THU0060 KNEE JOINT DISTRACTION INDUCED SHIFT FROM CATABOLIC TO ANABOLIC STATE OCCURS AFTER DISTRACTION PERIOD

Background:Knee joint distraction (KJD) is a validated joint-preserving treatment strategy for severe osteoarthritis (OA) that provides long-term clinical and structural improvement. Human trials and animal models indicate clear cartilage regeneration from 6 months and onwards post-KJD [1]. Recent work showed that during distraction, the balance between catabolic and anabolic indicators is directed towards catabolism, as indicated by collagen type 2 markers, proteoglycan (PG) turnover and a catabolic transcription profile.Objectives:To investigate the cartilage changes directly and 10 weeks after joint distraction in order to elucidate the shift from a catabolic to an anabolic cartilage state.Methods:Knee OA was induced bilaterally in 8 dogs according to the groove model. After 10 weeks of OA induction, all 8 animals were treated with knee joint distraction, employing the left knee as an OA control. After 8 weeks of distraction, 4 dogs were euthanized (KJDdirect) and after 10 weeks of follow-up the 4 remaining dogs (KJD+10). Macroscopic and microscopic cartilage degeneration was assessed using the OARSI canine scoring system. RT-qPCR was used to determine relative expression of aggrecan (ACAN)¸collagen type II(COL2α1), cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase-3 (MMP3) in the cartilage. PG content was determined by the Alcian Blue assay and the synthesis of PGs was determined using35SO42-as a tracer, as published before.Results:Macroscopic cartilage damage of the tibial plateau in the KJDdirectgroup was higher as compared to the OA control (OARSI score: 1.7±0.2 vs 0.6±0.3;p < 0.001). For KJD+10this difference persisted (OARSI score: 1.4±0.6 vs 0.6±0.3;p = 0.05). Microscopically, an increase in the total OARSI score was seen after 10 weeks post-KJD. This was mainly due to an increase of chondrocyte clusters at 10 weeks of follow-up, resulting in an increased sub score chondrocyte pathology. Remarkedly the sub score intensity of proteoglycan staining decreased directly after KJD (indicating a loss of PGs) but increased after 10 weeks of follow-up suggesting a mixed response depending on the item scored.Cartilage gene expression analysis showed downregulation ofCOL2α1(-1.3 ± 0.3), ACAN(-4.4 ± 1.0,p < 0.01) andCOMP(-1.7 ± 0.5) in thetgroup compared to OA control suggesting enhanced catabolic activity during KJD. In contrast, after 10 weeks of follow-up the expression ofCOL2α1andCOMPwere increased as compared to the OA control (2.6 ± 1.1 and 2.5 ± 1.2 respectively) as well as compared to the KJDdirecsituation (3.3 ± 1.4 and 4.2 ± 2.0).Expression ofMMP3was upregulated directly after KJD (4.4 ± 0.8) and downregulated after 10 weeks of follow up (-3.3 ± 0.8).Biochemical analysis of the tibia cartilage of the KJDdirectgroup revealed a lower PG content compared to the OA joint (20.1±10.3 mg/g vs 23.7±11.7 mg/g). At 10 weeks post-KJD this difference in PG content was gone (24.8±6.8 mg/g vs 25.4±7.8 mg/g). The PG synthesis rate directly after KJD appeared significantly lower vs. OA (1.4±0.6 nmol/h.g vs 5.9±4.4 nmol/h.g;p < 0.001)). 10 weeks post-KJD this difference was not detected (3.7±1.2 nmol/h.g vs 2.9±0.8 nmol/h.g), and the synthesis rate in the distracted knee was increased compared to directly after distraction (p < 0.01) indicating a shift upon follow-up.Conclusion:Further in-depth investigation of the material is ongoing and also includes the other joint tissues such as the bone and the synovial tissue. Irrespective, these first results on cartilage changes suggest that the shift from a catabolic to an anabolic state occurs within the weeksafterjoint distraction. As such, the post-distraction period seems to be essential in identifying key-players that support intrinsic cartilage repair.References:[1]Mastbergen SC, Nat Rev Rheumatol. 2013 May;9(5):277-90.Acknowledgments:TTW Technology Foundation: Perspectief P15-23, Dutch Arthritis Society: Long term Research Program LLP9Disclosure of Interests:Michelle Teunissen: None declared, Jelena Popov-Celeketic: None declared, Katja Coeleveld: None declared, Bjorn Meij: None declared, Floris Lafeber Shareholder of: Co-founder and shareholder of ArthroSave BV, Marianna Tryfonidou: None declared, Simon Mastbergen: None declared

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Knee Joint Distraction as Treatment for Osteoarthritis Results in Clinical and Structural Benefit: A Systematic Review and Meta-Analysis of the Limited Number of Studies and Patients Available

Cartilage ◽

10.1177/1947603520942945 ◽

2020 ◽

pp. 194760352094294

Author(s):

Mylène P. Jansen ◽

Tim A.E.J. Boymans ◽

Roel J.H. Custers ◽

Rutger C.I. Van Geenen ◽

Ronald J. Van Heerwaarden ◽

...

Keyword(s):

Systematic Review ◽

Knee Joint ◽

Structural Parameters ◽

Meta Analysis ◽

Tibial Osteotomy ◽

Control Groups ◽

Joint Distraction ◽

Short And Long Term

Objective Knee joint distraction (KJD) is a joint-preserving osteoarthritis treatment that may postpone a total knee arthroplasty (TKA) in younger patients. This systematic review and meta-analysis evaluates short- and long-term clinical benefit and tissue structure changes after KJD. Design MEDLINE, EMBASE, and Web of Science were searched for eligible clinical studies evaluating at least one of the primary parameters: WOMAC, VAS-pain, KOOS, EQ5D, radiographic joint space width or MRI cartilage thickness after KJD. Random effects models were applied on all outcome parameters and outcomes were compared with control groups found in the included studies. Results Eleven articles reporting on 7 different KJD cohorts with in total 127 patients and 5 control groups with multiple follow-up moments were included, of which 2 were randomized controlled trials. Significant improvements in all primary parameters were found and benefit lasted up to at least 9 years. Overall, outcomes were comparable with control groups, including high tibial osteotomy, although TKA showed better clinical response. Conclusions Current, still limited, evidence shows KJD causes clear benefit in clinical and structural parameters, both short- and long-term. Longer follow-up with more patients is necessary, to validate outcome and to potentially improve patient selection for this intensive treatment. Thus far, for younger knee osteoarthritis patients, KJD may be an option to consider.

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FRI0408 KNEE JOINT DISTRACTION AS TREATMENT FOR OSTEOARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1317 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 803.1-803

Author(s):

M. Jansen ◽

T. Boymans ◽

R. Custers ◽

R. Van Geenen ◽

R. Van Heerwaarden ◽

...

Keyword(s):

Knee Joint ◽

Cartilage Thickness ◽

Control Groups ◽

Younger Patients ◽

Time Points ◽

Joint Distraction ◽

Short And Long Term ◽

Tract Infections

Background:Knee osteoarthritis (OA) is a common cause of invalidity and is often treated with a total knee arthroplasty (TKA). While TKA is cost-effective, reduces pain and improves function, it brings a greater risk of a future revision surgery when performed in younger patients. Knee joint distraction (KJD) is a joint-preserving OA treatment that may postpone TKA and possibly prevent a revision. In the past years, multiple studies have investigated this surgical treatment.Objectives:To evaluate short- and long-term clinical benefit and tissue structure changes after KJD treatment for knee OA.Methods:MEDLINE, EMBASE and Web of Science were searched for eligible clinical studies evaluating a change in at least one of: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Score of pain (VAS-pain), Knee injury and Osteoarthritis Outcome Score (KOOS), EuroQol-5D (EQ5D), radiographic joint space width (JSW) or MRI cartilage thickness after KJD. The primary clinical and structural outcome parameters were the WOMAC and minimum JSW, respectively. Random effects models were applied on all outcome parameters and outcomes were compared with control groups found in the included studies. For continuous data the mean difference (MD) and 95% confidence interval (95%CI) were calculated and for dichotomous data the risk difference and 95%CI, following the Cochrane handbook.Results:In total 11 articles reporting on 7 different KJD cohorts with in total 127 patients and 5 control groups at multiple follow-up moments were included, with 2 of the studies being randomized controlled trials (RCTs). The WOMAC (figure 1) was compared to pre-treatment in 3 cohorts after 1 year (patients n=62) and 2 years (n=59) and in 1 cohort after 5 years (n=20) and 9 years (n=8), showing a significant increase at all time points (all p<0.001). The VAS-pain showed similar results at the same 4 time points, as did the KOOS and EQ5D, which were evaluated only after 1 (n=42) and 2 (n=39) years.The minimum (figure 2) and mean JSW are reported in 3 cohorts after 1 (n=59) and 2 (n=59) years and in 1 cohort after 5 (n=20) and 7 (n=8) years. Both JSW measures were statistically significantly increased after 1 and 2 years, but after 5 and 7 years the JSW increase was no longer statistically significant. Similarly, the MRI cartilage thickness showed an increase at 1 and 2 years, but not at 5 years (all n=20).Complications were reported in 5 studies with 87 patients, with 57 patients developing one or more pin tract skin infections, giving a risk of pin tract infections of 63% (95%CI 45-81), the majority of which could be treated with oral antibiotics. Only a small amount of other complications occurred and were all treated successfully.Overall, clinical and structural outcomes were comparable with control groups, including high tibial osteotomy and TKA as compared after 1 and 2 years in the two RCTs. Apart from pin tract infections, complications were not different in severity and number between control groups and KJD.Conclusion:KJD causes clear benefit in clinical and structural parameters over time, short- and long-term. Although the total number of patients is limited, effect sizes are large. Longer follow-up with more patients is necessary and could improve patient selection for this intensive treatment, while preventing pin tract infections could lighten the patients’ treatment burden. Irrespectively, KJD provides an additional option in joint-preserving treatments for OA and a viable alternative to joint replacement, especially in younger patients.Figure:Disclosure of Interests:Mylène Jansen: None declared, Tim Boymans: None declared, Roel Custers: None declared, Rutger Van Geenen: None declared, Ronald Van Heerwaarden: None declared, Maarten Huizinga: None declared, Jorm Nellensteijn: None declared, Rob Sollie: None declared, Sander Spruijt Consultant of: Consultancy to Zimmer Biomet Inc., Simon Mastbergen: None declared

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Ten-Year Results of Medial Open-Wedge High Tibial Osteotomy and Chondral Resurfacing in Severe Medial Osteoarthritis and Varus Malalignment

The American Journal of Sports Medicine ◽

10.1177/0363546518758016 ◽

2018 ◽

Vol 46 (6) ◽

pp. 1362-1370 ◽

Cited By ~ 40

Author(s):

Philipp Schuster ◽

Markus Geßlein ◽

Michael Schlumberger ◽

Philipp Mayer ◽

Raul Mayr ◽

...

Keyword(s):

Functional Outcome ◽

Cartilage Regeneration ◽

Tibial Osteotomy ◽

Open Wedge ◽

Varus Malalignment ◽

Medial Osteoarthritis ◽

Ikdc Score ◽

Chondral Resurfacing

Background: High tibial osteotomy (HTO) is a widely used treatment option for medial osteoarthritis and varus malalignment, especially in young patients with early osteoarthritis. Limited outcome data are available for this procedure in severe osteoarthritis, and no long-term data are available using newer implants. Purpose: To determine survivorship and functional results of medial open-wedge HTO combined with a chondral resurfacing (CR) procedure (abrasion plus microfracture) in severe medial osteoarthritis (Kellgren-Lawrence grade 3 and 4) and varus malalignment. Furthermore, factors that potentially influence the outcome were analyzed. Study Design: Case series; Level of evidence, 4. Methods: From September 2005 to December 2008, all cases of HTO (fixation with an angular-stable internal fixator) combined with CR were prospectively surveyed with regard to survival (Kaplan-Meier-method, not requiring arthroplasty) and functional outcome (subjective International Knee Documentation Committee [IKDC] score). Cartilage regeneration at the time of hardware removal, tibial bone varus angle (TBVA), pre- and postoperative mechanical medial proximal tibial angle (MPTA), and postoperative alignment were analyzed with regard to the result. Results: Seventy-nine knees were included (73 patients; mean age 50.9 ± 7.6 years). The follow-up rate was 90% at 10.0 ± 1.2 years (range, 8.3-12.1 years). Pre- and postoperative mechanical tibiofemoral axis were 9.6° ± 3.0° of varus and 0.6° ± 2.7° of valgus, respectively. Survival rate was 81.7% (95% CI, 72.5%-90.9%) at 10 years. Subjective IKDC score significantly improved from 44 ± 11 preoperatively to 70 ± 13 at one, 66 ± 15 at three, 66 ± 15 at five, and 65 ± 17 at ten years ( P < .001 at any point of follow-up). Poor cartilage regeneration and low preoperative IKDC score (<40) were associated with decreased survival. High preoperative TBVA was associated with better and an overcorrected MPTA (>95°) with inferior functional outcome at final follow-up, respectively. Conclusion: Even in cases of severe medial osteoarthritis and varus malalignment, HTO in combination with a CR procedure is a good to excellent treatment option. The role of the CR procedure remains unclear. Although good results are obtained with overcorrected MPTA, long-term functional outcome is inferior.

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Long term results after transepiphysal ACL reconstruction in children and adolescent

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967118s00017 ◽

2018 ◽

Vol 6 (4_suppl2) ◽

pp. 2325967118S0001

Author(s):

Christian Eberle ◽

Wolfgang Schopf ◽

Andree Ellermann

Keyword(s):

Acl Reconstruction ◽

Cartilage Damage ◽

Long Term Results ◽

Angular Deformity ◽

Leg Length ◽

Growth Disturbance ◽

Children And Adolescent ◽

The Mean

The aim of our study was to review the long term clinical and radiological (MRI) outcomes of adult patients who underwent ACL reconstruction as children or adolescent with emphasize to the features of growth disturbance, angular deformity, meniscal and cartilage damage and revision rate We retrospectively evaluated patient who underwent ACL reconstruction in our clinic with arthroscopic transepiphyseal technique using hamstrings graft in childhood or adolescence between the years 1997 and 2009. A total of 43 Patients were assessed. 25 male and 18 female. The average age at time of surgery was 13,5 years (8 - 16 y.), at time of assessement 22,4 years (18 - 30 y.) . The mean follow up was 10 years (4 - 16 years). The physical development of the patients was assessed with the Lysholm score and the Cincinnati Knee score scale, their satisfaction was recorded on the basis of the IKDC subjective knee evaluation form and the Tegner activity score . Leg deformity or leg length discrepancy was evaluated clinically by the observers. The instrumented Lachman test using KT1000 and manual Pivot shift test was performed to assess knee stability. MRI was used to detect graft integrity, cartilage and meniscal damages. No significant leg deformities or leg length discrepancy had been detected. The average Lysholm score was 91 points (83 - 100), the Cincinnati Knee Score was 90,4 (79 - 100) points on average . The mean IKDC score was 92 points (82 -100). The Tegner-Activity-Score changed from preop 6,8 (2-10) to post op 5,8 (2-9). 2 Patient underwent revision ACL reconstruction due to rerupture (3 and 9 years post op). 2 Patients underwent meniscal surgery during follow up (1 resection and one refixation). KT1000 evaluation showed 67% excellent, 21% good and in 12% bad results. The MRI scan showed 42 intact grafts and one unverifiable graft. One patient with cartilage damage up to 3° (ICRS), 3 patients with meniscal degeneration up to grade 2. Each patient showed a free range of motion Our data underlines that transepiphyseal ACL reconstruction in children and adolescent with hamstrings is a save procedure leading to good long term results without causing angular deformity or growth disturbance

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Regions at Risk in the Knee Joint of Young Professional Soccer Players: Longitudinal Evaluation of Early Cartilage Degeneration by Quantitative T2 Mapping in 3 T MRI

Cartilage ◽

10.1177/1947603520924773 ◽

2020 ◽

pp. 194760352092477

Author(s):

Hanna Schenk ◽

David Simon ◽

Leonie Waldenmeier ◽

Christoph Evers ◽

Rolf Janka ◽

...

Keyword(s):

At Risk ◽

Knee Joint ◽

T2 Mapping ◽

Cartilage Damage ◽

Cartilage Degeneration ◽

Soccer Players ◽

Young Professional ◽

Professional Soccer ◽

Playing Time

Purpose. The study aims to detect regions at risk for (pre-)osteoarthritis in the tibiofemoral joint of young professional soccer players by evaluating cartilage composition by T2 mapping in a 3 T magnetic resonance imaging setting. Methods. In this longitudinal study, 20 professional adolescent soccer players were included. Tibiofemoral cartilage was assessed by quantitative T2 mapping and T2 values were evaluated by regions of interest analysis. Statistical evaluation, using Wilcoxon signed-rank tests, was performed to compare global T2 values and subregional T2 values between a baseline and a follow-up investigation 4.3 years later. Based on the average of playing time (15 years) we divided the cohort in 2 groups and differences were evaluated. Results. When comparing baseline and follow-up, our findings showed statistically significant increases of the global medial tibial and femoral T2 values. The most noticeable results of the subregional T2 analysis were statistically significant increases in the medial posterior zones (deep femoral 36.1 vs. 39.5, P = 0.001; superficial femoral 57.0 vs. 62.4, P = 0.034; deep tibial 28.3 vs. 34.1, P = 0.009; superficial tibial 43.2 vs. 55.3, P = 0.002). Conclusion. The elevation of T2 values in the medial, especially medial posterior, compartment of the knee joint indicates that these regions are at risk for early cartilage degeneration already at the time of adolescence. The findings can help individualize and optimize training concepts and to be aware of the chronic stress on these vulnerable areas. Prevention programs should be established in young players to avoid further cartilage damage.

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Five-Year Follow-up of Knee Joint Distraction: Clinical Benefit and Cartilaginous Tissue Repair in an Open Uncontrolled Prospective Study

Cartilage ◽

10.1177/1947603516665442 ◽

2016 ◽

Vol 8 (3) ◽

pp. 263-271 ◽

Cited By ~ 22

Author(s):

Jan-Ton A.D. van der Woude ◽

Karen Wiegant ◽

Peter M. van Roermund ◽

Femke Intema ◽

Roel J.H. Custers ◽

...

Keyword(s):

Knee Joint ◽

Clinical Benefit ◽

Tissue Repair ◽

Magnetic Resonance Images ◽

Cartilage Thickness ◽

Cartilaginous Tissue ◽

X Ray ◽

Natural Progression ◽

Joint Distraction

Objective In end-stage knee osteoarthritis, total knee arthroplasty (TKA) may finally become inevitable. At a relatively young age, this comes with the risk of future revision surgery. Therefore, in these cases, joint preserving surgery such as knee joint distraction (KJD) is preferred. Here we present 5-year follow-up data of KJD. Design Patients ( n = 20; age <60 years) with conservative therapy resistant tibiofemoral osteoarthritis considered for TKA were treated. Clinical evaluation was performed by questionnaires. Change in cartilage thickness was quantified on radiographs and magnetic resonance images (MRI). The 5-year changes after KJD were evaluated and compared with the natural progression of osteoarthritis using Osteoarthritis Initiative data. Results Five-years posttreatment, patients still reported clinical improvement from baseline: ΔWOMAC (Western Ontario and McMaster Universities Arthritis Index) +21.1 points (95% CI +8.9 to +33.3; P = 0.002), ΔVAS (visual analogue scale score) pain −27.6 mm (95%CI −13.3 to −42.0; P < 0.001), and minimum radiographic joint space width (JSW) of the most affected compartment (MAC) remained increased as well: Δ +0.43 mm (95% CI +0.02 to +0.84; P = 0.040). Improvement of mean JSW (x-ray) and mean cartilage thickness (MRI) of the MAC, were not statistically different from baseline anymore (Δ +0.26 mm; P = 0.370, and Δ +0.23 mm; P = 0.177). Multivariable linear regression analysis indicated that KJD treatment was associated with significantly less progression in mean and min JSW (x-ray) and mean cartilage thickness (MRI) compared with natural progression (all Ps <0.001). Conclusions KJD treatment results in prolonged clinical benefit, potentially explained by an initial boost of cartilaginous tissue repair that provides a long-term tissue structure benefit as compared to natural progression. Level of evidence, II.

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SAT0649 Changes in cartilage quality (DGEMRIC) following knee joint distraction or high tibial osteotomy: a two-year follow-up

10.1136/annrheumdis-2017-eular.3400 ◽

2017 ◽

Author(s):

N Besselink ◽

S Mastbergen ◽

K Vincken ◽

L Bartels ◽

A Concepcion ◽

...

Keyword(s):

Knee Joint ◽

High Tibial Osteotomy ◽

Tibial Osteotomy ◽

Joint Distraction

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Long-Term Follow-up of90Yttrium-Treated Knee-Joint Arthritis

Scandinavian Journal of Rheumatology ◽

10.3109/03009747709095451 ◽

1977 ◽

Vol 6 (4) ◽

pp. 209-212 ◽

Cited By ~ 26

Author(s):

Erika Szanto

Keyword(s):

Knee Joint ◽

Long Term Follow Up ◽

Joint Arthritis

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Sporting Activity Is Reduced 11 Years After First-Generation Autologous Chondrocyte Implantation in the Knee Joint

The American Journal of Sports Medicine ◽

10.1177/0363546517716920 ◽

2017 ◽

Vol 45 (12) ◽

pp. 2762-2773 ◽

Cited By ~ 4

Author(s):

Benjamin Erdle ◽

Simon Herrmann ◽

Stella Porichis ◽

Markus Uhl ◽

Nadir Ghanem ◽

...

Keyword(s):

Magnetic Resonance ◽

Knee Joint ◽

Autologous Chondrocyte Implantation ◽

Repair Tissue ◽

Sporting Activity ◽

Chondrocyte Implantation ◽

Sporting Activities ◽

Autologous Chondrocyte

Background: Little is known about long-term sporting activity after periosteal autologous chondrocyte implantation (ACI-P) and its correlation to clinical, morphological, and ultrastructural cartilage characteristics on magnetic resonance imaging (MRI). Purpose: To evaluate long-term sporting activity after ACI-P and to correlate with clinical and MRI findings. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent ACI-P for isolated cartilage defects of the knee joint between 1997 and 2001 were analyzed for sporting ability for 3 different time points: lifetime until the onset of pain, the year before ACI-P, and 11 years (range, 9.0-13.4 years) postoperatively. Sporting activity was assessed and patients’ level of activity scaled using standardized questionnaires. MRI scans of the affected knee joint at follow-up were analyzed using the MOCART (magnetic resonance observation of cartilage repair tissue) score and T2 mapping. Results: Seventy of 86 patients (81% follow-up rate) consisting of 25 female and 45 male patients, with a mean age of 33.3 ± 10.2 years at the time of surgery, mean defect size of 6.5 ± 4.0 cm2, and 1.17 treated defects per patient, agreed to participate in the study at a mean 10.9 ± 1.1 years after ACI-P. Fifty-nine patients (69% of total; 84% of follow-up) agreed to MRI, allowing the complete evaluation of 71 transplant sites. Before the onset of symptoms (lifetime), 95.7% of patients played a mean 6.0 sporting activities at a competitive level. In the year before ACI-P, 81.4% of patients played a mean 3.4 sporting activities in 2.4 sessions during 5.4 hours per week at a recreational level. At follow-up, 82.9% of the patients played a mean 3.0 sporting activities in 1.8 sessions during 3.0 hours per week at a recreational level. In contrast to objective factors, 65.6% of the patients felt that their subjective sporting ability had improved or strongly improved after ACI-P, whereas 12.9% felt that their situation had declined or strongly declined, and 21.4% stated that their sporting ability had undergone no change because of surgery. Factors of sporting activity correlated significantly with clinical long-term outcomes. MRI analysis with a mean repair tissue T2 relaxation time of 35.2 milliseconds and mean MOCART score of 44.9 showed no conclusive significant correlation to sporting activity. Level of performance was the only sporting activity factor to show a weak correlation with subgroups of the MOCART score. Conclusion: The premorbid level of sporting and recreational activities cannot be achieved 11 years after ACI-P. The MRI results determined at this time point did not conclusively correlate with long-term sporting activity.

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