Session 11: DOS Best Paper

Kristoffer W Barfod^1,2, Lars Blønd³, Rasmus Kramer Mikkelsen^1,2, Jasmin Bagge¹, Lisbet Rosenkrantz Hölmich⁴, Thomas Kallemose⁵, Anders Troelsen⁶, Per Hölmich¹
1 Sports Orthopedic Research Center - Copenhagen (SORC-C), Department of Orthopedic Surgery, Copenhagen University Hospital, Amager-Hvidovre, Denmark. 2Unit of Sports Traumatology, Department of Orthopedic Surgery, Copenhagen University Hospital, Bispebjerg, Denmark. 3 Department of Orthopedic Surgery, The Zealand University Hospital of Køge, Denmark. 4 Department of Plastic Surgery, Copenhagen University Hospital, Herlev and Gentofte, Denmark. 5 Department of Clinical Research, Copenhagen University Hospital, Amager-Hvidovre, Denmark. 6 Clinical Orthopaedic Research Hvidovre, Department of Orthopedic Surgery, Copenhagen University Hospital, Amager-Hvidovre, Denmark.

Background: Point-of-care cell-based therapy of knee osteoarthritis is booming though evidence is lacking.
Aim: To investigate if treatment with a single injection of autologous micro-fragmented adipose tissue improved the patient-reported health compared to a placebo saline injection.
Materials and Methods: A blinded, randomized, placebo-controlled, effectiveness trial with 2-year follow-up. Patients were recruited from January 2019 through February 2022; follow-up was completed February 2024. Eligible patients were aged 18 to 70 years, suffering from pain and functional impairment of the knee and with Kellgren- Lawrence grades 2–3 in the tibiofemoral joint. 238 patients were assessed for eligibility and 120 included in the trial with 60 in each group. Abdominal adipose tissue was harvested by liposuction in all participants. The active treatment group was treated with an intraarticular injection of autologous micro-fragmented adipose tissue. The placebo group received an intraarticular injection of isotonic saline. Participants, investigators, and follow-up personnel were blinded to the intervention. The primary outcome was the Knee injury and Osteoarthritis Outcome Score 4 (KOOS4) evaluated at 6 months. Secondary outcomes were amongst others KOOS at 3, 12, and 24 months, the Tegner activity score, adverse events, and treatment failure.
Results: Data regarding the primary outcome was available for 115/120 (93%). Mean KOOS4 at 6 months was 55.5 (95% CI 51.4 to 59.6) for the active treatment group and 51.5 (95% CI 47.4 to 55.6) for the placebo group, and the between-group difference in change from baseline was 1.7 (-3.6-7.1) (p=0.52). There were no statistically significant differences in any of the secondary outcomes between the active treatment and the placebo group at any time point. Both groups showed statistically significant and clinically relevant improvements in outcomes from baseline to 6, 12 and 24 months. No adverse events were seen in any of the two groups.
Interpretation / Conclusion: This study shows that during the 2-year follow-up, there was no superiority of micro-fragmented adipose tissue compared to a placebo saline injection for the treatment of knee osteoarthritis.

Jacob Fyhring Mortensen^1,2, Paul Blanche³, Claes Sjørslev Blom⁴, Andreas Kappel⁵, Per Wagner Kristensen⁶, Martin Lindberg-Larsen⁷, Snorre Læssøe Stephensen¹, Søren Overgaard⁸, Frank Madsen⁹, Henrik Morville Schrøder¹⁰, Morten Vase¹¹, Lasse Enkebølle Rasmussen⁶, Svend Erik Østgaard⁵, Anders Odgaard¹²,
1. Department of Orthopaedic Surgery, Gentofte Hospital 2. Department of Orthopaedic Surgery, Nykøbing Falster Sygehus 3. Department of Biostatistics, University of Copenhagen 4. Department of Orthopaedic Surgery, Randers Sygehus 5. Department of Orthopaedic Surgery, Aalborg Universitetshospital 6. Department of Orthopaedic Surgery, Vejle Sygehus 7. Department of Orthopaedic Surgery, Odense Univesitets Hospital 8. Department of Orthopaedic Surgery, Bispebjerg Hospital 9. Department of Orthopaedic Surgery, Århus Universitetshospital 10. Department of Orthopaedic Surgery, Næstved Sygehus 11. Department of Orthopaedic Surgery, Silkeborg Sygehus 12. Department of Orthopaedic Surgery, Rigshospitalet

Background: Total Knee Arthroplasty (TKA) and Medial Unicompartmental Knee Arthroplasty (mUKA) are prominent options in the treatment of isolated anteromedial osteoarthritis, and it is debated which treatment is better in the short and long term.
Aim: This study compares the effects of mUKA versus TKA with the primary aim to determine the time-adjusted improvement in Oxford Knee Score during the first 2 years. The secondary aims included: The time-adjusted Forgotten Joint Score, Copenhagen Knee ROM scale, clinical ROM KOOS, SF36, EQ5D, and UCLA activity scale; Mean scores at 2 year follow-up including OKS and clinical ROM; Revisions and re-operations rates.
Materials and Methods: This was a double-blinded, multicenter randomized trial including all five regions in Denmark. Analysis was based on an “Intention to treat” method. Secondary outcomes were analyzed in a hierarchical sequential gatekeeping statistical procedure. Time-adjusted measures were determined from measurements at specific time points and calculating the area under the curve.
Results: Between August 2017 and April 2021, 1219 patients were assessed, of whom 350 patients were included in this study and randomly assigned to each arm. The mean time-adjusted OKS improvement differed between the two treatments by of 3.5(CI 2.3;4.7, p<0.001), in favour of mUKA. OKS at 2 years showed a mean difference of 2.7(CI 1.3;4, p<0.001), in favour of mUKA. All secondary outcomes were in favour of the mUKA, except for the EQ5D pain score. Cumulative proportions of re-operations were 2.3% (mUKA) and 6.9% (TKA), and showed a difference of 4.7% CI (0.2%; 9.8%), while revision surgery was 2.8% (mUKA) and 4% (TKA), with a difference of 1.2% CI (-3%; 5.7%), both in favour of mUKA.
Interpretation / Conclusion: The difference between the time-adjusted mean OKS improvement was statistically higher for mUKA compared to TKA, but the difference is below the minimal clinically important difference of approx. 5 OKS points. Most secondary outcomes were in favour of mUKA, along with revision and re-operation rates, which will be interesting to follow in the long term studies. This study weakly favours mUKA , but long term follow-up results are necessary before strong clinical recommendations can be made.

Troels Mark-Christensen^1,2, Kristian Thorborg^3,4,5, Thomas Kallemose², Thomas Bandholm^2,4,5,6
1. Department of Rehabilitation, Centre of Health, Regional Municipality of Bornholm, Rønne, Bornholm, Denmark; 2. Department of Clinical Research, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark; 3.Sports Orthopaedic Research Center – Copenhagen (SORC-C), Department of Orthopedic Surgery, Amager-Hvidovre Hospital, Institute for Clinical Medicine, Copenhagen University, Denmark; 4. Physical Medicine and Rehabilitation Research-Copenhagen (PMR-C), Department of Physical and Occupational Therapy, Copenhagen University Hospital, Amager-Hvidovre, Hvidovre, Denmark; 5. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 6. Department of Orthopedic Surgery, Copenhagen University Hospital, Amager and Hvidovre, Copenhagen, Denmark.

Background: The effectiveness of physical rehabilitation following total hip (THA) and knee (TKA) arthroplasty is questionable, and there is currently clinical equipoise concerning the need for physical rehabilitation after THA and TKA. To address clinical equipoise, fundamental effectiveness needs to be established, using a state-of-the-art randomised controlled trial design.
Aim: To compare the effectiveness of a 6-week program of home-based telerehabilitation, home- based rehabilitation or no physical rehabilitation following THA and TKA in terms of self-reported function.
Materials and Methods: This trial was designed as a 3-arm parallel-group randomized, controlled, superiority trial with blinded outcome assessments. Following discharge, 57 patients were randomized to home-based telerehabilitation, 56 to home-based rehabilitation, and 55 to no physical rehabilitation for 6 weeks. Outcome measures were assessed in an outpatient-setting at baseline (post-discharge), at the end of intervention (6 weeks – primary endpoint), and 3 and 12 months postoperatively. The primary outcome was the Hip disability and Osteoarthritis Outcome Score (HOOS)/ Knee injury and Osteoarthritis Outcome Score (KOOS)-subscale: function in daily living (ADL), where 0 points indicate severely reduced ADL function, and 100 points indicates full ADL function. For the ADL- subscale the minimal clinically relevant difference between treatment groups is 10 points.
Results: Comparing physical rehabilitation (home-based telerehabilitation and home-based rehabilitation) to no physical rehabilitation, the mean group- differences for the primary outcome and end- point were 3.3 (one-sided 95%CI: -10; p = 0.10) KOOS/HOOS ADL points at 6 weeks, and 1.9 (95%CI: -2.8; p = 0.25) and 2.6 (95%CI: -3.2; p = 0.23) points at the 3- and 12-months follow-ups, respectively.
Interpretation / Conclusion: Receiving physical rehabilitation following THA or TKA, is not superior to not receiving physical rehabilitation in terms of improving self-reported function – neither at the primary endpoint at 6 weeks, or at 3- and 12-months follow-up. Trial registration: NCT03750448 (23/11/2018).

Viktoria Lindberg-Larsen^1,2, Martin Lindberg-Larsen^3,4, Ole Ovesen³, Stine Thorhauge Zwisler¹, Peter Lindholm¹, Stine Hebsgaard¹, Robin Christensen^2,5, Søren Overgaard^3,6,7
1. Department of Anaesthesiology and Intensive Care Medicine, Odense University Hospital, Odense, Denmark 2. Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark 3. Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Odense, Denmark 4. Orthopaedic Research Unit, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark 5. Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark 6. Department of Orthopaedic Surgery and Traumatology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, Denmark 7. Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark

Background: Periacetabular osteotomy (PAO) for hip dysplasia is associated with postoperative pain. High-dose dexamethasone (DXMT), known to reduce pain and nausea in various surgeries, might offer similar effects following PAO.
Aim: Primary to compare the effect of one or two high doses of dexamethasone, relative to placebo, on postoperative morphine consumption after PAO.
Materials and Methods: A randomized, double-blind, placebo- controlled trial was conducted in patients aged 18 years or older, undergoing PAO due to hip dysplasia. Patients were randomized (1:1:1) into three groups: group 1 (DXMT/DXMT) received two doses of DXMT (24mg) intravenously (IV) preoperatively and 24 hours later; group 2 (DXMT/placebo) received one dose of DXMT preoperatively; group 3 (placebo/placebo). Placebo consisted of isotonic saline IV at relevant timepoints. The combined analyses of DXMT groups were only separated into DXMT groups if significant difference in the primary outcome was observed. Primary outcome was cumulative postoperative morphine consumption in mg within 48 hours from baseline. Key secondary outcomes included postoperative pain intensity during rest and activity performing Timed-Up and Go, postoperative nausea and vomiting, and antiemetic consumption at 24 and 48 hours postoperatively, and cumulative postoperative morphine consumption from 48 hours to day 14 post-operation. The main analyses were conducted on the Intention-to- Treat (ITT) population, with missing data handled using MCMC multiple imputation.
Results: Ninety patients were included in the ITT population, randomized to DXMT groups (n=60) and placebo (n=30); 58 and 28, respectively, completed trial. Mean age was 31 years and 79% were females. The mean cumulated postoperative morphine consumption was 92.0 mg (SE: 7.0) in the combined DXMT group and 94.8 mg (SE: 9.9) in the placebo group, corresponding to a between-group difference of -2.8 mg (95%CI: -26.6 to 21.1; P=0.82). There were no statistically significant differences observed between groups in any of the secondary outcomes at any time point.
Interpretation / Conclusion: High-dose dexamethasone did not reduce postoperative morphine use or improve any other secondary outcomes after PAO.

Thomas Frydendal^1,2,3, Robin Christensen^3,4, Inger Mechlenburg^5,6, Lone Ramer Mikkelsen^6,7, Claus Varnum^8,9, Anders Elneff Graversen⁸, Per Kjærsgaard-Andersen⁸, Peter Hvidbak Revald⁸, Christian Hofbauer⁸, Manuel Josef Bieder¹⁰, Haidar Qassim¹⁰, Mohammad Samir Munir¹⁰, Stig Storgaard Jakobsen^5,6, Sabrina Mai Nielsen^3,4, Kim Gordon Ingwersen*^1,3,9, Søren Overgaard*^11,12,13
1) Department of Physiotherapy, Lillebaelt Hospital – University Hospital of Southern Denmark, Vejle Hospital, Denmark 2) Department of Clinical Research, University of Southern Denmark, Odense, Denmark 3) Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark 4) Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense Denmark 5) Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus, Denmark 6) Department of Clinical Medicine, Aarhus University, Aarhus, Denmark 7) University Clinic for Orthopaedic Pathways (UCOP), Elective Surgery Centre, Regional Hospital Silkeborg, Denmark 8) Department of Orthopedic Surgery, Lillebaelt Hospital – University Hospital of Southern Denmark, Vejle Hospital, Vejle, Denmark 9) Department of Regional Health Research, University of Southern Denmark, Odense, Denmark 10) Department of Orthopedic Surgery, Næstved Hospital, Næstved, Denmark 11) Department of Orthopedic Surgery and Traumatology, Odense University Hospital, Odense, Denmark 12) Department of Orthopedic Surgery and Traumatology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, Denmark 13) Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark

Background: Total hip replacement (THR) is routinely recommended and increasingly used for severe hip osteoarthritis. No randomized trial has compared the effectiveness of this procedure to non-surgical treatment such as resistance training.
Aim: We aimed to evaluate whether total hip replacement provided superior improvements in self-reported hip pain and function compared with progressive resistance training.
Materials and Methods: This was a multicenter, randomized, controlled trial performed at one of four public orthopedic departments (Vejle, Odense, Aarhus, and Næstved) in Denmark. Patients aged 50 or older with hip pain, a clinical presentation and symptoms consistent with hip osteoarthritis, verified on radiographic imaging (joint space width narrowing below 2 mm), and with indication for THR assessed by a specialist in orthopedic surgery were considered eligible for trial enrollment. The resistance training program was delivered by physiotherapists in one-hour, individual, supervised sessions twice weekly for 12 weeks. The primary outcome was mean change in self- reported hip pain and function from baseline to 6 months after treatment was initiated measured by using the total score on the Oxford Hip Score (OHS). Secondary outcomes were a panel of self-reported pain, symptoms, function in activities of daily living, hip-related quality-of-life among others. Continuous outcomes were analyzed using repeated measures mixed effects linear models
Results: We enrolled 109 patients in the intention-to-treat population with a mean age of 68. 53 patients were randomly assigned to THR and 56 to resistance training. The improvement in the OHS was 15.9 points in patients assigned to total hip replacement and 4.5 points in patients assigned to resistance training, with a between-group difference of 11.4 points (95% confidence interval 8.9 to 14.0). All secondary outcomes had the same consistent trajectory pattern. At 6 months, 5 (9%) patients assigned to THR had not undergone surgery, and 12 (21%) assigned to resistance training had undergone THR.
Interpretation / Conclusion: THR provides clinically important superior improvements in self-reported hip pain and function compared with resistance training at 6 months. *Denotes co-senior authorship

Anna Trier Heiberg Brix^1,2, Tanja Gram Petersen³, Tine Nymark^1,2, Hagen Schmal^1,4, Martin Lindberg-Larsen^1,2, Katrine Hass Rubin^2,3
1. Department of Orthopedic Surgery and Traumatology, Odense University Hospital 2. Department of Clinical Research, University of Southern Denmark 3. OPEN - Open Patient Data Explorative Network, Odense University Hospital and University of Southern Denmark 4. Department of Orthopedics and Traumatology, University Medical Center Freiburg

Background: Patients who undergo major lower extremity amputation (MLEA) have the highest post-operative mortality among orthopedic patient groups. The co- morbidity profile for MLEA patients is often extensive and associated with elevated postoperative mortality.
Aim: This study primarily aimed to investigate the excess short- and long-term mortality following first and subsequent major lower extremity amputation. Secondarily, to examine the mediation role of post- amputation complications.
Materials and Methods: With data from the National Danish Patient Registry, 11,695 first-time MLEAs in patients aged >50 years were identified between January 1, 2010 and December 31, 2021, along with 58,466 controls matched 1:5 by age, sex, and region of residence. Mediators were identified through diagnosis codes (ICD-10) present in 6 months following MLEA.
Results: Excess mortality following MLEA was highest in the month following MLEA,HR 38.7 (95% CI (Confidence interval) 30.5-48.9) in women and HR 55.7 (CI 44.3-70.2) in men). Subsequent amputation resulted in an increased mortality the month after a subsequent amputation (overall HR 3.2 (CI 2.8-3.7) in women and HR 3.2 (CI 2.8-3.6) in men) and almost normalized after the first year. Sepsis explained the largest proportion of the association between MLEA and mortality with 16% (CI 11.7- 20.3) in women and 16.9% (CI 13.4-20.4) in men, although pneumonia also was a contributing factor, with 10.5% (CI 7.1-13.9) in women and 14.9% (CI 11.6-18.2) in men.
Interpretation / Conclusion: We found a notable high excess mortality in the month following MLEA, which persisted at elevated levels for years compared to controls. A subsequent amputation results in excess mortality in the following year, but declines after and normalizes after the first year. Sepsis and pneumonia arising after the amputation appeared to be significant factors that contributed to the increased mortality among MLEA patients