Publications by authors named "Wolfgang Wirth"

90 Publications

Do Ahlbäck scores identify subgroups with different magnitudes of cartilage thickness loss in patients with moderate to severe radiographic osteoarthritis? One-year follow-up data from the Osteoarthritis Initiative.

Skeletal Radiol 2021 Aug 4. Epub 2021 Aug 4.

Institute of Anatomy and Musculoskeletal Research, Paracelsus Medical University, Salzburg, Austria.

Objective: Kellgren-Lawrence grades (KLG) are frequently used for patient selection in clinical trials. The Ahlbäck radiographic grading system has been developed for moderate and severe knee OA. KLG 3 is comparable to Ahlbäck 1 and KLG 4 is subdivided into Ahlbäck 2-5. The objective of this study was to investigate if the Ahlbäck scoring system is able to subdivide patients with moderate to severe knee OA (KLG 3/4) into groups with different sensitivity to change in cartilage thickness.

Materials And Methods: This study was based on 108 Osteoarthritis Initiative (OAI) participants with KLG 3/4. Baseline KLG scores were available from the OAI database; Ahlbäck scores were performed using the same x-rays. Cartilage thickness change in the weight-bearing femorotibial cartilage was analysed from baseline and year 1 3D FLASH MRI for the entire femorotibial joint (FTJ), the medial (MFTC) and the lateral compartment (LFTC) and for the location-independent ordered values 1 and 16 (OV 1/OV 16) representing the subregions with largest loss (OV 1) and gain (OV 16) within each knee.

Results: Of the 108 patients, n = 30/78 had KLG 3/4. The corresponding Ahlbäck scores (1-5) were n = 30/33/36/9/10. Cartilage thickness changes between Ahlbäck groups showed no statistically significant difference for FTJ, MFTC, LFTC and OV 1, but change in OV 16 was significantly higher in Ahlbäck 4 knees (p = 0.03) compared to Ahlbäck 1-3 knees.

Conclusion: Radiographic knee OA grading with Ahlbäck scores was not superior to KLG for prediction of cartilage thickness loss over 1 year, in patients with moderate and severe knee OA supporting the continuous use of the easier and more widely used KLG.
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http://dx.doi.org/10.1007/s00256-021-03871-zDOI Listing
August 2021

Response letter to the Editor.

Semin Arthritis Rheum 2021 May 8. Epub 2021 May 8.

University of Maryland School of Medicine, Baltimore, MD, United States.

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http://dx.doi.org/10.1016/j.semarthrit.2021.05.001DOI Listing
May 2021

Superficial cartilage transverse relaxation time is associated with osteoarthritis disease progression - data from the FNIH biomarker study of the osteoarthritis initiative.

Arthritis Care Res (Hoboken) 2021 May 10. Epub 2021 May 10.

Department of Imaging and Functional Musculoskeletal Research, Institute of Anatomy and Cell Biology, Paracelsus Medical University Salzburg and Nuremberg, Salzburg, Austria.

Objective: To study whether layer-specific cartilage transverse relaxation time (T2), and/or longitudinal change is associated with clinically relevant knee osteoarthritis (OA) disease progression.

Methods: The FNIH biomarker consortium was a nested case-control study on 600 knees from 600 Osteoarthritis Initiative participants. Progressor knees had both medial tibiofemoral radiographic joint space width (JSW) loss (≥0.7 mm) and a persistent increase in WOMAC pain (≥9 on a 0-100 scale) at 24-48 month from baseline (n=194). Multi-echo spin-echo (MESE) MRIs for cartilage T2 analysis had been acquired in the right knees only (97 progressor knees). These were compared to 104 control knees without JSW or pain progression. 53 knees had JSW progression, and 57 pain progression only. Cartilage thickness segmentations obtained from DESS MRI were matched to MESE MRI, to extract superficial and deep femorotibial cartilage T2. Superficial medial femorotibial compartment (MFTC) T2 at baseline was the primary, and change in deep MFTC T2 between baseline and 12 months the secondary analytic outcome of this post-hoc exploratory study.

Results: Baseline superficial MFTC T2 was significantly elevated in progressor knees (adjusted mean 47.2ms [95% confidence interval [CI] 46.5, 48.0]) and JSW progression only knees (adjusted mean 47.3ms [95% confidence interval [CI] 46.3, 48.3]), respectively, vs non-progressor knees (45.8ms [95% CI 45.0, 46.5]) after adjustment for age, sex, BMI, WOMAC pain, and medial JSN grade (ANCOVA). Change in T2 was not significantly associated with case status.

Conclusions: Baseline superficial, but not deep, medial cartilage T2 is associated with clinically relevant disease progression in knee OA.
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http://dx.doi.org/10.1002/acr.24627DOI Listing
May 2021

The effects of sprifermin on symptoms and structure in a subgroup at risk of progression in the FORWARD knee osteoarthritis trial.

Semin Arthritis Rheum 2021 04 11;51(2):450-456. Epub 2021 Mar 11.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK. Electronic address:

Objective: To assess pain outcomes and cartilage thickness change in a subgroup at risk (SAR) of further progression in the FORWARD trial of knee osteoarthritis patients treated with sprifermin.

Methods: Patients were randomised 1:1:1:1:1 to: sprifermin 100 µg every 6 months (q6mo), 100 µg q12mo, 30 µg q6mo, 30 µg q12mo, or placebo for 18 months. SAR was defined as baseline medial or lateral minimum joint-space width (mJSW) 1.5-3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score 40-90 units. Follow-up to 3 years was included in the analysis. Treatment benefit was explored by repeated measures, linear dose-effect trends by timepoint.

Results: The SAR comprised 161 (29%) of 549 patients. Mean difference (95% CI) in WOMAC pain at year 3 for sprifermin 100 µg q6mo vs placebo SAR was -8.75 (-22.42, 4.92) for SAR vs 0.97 (-6.22, 8.16) for the intent-to-treat population. SAR placebo patients lost more cartilage over 2 years than the modified ITT (mITT) placebo arm (mean change from baseline, mm [SD]: -0.05 [0.10] vs -0.02 [0.07]). Net total femorotibial joint thickness gain with sprifermin 100 µg q6mo (adjusted mean difference from placebo [95% CI] was similar in the SAR and in the mITT group: 0.06 [0.01, 0.11] vs 0.05 [0.03, 0.07]).

Conclusions: Selection for low mJSW and moderate-to-high pain at baseline resulted in more rapid disease progression and demonstrated translation of structure modification (with maintained net benefit on total cartilage thickness) into symptomatic benefit. This subgroup may represent a target population for future trials.

Clinical Trial Registration: NCT01919164.
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http://dx.doi.org/10.1016/j.semarthrit.2021.03.005DOI Listing
April 2021

Changes in Cartilage Thickness and Denuded Bone Area after Knee Joint Distraction and High Tibial Osteotomy-Post-Hoc Analyses of Two Randomized Controlled Trials.

J Clin Med 2021 Jan 19;10(2). Epub 2021 Jan 19.

Department of Imaging & Functional Musculoskeletal Research, Institute of Anatomy & Cell Biology, Paracelsus Medical University Salzburg & Nuremberg, 5020 Salzburg, Austria.

High tibial osteotomy (HTO) and knee joint distraction (KJD) are joint-preserving treatments that unload the more affected compartment (MAC) in knee osteoarthritis. This post-hoc study compares two-year cartilage-thickness changes after treatment with KJD vs. HTO, and identifies factors predicting cartilage restoration. Patients indicated for HTO were randomized to KJD (KJD) or HTO treatment. Patients indicated for total knee arthroplasty received KJD (KJD). Outcomes were the MRI mean MAC cartilage thickness and percentage of denuded bone area (dABp) change two years after treatment, using radiographic joint space width (JSW) as the reference. Cohen's d was used for between-group effect sizes. Post-treatment, KJD patients ( = 18) did not show significant changes. HTO patients ( = 33) displayed a decrease in MAC cartilage thickness and an increase in dABp, but an increase in JSW. KJD ( = 18) showed an increase in MAC cartilage thickness and JSW, and a decrease in dABp. Osteoarthritis severity was the strongest predictor of cartilage restoration. Kellgren-Lawrence grade ≥3 showed significant restoration ( < 0.01) after KJD; grade ≤2 did not. Effect sizes between severe KJD and HTO patients were large for MAC MRI cartilage thickness (d = 1.09; = 0.005) and dABp (d = 1.13; = 0.003), but not radiographic JSW (d = 0.28; = 0.521). This suggests that in knee osteoarthritis patients with high disease severity, KJD may be more efficient in restoring cartilage thickness.
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http://dx.doi.org/10.3390/jcm10020368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835945PMC
January 2021

Longitudinal Change in Knee Cartilage Thickness and Function in Subjects with and without MRI-Diagnosed Cartilage Damage.

Cartilage 2020 Dec 24:1947603520980157. Epub 2020 Dec 24.

Department of Imaging & Functional Musculoskeletal Research, Institute of Anatomy & Cell Biology, Paracelsus Medical University, Salzburg, Austria.

Objective: Cartilage damage diagnosed by magnetic resonance imaging (MRI) is highly prevalent in the population. In this article, we explore whether such cartilage damage is associated with greater longitudinal change in 3D cartilage thickness and knee function in subjects without (risk factors of) knee osteoarthritis.

Design: Eighty-two knees of Osteoarthritis Initiative healthy reference cohort participants had baseline and 4-year follow-up MRI and knee function data. Baseline presence of semiquantitatively assessed MRI-based cartilage damage (MOAKS [MRI Osteoarthritis Knee Score] ≥ grade 1.0) was recorded by an experienced radiologist. Longitudinal femorotibial cartilage thickness change was determined after segmentation, using location-independent methodology. Knee function was evaluated by patient-reported outcomes and functional performance measures. Statistical comparisons included analysis of covariance adjusting for age, sex, and body mass index.

Results: Forty-five percent of the participants had cartilage damage in at least one femorotibial subregion; the cartilage thickness change score was 15% greater in participants with than in those without damage (1216 ± 434 vs. 1058 ± 277 µm). This difference reached borderline statistical significance with and without adjustment for age, sex, and body mass index ( = 0.05). No significant differences in the change of patient-reported outcomes of knee function (PASE [physical activity score of the elderly] and WOMAC [Western Ontario McMaster Osteoarthritis Index]) or chair stand test results were detected. Of those without femorotibial damage, 58% had cartilage damage in at least one femoropatellar subregion; these had a 9% greater femorotibial cartilage change score than those without femoropatellar or femorotibial damage (difference not statistically significant).

Conclusions: In the absence of osteoarthritis risk factors, semiquantitatively assessed MRI-based cartilage damage appears to be associated with greater longitudinal location-independent femorotibial cartilage thickness changes, but not with greater functional deteriorations.
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http://dx.doi.org/10.1177/1947603520980157DOI Listing
December 2020

A Deep Learning Automated Segmentation Algorithm Accurately Detects Differences in Longitudinal Cartilage Thickness Loss - Data from the FNIH Biomarkers Study of the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken) 2020 Dec 18. Epub 2020 Dec 18.

Department of Imaging and Functional Musculoskeletal Research, Institute of Anatomy and Cell Biology, Paracelsus Medical University Salzburg and Nuremberg, Salzburg, Austria.

Objective: To study the longitudinal performance of fully automated cartilage segmentation in knees with radiographic osteoarthritis (ROA). We evaluate the sensitivity to change in progressor knees from the Foundation National Institutes of Health OA Biomarkers Consortium between the automated and previously reported manual expert segmentation, and whether differences in progression rates between predefined cohorts can be detected by the fully automated approach.

Methods: The Osteoarthritis Initiative Biomarker Consortium was a nested case-control study. Progressor knees had both medial tibiofemoral radiographic joint space width loss (≥0.7 mm) and a persistent increase in WOMAC pain (≥9 on a 0-100 scale) after two years from baseline (n=194), whereas non-progressor knees did not have either of both (n=200). Deep learning automated algorithms trained on ROA or healthy reference (HRC) knees were used to automatically segment medial (MFTC) and lateral femorotibial cartilage on baseline and two-year follow-up MRIs. Findings were compared with previously published manual expert segmentation.

Results: The MFTC cartilage loss in the progressor cohort was -181±245µm by manual (SRM=-0.74), -144±200µm by ROA-based model (SRM=-0.72), and -69±231µm by HRC-based model segmentation (SRM=-0.30). The Cohen's D for rates of progression between progressor vs. non-progressor cohort was -0.84 (p<0.001) for manual, -0.68 (p<0.001) for automated ROA-model, and -0.14 (p=0.18) for automated HRC-model segmentation.

Conclusions: A fully automated deep learning segmentation approach not only displayed similar sensitivity to change of longitudinal cartilage thickness loss in knee OA as manual expert segmentation, but also effectively differentiates longitudinal rates of cartilage thickness loss between cohorts with different progression profiles.
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http://dx.doi.org/10.1002/acr.24539DOI Listing
December 2020

Accuracy and longitudinal reproducibility of quantitative femorotibial cartilage measures derived from automated U-Net-based segmentation of two different MRI contrasts: data from the osteoarthritis initiative healthy reference cohort.

MAGMA 2021 Jun 6;34(3):337-354. Epub 2020 Oct 6.

Department of Radiology, Stanford University, Stanford, CA, USA.

Objective: To evaluate the agreement, accuracy, and longitudinal reproducibility of quantitative cartilage morphometry from 2D U-Net-based automated segmentations for 3T coronal fast low angle shot (corFLASH) and sagittal double echo at steady-state (sagDESS) MRI.

Methods: 2D U-Nets were trained using manual, quality-controlled femorotibial cartilage segmentations available for 92 Osteoarthritis Initiative healthy reference cohort participants from both corFLASH and sagDESS (n = 50/21/21 training/validation/test-set). Cartilage morphometry was computed from automated and manual segmentations for knees from the test-set. Agreement and accuracy were evaluated from baseline visits (dice similarity coefficient: DSC, correlation analysis, systematic offset). The longitudinal reproducibility was assessed from year-1 and -2 follow-up visits (root-mean-squared coefficient of variation, RMSCV%).

Results: Automated segmentations showed high agreement (DSC 0.89-0.92) and high correlations (r ≥ 0.92) with manual ground truth for both corFLASH and sagDESS and only small systematic offsets (≤ 10.1%). The automated measurements showed a similar test-retest reproducibility over 1 year (RMSCV% 1.0-4.5%) as manual measurements (RMSCV% 0.5-2.5%).

Discussion: The 2D U-Net-based automated segmentation method yielded high agreement compared with manual segmentation and also demonstrated high accuracy and longitudinal test-retest reproducibility for morphometric analysis of articular cartilage derived from it, using both corFLASH and sagDESS.
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http://dx.doi.org/10.1007/s10334-020-00889-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154803PMC
June 2021

Is Laminar Cartilage Composition as Determined by T2 Relaxometry Associated with Incident and Worsening of Cartilage or Bone Marrow Abnormalities?

Cartilage 2020 Jun 12:1947603520932197. Epub 2020 Jun 12.

Chondrometrics GmbH, Ainring, Germany.

Objective: To test the hypothesis that superficial cartilage composition (T2) is associated with subsequent incidence or worsening of cartilage damage, and deep T2 with that of bone marrow lesions (BMLs) in knees without radiographic osteoarthritis (ROA).

Design: A total of 201 knees from the Osteoarthritis Initiative without ROA were included: 78 from the healthy reference cohort, 60 without ROA but with risk factors, and 63 without ROA but with contralateral ROA. Year 1 (Y1) superficial and deep cartilage T2 were derived in the medial and lateral (weightbearing) femur (MF/LF) and tibia (MT/LT), using sagittal multiecho spin echo magnetic resonance images. Cartilage and BMLs were assessed in the medial (MFTJ) and lateral femorotibial joint (LFTJ) at Y1 and 3 years later. Binary logistic regression statistics were applied.

Results: Incidence or worsening of cartilage damage was more frequent (MFTJ 15%, LFTJ 13%) than incidence or worsening of BMLs (6.0%, 4.5%). In knees with incident or worsening cartilage lesions in the MF and LT, deep layer T2 in the same plate was elevated (MF, 43.6 ± 4.0 vs. 41.3 ± 3.8 ms, = 0.047; LT, 33.8 ± 2.3 vs. 32.0 ± 2.2 ms, = 0.008) compared to those without. In knees with incident or worsening of BMLs in the LFTC and LT, superficial layer T2 was elevated (LFTJ, 49.6 ± 4.8 vs. 46.7 ± 3.1 ms; LT, 47.4 ± 4.9 vs. 44.0 ± 3.3 ms, both s = 0.04).

Conclusions: Contrary to our hypothesis, increased deep layer cartilage T2 was associated with subsequent worsening of cartilage damage, whereas superficial layer T2 was related to subsequent BML worsening. Yet, this relationship was observed in some, but not in all cartilage plates.
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http://dx.doi.org/10.1177/1947603520932197DOI Listing
June 2020

Changes in Medial Meniscal Three-Dimensional Position and Morphology As Predictors of Knee Replacement in Rapidly Progressing Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken) 2021 07;73(7):1031-1037

Paracelsus Medical University Salzburg and Nuremberg, Salzburg, Austria, and Chondrometrics GmbH, Ainring, Germany.

Objective: To assess whether quantitative changes in the meniscus predict progression from early knee osteoarthritis (OA) to knee replacement (KR).

Methods: A nested case-control study was conducted among Osteoarthritis Initiative participants: all 35 case knees with baseline Kellgren/Lawrence (K/L) grade ≤2 that had KR between 36 and 60 months were matched 1:1 by age, sex, and baseline K/L grade to 35 control knees without subsequent KR. Quantitative 3-dimensional medial meniscus position and morphologic measures were determined from magnetic resonance imaging at the visit just before KR and 2 years before. Paired t-tests and case-control odds ratios (ORs, standardized per SD of change in controls) were used to compare changes between groups.

Results: Cases (52% women, age 65 ± 7 years, body mass index [BMI] 30 ± 4 kg/m , K/L grades 0/1/2: 5/8/22 participants, respectively) and controls (52% women, age 64 ± 7 years, BMI 30 ± 5 kg/m , K/L grades 0/1/2: 9/4/22 participants, respectively) were similar. Compared to control knees, KR case knees displayed longitudinal changes, specifically, a decrease in tibial plateau coverage, an increase in meniscal extrusion, and a decrease in meniscal width. The odds for KR increased with greater reduction in the percentage of tibial plateau coverage (OR 2.28 [95% CI confidence interval (95% CI) 1.43, 3.64]), a greater increase in maximal extrusion (OR 1.40 [95% CI 1.12, 1.75]), and a greater reduction of mean meniscal width (OR 2.01 [95% CI 1.23, 3.26]). The odds for KR increased with medial compartment cartilage thickness loss (OR 2.86 [95% CI 1.51, 5.41]) for comparison.

Conclusion: Quantitative measures of meniscal position and morphology are associated with subsequent KR in knees with rapidly progressing knee OA. These findings show that structural changes of the meniscus are related to an important clinical and economic outcome of knee OA.
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http://dx.doi.org/10.1002/acr.24193DOI Listing
July 2021

Impact of Diabetes Mellitus on Knee Osteoarthritis Pain and Physical and Mental Status: Data From the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken) 2021 04 17;73(4):540-548. Epub 2021 Mar 17.

Chondrometrics GmbH, Ainring, Germany, and Paracelsus Medical University, Salzburg, Austria.

Objective: Diabetes mellitus (DM) appears to increase osteoarthritic knee pain, which may be related to greater adiposity and more advanced disease status often observed in individuals with osteoarthritis (OA) and DM. We aimed to assess whether OA knee pain and health status are worse in individuals with OA and DM, independent of these potential confounders.

Methods: We included 202 OA participants with DM and 2,279 without DM from the Osteoarthritis Initiative. Knee pain was evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and a numeric rating scale (NRS). Physical and mental status were assessed by the Medical Outcomes Study Short Form 12 (SF-12) questionnaire, physical component summary (PCS) score and mental component summary (MCS) score, and by the Center for Epidemiologic Studies Depression Scale (CES-D). Linear regression models assessed the influence of DM, adjusted for age, sex, body mass index (BMI), and radiographic severity.

Results: OA participants with DM reported worse knee pain and greater physical and mental issues compared with participants without DM. Individuals with DM had worse KOOS pain (β = -4.72 [95% confidence interval (95% CI) -7.22, -2.23]) and worse NRS pain (β = 0.42 [95% CI 0.04, 0.80]) independent of BMI, OA severity, age, and sex. The negative influence of DM was also apparent for SF-12 PCS (β = -3.49 [95% CI -4.73, -2.25]), SF-12 MCS (β = -1.42 [95% CI -2.57, -0.26]), and CES-D (β = 1.08 [95% CI 0.08, 2.08]).

Conclusion: Individuals with knee OA experience on average higher pain intensity and a worse physical and mental health status if they have DM. Linear regression models show that DM is a risk factor for higher pain, in addition to and independent of greater BMI and radiographic OA severity.
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http://dx.doi.org/10.1002/acr.24173DOI Listing
April 2021

Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of location in the femorotibial joint: post-hoc analysis of a randomised, placebo-controlled phase II clinical trial.

Ann Rheum Dis 2020 04 25;79(4):525-528. Epub 2020 Feb 25.

University of Maryland School of Medicine, Baltimore, Maryland, USA.

Objectives: In the phase II FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses (FORWARD) study, sprifermin demonstrated cartilage modification in the total femorotibial joint and in both femorotibial compartments by MRI in patients with knee osteoarthritis. Here, we evaluate whether sprifermin reduces cartilage loss and increases cartilage thickness, independent of location.

Methods: Patients were randomised 1:1:1:1:1 to three once-weekly intra-articular injections of 30 µg sprifermin every 6 months (q6mo); 30 µg sprifermin every 12 months (q12mo); 100 µg sprifermin q6mo; 100 µg sprifermin q12mo; or placebo. Post-hoc analysis using thinning/thickening scores and ordered values evaluated femorotibial cartilage thickness change from baseline to 24 months independent of location. Changes were indirectly compared with those of Osteoarthritis Initiative healthy subjects.

Results: Thinning scores were significantly lower for sprifermin 100 µg q6mo versus placebo (mean (95% CI) difference: 334 µm (114 to 554)), with a cartilage thinning score similar to healthy subjects. Thickening scores were significantly greater for sprifermin 100 µg q6mo, 100 µg q12mo and 30 µg q6mo versus placebo (mean (95% CI) difference: 425 µm (267 to 584); 450 µm (305 to 594) and 139 µm (19 to 259), respectively) and more than doubled versus healthy subjects.

Conclusions: Sprifermin increases cartilage thickness, and substantially reduces cartilage loss, expanding FORWARD primary results.

Trial Registration Number: NCT01919164.
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http://dx.doi.org/10.1136/annrheumdis-2019-216453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147175PMC
April 2020

Longitudinal changes in location-specific cartilage thickness and T2 relaxation-times after posterior cruciate ligament reconstruction for isolated and multiligament injury.

Clin Biomech (Bristol, Avon) 2020 10 23;79:104935. Epub 2019 Dec 23.

Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremburg, Salzburg, Austria. Electronic address:

Background: Knee cartilage undergoes pathological changes after anterior cruciate ligament rupture. However, little is known about the development and progression of structural pathology after posterior cruciate ligament (PCL) injury. This study aimed to determine the location-specific longitudinal changes in knee cartilage morphology (thickness) and composition (T2 relaxation-times) after PCL rupture and reconstruction (PCLR) and compare these to uninjured controls.

Methods: Fifteen adults (mean age 39 years (standard deviation 10), 12 men) with PCLR for isolated and multiligment injury had MRIs acquired at a minimum 5 years post-PCLR and 1 year later. Location-specific changes in knee cartilage thickness and T2 relaxation-times were determined quantitatively after segmentation, and compared with annualised cartilage changes in 13 active controls (mean age 45 years (standard deviation 4), 6 men).

Findings: Following PCLR, the annual loss of cartilage thickness was greatest in the medial femoral condyle (mean -4.0%, 95% confidence interval [95% CI] -6.7, -1.4), medial tibia (mean -3.7%, 95% CI -6.1, -1.3), and patella (mean -3.2%, 95% CI -4.7, -1.6). In the medial femoral condyle and trochlea, the PCLR group lost significantly more cartilage thickness than uninjured controls (mean difference -3.7%, 95% CI -0.9, -6.5; and -1.8%, 95% CI -0.1, -3.6, respectively). Deep and superficial zone T2 relaxation-times were relatively constant over time, without longitudinal differences between PCLR and control knees.

Interpretation: PCL reconstructed knees displayed substantially greater rates of cartilage loss in the medial tibiofemoral and patellofemoral compartments compared to uninjured controls, highlighting that the process of degeneration remains active many years after injury.
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http://dx.doi.org/10.1016/j.clinbiomech.2019.12.017DOI Listing
October 2020

Clinical evaluation of fully automated thigh muscle and adipose tissue segmentation using a U-Net deep learning architecture in context of osteoarthritic knee pain.

MAGMA 2020 Aug 23;33(4):483-493. Epub 2019 Dec 23.

ETH, Zurich, Switzerland.

Objective: Segmentation of thigh muscle and adipose tissue is important for the understanding of musculoskeletal diseases such as osteoarthritis. Therefore, the purpose of this work is (a) to evaluate whether a fully automated approach provides accurate segmentation of muscles and adipose tissue cross-sectional areas (CSA) compared with manual segmentation and (b) to evaluate the validity of this method based on a previous clinical study.

Materials And Methods: The segmentation method is based on U-Net architecture trained on 250 manually segmented thighs from the Osteoarthritis Initiative (OAI). The clinical evaluation is performed on a hold-out test set bilateral thighs of 48 subjects with unilateral knee pain.

Results: The segmentation time of the method is < 1 s and demonstrated high agreement with the manual method (dice similarity coeffcient: 0.96 ± 0.01). In the clinical study, the automated method shows that similar to manual segmentation (- 5.7 ± 7.9%, p < 0.001, effect size: 0.69), painful knees display significantly lower quadriceps CSAs than contralateral painless knees (- 5.6 ± 7.6%, p < 0.001, effect size: 0.73).

Discussion: Automated segmentation of thigh muscle and adipose tissues has high agreement with manual segmentations and can replicate the effect size seen in a clinical study on osteoarthritic pain.
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http://dx.doi.org/10.1007/s10334-019-00816-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351818PMC
August 2020

Baseline structural tissue pathology is not strongly associated with longitudinal change in transverse relaxation time (T2) in knees without osteoarthritis.

Eur J Radiol 2019 Sep 20;118:161-168. Epub 2019 Jul 20.

Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Strubergasse 21, 5020, Salzburg, Austria; Chondrometrics GmbH, 83404, Ainring, Germany.

Purpose: To evaluate whether baseline MRI-defined structural abnormalities are associated with subsequent change in laminar femorotibial cartilage transverse relaxation time (T2) of participants without radiographic signs, symptoms or risk factors for knee osteoarthritis (OA).

Method: We studied all right knees with longitudinal MRI data of the refined Osteoarthritis Initiative Healthy Reference cohort. Baseline osteophytes, effusion-synovitis, Hoffa-synovitis, bone marrow lesions, cartilage lesions, and meniscus morphology and - extrusion were scored semiquantitatively from MR images by an expert reader. Deep and superficial layer cartilage T2 was computed in the medial and lateral femorotibial compartment (MFTC/LFTC) at baseline and at 1- and 4-year follow-up from multi-echo spin-echo MR images. Statistical analyses were performed using UNIANOVA.

Results: 82 participants (age 54.1 ± 7.2y, BMI 24.2 ± 3.0 kg/m²; 61% women, bilateral Kellgren-Lawrence 0) were studied. Number of baseline MRI pathologies was not significantly associated with longitudinal change in MFTC or LFTC cartilage T2 over 1 or 4 years. Feature-specific analyses suggested that presence of baseline MFTC osteophytes may be associated with prolongation in superficial MFTC cartilage T2 over one (0.8 vs. 0.0 ms, p = 0.02) and four years (2.3 vs. 0.9 ms, p = 0.01), and that MFTC meniscal damage or extrusion may be associated with prolongation in deep layer T2 times over the first year (0.7 vs. 2.1 ms, p = 0.02).

Conclusions: Our study does not provide evidence that, in knees without radiographic OA, baseline structural MRI abnormalities are strongly related to compositional progression during normal aging and/or the potentially earliest phases of the disease as measured by cartilage T2.
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http://dx.doi.org/10.1016/j.ejrad.2019.07.013DOI Listing
September 2019

Reduction in Thigh Muscle Strength Occurs Concurrently but Does Not Seem to Precede Incident Knee Pain in Women: Data From the Osteoarthritis Initiative Cohort.

Am J Phys Med Rehabil 2020 01;99(1):33-40

From the Institute of Anatomy, Department of Imaging and Functional Musculoskeletal Research, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria (AR, WW, AGC, FE); Department of Orthopedic Surgery and Traumatology, Landesklinik Tamsweg, Tamsweg, Austria (AR); and La Trobe Sport and Exercise Medicine Research Centre, La Trobe University, School of Allied Health, Bundoora, Melbourne, Victoria, Australia (AGC).

Objective: The aim of the study was to investigate whether muscle strength declines before or concurrent with incident knee pain in subjects with and without radiographic knee osteoarthritis.

Design: Osteoarthritis initiative participants with incident knee pain (occurrence of infrequent/frequent knee pain during the past 12 mos at two consecutive follow-up time points (either years Y3 + Y4 or Y4 + Y5) were compared with controls (no incident knee pain) with 2-yr changes in knee extensor strength during BL➔Y2 (before) and Y2➔Y4 (concurrent).

Results: Two hundred two knees (49% women, 40% radiographic knee osteoarthritis) displayed incident pain, and 439 did not (46% women, 23% radiographic knee osteoarthritis). Women with radiographic knee osteoarthritis displayed a significantly greater (P = 0.04) reduction in knee extensor strength concurrent with incident pain compared with controls (mean = -17.6 N vs. +4.5 N), but men did not. A similar trend was observed in women without radiographic knee osteoarthritis, but this was not statistically significant (P = 0.08). There was no significant relationship with change in extensor strength before incident pain (P ≥ 0.43).

Conclusions: These results suggest that in women, incident knee pain is accompanied by a concurrent reduction in knee extensor strength, whereas loss in strength does not precede incident knee pain. The findings encourage interventional studies that attempt to attenuate a decline in extensor strength once knee symptoms occur.
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http://dx.doi.org/10.1097/PHM.0000000000001271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920538PMC
January 2020

Validation of a novel blinding method for measuring postoperative knee articular cartilage using magnetic resonance imaging.

MAGMA 2019 Dec 12;32(6):693-702. Epub 2019 Jul 12.

Wolf Orthopaedic Biomechanics Laboratory, Fowler Kennedy Sport Medicine Clinic, Western University, London, ON, Canada.

Objectives: To test PEEK implant-associated MRI artifacts, a method for blinding MRI readers, the repeatability of cartilage thickness measures before and 6 weeks after high tibial osteotomy (HTO), and the sensitivity to change of cartilage thickness 12 months after HTO.

Materials And Methods: Ten patients underwent HTO using a PEEK implant and 3 T-MRI before, 6 weeks and 12 months after surgery. Masks were applied to hide implant visibility on 48 MRI pairs, which were assessed by 7 readers (blinded to time). One blinded reader measured femorotibial cartilage thickness from masked MRIs.

Results: No artifacts were produced. Readers were unable to identify scans by time greater than by chance. Cartilage thickness before and 6 weeks after surgery was not significantly different and indicated excellent repeatability. Medial cartilage thickness increases 12 M postoperatively approached statistical significance (p = 0.06), with no lateral changes observed. Half of the participants had an increase in medial cartilage thickness at 12 M that exceeded the minimal detectable change. Standardized response mean values were moderate-to-large.

Discussion: Postoperative measures of cartilage thickness are repeatable, consistent and sensitive to change when artifact is eliminated, and a validated blinding technique is used. These results provide proof of concept for accurately measuring increases in medial knee articular cartilage after medial opening wedge HTO.
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http://dx.doi.org/10.1007/s10334-019-00766-yDOI Listing
December 2019

The association of physical activity and depression in patients with, or at risk of, osteoarthritis is captured equally well by patient reported outcomes (PROs) and accelerometer measurements - Analyses of data from the Osteoarthritis Initiative.

Semin Arthritis Rheum 2019 12 31;49(3):325-330. Epub 2019 May 31.

Paracelsus Medical University, Institute of Anatomy, Salzburg, Austria.

Objectives: Osteoarthritis (OA) patients are at increased risk of depression, and low levels of physical activity (PA) are a potential warning sign of depression. PA can be estimated by patient reported outcomes (PROs) or measured with accelerometers (ACCs). We explored which of these two best captures depression in patients with, or at risk of, OA.

Methods: 48-months data from the Osteoarthritis Initiative were cross-sectionally analysed. The dichotomized Centre for Epidemiological Studies Depression Scale score was used as outcome (depression y/n). The Physical Activity Scale for the Elderly (PASE) was selected as PRO. ACC-data comprised average minutes of daily moderate to vigorous activity. Two multivariable models (PRO-model/ACC-model) were compared directly and indirectly using areas under the curve (AUC) for the predicted probability of depression, penalized model selection criteria (PMSC) and log-likelihood ratio tests.

Results: AUCs from the ACC (0.71 [95% CI 0.67; 0.75]) and PRO model (0.72 [95% CI 0.68; 0.76]) were not significantly different (p = 0.28). Differences in PMSC were small (<10). The log-likelihood ratio test for the comparison of the ACC (ll -505.22) with the base model (ll -505.98) was not significant (LR chi = 1.52; p = 0.22), but the PRO model (ll -501.55) had a better fit than the base model (LR chi = 8.87; p < 0.01).

Conclusions: PRO and ACC data perform similarly in capturing depression. Indirect comparison even pleads for PROs. Costs of accelerometers and the additional burden for patients are in support of the PASE as an appropriate alternative to screen for depression in OA patients.
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http://dx.doi.org/10.1016/j.semarthrit.2019.05.009DOI Listing
December 2019

Association between changes in molecular biomarkers of cartilage matrix turnover and changes in knee articular cartilage: a longitudinal pilot study.

J Exp Orthop 2019 May 3;6(1):19. Epub 2019 May 3.

Julius Wolff Institute, Charité - Universitätsmedizin, Berlin, Germany.

Background: An early detection of Osteoarthritis is urgently needed and still not possible until today. The aim of the study was to assess whether molecular biomarkers of cartilage turnover are associated with longitudinal change in knee cartilage thickness during a 2 year period in individuals with increased risk of developing knee osteoarthritis. A secondary aim was to assess whether prior knee injury or subjective patient-reported outcomes at baseline (BL) were associated with articular cartilage changes. Nineteen volleyball players (mean age 46.5 ± 4.9 years, 47% male) with a 30-year history of regular high impact training were recruited. The serum biomarkers Cpropeptide of type II procollagen (CPII), cartilage oligomeric matrix protein (COMP), collagenase generated carboxy-terminal neoepitope of type II collagen (sC2C), cartilage intermediate layer protein 2 (CILP-2), and the urine biomarkers C-telopeptide of type II collagen (CTX-II) and collagenase-generated peptide(s) of type II collagen (C2C-HUSA) were assessed at BL and at 2 year follow up (FU). Femorotibial cartilage thinning, thickening and absolute thickness change between BL and FU was evaluated from magnetic resonance imaging. Subjective clinical status at BL was evaluated by the International Knee Documentation Committee Subjective Knee Form and the Short-Form 36 Physical Component Score.

Results: CILP-2 was significantly higher at FU and linearly associated with the absolute cartilage thickness change during the experimental period. Prior injury was a predictor of increased absolute cartilage thickness change.

Conclusion: Measuring the change in the cartilage biomarker CILP-2 might be a valid and sensitive method to detect early development of knee osteoarthritis as CILP-2 appears to be related to cartilage thickness loss in certain individuals with increased risk of developing knee osteoarthritis. Prior knee injury may be predictive of increased articular cartilage thickness change.
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http://dx.doi.org/10.1186/s40634-019-0179-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499840PMC
May 2019

Loss of patellofemoral cartilage thickness over 5 years following ACL injury depends on the initial treatment strategy: results from the KANON trial.

Br J Sports Med 2019 Sep 8;53(18):1168-1173. Epub 2019 Feb 8.

Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lunds Universitet, Lund, Sweden.

Objectives: To evaluate changes in patellofemoral cartilage thickness over 5 years after anterior cruciate ligament (ACL) injury and to determine the impact of treatment strategy.

Methods: 121 adults (ages 18-35 years, 26% women) had an ACL injury and participated in the KANON randomised controlled trial. Of those, 117 had available MRIs at baseline (<4 weeks post-ACL rupture) and at least one follow-up measurement (2, 5 years). Patellofemoral cartilage thickness was analysed by manual segmentation (blinded to acquisition order). Patellar, trochlear and total patellofemoral cartilage thickness changes were compared between as-randomised (rehabilitation+early ACL reconstruction (ACLR) (n=59) vs rehabilitation+optional delayed ACLR (n=58)) and as-treated groups (rehabilitation+early ACLR (n=59) vs rehabilitation +delayed ACLR (n=29) vs rehabilitation alone (n=29)).

Results: Patellofemoral cartilage thickness decreased -58 µm (95% CI -104 to -11 µm) over 5 years post-ACL rupture, with the greatest loss observed in trochlea during the first 2 years. Participants randomised to rehabilitation+early ACLR had significantly greater loss of patellar cartilage thickness compared with participants randomised to rehabilitation+optional delayed ACLR over the first 2 years (-25 µm (-52, 1 µm) vs +14 µm (-6 to 34 µm), p=0.02) as well as over 5 years (-36 µm (-78 to 5 µm) vs +18 µm (-7, 42 µm), p=0.02). There were no statistically significant differences in patellofemoral cartilage thickness changes between as-treated groups.

Conclusion: Patellofemoral (particularly trochlear) cartilage thickness loss was observed in young adults following acute ACL rupture. Early ACLR was associated with greater patellofemoral (particularly patellar) cartilage thickness loss over 5 years compared with optional delayed ACLR, indicating that early surgical intervention may be associated with greater short-term structural patellofemoral cartilage deterioration compared with optional delayed surgery.

Trial Registration Number: ISRCTN84752559; Post-results.
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http://dx.doi.org/10.1136/bjsports-2018-100167DOI Listing
September 2019

Association of adiposity measures in childhood and adulthood with knee cartilage thickness, volume and bone area in young adults.

Int J Obes (Lond) 2019 07 22;43(7):1411-1421. Epub 2018 Oct 22.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

Objective: To describe the associations of childhood and adulthood adiposity measures with knee cartilage thickness, volume and bone area in young adults.

Methods: Childhood and adulthood adiposity measures (weight, height, waist circumference and hip circumference) of 186 participants were collected in 1985 (aged 7-15 years) and during 2004-2006 (aged 26-36 years). Knee magnetic resonance imaging was conducted during 2008-2010 (aged 31-41 years) and cartilage thickness, volume and bone area were measured using a quantitative approach (Chondrometrics, Germany). Linear regressions were used to examine the above associations.

Results: The prevalence of overweight was 7.6% in childhood and 42.1% in adulthood. Childhood weight (β = - 5.57 mm/kg) and body mass index (BMI) (β = - 11.55 mm/kg/m) were negatively associated with adult patellar bone area, whereas adult weight was positively associated with bone area in medial femorotibial compartment (MFTC) (β = 3.37 mm/kg) and lateral femorotibial compartment (LFTC) (β = 2.08 mm/kg). Adult waist-hip ratio (WHR) was negatively associated with cartilage thickness (MFTC: β = - 0.011; LFTC: β = - 0.012 mm/0.01 unit), volume (Patella: β = - 20.97; LFTC: β = - 21.71 mm/0.01 unit) and bone area (Patella: β = - 4.39 mm/0.01 unit). The change in WHR z-scores from childhood to adulthood was negatively associated with cartilage thickness (MFTC: β = - 0.056 mm), volume (patella: - 89.95; LFTC: - 93.98 mm), and bone area (patella: - 20.74 mm). All p-values < 0.05.

Conclusions: Childhood weight and BMI were negatively but adult weight was positively associated with adult bone area. Adult WHR and the change in WHR from childhood to adulthood were negatively associated with cartilage thickness, volume, and bone area. These suggest early-life adiposity measures may affect knee structures in young adults.
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http://dx.doi.org/10.1038/s41366-018-0234-7DOI Listing
July 2019

Moderate Physical Activity and Prevention of Cartilage Loss in People With Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken) 2019 02;71(2):218-226

Paracelsus Medical University Salzburg and Nuremberg, Salzburg, Austria, and La Trobe University, Bundoora, Australia.

Objective: To examine the impact of physical activity on cartilage thickness loss in knee osteoarthritis (OA).

Methods: A total of 689 participants with radiographic knee OA at baseline (Kellgren/Lawrence grade ≥2) from the Osteoarthritis Initiative completed the Physical Activity Scale for the Elderly (PASE) questionnaires at annual intervals over 4 years. Magnetic resonance imaging-based cartilage thickness change in the medial femorotibial compartment (MFTC) over 4 years was the main outcome. The impact of PASE tertiles (low, moderate, or high) on changes in MFTC cartilage thickness was estimated using a mixed-effects model adjusted for baseline characteristics. Furthermore, stratification by sex was performed for secondary analyses.

Results: Structural progression of MFTC cartilage loss of -0.20 mm (95% confidence interval [95% CI] -0.22, -0.17) was observed in the entire cohort, with no significant difference between physical activity levels after adjustment for baseline characteristics. An interaction between sex and physical activity was observed in the adjusted analysis (P = 0.02). Stratification by sex showed that women with low physical activity had a statistically greater cartilage loss than women with moderate physical activity (adjusted between-group difference -0.09 mm [95% CI -0.16, 0.02]), whereas no significant differences were observed in men.

Conclusion: While physical activity was not associated with cartilage thickness loss in the whole cohort, this relationship significantly differed between sexes. In women, but not in men, moderate physical activity may slow down structural disease progression compared to low physical activity levels. For both men and women, high physical activity levels do not appear to be more detrimental than lower physical activity levels for cartilage thickness loss.
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http://dx.doi.org/10.1002/acr.23791DOI Listing
February 2019

Is muscle strength in a painful limb affected by knee pain status of the contralateral limb? - Data from the Osteoarthritis Initiative.

Ann Anat 2019 Jan 18;221:68-75. Epub 2018 Sep 18.

Department of Rehabilitation Medicine, University of Kansas, Kansas City, Kansas, United States.

Contralateral knee pain has been suggested to be associated with muscle weakness in a pain-free knee, potentially through a mechanism of central nervous inhibition. Whether contralateral knee pain also affects muscle strength in a painful knee, however, is unknown. Here we study the extent to which isometric muscle strength differs between matched painful limbs of people with unilateral knee pain vs. matched painful limbs people with bilateral knee pain. To that end, 163 participants with unilateral knee pain were identified from the Osteoarthritis Initiative. Unilaterally painful (UP) limbs were defined as having numerical rating scale (NRS) ≥4/10, infrequent/frequent pain in the painful limb, while contralateral pain-free limbs were defined by NRS=0-1, no/infrequent pain and Western Ontario and McMaster Universities Arthritis Index (WOMAC) ≤1. The comparator group were matched bilaterally painful (BP) limbs. Maximum isometric muscle strength (N) was compared between 1:1 matched BP and UP limbs. Extensor strength was found to be lower in BP limbs than in UP limbs, (-2.9%; p=0.39) but this difference was not statistically significant. Extensor strength was significantly lower in the UP vs. contralateral pain-free limbs (-6.2%; p<0.001). No differences were observed between BP and contralateral painful limbs (0.6%; p=0.87). In conclusion, the current results identify a slight reduction of maximum knee extensor strength in a painful limb, when the contralateral knee is also painful. In contrast to pain-free limbs, this effect did not reach statistical significance, but the overall findings support the concept of central nervous inhibition of muscle strength by contralateral knee pain.
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http://dx.doi.org/10.1016/j.aanat.2018.08.003DOI Listing
January 2019

Impact of exercise on articular cartilage in people at risk of, or with established, knee osteoarthritis: a systematic review of randomised controlled trials.

Br J Sports Med 2019 Aug 22;53(15):940-947. Epub 2018 Jun 22.

University of Southern Denmark, Odense, Denmark.

Objective: To investigate the impact of knee joint loading exercise on articular cartilage in people at risk of, or with established, knee osteoarthritis (OA) by conducting a systematic review of randomised controlled trials (RCTs).

Design: We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.

Data Sources: We performed a literature search with no restriction on publication year or language in MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials and Web of Science up to September 2017.

Eligibility Criteria: RCTs investigating the impact of exercise on MRI-assessed articular cartilage in people over 18 years of age.

Results: We included nine trials, including a total of 14 comparisons of cartilage morphometry, morphology and composition outcomes, of which two included participants at increased risk of knee OA and 12 included participants with knee OA. In participants at increased risk, one study comparison reported no effect on cartilage defects and one had positive effects on glycosaminoglycans (GAG). In participants with OA, six study comparisons reported no effect on cartilage thickness, volume or defects; one reported a negative effect and one no effect on GAG; two reported a positive effect and two no effect on collagen.

Conclusions: Knee joint loading exercise seems to not be harmful for articular cartilage in people at increased risk of, or with, knee OA. However, the quality of evidence was low, including some interventions studying activities considered outside the therapeutic loading spectrum to promote cartilage health.
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http://dx.doi.org/10.1136/bjsports-2017-098661DOI Listing
August 2019

Knee extensor muscle weakness and radiographic knee osteoarthritis progression.

Acta Orthop 2018 08 1;89(4):406-411. Epub 2018 May 1.

b Institute of Anatomy , Paracelsus Medical University Salzburg and Nuremburg , Salzburg , Austria.

Background and purpose - Knee extensor (KE) muscle weakness is a modifiable feature commonly observed in individuals with knee osteoarthritis (KOA) and constitutes a potential target for patient-specific interventions. Therefore, in this study, we explored whether KE weakness is associated with radiographic (medial and/or lateral) KOA progression and how this relationship differs depending on frontal plane knee alignment and sex. Patients and methods - We studied 3,075 knees (1,961 participants, 58% female) from the Osteoarthritis Initiative with radiographic Kellgren-Lawrence grade 1-3. Peak KE torque (Nm/kg) was assessed at baseline, and progression defined as fixed-location joint space width loss (≥ 0.7mm) in medial and lateral tibiofemoral compartments from baseline to 4-year follow-up. Knee-based generalized estimating equations, stratified by alignment (malaligned vs. neutral), estimated the relative risk (RR) of progression for those in the lowest (and middle) vs. highest KE torque group (split by tertiles). Secondary analyses explored whether this relationship was compartmental- or sex-specific. Results - Being in the lowest (or middle) compared with the highest torque group increased the risk of progression in neutrally aligned knees (relative risk [RR] 1.2 [95% CI 1.0-1.4]; and 1.2 [CI 1.0-1.4], respectively), but not after adjusting for age, sex, BMI, pain, and radiographic severity. In secondary analyses, women with neutral alignment in the lowest compared with the highest torque group had significantly increased risk of lateral compartment progression independent of age, BMI, disease severity, and pain (RR 1.3 [CI 1.0-1.8]). No association was observed between KE torque and KOA progression in men, irrespective of alignment. Interpretation - These results identify a potentially important clinical phenotype: KE weakness may be a more important risk factor for radiographic KOA progression in women without knee malalignment.
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http://dx.doi.org/10.1080/17453674.2018.1464314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066769PMC
August 2018

Responsiveness of Infrapatellar Fat Pad Volume Change to Body Weight Loss or Gain: Data from the Osteoarthritis Initiative.

Cells Tissues Organs 2018 1;205(1):53-62. Epub 2018 Feb 1.

Obesity is a potent risk factor for knee osteoarthritis (OA) that is driven by mechanical and potentially endocrine mechanisms, and it affects women more frequently than men. The infrapatellar fat pat (IPFP) represents a potential link between obesity, intra-articular inflammation and structural pathology. Here we investigate whether the IPFP is responsive to body weight loss/gain in women and how its responsiveness to weight change compares to that of subcutaneous fat (SCF) of the thigh. All female participants of the Osteoarthritis Initiative (OAI) with ≥10% weight loss/gain between baseline and a 2-year follow-up were included. Within-subject changes in IPFP volume and SCF cross-sectional areas (CSA) were determined from 3-T magnetic resonance imaging. Linear regression was used to assess the association between change in weight, IPFP volume, and SCF CSA. In the 38 participants with ≥10% weight loss over 2 years (age 59.3 ± 9.1 years, mean loss = 15.9%), there was a significant reduction in IPFP volume (-2.2%, p = 0.02) as well as in SCF CSA (-22%, p < 0.001). In the 34 participants with ≥10% gain (age 61.5 ± 8.7 years, mean gain = 15.9%), there was a significant increase in SCF CSA (+26%, p < 0.001) but not in IPFP volume (0.2%, p = 0.87). Weight change was significantly associated with SCF CSA change (r = 0.76, p < 0.001) but not with IPFP volume change (r = 0.11, p = 0.37). In this first longitudinal, observational study investigating the responsiveness of IPFP and SCF to weight change, IPFP morphology was found responsive to weight loss but not to weight gain. Overall, the responsiveness of the IPFP was substantially less than that of the SCF.
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http://dx.doi.org/10.1159/000485833DOI Listing
April 2019

Cartilage Morphological and Histological Findings After Reconstruction of the Glenoid With an Iliac Crest Bone Graft.

Am J Sports Med 2018 04 19;46(5):1039-1045. Epub 2018 Jan 19.

Department of Orthopedics and Traumatology, Paracelsus Medical University, Salzburg, Austria.

Background: The J-bone graft is presumably representative of iliac crest bone grafts in general and allows anatomic glenoid reconstruction in cases of bone defects due to recurrent traumatic anterior shoulder dislocations. As a side effect, these grafts have been observed to be covered by some soft, cartilage-like tissue when arthroscopy has been indicated after such procedures.

Purpose: To evaluate the soft tissue covering of J-bone grafts by use of magnetic resonance imaging (MRI) and histological analysis.

Study Design: Case series; Level of evidence, 4.

Methods: Patients underwent MRI at 1 year after the J-bone graft procedures. Radiological data were digitally processed and evaluated by segmentation of axial images. Independent from the MRI analysis, 2 biopsy specimens of J-bone grafts were harvested for descriptive histological analysis.

Results: Segmentation of the images revealed that all grafts were covered by soft tissue. This layer had an average thickness of 0.87 mm compared with 1.96 mm at the adjacent native glenoid. Of the 2 biopsy specimens, one exhibited evident hyaline-like cartilage and the other presented patches of chondrocytes embedded in a glycosaminoglycan-rich extracellular matrix.

Conclusion: J-bone grafts are covered by soft tissue that can differentiate into fibrous and potentially hyaline cartilage. This feature may prove beneficial for delaying the onset of dislocation arthropathy of the shoulder.
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http://dx.doi.org/10.1177/0363546517749813DOI Listing
April 2018

Sensitivity to change and association of three-dimensional meniscal measures with radiographic joint space width loss in rapid clinical progression of knee osteoarthritis.

Eur Radiol 2018 May 24;28(5):1844-1853. Epub 2017 Nov 24.

Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Strubergasse 21, 5020, Salzburg, Austria.

Objective: To determine whether 3D meniscal measures had similar sensitivity to longitudinal change as cartilage thickness; to what extent these measures are associated with longitudinal joint space width (JSW) change; and whether the latter associations differ between minimum (mJSW) and fixed-location JSW.

Methods: Two-year changes in medial meniscal position and morphology, cartilage thickness (MRI) and minimum and fixed-location JSW (radiography) were determined in 35 Osteoarthritis Initiative knees [12 men, age: 67 (51-77) years; 23 women, age: 65 (54-78) years], progressing from baseline Kellgren-Lawrence grade ≤2 to knee replacement within 3-5 years. Multiple linear regression assessed the features contributing to JSW change.

Results: Meniscal measures, cartilage thickness and JSW displayed similar sensitivity to change (standardised response mean≤|0.76|). Meniscal changes were strongly associated with JSW change (r≤|0.66|), adding ≤20% to its variance in addition to cartilage thickness change. Fixed-location JSW change (multiple r=72%) was more strongly related to cartilage and meniscal change than mJSW (61%). Meniscal morphology explained more of fixed-location JSW and meniscal position more of mJSW.

Conclusion: Meniscal measures provide independent information in explaining the variance of radiographic JSW change. Fixed-location JSW appears to be more reflective of structural change than mJSW and, hence, a potentially superior measure of structural progression.

Key Points: • 3D positional/morphological meniscal measures change in rapidly progressing knees. • Similar sensitivity to 2-year change of quantitative meniscal/cartilage measures in rapid progression. • Changes in meniscal measures are strongly associated with radiographic JSW change. • Meniscal change provides information to explain JSW variance independent of cartilage. • Fixed-location JSW reflects structural disease stage more closely than minimum JSW.
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http://dx.doi.org/10.1007/s00330-017-5140-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882640PMC
May 2018

Five-minute knee MRI for simultaneous morphometry and T relaxometry of cartilage and meniscus and for semiquantitative radiological assessment using double-echo in steady-state at 3T.

J Magn Reson Imaging 2018 05 1;47(5):1328-1341. Epub 2017 Nov 1.

Department of Radiology, Stanford University, Stanford, California, USA.

Background: Biomarkers for assessing osteoarthritis activity necessitate multiple MRI sequences with long acquisition times.

Purpose: To perform 5-minute simultaneous morphometry (thickness/volume measurements) and T relaxometry of both cartilage and meniscus, and semiquantitative MRI Osteoarthritis Knee Scoring (MOAKS).

Study Type: Prospective.

Subjects: Fifteen healthy volunteers for morphometry and T measurements, and 15 patients (five each Kellgren-Lawrence grades 0/2/3) for MOAKS assessment.

Field Strength/sequence: A 5-minute double-echo steady-state (DESS) sequence was evaluated for generating quantitative and semiquantitative osteoarthritis biomarkers at 3T.

Assessment: Flip angle simulations evaluated tissue signals and sensitivity of T measurements. Morphometry and T reproducibility was compared against morphometry-optimized and relaxometry-optimized sequences. Repeatability was assessed by scanning five volunteers twice. MOAKS reproducibility was compared to MOAKS derived from a clinical knee MRI protocol by two readers.

Statistical Tests: Coefficients of variation (CVs), concordance confidence intervals (CCI), and Wilcoxon signed-rank tests compared morphometry and relaxometry measurements with their reference standards. DESS MOAKS positive percent agreement (PPA), negative percentage agreement (NPA), and interreader agreement was calculated using the clinical protocol as a reference. Biomarker variations between Kellgren-Lawrence groups were evaluated using Wilcoxon rank-sum tests.

Results: Cartilage thickness (P = 0.65), cartilage T (P = 0.69), and meniscus T (P = 0.06) did not significantly differ from their reference standard (with a 20° DESS flip angle). DESS slightly overestimated meniscus volume (P < 0.001). Accuracy and repeatability CVs were <3.3%, except the meniscus T accuracy (7.6%). DESS MOAKS had substantial interreader agreement and high PPA/NPA values of 87%/90%. Bone marrow lesions and menisci had slightly lower PPAs. Cartilage and meniscus T , and MOAKS (cartilage surface area, osteophytes, cysts, and total score) was higher in Kellgren-Lawrence groups 2 and 3 than group 0 (P < 0.05).

Data Conclusion: The 5-minute DESS sequence permits MOAKS assessment for a majority of tissues, along with repeatable and reproducible simultaneous cartilage and meniscus T relaxometry and morphometry measurements.

Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1328-1341.
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http://dx.doi.org/10.1002/jmri.25883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899635PMC
May 2018

Brief Report: Loss of Muscle Strength Prior to Knee Replacement: A Question of Anatomic Cross-Sectional Area or Specific Strength?

Arthritis Rheumatol 2018 02 20;70(2):222-229. Epub 2017 Dec 20.

Paracelsus Medical University, Salzburg, Austria, and Chondrometrics, Ainring, Germany.

Objective: To determine whether loss in thigh muscle strength prior to knee replacement is caused by reductions of muscle strength in the anatomic cross-sectional area or by reductions of specific strength.

Methods: All 100 of the participants in the Osteoarthritis Initiative who underwent knee replacement and whose medical records included data on thigh isometric muscle strength and magnetic resonance imaging (MRI) (58 women, and 42 men, mean ± SD age 65 ± 8 years, mean ± SD body mass index [BMI] 29 ± 5 kg/m ) were matched with a control (no knee replacement) for age, sex, height, BMI, and radiographic severity. Thigh muscle anatomic cross-sectional area was determined by MRI at the research visit before knee replacement (time 0) and 2 years before time 0 (time -2). Specific strength (strength/anatomic cross-sectional area) was calculated, and the measures were compared by conditional logistic regression (i.e., odds ratio [OR] per standard deviation). ORs adjusted for pain (OR ) and 95% confidence intervals (95% CIs) were also calculated.

Results: Knee replacement cases had significantly smaller extensor (but not flexor) anatomic cross-sectional areas than controls at time 0 (women, OR 1.89 [95% CI 1.05-3.90]; men, OR 2.22 [95% CI 1.04-4.76]), whereas no significant differences were found at time -2. Women who had knee replacement showed lower levels of extensor specific strength than controls at time 0 (OR 1.59 [95% CI 1.02-2.50]), although this difference was not observed in men and did not maintain significance after adjustment for pain (OR 1.22 [95% CI 0.71-2.08]). Female cases lost significantly more extensor specific strength between time -2 and time 0 than controls (OR 3.76 [95% CI 1.04-13.60]), whereas no significant differences were noted at time -2, or in men.

Conclusion: Prior to knee replacement, a significant reduction in knee extensor strength appears to occur in women through 2 mechanisms: one driven by pain (loss of specific strength) and one independent of pain (loss of muscle anatomic cross-sectional area). Men who underwent knee replacement showed significantly reduced levels of extensor anatomic cross-sectional area, but not significantly lower strength or specific strength.
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http://dx.doi.org/10.1002/art.40343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788724PMC
February 2018
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