Osteophyte Score Research Articles

Dual-energy X-ray absorptiometry derived knee shape may provide a useful imaging biomarker for predicting total knee replacement: Findings from a study of 37,843 people in UK Biobank

ObjectiveWe aimed to create an imaging biomarker for knee shape using knee dual-energy x-ray absorptiometry (DXA) scans and investigate its potential association with subsequent total knee replacement (TKR), independently of radiographic features of knee osteoarthritis and established risk factors. MethodsUsing a 129-point statistical shape model, knee shape (expressed as a B-score) and minimum joint space width (mJSW) of the medial joint compartment (binarized as above or below the first quartile) were derived. Osteophytes were manually graded in a subset of images and an overall score was assigned. Cox proportional hazards models were used to examine the associations of B-score, mJSW and osteophyte score with TKR risk, adjusting for age, sex, height and weight. ResultsThe analysis included 37,843 individuals (mean age 63.7 years). In adjusted models, B-score was associated with TKR: each unit increase in B-score, reflecting one standard deviation from the mean healthy shape, corresponded to a hazard ratio (HR) of 2.25 (2.08, 2.43), while a lower mJSW had a HR of 2.28 (1.88, 2.77). Among the 6719 images scored for osteophytes, mJSW was replaced by osteophyte score in the most strongly predictive model for TKR. In ROC analyses, a model combining B-score, osteophyte score, and demographics outperformed a model including demographics alone (AUC ​= ​0.87 vs 0.73). ConclusionsUsing statistical shape modelling, we derived a DXA-based imaging biomarker for knee shape that was associated with kOA progression. When combined with osteophytes and demographic data, this biomarker may help identify individuals at high risk of TKR, facilitating targeted interventions.

Comprehensive in vitro and in vivo investigations of the therapeutic potential of Jeju lava seawater salt in osteoarthritis

Salts play a crucial role in maintaining human health by regulating fluid levels and supporting various physiological processes. However, conventional seawater-derived salts are associated with microplastic pollution and pose potential health risks. Jeju lava seawater (JLS), sourced exclusively from Jeju Island, has emerged as a unique alternative, free of microplastics and enriched with essential minerals such as magnesium, calcium, zinc, and iron. In this study, we investigated the effects of JLS on osteoarthritis (OA) pathogenesis, focusing on chondrocyte metabolism and OA development. We performed surgical destabilization of the medial meniscus to establish a murine model of OA. We examined the expression of catabolic and anabolic factors in JLS-treated chondrocytes. Our cell viability assay revealed that JLS treatment was not cytotoxic to chondrocytes at concentrations ≤ 0.5%. Additionally, JLS treatment resulted in a concentration-dependent increase in the expression of anabolic factors like aggrecan, SOX9, and COL2A1 while decreasing the expression of catabolic factors such as MMP3, MMP13, ADAMTS4, and ADAMTS5 in the chondrocytes stimulated with pro-inflammatory cytokines. Although not statistically significant compared to the control group, JLS intake slightly attenuated the OARSI score, osteophyte score, synovitis score, subchondral bone thickness, and osteophyte size in the mouse model of OA. Conclusively, these results suggest that JLS ameliorates OA by positively influencing chondrocyte metabolism, making it a promising therapeutic candidate for OA management.

Sex-Linked Discrepancies in C57BL6/J Mouse Osteoarthritis are Associated With the Gut Microbiome and are Transferrable by Microbiome Transplantation.

Females have reduced osteoarthritis (OA) in surgical models. The objective of the current study was to evaluate a sex-linked gut microbiome in the pathogenesis of OA. We induced OA via destabilization of the medial meniscus surgery in adult male and female C57BL6/J mice with and without opposite-sex microbiome transplantation. Eight weeks later, animals were euthanized, and OA severity, synovitis, and osteophyte scores were determined. Serum lipopolysaccharide was measured chromogenically, and serum cytokines were quantified via multiplex immunoassay. Cecal microbiome profiles were generated using 16S deep sequencing. Males had worse OA histology (3.5x, P = 6 × 10-7 ), synovitis (2.4x, P = 5 × 10-4 ), and osteophyte scores (3.7x, P = 3 × 10-4 ) than females. Male-into-female transplantation worsened all outcomes (histology 1.8x, P = 0.02; synovitis 2.0x, P = 3 × 10-5 ; osteophyte 2.1x, P = 0.01) compared to females, whereas female-into-male transplantation improved all outcomes except for synovitis (histology 0.53x, P = 2 × 10-4 ; osteophyte 0.28x, P = 5 × 10-4 ) compared to males. In the gut microbiome analysis, 44 clades were different in at least one group comparison; 5 clades were correlated with the Osteoarthritis Research Society International score (Lactobacillus R = -0.40, Aldercreutzia R = -0.40, rc4_4 R = -0.55, Sutterella R = -0.37, and Clostridiales R=0.36). In the cytokine analysis, 10 analytes were different in at least one group comparison; 3 were different in two groups (female and female-into-male transplants vs male comparisons, all reduced in female and female-into-male transplants), including interleukin-12 (0.66x, P = 0.02; 0.66x, P = 0.02, respectively), eotaxin (0.74x, P = 5 × 10-6 ; 0.57x, P = 0.03), and tumor necrosis factor ⍺ (0.49x, P = 0.03; 0.52x, P = 0.009). Sex-linked differences in the mouse gut microbiome are associated with OA outcomes, are reversible by opposite-sex microbiome transplantation, and are associated with serum cytokine changes.

OA susceptibility in mice is partially mediated by the gut microbiome, is transferrable via microbiome transplantation and is associated with immunophenotype changes

ObjectivesThe Murphy Roths Large (MRL)/MpJ ‘superhealer’ mouse strain is protected from post-traumatic osteoarthritis (OA), although no studies have evaluated the microbiome in the context of this protection. This study characterised...

Ultrasound reveals a high prevalence of CPPD in consecutive patients with knee pain.

The objective of this study is to estimate the prevalence of US findings indicative of calcium pyrophosphate deposition (CPPD) in patients with knee pain. Consecutive patients with knee pain, equally distributed among males and females in seven different age-decades (21-90 years), were enrolled in a cross-sectional study. The presence of US OMERACT-defined CPPD (medial and lateral menisci and femoral hyaline cartilage) and osteophytes (medial and lateral compartments of the tibiofemoral joint) was scored as presence/absence in both knees. Four hundred twenty participants were enrolled (210 men/210 women). Fibrocartilage and hyaline cartilage CPPDs were detected by US in 94/420 (22.4%) and 41/420 (9.8%) participants, respectively. No significant sex differences were noted. The prevalence and the extent of CPPD increased with age. Fibrocartilage and hyaline cartilage CPPDs were identified in 0/60 participants in the third decade, and in 28/60 (46.7%) and 14/60 (23.3%) participants in the ninth decade, respectively (p for trend < 0.01). While fibrocartilage and hyaline cartilage CPPD is virtually absent in subjects younger than 40 and 50 years old, their prevalence steeply increases above from these age groups. Age (aIRR, 1.03; 95% CI, 1.02-1.05), osteophyte score (aIRR, 1.40; 95% CI, 1.22-1.60), and hyaline cartilage CPPD score (aIRR, 2.68; 95% CI, 2.06-3.49) were associated with fibrocartilage CPPD score, whereas age (aIRR, 1.02; 95% CI, 1.01-1.05) and fibrocartilage CPPD score (aIRR, 2.92; 95% CI, 2.29-3.72) were associated with hyaline cartilage CPPD score in multivariable negative binomial regression analyses. In conclusion,we report the US prevalence of CPPD in patients with knee pain. Fibrocartilage CPPD occurs at a younger age and is more prevalent than hyaline cartilage CPPD. Key points • Fibrocartilage CPPD occurs at a younger age and is more prevalent than hyaline cartilage CPPD. • Fibrocartilage and hyaline cartilage CPPDs are virtually absent in subjects younger than 40 and 50 years old. •In subjects older than 80 years, fibrocartilage and hyaline cartilage CPPD prevalencerises up to 46.7% and 23.3%, respectively.

Association between lumbar endplate damage and bone mineral density in patients with degenerative disc disease

BackgroundTo explore the independent association between lumbar endplate damage and bone mineral density (BMD) in patients with degenerative disc disease (DDD).MethodsThis retrospective investigation was based out of a prospectively collected database from the Affiliated Kunshan Hospital of Jiangsu University. Data from 192 DDD patients, collected between December 2018 and January 2022, were chosen for the final analysis. The average total endplate score (TEPS) of lumbar(L) 1-L4 was assessed by magnetic resonance imaging (MRI), and represents the extent of endplate damage. Osteoporosis severity was assessed via the L1-L4 BMD evidenced by dual-energy x-ray absorptiometry (DXA). Other analyzed information included gender, age, body mass index (BMI), and osteophyte score (OSTS). Uni- and multivariate linear regression analyses were employed to evaluate the association between average TEPS and BMD of L1-L4. Moreover, the generalized additive model (GAM) was employed for non-linear association analysis.ResultsUpon gender, age, BMI, and OSTS adjustments, a strong independent inverse relationship was observed between average TEPS and BMD (β, -0.021; 95% CI, -0.035 to -0.007, P-value = 0.00449). In addition, the gender stratification analysis revealed a linear relationship in males, and a non-linear relationship in females. Specifically, there was a significantly stronger negative relationship between average TEPS and BMD in females, when the average TEPS was < 3.75 (β, -0.063; 95% CI, -0.114 to -0.013; P-value = 0.0157). However, at an average TEPS > 3.75, the relationship did not reach significance (β, 0.007; 95% CI, -0.012 to 0.027; P-value = 0.4592).ConclusionsThis study demonstrated the independent negative association between average TEPS and BMD values of L1-L4. Upon gender stratification, a linear relationship was observed in males, and a non-linear association in females. The findings reveal that patients with osteoporosis or endplate damage require more detailed examinations and treatment regimen.

Relationship between knee osteophytes and calcitonin gene-related peptide concentrations of serum and synovial fluid in knee of osteoarthritis.

To explore the relationship between knee osteophytes of osteoarthritic knee and calcitonin gene-related peptide (CGRP) concentrations of serum and synovial fluid (SF). 65 patients with knee medial compartment osteoarthritis (OA) were recruited and examined with weight-bearing radiographs of the entire lower limb. The concentrations of CGRP in serum/SF were also detected in surgery. The relationship between the concentrations of CGRP in serum/SF and osteophyte scores were detected with Spearman rank correlation coefficient. CGRP concentrations in serum and SF were significantly correlated with osteophyte score of overall knee respectively (R = 0.462, P < .001; R = 0.435, P < .001). In addition, a correlation tended to be observed about the relationship between CGRP concentrations in serum and SF and osteophyte scores of medial compartment (R = 0.426, P < .001; R = 0.363, P = .003), and osteophyte scores of lateral compartment (R = 0.429, P < .001; R = 0.444, P < .001). In this study, the relationship between CGRP in serum/SF and knee osteophyte scores in different subregions were explored, which showed significant positive correlations, that possibly reflecting the contribution of CGRP influencing osteophyte formation. Positive correlations between osteophyte scores and CGRP suggest that CGRP promote the growth of osteophyte formation. It has the potential to be selected as a biomarker for the assessment of severity in knee OA patients and predict the progression of knee OA. It also provides a potential therapeutic target to delay the progression and relieve the symptom of OA.

Mechanical stress and inflammation have opposite effects on Wnt signaling in human chondrocytes.

Dysregulation of Wingless and Int-1 (Wnt) signaling has been strongly associated with development and progression of osteoarthritis (OA). Here, we set out to investigate the independent effects of either mechanical stress (MS) or inflammation on Wnt signaling in human neocartilage pellets, and to relate this Wnt signaling to OA pathophysiology. OA synovium-conditioned media (OAS-CM) was collected after incubating synovium from human end-stage OA joints for 24 h in medium. Cytokine levels in the OAS-CM were determined with a multiplex immunoassay (Luminex). Human neocartilage pellets were exposed to 20% MS, 2% OAS-CM or 1 ng/mL Interleukin-1β(IL-1β). Effects on expression levels of Wnt signaling members were determined by reverse transcription-quantitative polymerase chain reaction. Additionally, the expression of these members in articular cartilage from human OA joints was analyzed in association with joint space narrowing (JSN) and osteophyte scores. Protein levels of IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor α, and granulocyte-macrophage colony-stimulating factor positively correlated with each other. MS increased noncanonical WNT5A and FOS expression. In contrast, these genes were downregulated upon stimulation with OAS-CM or IL-1β. Furthermore, Wnt inhibitors DKK1 and FRZB decreased in response to OAS-CM or IL-1β exposure. Finally, expression of WNT5A in OA articular cartilage was associated with increased JSN scores, but not osteophyte scores. Our results demonstrate that MS and inflammatory stimuli have opposite effects on canonical and noncanonical Wnt signaling in human neocartilage. Considering the extent to which MS and inflammation contribute to OA in individual patients, we hypothesize that targeting specific Wnt pathways offers a more effective, individualized approach.

Comparison of Kindlin-2 deficiency-stimulated osteoarthritis-like lesions induced by Prg4CreERT2 versus AggrecanCreERT2 transgene in mice

BackgroundGenetically modified mice are the most useful tools for investigating the gene functions in articular cartilage biology and the pathogenesis of osteoarthritis. The AggrecanCreERT2 mice are one of the most reported mouse lines used for this purpose. The Prg4 (proteoglycan 4) gene encodes the lubricin protein and is expressed selectively in chondrocytes located at the superficial layer of the articular cartilage. While the Prg4GFPCreERT2 knock-in inducible-Cre transgenic mice were generated a while ago, so far, few studies have used this mouse line to perform gene functional studies in cartilage biology. MethodsWe have recently reported that deleting the Fermt2 gene, which encodes the key focal adhesion protein Kindlin-2, in articular chondrocytes by using the AggrecanCreERT2 transgenic mice, results in spontaneous osteoarthritis (OA) lesions, which highly mimics the human OA pathologies. In this study, we have compared the Kindlin-2 deficiency-caused OA phenotypes induced by Prg4GFPCreERT2 with those caused by AggrecanCreERT2 using imaging and histological analyses. ResultsWe find that Kindlin-2 protein is deleted in about 75% of the superficial articular chondrocytes in the tamoxifen (TAM)-treated Prg4GFPCreERt2/+; Fermt2fl/fl mice compared to controls. At 6 months after TAM injections, the OARSI scores of AggrecanCreERT2/+; Fermt2fl/fl and Prg4GFPCreERt2/+; Fermt2fl/fl mice were 5 and 3, respectively. The knee joints histological osteophyte and synovitis scores were also significantly decreased in Prg4GFPCreERT2/+; Fermt2fl/fl mice compared to those in AggrecanCreERT2/+; Fermt2fl/fl mice. Furthermore, magnitudes of upregulation of the extracellular matrix-degrading enzymes Mmp13 and hypertrophic chondrocyte markers Col10a1 and Runx2 were decreased in Prg4GFPCreERT2/+; Fermt2fl/fl versus AggrecanCreERT2/+; Fermt2fl/fl mice. We finally examined the susceptibility of Prg4GFPCreERT2/+; Fermt2fl/fl mouse model to surgically induce OA lesions. The pathological features of OA in the TAM-DMM model exhibited significant enhancement in cartilage erosion, proteoglycan loss, osteophyte, and synovitis and an increase in OARSI score in articular cartilage compared with those in corn-oil DMM mice. ConclusionKindlin-2 loss causes milder OA-like lesions in Prg4GFPCreERT2/+;Fermt2fl/fl than in AggrecanCreERT2/+; Fermt2fl/fl mice. In contrast, Kindlin-2 loss similarly accelerates the destabilization of the medial meniscus-induced OA lesions in both mice.Translational Potential of this Article: Our study demonstrates that Prg4GFPCreERT2 is a useful tool for gene functional study in OA research. This study provides useful information for investigators to choose appropriate Cre mouse lines for their research in cartilage biology.

Association of Traumatic Knee Injury With Radiographic Evidence of Knee Osteoarthritis in Military Officers.

The association between knee injury and knee osteoarthritis (OA) is understudied relative to its importance, particularly in younger populations. This study was undertaken to examine the association of knee injury with radiographic features of knee OA in military officers, who have a physically demanding profession and high rates of knee injury. Participants were recruited in 2015-2017 from an existing program that enrolled 6,452 military officers during 2004-2009. Officers with a history of knee ligament or meniscal injuries (n=117 via medical record review) were compared to officers with no history of knee injury (n=143). Bilateral posteroanterior knee radiographs were obtained using a standardized fixed-flexion positioning frame. All images were read for Kellgren/Lawrence (K/L) grade, osteophyte (OST), and joint space narrowing (JSN) scores. Data were analyzed using linear-risk regression models with generalized estimating equations. Injured and noninjured participants were similar (mean age 28 years, mean body mass index 25 kg/m2 , ~40% female). The mean time from first knee injury to imaging among injured participants was 9.2 years. Compared with noninjured knees, greater prevalence of radiographic OA (K/L grade ≥ 2), OST (grade ≥ 1), and JSN (grade ≥ 1) was observed among injured knees, with prevalence differences of +16% (95% confidence interval [95% CI] 10%, 22%), +29% (95% CI 20%, 38%), and + 17% (95% CI 10%, 24%), respectively. Approximately 1 in 6 officers with prior knee injury progressed to radiographic OA by age 30 years. At the midpoint of a projected 20-year military career, officers with a history of traumatic knee injury have a markedly increased prevalence of knee radiographic OA compared to officers without injury.

Age estimation using vertebral bone spurs; Testing the efficacy of three methods on a European population

Age-at-death estimation is an essential step in both bioarchaeological and forensic studies when human remains are found, as this can also contribute to the identification of the individual. It is critical that age-at-death methods be tested verified in various populations, to obtain the most accurate estimation, making research into new age-at-death methods also imperative. Since osteophyte formation on the vertebral column increases with age, this can be used as a possible method of age-at-death estimation. Snodgrass (2004), Watanabe and Terazawa (2006) and Praneatpolgrang et al. (2019) have tested this method before and have provided promising results. We test the efficacy of Snodgrass (2004), Watanabe and Terazawa (2006), and Praneatpolgrang et al. (2019) on a 19th-century archivally recorded Dutch population. A total of 88 individuals, 40 males, and 48 females were scored for the degree of osteophyte formation on the vertebral column. In addition to testing the three methods above, population-specific regression equations were developed and tested. Accuracy percentages for estimating the age-at-death based on the mean osteophyte score of the entire vertebral column were obtained for all three methods (73.86%, 76.14%, and 72.73%, respectively). In this study, a general pattern of osteophyte formation could be established, which is useful for estimating the age at death. We therefore recommend that this method can be used, cautiously as a means of age-at-death estimation.

An Automatic Method for Assessing Spiking of Tibial Tubercles Associated with Knee Osteoarthritis.

Efficient and scalable early diagnostic methods for knee osteoarthritis are desired due to the disease's prevalence. The current automatic methods for detecting osteoarthritis using plain radiographs struggle to identify the subjects with early-stage disease. Tibial spiking has been hypothesized as a feature of early knee osteoarthritis. Previous research has demonstrated an association between knee osteoarthritis and tibial spiking, but the connection to the early-stage disease has not been investigated. We study tibial spiking as a feature of early knee osteoarthritis. Additionally, we develop a deep learning based model for detecting tibial spiking from plain radiographs. We collected and graded 913 knee radiographs for tibial spiking. We conducted two experiments: experiments A and B. In experiment A, we compared the subjects with and without tibial spiking using Mann-Whitney U-test. Experiment B consisted of developing and validating an interpretative deep learning based method for predicting tibial spiking. The subjects with tibial spiking had more severe Kellgren-Lawrence grade, medial joint space narrowing, and osteophyte score in the lateral tibial compartment. The developed method achieved an accuracy of 0.869. We find tibial spiking a promising feature in knee osteoarthritis diagnosis. Furthermore, the detection can be automatized.

Relation entre les modifications histologiques du ligament croisé antérieur et la fonction du genou chez les patients arthrosiques

BackgroundThe function of the anterior cruciate ligament (ACL) in osteoarthritis (OA) of the knee remains to be elucidated. The purpose of this study is to evaluate histological changes of the ACL in end-stage knee OA and to clarify the relationship between histological changes in the ACL and knee function. HypothesisThe hypothesis in this study was that ACL degeneration in knee OA is associated with decreased knee function. Patients and methodsEighty-two ACL specimens from 65 patients who underwent primary total knee arthroplasty (TKA) were investigated. The correlation between histological changes of the ACL (myxoid changes, chondroid metaplasia, total collagen degeneration, microcyst formation, vascular proliferation, and inflammatory cell infiltration) and knee function (range of motion, anterior tibial translation test, knee extension muscle strength, one-leg standing time, and functional reach test) were investigated. Age, body mass index, joint space narrowing, osteophyte formation, lower extremity alignment, and knee medial/lateral instability were also evaluated. ResultsMyxoid change in the ACLs was significantly negatively correlated with one-leg standing time. Chondroid metaplasia was not correlated with knee function. Collagen degeneration in the ACL was significantly negatively correlated with knee flexion angle and one-leg standing time. In addition, a negative correlation between microcyst formation and knee flexion angle was noted. Osteophyte formation, particularly lateral femoral intercondylar osteophytes, was correlated with myxoid changes. The other parameters did not correlate with ACL histological changes. DiscussionMyxoid changes in the ACL were shown to correlate with knee function. The osteophyte score, particularly as related to lateral femoral intercondylar osteophytes, correlated with the severity of myxoid changes in the ACL in knee OA. Precise ACL evaluation should be included in the indications for ACL-retaining surgeries because ACL degeneration may be related to decreased knee function after surgery. Level of evidenceIV, diagnostic case series.

Five-Year Structural Changes in the Knee Among Patients With Meniscal Tear and Osteoarthritis: Data From a Randomized Controlled Trial of Arthroscopic Partial Meniscectomy Versus Physical Therapy.

To estimate the risk of magnetic resonance imaging (MRI)-based structural changes in knee osteoarthritis (OA) among individuals with meniscal tear and knee OA, using MRIs obtained at baseline and 18 and 60 months after randomization in a randomized controlled trial of arthroscopic partial meniscectomy (APM) versus physical therapy (PT). We used data from the Meniscal Tear in Osteoarthritis Research (METEOR) trial. MRIs were read using the MRI OA Knee Score (MOAKS). We used linear mixed-effects models to examine the association between treatment group and continuous MOAKS summary scores, and Poisson regression to assess categorical changes in knee joint structure. Analyses assessed changes in OA between baseline and month 18 and between months 18 and 60. We performed both intention-to-treat and as-treated analyses. The analytic sample included 302 participants. For both treatment groups, more OA changes were seen during the early interval than during the later interval. ITT analysis revealed that, between baseline and month 18, APM was significantly associated with an increased risk of having a worsening cartilage surface area score, involving both any worsening across all knee joint subregions (risk ratio [RR] 1.35 [95% confidence interval (95% CI) 1.14, 1.61]) and the number of subregions damaged (RR 1.44 [95% CI 1.13, 1.85]) having a worsening effusion-synovitis score (RR 2.62 [95% CI 1.32, 5.21]), and having ≥1 additional subregion with osteophytes (RR 1.24 [95% CI 1.02, 1.50]). Significant associations were detected between months 18 and 60 only for having any subregion with a worsening osteophyte score (RR 1.28 [95% CI 1.04, 1.58]). These findings suggest that the association between APM and MRI-based structural changes in knee OA is most apparent during the initial 18 months after surgery. The reason for attenuation of this association over longer follow-up merits further investigation.

Relationship between histological changes of the anterior cruciate ligament and knee function in osteoarthritis patients

BackgroundThe function of the anterior cruciate ligament (ACL) in osteoarthritis (OA) of the knee remains to be elucidated. The purpose of this study is to evaluate histological changes of the ACL in end-stage knee OA and to clarify the relationship between histological changes in the ACL and knee function. HypothesisThe hypothesis in this study was that ACL degeneration in knee OA is associated with decreased knee function. Patients and methodsEighty-two ACL specimens from 65 patients who underwent primary total knee arthroplasty (TKA) were investigated. The correlation between histological changes of the ACL (myxoid changes, chondroid metaplasia, total collagen degeneration, microcyst formation, vascular proliferation, and inflammatory cell infiltration) and knee function (range of motion, anterior tibial translation test, knee extension muscle strength, one-leg standing time, and functional reach test) were investigated. Age, body mass index, joint space narrowing, osteophyte formation, lower extremity alignment, and knee medial/lateral instability were also evaluated. ResultsMyxoid change in the ACLs was significantly negatively correlated with one-leg standing time. Chondroid metaplasia was not correlated with knee function. Collagen degeneration in the ACL was significantly negatively correlated with knee flexion angle and one-leg standing time. In addition, a negative correlation between microcyst formation and knee flexion angle was noted. Osteophyte formation, particularly lateral femoral intercondylar osteophytes, was correlated with myxoid changes. The other parameters did not correlate with ACL histological changes. DiscussionMyxoid changes in the ACL were shown to correlate with knee function. The osteophyte score, particularly as related to lateral femoral intercondylar osteophytes, correlated with the severity of myxoid changes in the ACL in knee OA. Precise ACL evaluation should be included in the indications for ACL-retaining surgeries because ACL degeneration may be related to decreased knee function after surgery. Level of evidenceIV, Diagnostic case series.

Overexpression of Peroxiredoxin 3 in Cartilage Reduces the Severity of Age-Related Osteoarthritis But Not Surgically Induced Osteoarthritis in Mice.

ObjectiveThe study objective was to determine whether overexpression of the mitochondrial antioxidant peroxidase, peroxiredoxin 3 (Prx3), reduces the severity of osteoarthritis (OA) in mice.MethodsAge‐related OA (age 18 and 24 months) and OA induced by destabilization of the medial meniscus (DMM at age 6 months) were assessed in male mice that overexpress a human Prdx3 transgene encoding the Prx3 protein. Lox‐stop‐lox‐Prdx3 (iPrdx3) mice were crossed with aggrecan‐CreERT2 mice to produce iPrdx3AgCreERT2 or with Col2Cre to produce iPrdx3Col2Cre mice. Germline transgenics (Prdx3Tg) were also evaluated. Prx3 protein level was assessed by immunoblotting and functionally after induction of elevated mitochondrial hydrogen peroxide (H2O2) using menadione. Histological sections of stifle joints were scored for cartilage damage (Articular Cartilage Structure score [ACS]), osteophytes, and synovial hyperplasia and were evaluated by histomorphometry.ResultsOverexpression of Prx3 maintained mitochondrial membrane integrity and inhibited p38 phosphorylation in the presence of elevated H2O2. ACS scores of 18‐month‐old iPrdx3AgCreERT2 mice (mean ± SD, 4.88 ± 5.05) were significantly lower than age‐matched iPrdx3 controls (11.75 ± 6.34, P = 0.002) and trended lower in the 18‐month Prdx3Tg group (P = 0.14), whereas no significant differences between experimental and control groups at 24 months of age or in OA induced by DMM surgery were noted. Osteophyte scores trended lower in the 18‐month‐old Prdx3Tg group (P = 0.09) and at 24 months in the iPrdx3Col2Cre mice (P = 0.05). There were no significant group differences in synovial hyperplasia or histomorphometric measures.ConclusionOverexpression of the mitochondrial peroxidase Prx3 reduced the severity of age‐related OA, but not at advanced ages and not in DMM‐induced OA in younger mice.

Ultrasound-detected inflammation is more common in clinically manifest hand osteoarthritis than in painless bony enlarged finger joints: subanalysis of the population-based Bruneck study.

Purpose:The aim of this article is to examine the extent of structural and inflammatory lesions by ultrasound in elderly subjects with hand osteoarthritis (HOA) fulfilling the ACR classification criteria (Group A), in subjects with painless enlarged finger joints (Group B), and in individuals without clinical abnormalities at hands (Group C).Methods:This study was nested within the population-based, prospective Bruneck study; 293 subjects of ⩾65 years of age were assessed. Clinical and ultrasound assessment was conducted at wrists and finger joints. Gray scale synovitis (GSS), Power Doppler (PD), osteophytes, and erosions were scored semiquantitatively (0–3). The Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH), the Health Assessment Questionnaire (HAQ), and the Functional Index for Hand Osteoarthritis (FIHOA) were retrieved.Results:Most subjects had ⩾1 ultrasound abnormality, of which osteophytes were the most prevalent finding in all groups (Group A: 100%, Group B: 99.4%, and Group C: 93.9%). GSS and PD-signals were more common in Group A than in Group B (94% versus 67% and 33% versus 13%, respectively). In Group C, GSS was observed in 39.4% of subjects. In subjects with HOA, the SF-SACRAH correlated with osteophyte scores (corrcoeff = 0.48), and the FIHOA correlated with the osteophyte (corrcoeff = 0.42) and PD scores (corrcoeff = 0.33).Conclusion:GSS and PD were more frequent in patients with symptomatic HOA than in cases with painless bony enlargements and subjects without clinical joint abnormalities. Functional restriction in HOA is associated with structural and inflammatory ultrasound changes.

Association between radiographic hand osteoarthritis and bone microarchitecture in a population-based sample

BackgroundSubchondral bone plays an important role in the pathogenesis of radiographic osteoarthritis (OA). However, the bony changes that occur in hand OA (HOA) are much less understood. This study aimed to describe the association between radiographic HOA and high-resolution peripheral quantitative computed tomography (HRpQCT) measures of the hand and radius in a population-based sample.MethodsA total of 201 participants (mean age 72, 46% female) from the Tasmanian Older Adult Cohort (TASOAC) study underwent HRpQCT assessment of the 2nd distal and proximal interphalangeal (DIP, PIP), 1st carpometacarpal (CMC) joint, and distal radius. Radiographic HOA was assessed at the 2nd DIP, PIP joints, and the 1st CMC joint using the OARSI atlas.ResultsProximal osteophyte and joint space narrowing (JSN) scores were consistently more strongly associated with HRpQCT measures compared to the distal site with positive associations for indices of bone size (total and trabecular bone area and cortical perimeter but inconsistent for cortical area) and negative associations for volumetric bone mineral density (vBMD). There was a decrease in trabecular number and bone volume fraction with increasing osteophyte and JSN score as well as an increase in trabecular separation and inhomogeneity. Osteophyte and JSN scores in the hand were not associated with HRpQCT measures at the distal radius.ConclusionsThis hypothesis generating data suggests that bone size and trabecular disorganization increase with both osteophyte formation and JSN (proximal more than distal), while local vBMD decreases. This process appears to be primarily at the site of pathology rather than nearby unaffected bone.

ASSOCIATIONS BETWEEN PREDICTED AND ACTUAL STRUCTURAL PROGRESSION IN THE APPROACH COHORT

In the APPROACH study, machine learning models were trained to predict structural and pain progression of individual participants. Predicted progression was differentiated into a structural (S) and pain (P) progression score, where the score (range 0-1) reflected the likelihood of a participant being a progressor. Structural progression was defined as a decrease in minimum JSW of ≥0.3mm/year. Only participants with the estimated highest 75% combined (P+S) score after screening were included. To evaluate the associations between the predicted and actual structural progression according to different parameters over two years. 297 Participants were included at five European centers. Radiographs and 1.5T or 3T MRIs were acquired at baseline and two years. Minimum and mean medial and lateral tibiofemoral (TF) JSW, subchondral bone density, and osteophyte size were measured from radiographs. Medial and lateral cartilage thickness was measured from 3D SPGR MRI scans using manual, quality-controlled segmentations. Semi-quantitative MOAKS cartilage damage, bone marrow lesions (BML) and osteophytes scores were assessed from triplanar PDW and T1W sequences, summarized to overall medial and lateral scores. Progression was defined as two-year change greater than the smallest detectable change (SDC) for continuous measures or a change in ≥1 full MOAKS score, in the most affected compartment (MAC). For minimum JSW, progressors as predefined in the study protocol were analyzed as well. The association of S scores with progression was analyzed using logistic regression. Data was available for 237 participants. TF progression was seen most often in MRI cartilage thickness (38%) and radiographic bone density (39%) and osteophyte size (35%). S scores were not significantly associated with progression of any TF structural parameter besides minimum JSW, both based on the predefined progression criterion of ≤-0.6mm and on the SDC of <-0.49mm over two years. However, baseline minimum JSW was used for calculation of S scores, and after adjustment for baseline minimum JSW, the S scores were no longer associated with minimum JSW progression (both p>0.38). Selecting only participants with radiographic OA (KL grade ≥2, 53%) resulted in a higher percentage of progressors for all parameters (e.g. 50% MRI cartilage thickness) but this did not change results for S score association. Despite the use of machine learning models in the APPROACH cohort to only include participants that were predicted to show fast pain and/or structural progression, only around 1 in 6 participants was a structural progressor based on the predefined criterion. It is possible this number would have been lower without the model-based inclusion. Still, the S scores were generally not associated with progression. The machine learning model was trained using a different progression criterion than most criteria used in this validation; machine learning models trained on the actual criteria used for this analysis may have been more effective and is now possible with the data from the APPROACH cohort. EU/EFPIA Innovative Medicines Initiative Joint Undertaking (grant n° 115770) WW: Chondrometrics GmbH; FWR: Boston Imaging Core Lab, LLC IMI-APPROACH (NCT03883568) participants and investigators CORRESPONDENCE ADDRESS: m.p.jansen-36@umcutrecht.nl .

Elevated resting heart rate is associated with increased radiographic severity of knee but not hand joints

Although the resting heart rate (RHR) predicts the clinical outcomes of cardiovascular disease, chronic obstructive lung disease, diabetes mellitus, and the risk of cancer, its role in patients with musculoskeletal diseases, such as osteoarthritis (OA), remains unclear. We explored the association of the RHR with the extents of radiographic changes in the knees and hands of 2369 subjects from the Dong-gu Study. The radiographic hand and knee joint findings were graded semi-quantitatively; we calculated total hand and knee joint scores. Multiple linear regression was performed to examine the associations between the RHR and the radiographic characteristics of these joints. For the knee joints, the RHR was associated positively with the total (p < 0.01), osteophyte (p < 0.01), joint space narrowing (JSN; p < 0.01), and tibial attrition (p = 0.02) scores after adjustment for age, sex, body mass index, smoking status, alcohol consumption, educational and physical activity levels, and comorbidities. For the hand joints, the RHR was associated positively with the JSN (p = 0.01) and subchondral cyst (p < 0.01) scores after such adjustment. The RHR was not associated with the total, osteophyte, sclerosis, erosion, or malalignment score for the hand joints. This study is the first to reveal an association between the RHR and the radiographic severity of knee, but not hand, OA.