A 5-yr longitudinal study of type IIA collagen synthesis and total type II collagen degradation in patients with knee osteoarthritis--association with disease progression

Sharif, Mohammed; Kirwan, John R.; Charni, Nadine; Sandell, Linda J.; Whittles, CE; Garnero, Patrick

doi:10.1093/rheumatology/kel409

Cited by 102 publications

(85 citation statements)

References 29 publications

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“…These included studies measuring degradation and/or turnover products from cartilage, bone or the synovial membrane [109][110][111][112][113][114]. Indeed, the focus has been drawn away from the initial determination of individual markers such as hyaluronic acid (HA), C-telopeptide of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP), sulphate (KS)-5D4, urinary type II collagen-related epitopes, TGF-β1 and type II procollagen carboxy-propeptide (CPII), which are all excellent to determine patients at greatest risk of progression or to discriminate patients with more severe OA from those with less severe OA [109,110,115].…”

Section: Bone Markers In Oamentioning

confidence: 99%

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Tat

Lajeunesse

Pelletier

et al. 2010

Best Practice & Research Clinical Rheumatology

153

121

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Over the past few decades, significant progress has been made with respect to new concepts about the pathogenesis of osteoarthritis (OA). This article summarises some of the knowledge we have today on the involvement of the subchondral bone in OA. It provides substantial evidence that changes in the metabolism of the subchondral bone are an integral part of the OA disease process and that these alterations are not merely secondary manifestations, but are part of a more active component of the disease. Thus, a strong rationale exists for therapeutic approaches that target subchondral bone resorption and/or formation, and data evaluating the drugs targeting bone remodelling raise the hope that new treatment options for OA may become available.

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Section: Bone Markers In Oamentioning

confidence: 99%

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Tat

Lajeunesse

Pelletier

et al. 2010

Best Practice & Research Clinical Rheumatology

153

121

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“…Because the KOSTAR study only used a plain radiographic outcome, the contribution of meniscal damage cannot be evaluated. These data provide a snapshot of the overall pattern of JSN over 2 years but cannot provide information about the nature of cartilage breakdown; studies of potential biomarkers suggest that cartilage breakdown may occur in a phasic rather than linear manner (26,27). It will be important in future studies to evaluate the impact of these additional radiographic and other clinical and biochemical features in determining the factors that are associated with assignment of subjects to the different groups of rapid and slow progressors and nonprogressors.…”

Section: (3)mentioning

confidence: 99%

Identifying common trajectories of joint space narrowing over two years in knee osteoarthritis

Bartlett

Ling

Mayo

et al. 2011

Arthritis Care & Research

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Objective. Little is known about the natural history of knee osteoarthritis (OA). We sought to identify common patterns of joint space narrowing (JSN) in well-characterized knee OA patients in the placebo arm of a 2-year international study. Methods. We performed secondary data analyses of 622 adults ages 39 -80 years in North America (n ‫؍‬ 310) and Europe (n ‫؍‬ 312) with symptomatic knee OA. Fluoroscopically positioned semiflexed anteroposterior radiographs were obtained at 0, 12, and 24 months. Group-based trajectory modeling was used to identify distinctive groups of individuals with similar trajectories of JSN, taking into account sex, age, and body mass index. Results. Seven groups were identified. Four exhibited joint space width (JSW) stability over 2 years representing the most common trajectory (71%), which was unrelated to initial JSW. Atypical courses included slow, rapid, and moderate progressors; most had significant JSN at study entry. Slow progressors (20%) had a mean JSN of 0.2 mm over 2 years. Only 2% of the sample demonstrated rapid JSN (2.1 mm), while 7% had JSN of 0.7 mm. Rapid progressors tended to be men, while slow and moderate progressors were older and heavier. Conclusion. Most (70%) people with OA demonstrated no significant JSN over 2 years; 20% showed slow progression, 7% had moderate, and 2% had rapid JSN. Progressors tended to have less JSW at study entry and were older and heavier; rapid progressors were more likely to be men. Understanding common patterns of the course of knee OA may offer new opportunities to target those at greatest risk of disability.

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“…Therefore, the identification and validation of biomarkers that predict the efficacy of potential OA drugs faster and/or with fewer patients is important for the development of DMOADs. Many biomarkers reflecting degradation of various tissues in OA joints have been described, but their predictive value as surrogates for JSN is still under investigation (8)(9)(10)(11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

Cartilage degradation biomarkers predict efficacy of a novel, highly selective matrix metalloproteinase 13 inhibitor in a dog model of osteoarthritis: Confirmation by multivariate analysis that modulation of type ii collagen and aggrecan degradation peptides parallels pathologic changes

Settle¹,

Vickery²,

Nemirovskiy³

et al. 2010

Arthritis & Rheumatism

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Objective. To demonstrate that the novel highly selective matrix metalloproteinase 13 (MMP-13) inhibitor PF152 reduces joint lesions in adult dogs with osteoarthritis (OA) and decreases biomarkers of cartilage degradation.Methods. The potency and selectivity of PF152 were evaluated in vitro using 16 MMPs, TACE, and ADAMTS-4 and ADAMTS-5, as well as ex vivo in human cartilage explants. In vivo effects were evaluated at 3 concentrations in mature beagles with partial medial meniscectomy. Gross and histologic changes in the femorotibial joints were evaluated using various measures of cartilage degeneration. Biomarkers of cartilage turnover were examined in serum, urine, or synovial fluid. Results were analyzed individually and in combination using multivariate analysis.Results. The potent and selective MMP-13 inhibitor PF152 decreased human cartilage degradation ex vivo in a dose-dependent manner. PF152 treatment of dogs with OA reduced cartilage lesions and decreased biomarkers of type II collagen (type II collagen neoepitope) and aggrecan (peptides ending in ARGN or AGEG) degradation. The dose required for significant inhibition varied with the measure used, but multivariate analysis of 6 gross and histologic measures indicated that all doses differed significantly from vehicle but not from each other. Combined analysis of cartilage degradation markers showed similar results.Conclusion. This highly selective MMP-13 inhibitor exhibits chondroprotective effects in mature animals. Biomarkers of cartilage degradation, when evaluated in combination, parallel the joint structural changes induced by the MMP-13 inhibitor. These data support the potential therapeutic value of selective MMP-13 inhibitors and the use of a set of appropriate biomarkers to predict efficacy in OA clinical trials.Osteoarthritis (OA) is a chronic degenerative joint disease affecting primarily aged or injured joints. The disease is characterized by an imbalance between cartilage synthesis and degradation, with increased breakdown of matrix components leading to proteoglycan loss and cartilage fibrillation, eventually resulting in severe cartilage defects. These changes are irreversible, and the only treatment other than palliative symptom control is total joint replacement. Therefore, the discovery of a disease-modifying osteoarthritis drug (DMOAD) would fill a large unmet medical need.

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A 5-yr longitudinal study of type IIA collagen synthesis and total type II collagen degradation in patients with knee osteoarthritis--association with disease progression

Cited by 102 publications

References 29 publications

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Identifying common trajectories of joint space narrowing over two years in knee osteoarthritis

Cartilage degradation biomarkers predict efficacy of a novel, highly selective matrix metalloproteinase 13 inhibitor in a dog model of osteoarthritis: Confirmation by multivariate analysis that modulation of type ii collagen and aggrecan degradation peptides parallels pathologic changes

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