniscus and mean extrusion in the central 5 and in the central slice were greater for progressor than non-progressor knees (Cohen’s D 0.58–0.66). No significant differences were observed for medial tibial coverage or mean extrusion (entire meniscus). Among medial meniscus morphology measures, only mean height differed between progressor vs non-progressor knees (Cohen’s D 0.40). Among lateral meniscus measures, height and volume were greater in progressor vs. non-progressor knees (Cohen’s D 0.46–0.83). Mean extrusion measures were highly correlated between the entire meniscus and the central (r = 0.88) or the central 5 (r = 0.93) slices. 3D maximum and central medial meniscus extrusion may serve as predictors for subsequent structural progression. Central meniscus extrusion measures could substitute 3D extrusion measurement across the entire meniscus.

Structural progressor thresholds of femorotibial cartilage change over 1 to 4-years for different MRI orientations and contrasts – data from the osteoarthritis initiative

Structural progressor thresholds of femorotibial cartilage change over 1 to 4-years for different MRI orientations and contrasts – data from the osteoarthritis initiative

The clinical trajectory of people with knee osteoarthritis: secondary analysis of a follow-up assessment following a two-year supplemental intervention

Purpose: To report the clinical trajectory of physical function in people with knee osteoarthritis (OA) four years following a two-year daily intervention involving daily glucosamine and chondroitin sulfate supplements. Secondary objective is to determine if baseline patellofemoral OA features identified on magnetic resonance imaging (MRI) at baseline predict changes in physical function, pain and quality of life two and four years following a supplement intervention. Methods: This is a secondary analysis of a two-year randomised placebo-controlled trial, the Long-term Evaluation of Glucosamine Sulfate (LEGS) trial. Physical function was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, two (2011; post-intervention) and four years (2013; two years after formal treatment) with a mailed survey. The minimal clinically important difference of 9.1 was used to identify symptomatic improvement/worsening. Patellofemoral OA features at baseline were evaluated for bone marrow lesions (BMLs), full thickness cartilage loss and osteophytes using the MRI Osteoarthritis Knee Score. Generalised estimating equations determined if patellofemoral OA features were associated with symptomatic improvement/worsening. Results: Of 303 participants, 87% completed two year and 56% completed four year follow-up questionnaires. There were no differences in the number of people followed up between the supplemental groups. From baseline, 41% improved in physical function at two year follow-up, 47% had no change and 13% worsened (Fig 1). From post-intervention, 20% demonstrated further improvement at four years, 60% had no change and 20% worsened. Of people who improved at two-year follow up, 67% had no further changes at four year follow-up (Fig 1). Presence of BMLs in the patellofemoral joint predicted functional improvement at two-year follow-up (OR 0.44, 95% CI 0.24-0.82), and no other patellofemoral features on MRI were associated with clinical changes over time. Conclusions: Majority of people remained the same or improved in physical function, pain and quality of life scores over four years (range=20-60%), indicating that people with knee OA were not likely to functionally decline after an intervention. Most OA features in the patellofemoral joint did not predict symptomatic changes. However, the presence of patellofemoral BMLs predicted improvement in physical function at two-year follow up. Although this finding may be incidental, baseline physical function scores could have potentially influenced the results. However, since baseline physical function scores were adjusted for in the model and the model remained significant, a true effect of patellofemoral BMLs on improved physical function was demonstrated. Overall, the findings from this study demonstrate the importance of understanding the clinical trajectory of people with knee OA. Patients and clinicians need to be made aware of the high proportion of participants who do not have clinical worsening four years following initial start of treatment with supplements, as well as the moderate number of participants likely to demonstrate improvement in physical function either within two or four years.

Impact of contralateral radiographic status on longitudinal change of cartilage transverse relaxation time (T2) in radiographically normal knees, a model of early OA? – data from the osteoarthritis initiative

Purpose: Evaluating treatment for modifying structural progression at an early stage of OA requires models that display subtle synovial tissue alterations that occur early in the disease process, but still have a reasonable likelihood of progression. We have previously shown that radiographically normal (KLG0) knees with definite contralateral (CL) radiographic OA had a greater likelihood of incident ROA, and that KLG0 knees with CL radiographic joint space narrowing (JSN) displayed greater cartilage loss than those with radiographically normal CL knees. The purpose of this study was to use this model of “early” OA of a KLG0 case knee in a person with CL (non-posttraumatic) ROA, to determine whether baseline values and longitudinal change in cartilage composition differ compared with those with radiographically normal CL knees (controls). Methods: The data were obtained from the Osteoarthritis Initiative (OAI). 150 KLG0 case knees displayed CL ROA (KLG2-4; central readings vs.0.7), without reporting previous injury to that knee. Of those, 63 (50.8% female, age: 64.2±8.8 y, BMI: 27.6±4.4 kg/m2) were right knees with multi-echo spin-echo (MESE) MRIs (Fig.1) to support analysis of the cartilage transverse relaxation time (T2), a method previously shown to be related to cartilage composition and mechanical properties. 23 were CL KLG2 without JSN, 22 KLG2 with JSN grade1, 13 KLG3, and 5 KLG 4. The 63 case knees were matched 1:1 with 63 KLG0 controls of persons who were bilaterally KLG0 and had the same sex, similar age (64.3±8.7 y), and BMI (27.3±4.0 kg/m2). The 3-year change in cartilage T2 (between year 1 and 4 [Y1/4] follow-up) was determined from sagittal MESE MRIs (Fig.), analyzing the superficial and deep 50% of the cartilage in each of 16 femorotibial joint (FTJ) subregions. The mean T2-values across the superficial and deep cartilage layers of the entire FTJ were the primary analytic focus. Exploratory measures included T2 of the medial and lateral femorotibial compartment (MFTC/LFTC) and location-independent T2 shortening and lengthening scores (i.e. the sum of all negative / positive femorotibial subregion T2 changes). Results: The baseline T2 (Y1) was significantly greater in the case than in control KLG0 knees, both in the superficial and deep FTJ cartilage layers (paired t-test: p=0.01; Cohen’s D=0.40; and p=0.04; Cohen’s D=0.34, respectively). In the superficial layer, the effect tended to be stronger in the medial than in the lateral, and in the deep layer stronger in the lateral than in the medial compartment (Table 1).Table 1Cartilage T2 at the beginning of the observation intervalCase KLG0 kneesControl KLG0 kneesDifferenceSuperficial LayerMeanSD95% CIMeanSD95% CIPCohen DFTJ48.73.447.849.547.42.846.748.10.010.40MFTC49.24.248.150.347.73.746.848.60.020.37LFTC48.13.747.249.147.13.046.347.90.050.31Deep LayerFTJ37.72.337.238.337.02.036.537.50.040.34MFTC38.22.637.538.937.82.537.238.40.320.16LFTC37.32.636.637.936.22.235.736.80.010.44 Open table in a new tab When restricting analysis to those with CL JSN, the effect size (Cohen’s D) was 0.49 in the superficial and to 0.36 in the deep layer (data not shown). The longitudinal increase in medial and lateral T2 from Y1 to Y4 of the case knees was significantly different from zero; it also tended to be greater in case than in control KLG0 knees, but the case-control differences did not reach statistical significance (data not shown). Only when restricting the analysis to those with CL JSN, we observed a significantly (p<0.05) greater increase in deep layer T2 in the case than in the control knees in the FTJ, and also in the lateral compartment and location-independent lengthening score (Cohen’s D 0.45-0.46). No significant differences were observed in the longitudinal changes of the superficial layer (Table 2).Table 2Longitudinal change in T2 over 3 years of observationKLG0 with CL JSNKLG0 with CL KLG0DifferenceSuperficial LayerMeanSD95% CIMeanSD95% CIPCohen DFTJ1.01.90.41.60.91.50.41.40.850.04MFTC1.42.50.62.21.42.20.72.10.950.01LFTC0.62.2-0.21.30.41.9-0.21.00.820.06Decrease-15.316.1-20.4-10.1-15.110.2-18.4-11.80.96-0.01Increase31.717.726.037.429.717.824.035.40.610.11Deep LayerFTJ1.12.50.31.90.11.7-0.40.70.040.46MFTC1.33.30.22.40.32.4-0.41.10.140.34LFTC0.92.50.11.7-0.11.8-0.60.50.040.45Decrease-13.413.5-17.7-9.0-18.217.0-23.7-12.80.150.32Increase32.329.522.941.721.812.717.725.80.050.46 Open table in a new tab The increase in deep layer T2 was significantly correlated with location-independent measures of cartilage thickness loss in the FT joint (r=-0.27, p<0.01). Conclusions: This is the first study to explore whether cartilage T2 is sensitive to identifying compositional changes in cartilage in a model of “early” knee OA, i.e. a KLG0 knee with a CL non-posttraumatic ROA knee. Significant differences in superficial and deep layer cartilage T2 were observed at the beginning of the longitudinal observation interval. Similar to previous observations for the change in location-independent measures of cartilage thickness, significant longitudinal differences in T2 lengthening between case and control knees were observed in knees with CL JSN. These differences were limited to the deep layer, and were most prominent in the lateral femorotibial compartment. KLG0 knees with CL JSN hence may represent a model of early OA in which structure modification can be studied at an early disease stage.

Cartilage thickness loss correlates to UTE-T2* early after acl reconstruction

Cartilage thickness loss correlates to UTE-T2* early after acl reconstruction

Moderate Physical Activity and Prevention of Cartilage Loss in People With Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

To examine the impact of physical activity on cartilage thickness loss in knee osteoarthritis (OA). A total of 689 participants with radiographic knee OA at baseline (Kellgren/Lawrence grade ≥2) from the Osteoarthritis Initiative completed the Physical Activity Scale for the Elderly (PASE) questionnaires at annual intervals over 4 years. Magnetic resonance imaging-based cartilage thickness change in the medial femorotibial compartment (MFTC) over 4 years was the main outcome. The impact of PASE tertiles (low, moderate, or high) on changes in MFTC cartilage thickness was estimated using a mixed-effects model adjusted for baseline characteristics. Furthermore, stratification by sex was performed for secondary analyses. Structural progression of MFTC cartilage loss of -0.20 mm (95% confidence interval [95% CI] -0.22, -0.17) was observed in the entire cohort, with no significant difference between physical activity levels after adjustment for baseline characteristics. An interaction between sex and physical activity was observed in the adjusted analysis (P = 0.02). Stratification by sex showed that women with low physical activity had a statistically greater cartilage loss than women with moderate physical activity (adjusted between-group difference -0.09 mm [95% CI -0.16, 0.02]), whereas no significant differences were observed in men. While physical activity was not associated with cartilage thickness loss in the whole cohort, this relationship significantly differed between sexes. In women, but not in men, moderate physical activity may slow down structural disease progression compared to low physical activity levels. For both men and women, high physical activity levels do not appear to be more detrimental than lower physical activity levels for cartilage thickness loss.

Fibroblast growth factors: Potential novel targets for regenerative therapy of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disorder and is the leading cause of disability of people, which negatively impact people's physical and mental health. Although OA causes great socioeconomic burden and individual suffering, no effective treatment options are provided so far. This is partially resulted from poor regenerative activity of articular cartilage and our incomplete understanding of the underlying mechanism of OA. Traditional drug therapies such as acetaminophen and opioids are effective in relieving pain but do not reverse cartilage damage and are often associated with adverse events. Therefore, it is necessary to find effective OA drugs. In recent years, novel regenerative therapies have received much attention because they can effectively promote tissue repair and regeneration. The fibroblast growth factor (FGF) signaling has been suggested to involve in cartilage homeostasis for decades. The current research shows that sprifermin/recombinant FGF18 significantly reduces the loss of cartilage thickness and volume without serious side effects, thus warrants a continued research for potential new medications of OA. This review mainly highlights the current research progress on FGFs and FGF receptors as a potential therapeutic target for OA.

Mesenchymal Stem Cell Therapy in Osteoarthritis and Regenerative Medicine.

Mesenchymal Stem Cell Therapy in Osteoarthritis and Regenerative Medicine.

Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee – data from the Osteoarthritis Initiative

To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (OA), but without contralateral trauma history, display greater cartilage thickness loss than knees from subjects with bilaterally radiographically normal knees. 828 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative [OAI] were studied; 150 case knees displayed definite radiographic knee OA (KLG≥2) contralaterally, and had MRI double echo steady state (DESS) images available at 12 and 48 month follow-up. 678 reference knees displayed KLG0 at the contralateral side. Cartilage thickness change was determined in femorotibial subregions and location-independent cartilage thinning scores were computed. Case and reference knees were compared using ANCOVA. Of the 150 KLG0 case knees, 108 had a contralateral KLG2 knee (50 without, and 58 with joint space narrowing [JSN]), 31 a KLG3 and 11 a KLG4 knee. The cartilage thinning score tended to be greater in case than reference knees; the cartilage thinning score in KLG0 case knees with contralateral radiographic JSN (-858μm; [95% confidence interval-1016,-701μm]) was significantly greater (P=0.0012) than that in bilaterally KLG0 reference knees (-634μm; [-673,-596μm]), whereas KLG0 knees with contralateral KLG2 without JSN only showed relatively small thinning scores (-530μm, [-631,-428μm]). Region-specific analysis suggested greater rates of cartilage loss in case than in reference knees in the lateral, rather than medial, femorotibial compartment. Radiographically normal knees with contralateral JSN may serve as a human model of early OA, for testing disease modifying drugs in clinical trials designed to prevent cartilage loss before the onset of radiographic change. CLINICALTRIALS. NCT00080171.