Associations of CTX-II with biochemical markers of bone turnover raise questions about its tissue origin: new insights from CHECK

Klerk, B de; Lafeber, F.P.; Spil, W.E. van

doi:10.1136/annrheumdis-2014-205494

Cited by 8 publications

(5 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CTX-II is a neoepitope located in the C-terminal telopeptide and generated enzymatically whereas Coll2–1 is a peptide located in triple helix and released after denaturation of the collagen [45]. Secondly, there is evidence that urinary level of CTX-II is influenced by bone remodeling which is not demonstrated for Coll2–1 [46, 47]. Therefore, we can hypothesize that metabolic change induced by viscosupplementation in a single joint is not sufficient to influence the urinary CTX-II level resulting from bone and cartilage remodeling, while as demonstrated previously, Coll2–1 is sensitive to changes occurring in one single joint [42, 48].…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan derivative HYMOVIS® increases cartilage volume and Type II collagen turnover in osteoarthritic knee: data from MOKHA study

Henrotin

Bannuru

Malaise

et al. 2019

BMC Musculoskelet Disord

View full text Add to dashboard Cite

Background The objective of this pilot study was to identify biological, clinical or structural biomarkers of an intra-articular hyaluronic acid injection efficacy (HYMOVIS®) for the design of a larger placebo-controlled clinical trial studying the disease-modifying activity of this treatment. Methods Forty six patients with symptomatic knee Osteoarthritis (OA) were enrolled in this open-label, prospective, multicenter, pilot study. Patients received two treatment cycles of intra-articular injections (3 mL) of HYMOVIS® (8 mg/mL of hyaluronic acid hexadecylamide) at 6 months interval. Each treatment cycle involved two intra-articular injections 1 week apart. All patients had Magnetic Resonance Imaging (MRI) of the target knee at baseline and 1 year, and blood samples to assess joint biomarkers. The primary outcome was the change in type II collagen-specific biomarkers (Coll2–1, Coll2–1NO2 and CTX-II) after HYMOVIS® treatment versus baseline. Secondary endpoints included levels changes in aggrecan chondroitin sulfate 846 epitope (CS-846), Cartilage Oligomeric Matrix Protein (COMP), procollagen type II N-terminal propeptide (PIIANP), Matrix Metalloprotease (MMP)-3, Myeloperoxidase (MPO) and Interleukin (IL)-6 serum biomarkers, the ratio Coll2–1/PIIANP, CTX-II/PIIANP, variation of MRI cartilage volume, and Knee injury and Osteoarthritis Outcome Score (KOOS) index. Results Coll2–1 serum levels significantly increased overtime while Coll2–1NO2 levels were only increased at D360. Serum PIIANP levels also progressively and significantly enhanced with time. In contrast, other serum biomarker levels including CTX-II, CS-846, COMP, MMP-3, MPO or IL-6 did not change significantly overtime. Interestingly, the ratios Coll2–1/PIIANP and CTX-II/PIIANP decreased, indicating a decrease of cartilage catabolism. Compared to baseline value, MRI cartilage volume and thickness increased in lateral femoral and lateral trochlea compartments and not in medial compartment. These results, in addition to an improvement of T2 mapping score suggest a positive structural effect of the product. Interestingly, WORMS effusion score, an indicator of synovitis, significantly decreased. Finally, global KOOS score and subscales significantly increased overtime while pain at rest, walking pain and patients or investigators global assessment of disease activity decreased. The safety profile was favorable with a low incidence of injection-site pain. Conclusion HYMOVIS®, a well-tolerated intra-articular treatment, significantly enhanced type II collagen turnover as suggested by the increase in Coll2–1 and PIIANP levels and cartilage volume observed by MRI in lateral knee compartment. Importantly, this study provides critical information for the design of a larger phase III clinical trial investigating Disease Modifying effect of HYMOVIS®. Trial registration http://www.isrctn.com/ISRCTN12227846 11/02/2015.

show abstract

Section: Discussionmentioning

confidence: 99%

Hyaluronan derivative HYMOVIS® increases cartilage volume and Type II collagen turnover in osteoarthritic knee: data from MOKHA study

Henrotin

Bannuru

Malaise

et al. 2019

BMC Musculoskelet Disord

View full text Add to dashboard Cite

show abstract

“…Also, CTX-II is usually used as a cartilage marker, while it sometimes is regarded as a BTM. 22 23 Thus, additional research on the cartilage markers may be needed.…”

Section: Discussionmentioning

confidence: 99%

Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose–response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial

et al. 2015

View full text Add to dashboard Cite

ObjectivesTo evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA).MethodsIn this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months.ResultsDenosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo.ConclusionsAddition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction.Trial registration numberJapicCTI-101263.

show abstract

“…Moreover, there are doubts about the specificity of these markers. COMP, for example, is also synthesised by synovial and tendon cells, while CTX-II has been shown to increase in parallel with bone biomarkers, and there have been suggestions that it reflects mainly an increase in calcified cartilage tissue [ 33 , 34 ]. This lack of specificity is highlighted by depression of CTX-II after osteoporosis treatments and an association with disc degeneration [ 35 ].…”

Section: Biochemical Biomarkers Of Musculoskeletal Ageingmentioning

confidence: 99%

Developing a toolkit for the assessment and monitoring of musculoskeletal ageing

et al. 2018

View full text Add to dashboard Cite

The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The Medical Research Council–Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of CIMA’s objectives is to ‘Identify and share optimal techniques and approaches to monitor age-related changes in all musculoskeletal tissues, and to provide an integrated assessment of musculoskeletal function’—in other words to develop a toolkit for assessing musculoskeletal ageing. This toolkit is envisaged as an instrument that can be used to characterise and quantify musculoskeletal function during ‘normal’ ageing, lend itself to use in large-scale, internationally important cohorts, and provide a set of biomarker outcome measures for epidemiological and intervention studies designed to enhance healthy musculoskeletal ageing. Such potential biomarkers include: biochemical measurements in biofluids or tissue samples, in vivo measurements of body composition, imaging of structural and physical properties, and functional tests. This review assesses candidate biomarkers of musculoskeletal ageing under these four headings, details their biological bases, strengths and limitations, and makes practical recommendations for their use. In addition, we identify gaps in the evidence base and priorities for further research on biomarkers of musculoskeletal ageing.

show abstract

Associations of CTX-II with biochemical markers of bone turnover raise questions about its tissue origin: new insights from CHECK

Cited by 8 publications

References 4 publications

Hyaluronan derivative HYMOVIS® increases cartilage volume and Type II collagen turnover in osteoarthritic knee: data from MOKHA study

Hyaluronan derivative HYMOVIS® increases cartilage volume and Type II collagen turnover in osteoarthritic knee: data from MOKHA study

Developing a toolkit for the assessment and monitoring of musculoskeletal ageing

Contact Info

Product

Resources

About