Progression Of Osteoarthritis In Patients Research Articles

Providing a computationally derived, mechanically optimised target correction during preoperative planning can improve joint contact mechanics of hip dysplasia treated with periacetabular osteotomy.

Preoperative identification of acetabular corrections that optimally improve joint stability and reduce elevated contact stresses could further reduce osteoarthritis progression in patients with hip dysplasia who are treated with periacetabular osteotomy (PAO). The purpose of this study was to investigate how providing patient-specific, mechanically optimal acetabular reorientations to the surgeon during preoperative planning affected the surgically achieved correction. Preoperative CT scans were used to create patient-specific hip models for 6 patients scheduled for PAO. A simulated acetabular fragment was extracted from the preoperative pelvis model and computationally rotated to simulate candidate acetabular reorientations. For each candidate, discrete element analysis was used to compute contact stresses during walking, which were summed over the gait cycle and scaled by patient age to obtain chronic contact stress-time exposure. The ideal patient-specific reorientation was identified using a cost function that balances minimising chronic stress exposures and achieving surgically acceptable acetabular coverage angles. The optimal reorientation angles and associated contact mechanics were provided to the surgeon preoperatively. After PAO was performed, a model of the surgically achieved correction was created from a postoperative CT scan. Radiographic coverage and contact mechanics were compared between preoperative, optimal, and surgically achieved orientations. While surgically achieved reorientations were not significantly different from optimal reorientations in radiographically measured lateral (p = 0.094) or anterior (p = 0.063) coverage, surgically achieved reorientations had significantly (p = 0.031) reduced total contact area compared to optimal reorientations. The difference in lateral coverage and peak chronic exposure between surgically achieved and optimal reorientations decreased with increasing surgeon experience using the models (R² = 0.758, R2 = 0.630, respectively). Providing hip surgeons with a patient-specific, computationally optimal reorientation during preoperative planning may improve contact mechanics after PAO, which may help reduce osteoarthritis progression in patients with hip dysplasia.

Correlation between Subchondral Insufficiency Fracture of the Knee and Osteoarthritis Progression in Patients with Medial Meniscus Posterior Root Tear

A medial meniscus posterior root tear (MMPRT) contributes to knee joint degeneration. Arthroscopic transtibial pullout repair (ATPR) may restore biomechanical integrity for load transmission. However, degeneration persists after ATPR in certain patients, particularly those with preoperative subchondral insufficiency fracture of the knee (SIFK). We explored the relationship between preoperative SIFK and osteoarthritis (OA) progression in retrospectively enrolled patients who were diagnosed as having an MMPRT and had received ATPR within a single institute. Based on their preoperative magnetic resonance imaging (MRI), these patients were then categorized into SIFK and non-SIFK groups. OA progression was evaluated by determining Kellgren–Lawrence (KL) grade changes and preoperative and postoperative median joint widths. SIFK characteristics were quantified using Image J (Version 1.52a). Both groups exhibited significant post-ATPR changes in medial knee joint widths. The SIFK group demonstrated significant KL grade changes (p < 0.0001). A larger SIFK size in the tibia and a greater lesion-to-tibia length ratio in the coronal view were positively correlated with more significant KL grade changes (p = 0.008 and 0.002, respectively). Thus, preoperative SIFK in patients with an MMPRT was associated with knee OA progression. Moreover, a positive correlation was observed between SIFK lesion characteristics and knee OA progression.

The joint line convergence angle (JLCA) correlates with intra-articular arthritis.

Knees with unicompartmental varus osteoarthritis (OA) usually display a combination of tibiofemoral bony deformity and increased joint line convergence angle (JLCA). The JLCA is a product of intra-articular deformity and lateral soft tissue laxity. This study aims to define the correlation between the JLCA and progression of OA. A retrospective radiological analysis of 501 patients, who underwent either high tibial osteotomy (HTO) or unicompartmental knee arthroplasty (UKA), was performed. The preoperative OA grade was reported based on the Ahlbäck and the Kellgren-Lawrence (KL). The hip-knee-ankle angle (HKA), the medial proximal tibial angle (MPTA), the mechanical lateral distal femoral angle (mLDFA) and the joint line convergence angle (JLCA) were recorded. The primary outcome was the relationship between the JLCA values and the OA grade. The secondary outcomes were comparing the JLCA and other alignment parameter values between HTO and UKA groups. A total of 501 (59.3% females n = 297) cases were included, comprising 293 cases of HTO and 208 cases of UKA. Patients had a mean age of 57.63 ± 8.97 years, a mean BMI of 28.37 ± 7.39 kg/m2. Patients with Ahlbäck grade 2 represented 49.3% of all patients (n = 247) and patients with KL grade 3 represented 54.7% of all patients (n = 274). A high JLCA was observed in both groups. The reported mean JLCA in the UKA group was 3.69 ± 2.1°, and in the HTO group was 2.93 ± 1.82. There was a significant association between the increase in the JLCA and the progression of OA based on both the Ahlbäck and KL grades (both p values < 0.001). The mean JLCA in patients with Ahlbäck grades 1 and 4 was 1.48 ± 1.32°, and 7 ± 0.93°, respectively. The mean JLCA in patients with KL grades 1 and 4 was 1.77 ± 1.42°, and 4.89 ± 1.73°, respectively. The mean recorded preoperative HKA angle in the UKA group was 175.06 ± 3.08°, and in the HTO group was 173.26 ± 3.02°, whereas the mean MPTA was 88.63 ± 1.72° for the UKA group and 89.31 ± 2.29° for the HTO group. The JLCA progressively increases with osteoarthritis progression in patients with unicompartmental varus knee osteoarthritis. The JLCA can potentially be used as a grading parameter for osteoarthritis progression akin to Ahlbäck and Kellgren-Lawrence grading systems.

Do Glucocorticoid Injections Increase the Risk of Knee Osteoarthritis Progression Over 5 Years?

Recent findings have demonstrated that intraarticular (IA) glucocorticoid injections can be deleterious for knees with osteoarthritis (OA). This study was undertaken to assess, in a real-life setting, the risk of knee OA progression in patients who received IA glucocorticoid injections over a 5-year follow-up period. We used marginal structural modeling with inverse probability of treatment weighting to determine the causal association between IA glucocorticoid injections and the 5-year risk of disease progression in patients with symptomatic knee OA from the Knee and Hip Osteoarthritis Long-term Assessment cohort. OA progression was defined as an incident total knee replacement (TKR) and/or radiographic worsening (Kellgren/Lawrence [K/L] grade or joint space narrowing [JSN]). We also examined these outcomes in knees that received IA hyaluronan (IAHA) injections. Among the 564 patients with knee OA included in the study sample, 51 (9.0%) and 99 (17.5%) received IA glucocorticoid or IAHA injections, respectively, and 414 (63.1%) did not receive any injection during follow-up. Compared to untreated knees, those treated with IA glucocorticoid injections had a similar risk of incident TKR (hazard ratio [HR] 0.92 [95% confidence interval (95% CI) 0.20, 4.14]; P = 0.91) or K/L grade worsening (HR 1.33 [95% CI 0.64, 2.79]; P = 0.44). IAHA injections had no effect on the risk of TKR (HR 0.81 [95% CI 0.14, 4.63]; P = 0.81) or K/L grade worsening (HR 1.36 [95% CI 0.85, 2.17]; P = 0.20). Similar results were obtained for JSN, and when TKR and radiographic outcomes were combined. In this study, IA glucocorticoid injections for symptomatic knee OA did not significantly increase the 5-year risk of incident TKR or radiographic worsening. These findings should be interpreted cautiously and replicated in other cohorts.

ROLE OF OSTEOPROTEHERIN IN BONE TISSUE METABOLISM IN PATIENTS WITH OSTEOARTHRITIS AND OBESITY

SUMMARY. Osteoarthritis (OA) leads to the degeneration of the articular cartilage, and as a cause of disability it ranks first among the diseases of the musculoskeletal system. Currently, a number of researchers believe that OA can be considered in the context of metabolic syndrome, one of the components of which is obesity. According to modern concepts, muscle tissue is one of the most important human endocrine organs, since it produces a large amount of biologically active substances, hormones and special cytokines (myokines). The latter are cellular regulators of growth and degradation, and support the function of muscle mitochondria. Thus, in the course and progression of OA in patients with increased body weight and obesity, two endocrine-dependent organs "compete" – adipose and muscle tissues. In this case, we should expect not a potentiation of their impact, but a new qualitative effect. And this result of the combined course can be considered the formation of secondary osteoporosis. The aim – to optimize the diagnosis of osteopenic conditions in young people with osteoarthritis occurring against the background of overweight/obesity by determining the role of osteoprotegerin in the formation of complications. Materials and Methods. The research included the evaluation of osteoprotegerin values in 75 people with osteoarthritis (OA) proceeding against the background of obesity (main group), and 50 patients with isolated OA (comparison group). The control group consisted of 37 apparently healthy individuals. The diagnosis of OA was established based on the order of the Ministry of Health of Ukraine dated 10/12/2006 "On the provision of medical care to patients with osteoarthritis", the unified diagnostic criteria of the Association of Rheumatologists of Ukraine (2004) and the criteria of the American College of Rheumatology. The presence and severity of obesity was assessed according to the criteria of the International Diabetes Federation (IDF, 2005) based on the calculation of the body mass index (BMI) according to the Quetelet index. Results. When calculating the content of osteoprotegerin (OCG) it was found that in both examined groups this value exceeded the control values: 1.9 times in patients of the main group and 1.4 times in the comparison group. When the BMI changes in all groups of subjects, there was a significant increase in the OCG relative to control indicators. It was also found that the development and course of osteoarthritis in patients with overweight or obesity occurs against the background of increased serum osteoprotegerin. Conclusions. The course of osteoarthritis is accompanied by a significant increase of serum osteprotegerin, the level of which increases with increasing body weight. Serum osteoprotegerin indicator correlates with the radiological stage of the disease and has a maximum value at third stage of the disease. The presence of OA in obese patients is an unfavorable background for the formation of osteoporotic conditions, one of the mechanisms of which is an increase in serum osteprotegerin, a glycoprotein with an apoptotic effect at the level of osteoclasts.

Mild inflammation persists in the glenohumeral joint of patients with shoulder instability: Cross-sectional study

ObjectiveApproximately two-thirds of patients with history of shoulder dislocation may develop osteoarthritis (OA) of the glenohumeral joint. However, the biochemical mechanisms underlying the association between dislocation and OA are largely unknown. This study aimed to investigate macrophage markers and inflammatory cytokine expression associated with shoulder instability (SI) in comparison to rotator cuff tears (RCTs). DesignThis study included 30 patients with SI and 30 patients with RCTs. Synovial membrane samples were harvested from the rotator interval during the arthroscopic anatomical repair for both groups. The localization of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and cluster of differentiation (CD) 68 in synovial membranes was determined by immunohistochemistry. Transcript-level expressions of the inflammatory cytokines (TNFA and IL1B) and macrophage markers pan-CD68 and -M1 (CD80 and CD86) were quantified. CD80 and CD86 expression in macrophages from the SI group was confirmed using flow cytometry. ResultsTNF-α, IL-1β, and CD68 were expressed in the synovial lining layer of the synovial tissue in both groups. In addition, the mRNA expressions of TNFA, IL1B, CD68, and CD80 were significantly higher in the SI group compared to the RCT group (P ​= ​0.012, 0.014, 0.022, 0.003, respectively). In samples from the SI group, 96.3% of CD68+/CD14+ macrophages were CD86-positive, whereas 2.5% of CD68+/CD14+/CD86+ cells were CD80-positive. ConclusionsPatients with SI had higher mRNA levels of TNFA, IL1B, CD68, and CD80 than those with RCTs. These findings may partially explain the biochemical mechanism underlying the frequent development and progression of osteoarthritis in patients with SI.

Role interlake 18 in the course and progression of osteoarthritis in patients with obesityRole interlake 18 in the course and progression of osteoarthritis in patients with obesity

musculoskeletal disorders are an extremely common pathology. They are the most common cause of chronic pain and disability: every minute, more than 30% of adults suffer from joint pain or limited physical activity. These diseases significantly affect the psychosocial status of patients, their families, and caregivers. The course of joint diseases leads to loss of mobility, social autonomy; such patients have higher rates of hospitalization and mortality. That is, the quality of life significantly deteriorates, and the financial costs of health care for patients and society increase. It is proved that one of the predictors of arthrosis is overweight. In the pathogenesis of osteoarthritis and obesity, proinflammatory cytokines play an important role, the excess synthesis of which leads to the progression and chronicity of the process. Therefore, the aim of our study was to determine the dependence of interleukin-18 activity in patients with osteoarthritis, which occurs on the background of obesity and without it. The study presents the study of interleukin-18 in 75 people with osteoarthritis (OA), which occurred on the background of obesity (main group), and 50 patients with isolated OA (comparison group). The control group consisted of 37 healthy individuals. The diagnosis of OA was established based on the order of the Ministry of Health of Ukraine of 12.10.2006 "On medical care for patients with osteoarthritis", unified diagnostic criteria of the Association of Rheumatologists of Ukraine (2004), and the criteria of the American College of Rheumatologists. The presence and severity of obesity were assessed according to the criteria of the International Diabetes Federation (IDF, 2005) based on the calculation of body mass index (BMI) according to the Kettle formula. When determining the level of IL-18 in the main group, it was found that the content of this cytokine was almost two times higher than the reference values (p &lt;0.05). In the comparison group, the activity of IL-18 increased 1.6 times (p &lt;0.05). Comparison of the content of IL-18 between the study groups allowed us to determine its increase in the presence of obesity by almost 1.2 times. The increase in IL-18 content depended on the radiological stage of joint damage: the maximum value was recorded in patients of the main group with stage 2 symptoms. Apparently, such results are a consequence of the predominance of the inflammatory reaction in the progression of the pathology due to the comprehensive involvement of extra-articular components (ligaments, tendons, bags, etc.). Slightly lower levels of IL-18 in stage 1 OA are likely to be due to the involvement of a limited portion of joint tissue, while the 3rd radiological stage is characterized by a predominance of dystrophic processes. In patients with osteoarthritis, an increase in the content of IL-18 in the serum is determined, which is associated with the development of the inflammatory process in the components of the joint. The content of IL-18 has a direct correlation with overweight / obesity and the radiological stage of the process in the joints. Increased proinflammatory cytokine IL-18, which is a component of the immune system and simultaneously synthesized by adipocytes of adipose tissue, can be considered a factor that will contribute to the preservation of chronic pain and progression of the pathology. Dynamic control of IL-18 activity should be used as an indicator of the effectiveness of therapy.

Automated Risk Stratification of Hip Osteoarthritis Development in Patients With Femoroacetabular Impingement Using an Unsupervised Clustering Algorithm: A Study From the Rochester Epidemiology Project.

Background:Studies evaluating the natural history of femoroacetabular impingement (FAI) are limited.Purpose:To stratify the risk of progression to osteoarthritis (OA) in patients with FAI using an unsupervised machine-learning algorithm, compare the characteristics of each subgroup, and validate the reproducibility of staging.Study Design:Cohort study (prognosis); Level of evidence, 2.Methods:A geographic database from the Rochester Epidemiology Project was used to identify patients with hip pain between 2000 and 2016. Medical charts were reviewed to obtain characteristic information, physical examination findings, and imaging details. The patient data were randomly split into 2 mutually exclusive sets: train set (70%) for model development and test set (30%) for validation. The data were transformed via Uniform Manifold Approximation and Projection and were clustered using Hierarchical Density-based Spatial Clustering of Applications with Noise.Results:The study included 1071 patients with a mean follow-up period of 24.7 ± 12.5 years. The patients were clustered into 5 subgroups based on train set results: patients in cluster 1 were in their early 20s (20.9 ± 9.6 years), female dominant (84%), with low body mass index (<19 ); patients in cluster 2 were in their early 20s (22.9 ± 6.7 years), female dominant (95%), and pincer-type FAI (100%) dominant; patients in cluster 3 were in their mid 20s (26.4 ± 9.7) and were mixed-type FAI dominant (92%); patients in cluster 4 were in their early 30s (32.7 ± 7.8), with high body mass index (≥29 ), and diabetes (17%); and patients in cluster 5 were in their early 30s (30.0 ± 9.1), with a higher percentage of males (43%) compared with the other clusters and with limited internal rotation (14%). Mean survival for clusters 1 to 5 was 17.9 ± 0.6, 18.7 ± 0.3, 17.1 ± 0.4, 15.0 ± 0.5, and 15.6 ± 0.5 years, respectively, in the train set. The survival difference was significant between clusters 1 and 4 (P = .02), 2 and 4 (P < .005), 2 and 5 (P = .01), and 3 and 4 (P < .005) in the train set and between clusters 2 and 5 (P = .03) and 3 and 4 (P = .01) in the test set. Cluster characteristics and prognosis was well reproduced in the test set.Conclusion:Using the clustering algorithm, it was possible to determine the prognosis for OA progression in patients with FAI in the presence of conflicting risk factors acting in combination.

METTL3-mediated m6A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression

ObjectiveThe aim of the study was to investigate the role and regulatory mechanisms of fibroblast-like synoviocytes (FLSs) and their senescence in the progression of osteoarthritis (OA).MethodsSynovial tissues from normal patients...

Facet Joint Violation by Thoracolumbar Percutaneous Pedicle Screw and Its Effect on Progression of Facet Joint Osteoarthritis.

Study DesignA retrospective study.PurposeThis study aimed to investigate the rate and associated factors of facet violation (FV) in percutaneous pedicle screws (PPS) from the thoracic to the lumbar spine and the effect of FV on facet osteoarthritis (OA) progression.Overview of LiteratureSome reports claim PPS has a higher FV rate than conventional open surgery. However, previous reports of FV in PPS were limited to the lumbar spine; only a few reports included the thoracic spine.MethodsThe present study includes 1,028 PPS inserted from T4 to S1 in 218 patients. The rate of FV and facet OA progression after FV were assessed using computed tomography (CT) scans conducted postoperatively at 1 week and 6 months or more. To identify factors associated with FV or facet OA progression after FV, a multivariate logistic regression analysis was conducted. To investigate whether FV caused facet OA progression, we compared OA progression between patients with FV and matched controls.ResultsFV was observed in 68 (6.6%) of the 1,028 facets, and the thoracic spine was identified as an independent factor associated with FV. OA progression was detected in 48.2% of the cases with FV via CT scans conducted postoperatively at a mean duration of 22.6 months. The time between CT scans was identified as an independent factor for facet OA progression after FV. The rate of OA progression in patients with FV was significantly greater than that of the controls.ConclusionsFV was observed in 6.6% of the patients, and the thoracic spine was identified as an independent factor associated with FV. OA progression of a violated facet occurs over time. FV is considered a complication leading to facet OA progression.

Validation of a three dimensional musculoskeletal ultrasound system for use in hands and wrists

Purpose: The effect of chronic synovitis on the progression of osteoarthritis pathology is a relatively new but supported concept in the fields of rheumatology and hand surgery that has been linked to pain and disability in patients. Currently, the gold standard for diagnosing synovitis in the wrists and hands is a clinical examination and the use of 2 dimensional (2D) musculoskeletal ultrasound imaging (US). Major limitations associated with this method are the lack of quantitative measurement tools available and the fact that physicians have to be able to mentally reconstruct the patient’s 3-dimensional anatomy from the 2-dimensional images provided. These limitations can be overcome by using a 3-dimensional ultrasound (3DUS) system to quantitatively measure the size of synovial hypertrophy, effusions, ganglions and osteophytes as well as having a 3D reconstruction of the patient’s hand. The aim of this work is to develop a 3D ultrasound system for imaging the hand and wrist. This paper reports on the development, geometric, and volumetric validation for wrist/hand 3D ultrasound imaging. Methods: A mechatronic wrist/hand imaging system was designed and created to operate with a conventional 2D US imaging system. The scanning system features a motor which contains a single integrated electromagnetic encoder that records the rotational position of the motor. This motor drives a lead screw which in turn moves the transducer, which is submerged in a water bath, along the linear axis to acquire a series of 2D images. The encoder information provides the software with the position of each 2D ultrasound frame. These conventional diagnostic 2D US images are then reconstructed into a 3D US images from a licensed ultrasound machine. The geometric validation of the system was done using a multi-layered monofilament grid phantom with spacings of 10 mm and the Euclidean distances between the wires were measured. The volumetric validation was conducted using a simulated synovial tissue phantom and the images were analyzed using 3D-Slicer to manually segment individual slices in the 3D image. These slices were then interpolated to construct a 3D segmentation of the phantom. This process was repeated over four days to test the intra-rater reliability of the system. The 3D volumes were compared to those found using magnetic resonance imaging (MRI) and the known volume of the agar phantom. Results: The largest error and variance recorded from the geometric validation measurements was 0.0856± 0.0087mm and was acquired from the reconstruction plane. The remaining linear measurement errors were all < 1%. The error between the mean phantom volume measurements and the known synovium phantom volume was 5.99% and 2.43% for the 3D US device and MRI respectively. Linear regression for volumetric measures revealed an R2 value of 0.4736 with a p-value of 0.20, revealing no significant correlation between the measurements made over the course of 4 days for the 3D US device. The percent difference in the volume measurements from the 3D US device and MRI was 0.814%. Conclusions: A mechatronic 3D ultrasound imaging system was developed for the wrist and hand. Successful geometric and volumetric validation demonstrates feasibility for implementation in a clinical setting. Current work evaluates system ability to accurately and quantitatively classify synovitis in first carpometacarpal joint and distal radial injury patients to investigate the relationship between chronic inflammation and the progression of osteoarthritis in patients.

Prior Pelvic Osteotomy Affects the Outcome of Subsequent Total Hip Arthroplasty

BackgroundAlthough pelvic osteotomy (PO) is an important surgical procedure that can alleviate symptoms and potentially slow progression of osteoarthritis in patients with development dysplasia of the hip, some patients eventually require conversion to total hip arthroplasty (THA). This study aimed to determine the outcome of conversion THA in patients with prior PO. MethodsForty nine patients with a history of prior PO who underwent conversion THA at a single institution were matched at a 1:3 ratio based on the date of surgery, age, gender, and body mass index with 147 developmental dysplasia of the hip patients who underwent primary THA without prior PO. A retrospective chart review was performed to compare outcomes at a minimum follow-up of 2 years. ResultsPatients with prior PO required more supplemental screw fixation for the acetabular component (59.2% vs 38.1%, P = .016), more autologous bone grafting (24.5% vs 11.6%, P = .048), had a longer mean operative time (106.0 vs 79.8 minutes, P < .001), and greater estimated blood loss (350.0 vs 206.8 mL, P = .015). Patients with prior PO had smaller cup version angle (26.0° vs 29.0°, P = .012) and greater discrepancy in the limb length (10.3 vs 7.26 mm, P = .041). Eight hips (16.3%) with prior PO and 6 (4.1%) without osteotomy required reoperation (P = .008). There was no difference in outcome scores at the latest follow-up.Conclusion: THA after prior PO is technically demanding, leading to longer operative times, greater blood loss, and variation in implant placement. Although functional outcomes are similar, THA after a prior PO is more likely to require reoperation. ConclusionTHA after prior PO is technically demanding, leading to longer operative times, greater blood loss, and variation in implant placement. Although functional outcomes are similar, THA after a prior PO is more likely to require reoperation.

FRI0426 EMOTIONAL COMPONENTS AND INFLAMMATION ARE HIGHLY RELEVANT IN PAIN REPORTED BY KNEE OSTEOARTHRITIC PATIENTS

Background:Osteoarthritis (OA) is a leading cause of disability in elderly and the most frequent form is knee OA (KOA) (1). Pain is the principal symptom that leads patients to visit clinicians, and it is the main reason, together with functionality, for patients to undergo a total knee replacement (TKR) after apparently unsuccessful conservative (CNV) treatments (2). It is well-known that there is a poor correlation between the radiographic severity (based on Kellgren &amp; Lawrence (KL) score) and the reported pain (3), so other variables may be responsible for the intensity of pain.Objectives:Identifying the leading causes of pain in each patient would improve the management of the disease. In this study we aim to investigate the role of emotional components, nociception process and inflammation in treatment decision, as a global measure of pain suffered by KOA patients, taking into account sex, age and BMI.Methods:KOA patients, carefully selected to be idiopathic, graded 2-3 in KL, were recruited at Hospital del Mar. The following variables were recorded: WOMAC, Hospital Anxiety and Depression Scale (HAD), Pain Catastrophizing Scale (PCS), tender points (TP) (measure with a pressure algometer at points defined in the Arendt-Nielsen extended peripatellar map), synovial hypertrophy (SH) and effusion (SE) (measure by ultrasounds), and PCR and ESR serum levels. Patients were classified according to 4 factors: treatment (CNV/TKR), sex, age (60-67/68-75) and BMI (&lt;30/&gt;30). All groups were balanced. Multivariate and correlations analysis were performed.Results:Eighty-seven patients have been recruited. Patients from the TKR group present significant higher WOMAC (p=0.000), PCS (p=0.002) and SE (p= 0.038) values than CNV ones, without interaction with the other factors, except for SE, that presents interaction with BMI (Fig. 1). Women reported significant upper WOMAC (p=0.001) and HAD rates (p=0.020), but also higher number of TP and ESR levels (p= 0.000 and 0.002, respectively). The level of sensitization was significantly higher in women than in men (p=0.000). Several significant correlations were found, mainly between WOMAC and emotional components, as well as between TP and WOMAC, PCS, and inflammation markers (Table 1).Conclusion:PCS is an emotional component that could explain in part the lack of correlation between joint status and patient’s symptomatology. Working out strategies for pain management could improve this PCS values and therefore reduce the need for TKR. Furthermore, this study also highlights the two mainly types of OA etiology: mechanical and inflammatory. It suggests that inflammation is mostly responsible for OA progression in patients with low BMI, and plays a strong role in women pathology. Finally, specific treatments targeting central pain sensitization could also improve the management of the pathology in women.

Multiple umbilical cord–derived MSCs administrations attenuate rat osteoarthritis progression via preserving articular cartilage superficial layer cells and inhibiting synovitis

Background/objectivesArticular cartilage erosion probably plays a substantial role in osteoarthritis (OA) initiation and development. Studies demonstrated that umbilical cord–derived mesenchymal stem cells (UCMSCs) could delay chondrocytes apoptosis and ameliorate OA progression in patients, but the detailed mechanisms are largely uncharacterised. In this study, we aimed to study the effects of UCMSCs on monosodium iodoacetate (MIA)–induced rat OA model, and explore the cellular mechanism of this effect. MethodsIntra-articular injection of 0.3 ​mg MIA in 50 ​μL saline was performed on the left knee of the 200 ​g weight male Sprague-Dawley rat to induce rat knee OA. A single dose of 2.5 ​× ​105 undifferentiated UCMSCs one day after MIA or three-time intra-articular injection of 2.5 ​× ​105 UCMSCs on Days 1, 7 ​and 14 were given, respectively. Four weeks after MIA, joints were harvested and processed for paraffin sections. Safranine-O staining, haematoxylin and eosin staining ​and immunohistochemistry of MMP-13, ADAMTS-5, Col-2, CD68 ​and CD4 were performed to observe cartilage erosion and synovium. For in vitro ​studies, migration ability of cartilage superficial layer cells (SFCs) by UCMSCs were accessed by transwell assay. Furthermore, catabolism change of MIA-induced SFCs by UCMSCs was performed by real-rime polymerase chain reaction of Col-X and BCL-2 genes. CCK-8 assay was performed to check proliferation ability of SFCs by UCMSCs-conditioned media. ResultIn this study, we locally injected human UCMSCs, which is highly proliferative and noninvasively collectible, into MIA-induced rat knee OA. An important finding is on obviously ameliorated cartilage erosion and decreased OA Mankin score by repeated UCMSCs injection after MIA injection compared with single injection, both of which attenuated OA progression compared with vehicle. Interestingly, we observed significantly increased number of SFCs on the articular cartilage surface, probably related to elevated proliferation, mobilisation and inhibited catabolism marker: Col-X and BCL-2 gene expression of cultured SFCs by UCMSCs-conditioned media treatment in vitro. In addition to the change of unique SFCs, catabolism markers of ADAMTS-5 and MMP-13 were substantially upregulated in the whole cartilage layer chondrocytes as well. Strikingly, MIA-induced inflammatory cells infiltration, on both CD4+ Th cells and CD68+ macrophages, and hyperplasia of the synovium, which was alleviated by repeated UCMSCs injection. ConclusionOur study demonstrated a critical role of repeated UCMSCs dosing on preserving SFCs function, cartilage structure and inhibiting synovitis during OA progression, and thus provided mechanistic proof of evidence for the use of UCMSCs on OA patients in the future. The translational potential of this articleUCMSCs are a relatively “young” stem cell, and noninvasively collectible. In our study, we clearly demonstrated that it could effectively delay OA progression, possibly through reserving SFCs function and inhibiting synovitis. Therefore, it could be a new promising therapeutic cell source for OA after further clinical trials.

Association between knee alignment, articular cartilage degradation, and subchondral trabecular bone remodeling in patients with knee osteoarthritis

Purpose: Knee osteoarthritis (OA) is a common disabling disease involving the entire joint tissue, its onset and progression are affected by many factors. However, the current number of studies investigating the relationship between subchondral trabecular bone (STB), knee alignment and articular cartilage degradation is limited. We aimed to investigate the variation in tibial plateau STB remodeling in knee OA patients and their association with knee alignment (hip-knee-ankle, HKA, angle) and articular cartilage degradation. Methods: Forty-three knee OA patients scheduled for total knee arthroplasty (TKA) underwent preoperative radiography to measure the HKA angle and Kellgren-Lawrence grade. Tibial plate specimens collected from TKA was used for histology, histomorphometric measurements, and immunohistochemistry to assess subchondral bone remodeling and cartilage degradation ((OARSI score). Correlations between HKA angle, OARSI score, and STB remodeling parameters were evaluated. Differences in STB remodeling parameters between varus and valgus groups based on the HKA angle were examined. Results: The HKA angle was significantly correlated with all STB remodeling parameters (p<0.01). The HKA angle was more correlated with the medial-to-lateral ratios of the remodeling parameters than with the medial or lateral tibia plateaus. The HKA angle and all STB remodeling parameters are significantly correlated with OARSI score (p<0.01). Conclusions: The variation of tibial plateau STB structural and remodeling indices is associated with the HKA angle and cartilage degradation. Knee malalignment causes the abnormal STB remodeling and microstructural sclerosis potentially affecting transmission of loading stress from the cartilage to the subchondral bone, and then resulting in accelerated OA progression in patients with knee OA. The results indicate that correction of knee malalignment could affect STB remodeling and then intervene the occurrence and development of OA. In addition, the improvement in subchondral bone with bone-metabolism agents may help mitigate OA progression.

Articular Cartilage Degradation and Aberrant Subchondral Bone Remodeling in Patients with Osteoarthritis and Osteoporosis.

Osteoarthritis (OA) and osteoporosis (OP) are two skeletal disorders associated with joint structures. Occasionally, OA and OP occur in the same patient. However, the effect of OP changes on OA progression in patients with osteoporotic OA (OP-OA) has not been reported, especially the potential association between subchondral bone and articular cartilage. Thus we investigated the alterations in the microstructure, biomechanical properties, and remodeling of subchondral bone as well as their association with cartilage damage in the hip joint of patients with OP-OA. Thirty-nine femoral head specimens were obtained from patients who underwent total hip arthroplasty (OA group, n = 19; OP-OA group, n = 20), and healthy specimens from cadaver donors were used (control group, n = 10). The microstructure and biomechanical properties of subchondral bone were evaluated by micro-computed tomography and micro-finite-element analysis. Histology, histomorphometric measurements, and immunohistochemistry were used to assess subchondral bone remodeling and cartilage damage. Linear regression analysis was performed to elucidate the relationship between subchondral bone and articular cartilage. In the subchondral bone of the OP-OA group, compared with that of the OA group, aberrant bone remodeling leads to an inferior microstructure and worsening biomechanical properties, potentially affecting transmission of loading stress from the cartilage to the subchondral bone, and then resulting in accelerated OA progression in patients with OP-OA. The results indicate that changes in subchondral bone could affect OA development and the improvement in subchondral bone with bone-metabolism agents may help mitigate OA progression when OP and OA coexist in the same patients. © 2019 American Society for Bone and Mineral Research.

Deteriorating subchondral bone microstructure accelerates osteoarthritis progression in developmental dysplasia of the hip than in primary osteoarthritis

Purpose: Developmental dysplasia of the hip (DDH) is recognized as a frequent cause of secondary osteoarthritis (OA). Compared with primary hip OA, DDH often causes changes in the anatomical hip structure and leads to more severe symptoms and imaging manifestations. However, the subchondral bone microstructure and biomechanical property of patients with DDH has not been previously evaluated. Thus, we aimed to analyze the subchondral bone and its association with articular cartilage damage in DDH and primary hip OA through a novel technique for microstructural observation, the individual trabecula segmentation (ITS) analysis. We hypothesized that the changes of subchondral bone in DDH could partly account for the acceleration of OA progression. Methods: Thirty-three femoral head specimens obtained from patients underwent total hip arthroplasty (DDH, n=17; primary OA, n=16) were scanned using Micro-CT, and the selected volume of interest (VOI) was processed by ITS to obtain the microstructural types of subchondral bone. The biomechanical property of VOI was analyzed by micro-finite element analysis (μFEA) and cartilage damage was evaluated by the histology. Moreover, the linear regression analysis was utilized to indicate the association between microstructures, biomechanical property and articular cartilage. Results: Compared with the OA group, the DDH group showed lower total bone volume fractions (BV/TV) and plate bone volume fractions (pBV/TV) by the ITS-based analysis (p<0.05). The plate-to-rod ratio was significantly higher in the OA group than in the DDH group (p<0.05). Remarkably, there were varying degrees of discrepancy between the two groups in pTb.N/rTb.N (plate/rod trabecular number), pTb.Th/rTb.Th (plate/rod trabecular thickness), pTb.S/rTb.L (plate surface area and rod length) and P-P Junc.D/R-R Junc.D/P-R Junc.D (junction density with different trabecular modes). Moreover, the μFEA, histology and linear regression analysis revealed that the subchondral bone in patients with DDH had inferior biomechanical property, and the cartilage damage was severer than patients with OA due to the different subchondral bone microstructures. Conclusions: In this study, our findings detected a less connected, more widely separated trabecular network and deteriorating subchondral bone microstructure in patients with DDH than those with primary OA. The mass and type changes of subchondral bone may contribute to worsening biomechanical property and cartilage damage, thus leading to the acceleration of OA progression in patients with DDH.

A Possible New Radiographic Predictor of Progression of Osteoarthritis in Developmental Dysplasia of the Hip: The Center Gap.

Patients with comparable severities of developmental dysplasia of the hip (DDH) may variably progress to osteoarthritis (OA) over time. Although joint congruency may be associated with OA progression in patients with DDH, it has only been assessed subjectively. We assessed the gap between the rotational centers of the acetabulum and femoral head (center gap) as a possible predictive measure of OA progression in patients with DDH. In patients with bilateral DDH, we asked: (1) What is the probability of OA progression (Tönnis grade) or symptom development (pain) in the asymptomatic contralateral hip of patients with DDH undergoing unilateral joint-preserving surgery? (2) Is the center gap measurement associated with OA progression or symptom development in these hips? (3) Is the center gap measurement correlated with previous radiographic parameters? A total of 297 patients (319 hips) underwent unilateral eccentric rotational acetabular osteotomy at our institution between July 1989 and December 1999. We performed no other joint-preserving surgery to treat patients with DDH during this timeframe. The inclusion criteria for the study were patients younger than 55 years of age, the contralateral hip classified as Tönnis Grade 0, no previous surgical interventions, and asymptomatic at the time of eccentric rotational acetabular osteotomy (155 patients, 155 hips). The exclusion criteria were a contralateral hip without dysplasia (four patients, four hips), loss to followup before 10 years (42 patients, 42 hips [27%]), or missing medical records or radiographs (21 patients, 21 hips [14%]). The remaining 88 patients (88 hips; 11 males and 77 females) with a mean age of 39 years (range, 17-53 years) and mean followup of 20 years (range, 10-27 years) were analyzed. From the institutional database, radiographic parameters including the center gap in the AP view were assessed using radiographs at the time of eccentric rotational acetabular osteotomy, and the Tönnis grade was recorded 1 year postoperatively and annually thereafter retrospectively. We defined migration of the rotational center of the femoral head based on the rotational center of the acetabulum in the horizontal plane as center gap X (mm) and in the vertical plane as center gap Y (mm) and defined the absolute value between the centers as center gap distance (mm). Using κ statistics, intra- and interobserver reliabilities were determined to be 0.896 and 0.857 for center gap X, 0.912 and 0.874 for center gap Y, and 0.912 and 0.901 for the center gap distance, respectively. When patients reported any contralateral ipsilateral hip pain during clinic visits, the hip was considered symptomatic. Kaplan-Meier survivorship analyses were performed with OA progression or symptom development in the nonoperative hip as the endpoint. Multivariate analyses were performed to assess risk factors for each outcome using the Cox proportional hazards model. Correlation analyses between the center gap and other parameters including lateral center-edge angle, femoral head extrusion index, acetabular depth-to-width index, femoral head lateralization, minimum width of the joint space, head sphericity, and joint congruency were performed using Pearson's correlation coefficient. At 20 years postoperatively, the probability of OA progression in the nonoperative hip was 13% (95% confidence interval [CI], 7.1-22.1) and the probability of symptom development was 34% (95% CI, 24.7-46.1). The center gap X measurements in the groups with OA progression (lateral 2.0 ± 2.1 [SD] mm) or symptom development (lateral 0.9 ± 2.4 mm) took a more lateral direction than those in the group without OA progression (medial 0.4 ± 2.1 mm) or symptom development (medial 0.5 ± 2.0 mm) (OA progression, p < 0.001; symptom development, p = 0.005). The center gap Y measurements in the groups with OA progression (distal 2.7 ± 7.1 mm) or symptom development (distal 2.1 ± 6.0 mm) took a more distal direction than those in the group without OA progression (proximal 1.6 ± 6.2 mm) or symptom development (proximal 2.5 ± 6.1 mm) (OA progression, p = 0.027; symptom development, p = 0.001). Independent risk factors for OA progression were the femoral head extrusion index (hazard ratio [HR], 1.11; 95% CI, 1.01-1.22; p = 0.028) and the center gap X (HR, 1.52; 95% CI, 1.07-2.16; p = 0.019), whereas no independent risk factors for symptom development were found. The center gap in the horizontal plane had no correlations with any other radiographic parameter studied. The center gap in the horizontal plane had a modest association with OA progression in this group of patients with DDH. Future studies are needed to determine the normal value of the center gap for patients without DDH and to assess the center gap in lateral radiographic views. Level IV, prognostic study.

Clinical and radiological outcome at mean follow-up of 11 years after hip arthroscopy.

The use of hip arthroscopy (HA) has substantially increased over the last decade. However, while the benefits of HA after 1year in patients with femoroacetabular impingement (FAI) are well documented, long-term data on the progression of osteoarthritis (OA) or patient-reported outcomes (PROMs) are lacking. To evaluate long-term clinical and radiological outcomes after HA. Preoperative clinical records, operative notes, and radiographs from all patients who underwent HA at our hospital between 1998 and 2006 were reviewed. Exclusion criteria were previous hip surgery or diagnostic HA. Primary endpoints were subsequent total hip arthroplasty (THA) or other hip surgery. Secondary endpoints were OA progression and PROMs. HA was performed in 92 consecutive patients from 1998 to 2006. Indications for HA were FAI, labral lesions, early OA, and focal osteochondral defects. Mean follow-up was 11.2years (SD 2.5, range 7.9-16). Data from 43 patients were available for analysis; 38 patients were excluded, and 11 were lost to follow-up. 20 patients had subsequent hip surgery, of which 11 patients required THA. 33 patients (77%) stated that they would undergo HA again under the same circumstances. Longitudinal radiological analysis showed no significant OA progression in patients without THA. The Forgotten Joint Score-12 was the only PROM to significantly differ between patients who had no further surgery and patients who had undergone revision (p = 0.037). There was no significant OA progression on plain radiography at an average of 11years post-HA. Sound indication criteria is essential, as 45% of patients required subsequent surgery.

Tumor necrosis factor-inhibitor treatment duration is associated with lower risk of hand osteoarthritis progression in patients with recent-onset rheumatoid arthritis after 10-year follow-up

Tumor necrosis factor-inhibitor treatment duration is associated with lower risk of hand osteoarthritis progression in patients with recent-onset rheumatoid arthritis after 10-year follow-up