| 1. |
- Watt, F. E., et al.
(författare)
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Towards prevention of post-traumatic osteoarthritis : report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury
- 2019
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:1, s. 23-33
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.
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| 2. |
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| 3. |
- Roemer, Frank W., et al.
(författare)
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Structural effects of sprifermin in knee osteoarthritis : a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial
- 2016
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 17:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Background: A recent publication on efficacy of Sprifermin for knee osteoarthritis (OA) using quantitatively MRI-defined central medial tibio-femoral compartment cartilage thickness as the structural primary endpoint reported no statistically significant dose response. However, Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral tibio-femoral cartilage thickness. Based on these preliminary promising data a post-hoc analysis of secondary assessment and endpoints was performed to evaluate potential effects of Sprifermin on semi-quantitatively evaluated structural MRI parameters. Aim of the present analysis was to determine effects of sprifermin on several knee joint tissues over a 12 month period. Methods: 1.5 T or 3 T MRIs were acquired at baseline and 12 months follow-up using a standard protocol. MRIs were read according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring system (in 14 articular subregions) by four muskuloskeletal radiologists independently. Analyses focused on semiquantitative changes in the 100 μg subgroup and matching placebo of multiple MRI-defined structural alterations. Analyses included a delta-subregional and delta-sum approach for the whole knee and the medial and lateral tibio-femoral (MTFJ, LTFJ), and patello-femoral (PFJ) compartments, taking into account number of subregions showing no change, improvement or worsening and changes in the sum of subregional scores. Mann-Whitney − Wilcoxon tests assessed differences between groups. Results: Fifty-seven and 18 patients were included in the treatment and matched placebo subgroups. Less worsening of cartilage damage was observed from baseline to 12 months in the PFJ (0.02, 95 % confidence interval (CI) (−0.04, 0.08) vs. placebo 0.22, 95 % CI (−0.05, 0.49), p = 0.046). For bone marrow lesions (BMLs), more improvement was observed from 6 to 12 months for whole knee analyses (−0.14, 95 % CI (−0.48, 0.19) vs. placebo 0.44, 95 % CI (−0.15, 1.04), p = 0.042) although no significant effects were seen from the baseline visit, or in Hoffa-synovitis, effusion-synovitis, menisci and osteophytes. Conclusions: In this post-hoc analysis cartilage showed less worsening from baseline to 12 months in the PFJ, and BMLs showed more improvement from 6 to 12 months for the whole knee. Trial registration: ClinicalTrials.gov identifier: NCT01033994 .
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| 4. |
- Svensson, Fredrik, et al.
(författare)
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Meniscal body extrusion and cartilage coverage in middle-aged and elderly without radiographic knee osteoarthritis
- 2019
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 29:4, s. 1848-1854
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine meniscal extrusion and cartilage coverage on magnetic resonance (MR) images and factors associated with these parameters in knees of middle-aged and elderly persons free from radiographic tibiofemoral osteoarthritis (OA). Methods: Seven hundred eighteen persons, free of radiographic tibiofemoral OA, aged 50–90 years from Framingham, MA, USA, were included. We measured meniscal extrusion on 1.5 T MRI of both knees to evaluate both medial and lateral meniscal body extrusion and cartilage coverage. We also determined meniscal morphology and structural integrity. The multivariable association with age, body mass index (BMI), and ipsilateral meniscal damage was also evaluated. Results: The mean meniscal body extrusion medially was 2.7 mm and laterally 1.8 mm. The tibial cartilage coverage was about 30% of ipsilateral cartilage surface (both compartments). The presence of ipsilateral meniscal damage was associated with more extrusion in only the medial compartment, 1.0 mm in men and 0.6 mm in women, and less cartilage coverage proportion, -5.5% in men and -4.6% in women. Conclusions: Mean medial meniscal body extrusion in middle-aged or older persons without radiographic tibiofemoral OA approximates the commonly used cutoff (3 mm) to denote pathological extrusion. Medial meniscal damage is a factor associated with medial meniscal body extrusion and less cartilage coverage. Key Points: • Medial meniscal extrusion in middle-aged/older persons without OA is around 3 mm. • Lateral meniscal extrusion in middle-aged/older persons without OA is around 2 mm. • Meniscal damage is associated with medial meniscal extrusion and less cartilage coverage.
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| 5. |
- Svensson, F., et al.
(författare)
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Scrutinizing the cut-off for “pathological” meniscal body extrusion on knee MRI
- 2019
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 29:5, s. 2616-2623
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Medial meniscal body extrusion ≥ 3 mm on MRI is often considered “pathologic.” The aims of this study were to (1) assess the adequacy of 3 mm as cut-off for “pathological” extrusion and (2) find an optimal cut-off for meniscal extrusion cross-sectionally associated with radiographic knee osteoarthritis, bone marrow lesions (BMLs), and cartilage damage. Methods: Nine hundred fifty-eight persons, aged 50–90 years from Framingham, MA, USA, had readable 1.5 T MRI scans of the right knee for meniscal body extrusion (measured in mm). BMLs and cartilage damage were read using the whole organ magnetic resonance imaging score (WORMS). Knee X-rays were read according to the Kellgren and Lawrence (KL) scale. We evaluated the performance of the 3-mm cut-off with respect to the three outcomes and estimated a new cut-off maximizing the sum of sensitivity and specificity. Results: The study persons had mean age of 62.2 years, 57.0% were women and the mean body mass index was 28.5 kg/m2. Knees with radiographic osteoarthritis, BMLs, and cartilage damage had overall more meniscal extrusion than knees without. The 3-mm cut-off had moderate sensitivity and low specificity for all three outcomes (sensitivity between 0.68 [95% CI 0.63–0.73] and 0.81 [0.73–0.87], specificity between 0.49 [0.45–0.52] and 0.54 [0.49–0.58]). Using 4 mm maximized the sum of sensitivity and specificity and improved the percentage of correctly classified subjects (from between 54 and 61% to between 64 and 79%). Conclusions: The 4-mm cut-off may be used as an alternative cut-off for denoting pathological meniscal extrusion. Key Points: • Medial meniscal body extrusion is strongly associated with osteoarthritis. • The 3-mm cut-off for medial meniscal body extrusion has high sensitivity but low specificity with respect to bone marrow lesions, cartilage damage, and radiographic osteoarthritis. • The 4-mm cut-off maximizes the sensitivity and specificity with respect to all three osteoarthritis features.
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| 6. |
- Thorlund, Jonas B., et al.
(författare)
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Effect of Knee Extensor Strength on Incident Radiographic and Symptomatic Knee Osteoarthritis in Individuals With Meniscal Pathology : Data From the Multicenter Osteoarthritis Study
- 2016
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X. ; 68:11, s. 1640-1646
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Tidskriftsartikel (refereegranskat)abstract
- Objective: High knee extensor strength may be important to protect against the development of knee osteoarthritis (OA) in populations at elevated risk, such as individuals with meniscal pathology. We investigated the extent to which high knee extensor muscle strength was associated with a decreased risk of developing radiographic or symptomatic knee OA in individuals with medial meniscal pathology. Methods: We studied knees that at the baseline visit of the Multicenter Osteoarthritis Study had medial meniscal pathology but did not have radiographic knee OA (373 knees in 373 participants) or symptomatic knee OA (combination of radiographic knee OA and frequent knee symptoms; 531 knees in 531 participants). Isokinetic knee extensor strength was measured at baseline, and participants were followed for development of incident radiographic knee OA or incident symptomatic knee OA at 84 months. Separate binomial regression analyses with robust SEs adjusted for age, history of knee surgery, physical activity level, and clinic site were conducted for men and women. Results: High knee extensor strength (normalized by allometric scaling) was associated with a reduced risk of radiographic knee OA in women (relative risk [RR] 0.52, 95% confidence interval [95% CI] 0.29–0.94) but not in men (RR 0.56, 95% CI 0.27–1.16). High knee extensor strength did not protect against the development of symptomatic knee OA, either in women or men. Conclusion: The results only partly confirm the hypothesis that high knee extensor muscle strength protects against later development of knee OA in individuals with medial meniscal pathology.
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