Displaying One Session

Potsdam 1 Free Papers
Session Type
Free Papers
Date
14.04.2022
Time
14:15 - 15:45
Room
Potsdam 1
CME Evaluation
Podium Presentation Culture Models

18.3.1 - Co-administration of Glucocorticoid and Hyaluronic Acid in a 2D-Culture With Cytokine-Treated Osteoarthritic Chondrocytes

Presentation Topic
Culture Models
Date
14.04.2022
Lecture Time
14:15 - 14:24
Room
Potsdam 1
Session Type
Free Papers
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Intra-articular injections of glucocorticoids (GC) or hyaluronic acid (HA) are commonly used interventions for patients suffering from knee osteoarthritis (OA). Efforts are made to combine both substances to achieve a chondroprotective and anti-inflammatory effect. Clinical studies have shown benefits, but still, data on the cellular level are lacking. This study aimed to investigate the effect of a GC, HA, and a mix of both substances on cytokine-treated chondrocytes in vitro.

Methods and Materials

Chondrocytes isolated from human articular cartilage were seeded on 6- and 24-wells. Mimicking OA's inflammatory state, cells were treated with pro-inflammatory cytokines (IL-1β, IL-17) for six days, whereby after three days, test substances (10%) were added to the culture medium. To investigate the test substances' impact, chondrocytes were analyzed on day three and day six concerning their morphology, expression of anabolic and catabolic genes, metabolic activity, cytokine release, and reactive oxygen species (ROS).

Results

Catabolic (MMP3, MMP13) and inflammatory (iNOS) markers were less expressed in cells treated with GC and co-administration (GC+HA) compared to HA alone. In addition, co-administration and HA showed better metabolic activity than GC alone, while GC and GC+HA reduced pro-inflammatory cytokine release. In contrast, GC leads to a reduced ROS production in comparison to HA and co-administration. Furthermore, F-actin levels were increased in cells treated with HA or co-administration.

Conclusion

Supplementing cytokine treated osteoarthritic chondrocytes with 10% of GC or a combination of GC and HA had an anti-inflammatory effect as shown in gene expression (catabolic genes) results and cytokine release. On the other hand, HA alone showed no anti-inflammatory effect but led in the combination to reduced adverse effects of GC. Therefore, it can be concluded that the combination product was favorable compared to single substances.

Collapse
Podium Presentation Osteoarthritis

18.3.2 - Evaluation of the Effect of Celecoxib on Cartilage in Vitro and in a Rat Osteoarthritis Model

Presentation Topic
Osteoarthritis
Date
14.04.2022
Lecture Time
14:24 - 14:33
Room
Potsdam 1
Session Type
Free Papers
Disclosure
T.J.M. Welting and M.M.J. Caron are listed as inventor on patents: WO2017178251, WO2017178253 and US 20130123314. T.J.M. Welting, P.J. Emans and L.W. van Rhijn have shares in Chondropeptix BV.

Abstract

Purpose

Celecoxib, a non-steroidal anti-inflammatory drug and selective cyclooxygenase-II inhibitor, is used to reduce pain and inflammation in knee osteoarthritis patients. However, its potential protective effect on cartilage degeneration is disputed. In this study, we aimed to investigate the chondroprotective effect of celecoxib on cartilage-secreted molecules and gene expression in vitro, and its protective effect on cartilage in vivo.

Methods and Materials

Sixteen articular cartilage explants (tibia and femur, MEC 08-04-028) from osteoarthritis patients cultured for 24 hours with 10µM celecoxib or dimethyl sulfoxide (v/v 1:1000, vehicle). Secreted prostaglandin (PGE2, PGF, PGD2 and TXB2) concentrations were determined by ELISA and secreted proteins were measured with label-free liquid chromatography tandem mass spectrometry in conditioned media. To determine celecoxib chondroprotective effects in vivo, an osteoarthritis rat model (ACLT/pMMx model, DEC13-052) was used to investigate cartilage osteoarthritis-related degeneration 4 weeks after an intra-articular injection of celecoxib or control (92.25ng celecoxib or 25μl 0.9% NaCl) treatment. Histopathological scoring was applied to score osteoarthritis severity 12 weeks after injection.

Results

PGE2 (23397 vs 387 pg/100mg), PGF (5500 vs 401 pg/100mg), PGD2 (3386 vs 159 pg/100mg) and TXB2 (397 vs 176 pg/100mg) release by cartilage explants was significantly reduced in the celecoxib treated group. Furthermore, mass spectrometry analysis revealed a significant increase of TIMP-2 and reduction of target of Nesh-SH3 and SPARC protein secreted by cartilage samples treated with celecoxib. In the in vivo study, cartilage degeneration in rat knees treated with celecoxib was significantly reduced (average OARSI score 4.9 (osteoarthritis) vs 1.9 (control)).

prostaglandins.pngproteins.png

Conclusion

In this study, we found an anti-inflammatory and chondroprotective effect of celecoxib on cartilage in vitro, and a protective effect for cartilage degeneration in vivo. This will add hopeful information to the ongoing discussion on the conflicting results for celecoxib in the use for osteoarthritis treatment.

Collapse
Podium Presentation Osteoarthritis

18.3.3 - Diabetes is Associated With an Increased Osteoarthritis Incidence in Non-Human Primates

Presentation Topic
Osteoarthritis
Date
14.04.2022
Lecture Time
14:33 - 14:42
Room
Potsdam 1
Session Type
Free Papers
Disclosure
M.Cline: Research support: Roche N.Mohamed: none J.Olson: none C.Patel: none J.Plate: Research support: Biocomposites Inc., Consultancy: Smith & Nephew, Total Joint Orthopedics, Other: (Publishing royalties): VisualDX J.Willey: none

Abstract

Purpose

Cartilage breakdown in the joint, or osteoarthritis (OA), and diabetes share several risk factors including obesity and metabolic changes. Tracking these conditions in humans may be difficult, but non-human primates (NHPs) are a fully-translatable model longitudinally tracked at our institution with annual computed tomography (CT) scans. This study was designed to assess the relationship between OA, diabetes, and obesity in NHPs. We hypothesize that OA will be significantly associated with the presence of diabetes.

Methods and Materials

201 rhesus macaques were analyzed (mean age=11.6 years). 163 were irradiated prior to study enrollment, while 38 were adopted as controls. Radiation was assessed as a potential confounder of OA and diabetes development. Osteoarthritis was determined from annual CT scans using a modified Kellgren-Lawrence (KL) grading system for the knee, hip, and shoulder joints, and spine. Diabetes and obesity were determined from health records. Descriptive statistics and chi-square analyses were performed using SPSS. All significance values were set at p<0.05.

Results

No relationship was seen between radiation and overall OA status (p=0.208). However, OA was significantly higher in non-irradiated animals for the knee (p=0.049), hip (p=0.002), shoulder (p=0.003), and spine (p=0.003). Radiation was not associated with diabetes (p=0.264), and obesity was more common in the non-irradiated cohort (p=0.008).

Diabetic animals had significantly higher incidences of OA of the knee (p=0.001), hip (p<0.001), shoulder (p<0.001), and spine (p=0.001), resulting in a higher incidence of overall OA in diabetic NHPs (p<0.001). Obesity was significantly higher among diabetics (p<0.001), and was significantly associated with all arthritic joints (all p<0.001).

Conclusion

Osteoarthritis of all joints was significantly higher in diabetic and obese NHPs. Radiation had no effect on OA or diabetes. Co-incidence of diabetes and obesity appears to play a signifcant part in joint degeneration, and provides a foundation for future investigative studies to determine the pathways that may potentiate these diseases.

Collapse
Podium Presentation Cartilage and Meniscus

18.3.4 - Synovial Fluid Fracture Hematoma Causes Cartilage Damage and Chondrocyte Death That is Partially Attenuated by Anti-Inflammatory Agents

Presentation Topic
Cartilage and Meniscus
Date
14.04.2022
Lecture Time
14:42 - 14:51
Room
Potsdam 1
Session Type
Free Papers
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Intra-articular ankle fracture (IAF) causes post-traumatic osteoarthritis (PTOA) but the exact mechanism is unknown. Pro-inflammatory mediators have been shown to be present in the synovial fluid fracture hematoma (SFFH), but have not been linked to cartilage damage. The purpose of this study was to determine if the SFFH causes cartilage damage and whether this damage can be attenuated by commercially available therapeutic agents.

Methods and Materials

SF was obtained from 54 intra-articular ankle fractures and cultured with cartilage discs from the dome of fresh allograft human tali and randomly assigned to one of the following groups: (A) control—media only, (B) SFFH from days 0-2 after fracture, (C) SFFH from days 3-9, and (D) SFFH from days 10-14, (E) group B + IL-1Ra, and (F) group B + doxycycline. The cartilage discs underwent histological evaluation for cell survival and cartilage matrix components. The spent media were analyzed for inflammatory mediators.

screen shot 2021-10-12 at 6.32.59 am.png

Results

Cartilage discs cultured with SFFH in groups B, C, and D demonstrated significantly increased production of cytokines, metalloptoteinases (MMPs), and extracellular matrix breakdown products. Safranin O staining was significantly decreased in group B. The negative effects on cartilage were partially attenuated with the addition of either IL-1RA or doxycycline. There was no difference in chondrocyte survival among the groups.

screen shot 2021-10-12 at 6.32.44 am.png

Conclusion

Exposure of uninjured cartilage to IAF SFFH caused activation of cartilage damage pathways evident through cartilage disc secretion of inflammatory cytokines, MMPs, and cartilage matrix fragments. The addition of IL-1Ra or doxycycline to SFFH culture partially attenuated this response.

Collapse
Podium Presentation Osteoarthritis

18.3.5 - The Synovial Environment Steers Cartilage Deterioration and Regeneration

Presentation Topic
Osteoarthritis
Date
14.04.2022
Lecture Time
14:51 - 15:00
Room
Potsdam 1
Session Type
Free Papers
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Osteoarthritis (OA) is initiated by trauma in the joint that fails to heal. The trauma leads to activation of immune cells that orchestrates neighboring progenitor cells to migrate to the injured site where they attach, proliferate and undergo differentiation for regeneration to occur. It is currently not understood why this process fails upon chondral injury in the synovial joint.

Methods and Materials

Synovial fluid(SF) collected from patients diagnosed with early OA was processed to separate cells and SF. Cells were assessed for attachment, proliferation, migration and chondrogenic differentiation in the presence/absence of SF. Characterization of the SF led to the development of an immunomodulatory cell-treatment based on cartilage activated T-cells and progenitor cells. The cell treatment was evaluated by intra-articular injection in a rat model of Monosodium Iodoacetate-(MIA) induced OA. OA progression and resolution was evaluated by histology and IHC three weeks post cell-injection. In a final step the autologus treatment was evaluated in a compassionate use clinical study.

Results

SF-derived progenitor cells were able to attach, migrate, proliferate and undergo chondrogenic differentiation under standard conditions.

These abilities were impaired (p<0.05) in the presence of 10% SF, figure 1.icrs figure 1.jpg Characterization of the SF confirmed de-differentiation of healthy articular chondrocytes as well as activation of pro-inflammatory events including neutrophil migration and elastase activity together with lymphocyte proliferation. Intraarticular injection of the pro-regenerative cell treatment in a rat OA-model led to articular cartilage regeneration confirmed by a matrix rich in glycosaminoglycans, collagen type 2 and Lubricin, figure 2. icrs figure 2.jpg

The treatment led to an improved OARSI score for matrix degradation of 0 (p<0.05), from 4 in the non-treated control. In a clinical study for compassionate use, the immunomodulatory treatment restored deteriorated articular cartilage upon trauma-induced OA.

Conclusion

These findings confirm the crucial role of a balanced immune environment as a way to regenerate hyaline articular cartilage while treating degenerative joint disease.

Collapse
Podium Presentation Cartilage /Cell Transplantation

18.3.6 - One-Stage Cartilage Recycling Facilitated by Adipose MSCs Safe and Clinically Effective (RECLAIM)

Presentation Topic
Cartilage /Cell Transplantation
Date
14.04.2022
Lecture Time
15:00 - 15:09
Room
Potsdam 1
Session Type
Free Papers
Disclosure
Dr. D.B. Saris, Cartilage: Governing board, JRF: Research, Smith & Nephew. Dr. A.J. Krych, Arthrex, Inc, study conduct; grants from Aesculap/B.Braun, Ceterix, Histogenics, ICRS. Dr. A.B. Dietz, inventor, Mill Creek Life Sciences

Abstract

Purpose

Working towards safe and reliable one stage cell-based cartilage repair requires FDA monitored IND validation of MSC facilitated cartilage repair. This study evaluates the reproducibility and novel allogeneic cell source and allows comparison to a European cohort.The purpose of this study was to assess the safety and initial clinical outcomes following REcycled CartiLage Auto/Allo IMplantation for the Treatment of Focal Knee Cartilage Defects (RECLAIM).

Methods and Materials

This was a single-arm interventional FDA IND study conducted on 25 patients with age ranging between 21 and 40 years old. Following the RECLAIM procedure, patients were queried for adverse events, clinical outcomes were evaluated using patient reported outcomes that included the KOOS (Knee injury and Osteoarthritis Outcome Score), visual analog scale for pain. Repeated measure analysis ANOVA was used to test statistical significance p<.5. Results for all treated patients with a minimum of 12 months follow up or earlier safety issue are reported.

Results

Among 13 participants who completed the 12-month follow-up there were no treatment related adverse event. Complications and adverse events were as predicted from previous studies. Participants experienced clinically relevant and statistically significant improvements in mean VAS pain and all KOOS subscales scores at 3, 6 and 12 months. (Figure1).

icrs_repetedmeasures_figue1.jpg

Conclusion

RECLAIM is a feasible one-stage cartilage regeneration option, demonstrating good safety profile and encouraging clinical outcomes in this phase 1 trial. Also, improvements in pain, function, and quality of life were achieved in this small cohort of patients with symptomatic cartilage defects of the knee. Overall, these results provide external validation and confirm comparability, safety and initial effectiveness of IMPACT and RECLAIM procedure.

Collapse
Podium Presentation Osteoarthritis

18.3.7 - Grip on Knee Osteoarthritis: Joint Distraction Versus Arthroplasty (GODIVA) - A Large Randomized Controlled Multicenter Trial

Presentation Topic
Osteoarthritis
Date
14.04.2022
Lecture Time
15:09 - 15:18
Room
Potsdam 1
Session Type
Free Papers
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

For relatively young (≤65 year) patients with end-stage knee osteoarthritis (OA) with persistent, pain, insufficiently responding to conservative management, knee arthroplasty (KA) is a frequently applied treatment. A primary KA in this age group often requires revision surgery later in life. Revision surgery is complex, costly, and accompanied by multiple complications. Knee joint distraction (KJD) is a joint preserving treatment that delays the need for primary KA. KJD has proven to be effective in reducing pain and stiffness and improving function in studies (Jansen M, et al. Cartilage 2020). In a pilot study KJD was slightly less effective than KA, although not statistically significant (Jansen M, et al. Cartilage 2021). Therefore, this study aims to determine whether KJD is non-inferior on patient reported outcome as compared to KA for these patients.

Methods and Materials

Pragmatic, open, randomized, multi-centre (fig), non-inferiority trial with 2 year follow-up. 1,200 knee OA patients ≤65 year indicated for a KA are randomized (1:1) to KJD or KA. KA and KJD are indicated and executed in regular practice in line with national guidelines and recommendations for practice, respectively. KJD treatment uses an external fixation frame, distracting the two bony ends of the knee joint at 5mm according to prescribed procedures for six weeks (fig), with full weight-bearing allowed and encouraged. Rehabilitation is according to regular practice. Primary and secondary outcomes are pain, stiffness, physical functioning (WOMAC), quality of life (EQ-5D), adverse events and cost-effectiveness. All over 24 months.

figure 1.jpg

Results

As discussed and endorsed with all stakeholders, including patient and professional associations, this study needs to demonstrate non-inferiority of KJD compared to KA with a non-inferiority limit of 15 points on the WOMAC total score.

Conclusion

This study will determine the place of knee distraction in the treatment of relatively young end-stage knee OA patients.

Collapse
Podium Presentation Osteoarthritis

18.3.8 - Surgical Management of the Young Degenerative Knee: “Power Ranking” the Options

Presentation Topic
Osteoarthritis
Date
14.04.2022
Lecture Time
15:18 - 15:27
Room
Potsdam 1
Session Type
Free Papers
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Management of young patients with degenerative joint disease (DJD) of the knee is challenging. The spectrum of surgical options include joint preservation and arthroplasty. Direct clinical comparison of these procedures would be useful. We sought to compare the “treatment effect” of various surgical interventions in young patients with knee DJD.

Methods and Materials

Our institution’s registry identified 283 patients age 30-50 who underwent surgery for DJD of the knee by a single surgeon: 68 TKA, 60 UKA, 96 osteochondral allograft (OCA) transplantation, 35 distal femoral osteotomy (DFO), and 24 high tibial osteotomy (HTO) were included. Knee injury and Osteoarthritis Outcome Scores (KOOS) were captured preoperatively and postoperatively. KOOS subscales include symptoms, pain, activities of daily living, sports and recreation, and quality of life.

Results

Mean follow-up was 5.2 years (range, 2-14 years). Mean age was 42 years. Clinically significant improvements were seen on every KOOS subscale for all treatments (p<0.001) (Table 1.) Largest improvement in symptoms was for UKA (30 points). OCA had the lowest improvement (17 points), but pre and postoperative mean scores were highest. Best pain score improvement was for TKA and UKA (both 29 points). Lowest pain score improvement was for OCA (19 points). ADL scores improved most for TKA (31 points) and least for OCA (18 points). Improvement in sports and recreation was similar for TKA, UKA, OCA, and DFO (34, 33, 35, and 39 respectively and lowest for HTO (17 points). Quality of life improved most for TKA (42 points), followed by HTO (37 points) and UKA (36 points).

table 1. koos change scores.jpg

Conclusion

Arthroplasty had the largest treatment effects for symptoms, pain, and activities of daily living. Osteotomy had the largest treatment effects for sports and recreation (DFO) and quality of life (HTO). OCA had the lowest treatment effects but highest mean KOOS scores.

Collapse
Podium Presentation Osteoarthritis

18.3.9 - Does Sedentary Lifestyle Lead To Increased Osteoarthritis Among Diabetic Patients?

Presentation Topic
Osteoarthritis
Date
14.04.2022
Lecture Time
15:27 - 15:36
Room
Potsdam 1
Session Type
Free Papers
Disclosure
NS Mohamed (N), RE Delanois (Baltimore City Medical Society.: Board or committee member, Biocomposites, Inc.: Research support, CyMedica Orthopedics: Research support, DePuy Synthes Product, Inc.: Research support, Flexion Therapeutics: Research support,

Abstract

Purpose

The number of global osteoarthritis sufferers has risen over 48% in the past 30 years, and is a leading cause of disability in older adults. Diabetics are at greater risk of osteoarthritis and cartilage degradation, often requiring surgical intervention to alleviate pain and dysfunction. A lack of physical activity, frequently concurrent in Type 2 diabetic patients, also increases the risk of osteoarthritis. The resulting sedentary lifestyle could further exacerbate arthritic changes in this population. We compare 5-year incidences of osteoarthritis, joint pain, and joint replacement between matched sedentary and non-sedentary diabetic patients in the United States.

Methods and Materials

Diabetic patients from 2010-2018 were identified using the PearlDiver Supercomputer. Those with a sedentary diagnosis were propensity-matched 1:1 to non-sedentary patients based on demographics (n=2,238 each). Osteoarthritis and joint pain within 5 years were compared utilizing chi-square. A sub-cohort of osteoarthritic diabetic patients with/without sedentary lifestyle were also propensity-matched (n=1,033 each), comparing total knee arthroplasty (TKA) and total hip arthroplasty (THA) incidences within 5 years.

Results

Between sedentary and non-sedentary diabetic patients, there were no significant demographic differences (all p>0.910). Sedentary patients had a significantly higher 5-year incidence of osteoarthritis (p<0.001), and a significantly higher 5-year incidence of joint pain (p<0.001). Within the sub-cohort of diabetic patients with osteoarthritis, no significant differences were observed in demographics (all p>0.994). There were no significant differences between sedentary and non-sedentary patients in TKA (p=0.114) or THA (p=0.726) at 5 years.

Conclusion

Lack of physical activity among diabetic patients may exacerbate both osteoarthritis and joint pain within 5 years. Conversely, it did not increase joint replacements. Osteoarthritic changes are likely augmented with sedentary lifestyle, but may not necessitate arthroplasty in the same timeframe. Sedentary diabetic patients represent a target population that could benefit from early intervention and access to recovery exercises to improve joint function and prevent osteoarthritis progression.

Collapse
Podium Presentation Osteoarthritis

18.3.10 - The Value of Ankle Joint Distraction in Hemophilic Arthropathy: Three-year Follow-up From the First Prospective Pilot Study

Presentation Topic
Osteoarthritis
Date
14.04.2022
Lecture Time
15:36 - 15:45
Room
Potsdam 1
Session Type
Free Papers
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Hemophilic ankle arthropathy (HAA) causes major morbidity in (young) patients. Often major surgical interventions like arthrodesis are indicated impacting quality of life severely. Joint distraction has been demonstrated a good joint-preserving alternative in osteoarthritis and retrospective evaluation of three patients with HAA treated with ankle joint distraction (AJD) showed evident clinical and structural improvements. This open prospective study aims to add evidence for the value of AJD in HAA.

Methods and Materials

Patients ≥18 and ≤55 years with severe complaints of HAA and eligalble for arthrodesis were included in this open prospective study. AJD was applied for 8-10 weeks by use of an external frame with 5mm distraction. Data on clinical efficacy and tissue structure changes were gathered before distraction and 6, 12, 24 and 36 months after distraction.

Results

So far eight cases (age 21-53 years) are included. The pain scores decreased significantly at on year which further decreased over time as assessed by the Visual Analogue Score and Ankle Osteoarthritis Score pain score (see figure). Similar, the median AOS function score decreased significantly over time The functional limitations as assessed by the Hemophilia Activities List for simple lower extremities functions improved significantly. The range of motion of the joint was maintained. MRI showed decreased edema and subchondral cysts and thickened cartilage indicating sustainable structural improvements. The main side effect was pin tract infection (6 patients), effectively treated with a short course of antibiotics. There were no adverse bleeding events. In none of the patients the originally indicated arthrodesis was performed.

figure.jpg

Conclusion

This first prospective pilot study showed that AJD in HAA results in decreased pain, improved function, and tissue repair for prolonged time. Though explorative, this joint-preserving therapy may be promising to be an joint preserving surgical intervention.

Collapse