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- Cibere, Jolanda, et al.
(författare)
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Association of Biomarkers With Pre-Radiographically Defined and Radiographically Defined Knee Osteoarthritis in a Population-Based Study
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 60:5, s. 1372-1380
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate 10 biomarkers in magnetic resonance imaging (M RI)-determined, pre-radiographically defined osteoarthritis (pre-ROA) and radiographically defined OA (ROA) in a population-based cohort of subjects with symptomatic knee pain. Methods. Two hundred one white subjects with knee pain, ages 40-79 years, were classified into OA subgroups according to MRI-based cartilage (MRC) scores (range 0-4) and Kellgren/Lawrence (K/L) grades of radiographic severity (range 0-4): no OA (MRC score 0, K/L grade <2), pre-ROA (MRC score > 1, K/L grade <2), or ROA (MRC score >= 1, K/L grade >= 2). Urine and serum samples were assessed for levels of the following biomarkers: urinary biomarkers C-telopeptide of type II collagen (uCTX-II), type II and types I and II collagen cleavage neoepitopes (uC2C and uC1,2C, respectively), and N-telopeptide of type I collagen, and serum biomarkers sC1,2C, sC2C, C-propeptide of type II procollagen (sCPII), chondroitin sulfate 846 epitope, cartilage oligomeric matrix protein, and hyaluronic acid. Multicategory logistic regression was performed to evaluate the association of OA subgroup with individual biomarker levels and biomarker ratios, adjusted for age, sex, and body mass index. Results. The risk of ROA versus no OA increased with increasing levels of uCTX-II (odds ratio [OR] 3.12, 95% confidence interval [95% CI] 1.35-7.21), uC2C (OR 2.13, 95% CI 1.04-4.37), and uC1,2C (OR 2.07, 95% CI 1.06-4.04), and was reduced in association with high levels of sCPII (OR 0.53, 95% CI 0.30-0.94). The risk of pre-ROA versus no OA increased with increasing levels of uC2C (OR 2.06, 95% CI 1.05-4.01) and uC1,2C (OR 2.06, 95% CI 1.12-3.77). The ratios of type II collagen degradation markers to collagen synthesis markers were better than individual biomarkers at differentiating the OA subgroups, e.g., the ratio of [uCTX-II] [uC1,2C] to sCPII was associated with a risk of ROA versus no OA of 3.47 (95% CI 1.34-9.03) and a risk of pre-ROA versus no OA of 2.56 (95% CI 1.03-6.40). Conclusion. Different cartilage degradation markers are associated with pre-ROA than are associated with ROA, indicating that their use as diagnostic markers depends on the stage of OA. Biomarker ratios contrasting cartilage degradation with cartilage synthesis are better able to differentiate OA stages compared with levels of the individual markers.
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| 2. |
- Gossec, Laure, et al.
(författare)
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OMERACT/OARSI initiative to define states of severity and indication for joint replacement in hip and knee osteoarthritis
- 2007
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 34:6, s. 1432-1435
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Time to theoretical indication of joint replacement surgery has been proposed as a primary outcome for potential structure-modifying interventions for osteoarthritis (OA). The objectives of this OMERACT/OARSI Working Group were to identify pain, physical function, and structure states that represent the progression from early to late disease for individuals with OA of the hip and knee, and to create a composite measure of these 3 domains to define states of OA severity and a surrogate measure of "need for joint replacement surgery." Methods. For pain, focus groups and one-on-one interviews were used. For function, Rasch analysis was performed on existing indices - the Hip Dysfunction and Osteoarthritis Outcome Score (HOOS) and the Knee injury and Osteoarthritis Outcome Score (KOOS), each of which subsumes the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) questions. For structure, a comparison of existing indices (Kellgren-Lawrence, OARSI stages, and joint space width) was performed for the hip and the knee. Results. For pain, key features of pain that are most distressing to people with OA from early to late disease were identified. For function, the reduction of the number of items based on the existing indices continues. For structure, the analysis is also ongoing. Conclusion. Preliminary results were presented at OMERACT 8; the final objective will be to combine the 3 domains (pain, function, and structure) and to create a composite index that could define states of severity and "need for total joint replacement," which could be used to evaluate treatment response to disease-modifying drugs in OA clinical trials.
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| 3. |
- Hunt, Michael A., et al.
(författare)
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Relationships amongst osteoarthritis biomarkers, dynamic knee joint load, and exercise: results from a randomized controlled pilot study
- 2013
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 14:115
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known about the relationships of circulating levels of biomarkers of cartilage degradation with biomechanical outcomes relevant to knee osteoarthritis (OA) or biomarker changes following non-pharmacological interventions. The objectives of this exploratory, pilot study were to: 1) examine relationships between biomarkers of articular cartilage degradation and synthesis with measures of knee joint load during walking, and 2) examine changes in these biomarkers following 10 weeks of strengthening exercises. Methods: Seventeen (8 male, 9 female; 66.1 +/-11.3 years of age) individuals with radiographically-confirmed medial tibiofemoral OA participated. All participants underwent a baseline testing session where serum and urine samples were collected, followed by a three-dimensional motion analysis. Motion analysis was used to calculate the external knee adduction moment (KAM) peak value and impulse. Following baseline testing, participants were randomized to either 10 weeks of: 1) physiotherapist-supervised lower limb muscle strengthening exercises, or 2) no exercises (control). Identical follow-up testing was conducted 11 weeks after baseline. Biomarkers included: urinary C-telopeptide of type II collagen (uCTX-II) and type II collagen cleavage neoepitope (uC2C), serum cartilage oligomeric matrix protein (sCOMP), serum hyaluronic acid (sHA) and serum C-propeptide of type II procollagen (sCPII). Linear regression analysis was used to examine relationships between measures of the KAM and biomarker concentrations as baseline, as well as between-group differences following the intervention. Results: KAM impulse predicted significant variation in uCTX-II levels at baseline (p = 0.04), though not when controlling for disease severity and walking speed (p = 0.33). KAM impulse explained significant variation in the ratio uCTX-II; sCPII even when controlling for additional variables (p = 0.04). Following the intervention, changes in sCOMP were significantly greater in the exercise group compared to controls (p = 0.04). On average those in the control group experienced a slight increase in sCOMP and uCTX-II, while those in the exercise group experienced a reduction. No other significant findings were observed. Conclusions: This research provides initial evidence of a potential relationship between uCTX-II and knee joint load measures in patients with medial tibiofemoral knee OA. However, this relationship became non-significant after controlling for disease severity and walking speed, suggesting further research is necessary. It also appears that sCOMP is amenable to change following a strengthening intervention, suggesting a potential beneficial role of exercise on cartilage structure. Trial registration: Clinicaltrials. gov NCT01241812
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