Markers Of Cartilage Turnover Research Articles

The Impact of Weight-bearing Exercise, Non–Weight-bearing Exercise, and Cardiovascular Stress on Biochemical Markers of Cartilage Turnover in Patients With Mild to Moderate Knee Osteoarthritis: A Sequential, Cross-Over, Clinical Study

Objective To investigate how running, cycling, and sedentary cardiovascular stress impact biomarkers of cartilage turnover acutely in subjects with knee osteoarthritis (OA). Design This was a sequential, cross-over, clinical study. Forty subjects with primary knee OA underwent moderate-to-high-intensity cycling, running, and adrenaline infusion on separate days. Blood was sampled before, during, and at 6-time points after intervention. On a control day, similar samples were taken. Biomarkers of type II collagen degradation (C2M, T2CM, Coll2-1, Coll2-1NO2), formation (PRO-C2), and aggrecan degradation (ARGS) were measured. Results Mean age was 60.4 years, 40% were male, 45% had cumulated Kellgren-Lawrence (KL)-grade (Right + Left knee) of 2 to 3 and 55% had 4 to 6. Analyzing overall changes, area under the curve was significantly lower compared with resting values for ARGS and C2M after cycling and for ARGS after running. Considering individual time points, peak changes in biomarker levels showed reduction in C2M shortly following cycling (T20min = −12.3%, 95% confidence interval [CI]: −19.3% to −5.2%). PRO-C2 increased during cycling (T10min = 14.0%, 95% CI = 4.1% to 23.8%) and running (T20min = 16.5%, 95% CI = 4.3% to 28.6%). T2CM decreased after cycling (T50min = −19.9%, 95% CI = −29.2% to −10.6%), running (T50min = −22.8%, 95% CI = −32.1% to −13.5%), and infusion of adrenaline (peak, T50min = −9.8%, 95% CI = −20.0% to 0.4%). A latent increase was seen in Coll2-1 240 minutes after running (T260min = 21.7%, 95% CI = −1.6% to 45.1%). Conclusion Exercise had an impact on cartilage markers, but it did not suggest any detrimental effect on cartilage. Changes following adrenaline infusion suggest a sympathomimetic influence on the serological composition of biomarkers.

Effects of Etanercept and Adalimumab on Serum Levels of Cartilage Remodeling Markers in Women with Rheumatoid Arthritis.

Tumor necrosis factor α inhibitor (TNFαI) therapy is associated with a significant inhibition of radiographic progression, resulting in improved physical function and quality of life among patients with rheumatoid arthritis (RA). The mechanism by which TNFαI prevent joint destruction is still unknown. In this study, the effect of 15-month anti-TNF-α therapy in combination with methotrexate on circulating levels of biochemical markers of cartilage turnover in female RA patients was assessed. Serum levels of collagen type II C-terminal cleavage neoepitope (C2C), C-terminal propeptide of type II collagen (PIICP), cartilage oligomeric matrix protein (COMP), and matrix metalloproteinase-3 (MMP-3) were evaluated using immunoassays at baseline and 15 months after the start of TNFαI treatment. Baseline COMP, C2C, and MMP-3 levels and C2C/PIICP ratios were significantly higher in women with RA compared with those observed in the healthy subjects. No differences in PIICP levels between the controls and the women with RA were observed. After 15 months of TNFαI treatment, serum levels of C2C, COMP, and MMP-3 decreased, whereas the levels of PIICP increased but were still not different from those of the controls. These changes were accompanied by significantly reduced C2C/PIICP ratios. Before the start of TNFαI therapy, serum levels of COMP significantly correlated with the patients' ages (p < 0.05) and their 28-joint disease activity score values based on their erythrocyte sedimentation rates (DAS28-ESR; p < 0.05). Moreover, multiple linear regression analysis showed that baseline COMP levels retained a significant association with DAS28-ESR value (β = 287.74, p = 0.022, R2 model = 0.25) after model adjustments. The largest area under the ROC curve was obtained for C2C/PIICP ratios (AUC: 0.830, 95% CI: 0.727-0.932, p < 0.001). Our results suggest that long-term anti-TNF-α therapy combined with MTX has a beneficial effect on cartilage remodeling that is associated with clinical improvement among RA patients. Serum C2C/PIICP ratios may help to monitor the effectiveness of anti-TNF-α treatment among RA patients.

Inactivation of the gene encoding procalcitonin prevents antibody-mediated arthritis.

Procalcitonin (PCT) is applied as a sensitive biomarker to exclude bacterial infections in patients with rheumatoid arthritis (RA) flare-ups. Beyond its diagnostic value, little is known about the pathophysiological role of PCT in RA. Collagen antibody-induced arthritis (CAIA) was induced in Calca-deficient mice (Calca-/-), lacking PCT (n = 15), and wild-type (WT) mice(n = 13), while control (CTRL) animals (n = 8 for each genotype) received phosphate-buffered saline. Arthritis severity and grip strength were assessed daily for 10 or 48days. Articular inflammation, cartilage degradation, and bone lesions were assessed by histology, gene expression analysis, and µ-computed tomography. Serum PCT levels and intra-articular PCT expression increased following CAIA induction. While WT animals developed a full arthritic phenotype, Calca-deficient mice were protected from clinical and histological signs of arthritis and grip strength was preserved. Cartilage turnover markers and Tnfa were exclusively elevated in WT mice. Calca-deficient animals expressed increased levels of Il1b. Decreased bone surface and increased subchondral bone porosity were observed in WT mice, whileCalca-deficiency preserved bone integrity. The inactivation of Calca and thereby PCT provided full protection from joint inflammation and arthritic bone loss in mice exposed to CAIA. Together with our previous findings on the pathophysiological function of Calca-derived peptides, these data indicate an independent pro-inflammatory role of PCT in RA.

GAAGs, COMP, and YKL-40 as Potential Markers of Cartilage Turnover in Blood of Children with Juvenile Idiopathic Arthritis Treated with Etanercept—Relationship with ADAMTS4, ADAMTS5, and PDGF-BB

We quantified galactosaminoglycans (GAAGs), oligomeric cartilage matrix protein (COMP), and human cartilage glycoprotein 39 (YKL-40) in blood obtained from juvenile idiopathic arthritis (JIA) before and during 2-year treatment with etanercept (ETA), as potential biomarkers of cartilage extracellular matrix (ECM) dysfunction and indicators of efficacy of biologic therapy. We also evaluated the relationship of the mentioned markers with the factors that regulate their metabolism, disintegrin and thrombospondin motif metalloproteinases 4 (ADAMTS4), ADAMTS5, and platelet-derived growth factor BB (PDGF-BB). Methods: We studied 38 children diagnosed with JIA and 45 healthy children. We quantified GAAGs by assessing the concentration of unsaturated disaccharide units formed by digestion of isolated glycosaminoglycans with chondroitinase ABC, while COMP, YKL-40, and PDGF-BB were quantified using immunoenzymatic methods. Results: Compared to the control group, GAAGs and COMP levels were significantly lower, while YKL-40 levels were higher in the blood of patients with aggressive JIA, qualified for ETA treatment. ETA therapy leading to clinical improvement simultaneously promoted normalization of COMP and YKL-40 levels, but not GAAGs. After 24 months of taking ETA, glycan levels were still significantly lower, relative to controls. GAAGs, COMP, and YKL-40 levels were significantly influenced by ADAMTS4, ADAMTS5, and PDGF-BB levels both before and during ETA treatment. Conclusions: The dynamics of changes in marker concentrations during treatment seem to indicate that measurement of COMP and YKL-40 levels can be used to assess the chondroprotective biological efficacy of therapy. In contrast, changes in GAAGs concentrations reflect systemic extracellular matrix transformations in the course of JIA.

Does moderate intensity impact exercise and non-impact exercise induce acute changes in collagen biochemical markers related to osteoarthritis? – An exploratory randomized cross-over trial

To investigate acute changes in biochemical markers of cartilage turnover in response to moderate intensity exercise with and without joint impact in humans with knee osteoarthritis. We conducted a randomized, cross-over, exploratory clinical study. Twenty subjects with knee osteoarthritis (OA) were randomized, of which twenty completed 30min of cycling and 15 completed 30min of running on days 1week apart. Fasting blood samples were taken before, immediately after and 1, 2, 3, and 24h after activity was initiated. Midstream spot urine was sampled before and after activity. Serum samples were analyzed for concentrations of fragment of type II collagen degradation, C2M, fragment of type VI collagen degradation, C6M, cartilage oligomeric matrix protein, COMP, marker of type II collagen formation, PRO-C2, and urine for marker of crosslinked type II collagen degradation, CTX-II. To establish a reference, all subjects had similar samples taken during rest on a separate day. Data was analyzed in a restricted maximum likelihood based random effects linear mixed model. C2M trended to increase after cycling compared running (13.49%, 95%CI:-0.36-27.34%) and resting (12.88%, 95%CI: 0.2-25.6%) and the type II collagen formation/degradation ratio switched towards degradation after cycling, but not running. C6M trended to decrease after cycling (-8.1%, 95%CI:-14.8 to-1.4%) and running (-6.8%, 95%CI:-14.16-0.55%). In persons with knee OA moderate intensity exercise without joint impact may induce acute changes in circulating levels of biochemical markers reflecting type II and VI collagen degradation.

Does long term colchicine prevent degradation of collagen fiber network in osteoarthritis?

Several studies have shown that colchicine exhibits an improvement in the symptoms of knee osteoarthritis (OA) but its effect on disease progression is unknown. To clarify the mechanism of action this study was done to see if colchicine prevents degradation of collagen fiber network in OA by studying serum cartilage oligomeric matrix protein (COMP) levels, a marker of cartilage turnover, over a period of 1 year. Seventy-five patients received colchicine plus paracetamol and 75 received placebo alone for the same time period. Serum COMP assays were done at baseline, 2 months and 1 year by enzyme-linked immunosorbent assay. These markers were compared between visits using repeated measures analysis of variance. Serum COMP levels in the paracetamol-alone group did not show significant change between baseline and 2 months; however, there was a significant increase in serum COMP levels from 2 months to 1 year, suggesting increased uncoupling of proteoglycans from collagen and disease progression. No such change was seen in the colchicine group, signifying lack of progression of disease in this group. Colchicine may act as a disease-modifying agent in OA.

Osteoarthritic sclerotic subchondral osteoblasts secreted elevated concentration of Fibulin-3 fragments in vitro

Osteoarthritic sclerotic subchondral osteoblasts secreted elevated concentration of Fibulin-3 fragments in vitro

Associations of markers of matrix metabolism, inflammation markers, and adipokines with superior cam deformity of the hip and their relation with future hip osteoarthritis

First, to study how markers of matrix metabolism, inflammation markers, and adipokines relate to (superior) cam deformity and (possible) cam impingement of the hip. Second, to investigate whether they can identify subjects with cam deformity that are at risk of future hip osteoarthritis (OA). In a cohort of 1002 subjects (CHECK), (superior) cam deformity was defined by an alpha angle >60° on anteroposterior pelvic radiographs and (possible) cam impingement by a cam deformity together with internal hip rotation ≤20°. Hip OA at 5-year follow-up was defined by Kellgren and Lawrence grade ≥2 or total hip replacement. Subjects with (superior) cam deformity and (possible) cam impingement showed lower levels of bone turnover markers (uCTX-I, uNTX-I, sPINP, sOC) than those without. Cam deformity was positively associated with future hip OA, but associations were weaker at high levels of bone turnover. sCOMP and sHA levels were higher in subjects with cam deformity, while other cartilage and synovium markers were not. Some markers of inflammation (pLeptin, pAdiponectin, and erythrocyte sedimentation rate) were lower in presence of cam deformity and cam impingement, but high-sensitivity C-reactive protein was not. Most associations depended largely on gender differences. Bone metabolism may be relevant in the pathogenesis of (superior) cam deformity and in the development of (superior) cam deformity into hip OA. Subjects with cam deformity and cam impingement surprisingly showed lower levels of inflammation markers and adipokines. Associations of cartilage turnover markers with cam deformity and cam impingement were less obvious.

AB0825 Investigation of Effects on Bone Metabolism of Anti-TNF BIOLOGICS and Bisphosphonates in Patients with Rheumatoid Arthritis

BackgroundTreatment for rheumatoid arthritis has become to obtain remission as biologics are widely used. Nonetheless, the main target of the treatment is synovitis and evaluation and treatment for osteoporosis with...

AB0082 The efficacy of anti-tnf treatment on urinary type-ii collagen c-telopeptyde levels in patients with rheumatoid arthritis

BackgroundThe aim of the present study was to evaluate the efficacy of anti-TNF treatment on urinary type-II collagen C-telopeptyde (CTX-II) levels which is a cartilage destruction marker in patients with...

Imaging biopsy composition at ACL reconstruction.

Early-stage osteoarthritis (OA) includes glycosaminoglycan (GAG) loss and collagen disruption that cannot be seen on morphological magnetic resonance imaging (MRI). T1ρ MRI is a measurement that probes the low-frequency rate of exchange between protons of free water and those from water associated with macromolecules in the cartilage's extracellular matrix. While it has been hypothesized that increased water mobility resulting from early osteoarthritic changes cause elevated T1ρ MRI values, there remain several unknown mechanisms influencing T1ρ measurements in cartilage. The purpose of this work was to relate histological and biochemical metrics directly measured from osteochondral biopsies and fluid specimens with quantitative MRI-detected changes of in vivo cartilage composition. Six young patients were enrolled an average of 41 days after acute anterior cruciate ligament (ACL) rupture. Femoral trochlear groove osteochondral biopsies, serum, and synovial fluid were harvested during ACL reconstruction to complement a presurgery quantitative MRI study (T1ρ, T2, delayed gadolinium-enhanced MRI of cartilage [dGEMRIC] relaxation times). A high-resolution MRI scan of the excised osteochondral biopsy was also collected. Analyses of in vivo T1ρ images were compared with ex vivo T1ρ imaging, GAG assays and histological GAG distribution in the osteochondral biopsies, and direct measures of bone and cartilage turnover markers and "OA marker" 3B3 in serum and synovial fluid samples. T1ρ relaxation times in patients with a torn ACL were elevated from normal, indicating changes consistent with general fluid effusion after blunt joint trauma. Increased chondrogenic progenitor cell (CPC) production of chondroprotective lubricin may relate to cartilage surface disruption by blunt trauma and CPC amplification of joint inflammation. Disparity between ex vivo and matched in vivo MRI of trochlear cartilage suggests MRI signal differences that may be related to the synovial fluid environment. T1ρ is emerging as a promising MRI biomarker to relate noninvasive measures of whole-joint condition and cartilage composition to direct measures of cartilage changes in the acute phase of joint injuries.

Exploratory biomarker analysis reveals a genetic epistatic interaction in interleukin 1 receptor antagonist (IL1RN) gene associated to cartilage volume growth measured by MRI in response to sprifermin therapy in patients with knee radiographic osteoarthritis

Exploratory biomarker analysis reveals a genetic epistatic interaction in interleukin 1 receptor antagonist (IL1RN) gene associated to cartilage volume growth measured by MRI in response to sprifermin therapy in patients with knee radiographic osteoarthritis

The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage.

ObjectiveSalmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3)-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the explants.MethodsEarly chondrocyte hypertrophy was induced in bovine articular cartilage explants by stimulation over four days with 20 ng/mL T3. The degree of hypertrophy was investigated by molecular markers of hypertrophy (ALP, IHH, COLX and MMP13), by biochemical markers of cartilage turnover (C2M, P2NP and AGNxII) and histology. The expression of the CTR was detected by qPCR and immunohistochemistry. T3-induced explants were treated with salmon or human calcitonin. Calcitonin down-stream signaling was measured by levels of cAMP, and by the molecular markers.ResultsCompared with untreated control explants, T3 induction increased expression of the hypertrophic markers (p<0.05), of cartilage turnover (p<0.05), and of CTR (p<0.01). Salmon, but not human, calcitonin induced cAMP release (p<0.001). Salmon calcitonin also inhibited expression of markers of hypertrophy and cartilage turnover (p<0.05).ConclusionsT3 induced early hypertrophy of chondrocytes, which showed an elevated expression of the CTR and was thus a target for salmon calcitonin. Molecular marker levels indicated salmon, but not human, calcitonin protected the cartilage from hypertrophy. These results confirm that salmon calcitonin is able to modulate the CTR and thus have chondroprotective effects.

Cartilage Oligomeric Matrix Protein Associates Differentially with Erosions and Synovitis and Has a Different Temporal Course in Cyclic Citrullinated Peptide Antibody (Anti-CCP)-positive versus Anti-CCP-negative Early Rheumatoid Arthritis

Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings. A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years. Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p < 0.001] and remained elevated at 4 years [10.8 U/l (IQR 10.2, 11.7); p < 0.001]. At baseline, anti-CCP-positive patients had lower COMP than anti-CCP-negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals. Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by modifying cartilage metabolism.

Moderate loading of the human osteoarthritic knee joint leads to lowering of intraarticular cartilage oligomeric matrix protein

The non-pharmacological treatment of osteoarthritis (OA) includes exercise therapy; however, little is known about the specific effect of exercise on the joint per se. The purpose of the present study was to investigate the direct effects of a load-bearing exercise upon cartilage in a single, human osteoarthritic joint determined by biochemical markers of cartilage turnover and inflammation in the synovial fluid (SF), serum and urine. Eleven subjects with OA of the knee(s), but with no other joint- or inflammatory disorders, volunteered for the study and had samples of blood, urine and synovial fluid drawn both at baseline and following 30-min one-legged knee-extension exercise. Workload: 60% of 1 RM (Repetition Maximum). Determination of cartilage oligomeric matrix protein (COMP), aggrecan, C-terminal collagen II peptide (CTX-II) and interleukin (IL)-6 were performed in synovial fluid (SF), serum and urine. A significant decrease was found in SF concentration of COMP following exercise, whereas aggrecan, CTX-II and IL-6 remained unchanged. No differences in any of the tested markers were found in serum and urine between baseline and post-exercise. Thirty minutes of mechanical loading of a single knee joint in human subjects with knee OA resulted in a reduced COMP concentration in SF.

Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis development in B10.Q-ncf1*/* mice with collagen-induced chronic arthritis

BackgroundCollagen-induced arthritis (CIA) is an often-used murine model for human rheumatoid arthritis (RA). Earlier studies have shown potent anti-arthritic effects with the female sex hormone estradiol and the selective estrogen receptor modulator (SERM) raloxifene in CIA in DBA/1-mice. B10.Q-ncf1*/*mice are B10.Q mice with a mutated Ncf1 gene. In B10.Q-ncf1*/*mice, CIA develops as a chronic relapsing disease, which more accurately mimics human RA. We investigated the role of endogenous and exogenous sex steroids and raloxifene in the course of this model of chronic arthritis. We also examined whether treatment would prevent the development of inflammation-triggered generalized osteoporosis.MethodsFemale B10.Q-ncf1*/*mice were sham-operated or ovariectomized, and CIA was induced. 22 days later, when 30% of the mice had developed arthritis, treatment with raloxifene, estradiol or vehicle was started, and the clinical disease was evaluated continuously. Treatment was continued until day 56 after immunization. At termination of the experiment (day 73), bone mineral density (BMD) was analyzed, paws were collected for histological examination, and sera were analyzed for markers of cartilage turnover and pro-inflammatory cytokines.ResultsRaloxifene and estradiol treatment, as well as endogenous estrogen, decreased the frequency of arthritis, prevented joint destruction and countered generalized osteoporosis. These effects were associated with lower serum levels of the pro-inflammatory cytokine IL-6.ConclusionsThis is the first study to show that raloxifene and estradiol can ameliorate established erosive arthritis and inflammation-triggered osteoporosis in this chronic arthritis model. We propose that treatment with raloxifene could be a beneficial addition to the treatment of postmenopausal RA.

Rapid and sustained improvement in bone and cartilage turnover markers with the anti–interleukin‐6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: Results from a substudy of the multicenter double‐blind, placebo‐controlled trial of tocilizumab in inadequate responders to methotrexate alone

To investigate the effects of tocilizumab (TCZ) added to a stable dosage of methotrexate (MTX) on biochemical markers of bone and cartilage metabolism in patients in the multicenter double-blind, placebo-controlled OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders) study who have moderate-to-severe rheumatoid arthritis (RA) and an inadequate response to MTX. Included in this study were 416 of the 623 patients with active RA enrolled in the OPTION study. Patients were randomized to receive TCZ (4 mg/kg or 8 mg/kg) or placebo intravenously every 4 weeks, with MTX continued at the stable prestudy doses (10-25 mg for 20 weeks, with a final followup at week 24). Serum biochemical markers of bone formation (osteocalcin, N-terminal propeptide of type I collagen [PINP]), bone resorption (C-terminal crosslinking telopeptide of type I collagen [CTX-I] and C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases [ICTP]), cartilage metabolism (N-terminal propeptide of type IIA collagen [PIIANP]), collagen helical peptide [HELIX-II]), and matrix metalloproteinase 3 (MMP-3) were measured at baseline and at weeks 4, 16, and 24. TCZ induced marked dose-dependent reductions in PIIANP, HELIX-II, and MMP-3 levels at week 4 that were maintained until week 24, an effect associated with increased levels of bone formation markers that were significant as compared with placebo only for PINP and only at 4 weeks (P < 0.01 for both TCZ doses). TCZ induced significant decreases in the bone degradation markers CTX-I and ICTP, providing initial evidence of a beneficial effect on bone turnover. TCZ-treated patients who met the American College of Rheumatology 50% improvement criteria (achieved an ACR50 response) or achieved clinical remission (as determined by a Disease Activity Score in 28 joints <2.6) at week 24 had greater reductions in ICTP, HELIX-II, and MMP-3 levels as compared with ACR50 nonresponders. TCZ combined with MTX reduces systemic bone resorption, cartilage turnover, and proteolytic enzyme MMP-3 levels, which provides evidence of a limitation of joint damage and possible beneficial effects on skeletal structure in patients with established moderate-to-severe RA.

High Serum Cartilage Oligomeric Matrix Protein Determines the Subset of Patients with Early-Stage Rheumatoid Arthritis with High Serum C-Reactive Protein, Matrix Metalloproteinase-3, and MRI-Proven Bone Erosion

To identify the significance of serum cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in patients with early-stage rheumatoid arthritis (RA) in relation to other serologic variables and magnetic resonance imaging (MRI) features. Ninety-eight patients with early-stage RA, whose disease duration from onset was less than 2 years, were enrolled. The objective measures at baseline were Disease Activity Score (DAS28), serum C-reactive protein (CRP), serum matrix metalloproteinase-3 (MMP-3), serum antibodies against cyclic citrullinated peptide (anti-CCP), and MRI features of both wrist and finger joints. The MRI features included the number of sites scored positive for synovitis, bone edema, and bone erosion. Serum COMP concentration was not different among groups identified with low, moderate, and high DAS28-CRP values. However, COMP values were statistically high in subjects positive for bone erosions on MRI compared with the subjects who were negative for bone erosions. A positive correlation of COMP with CRP and with MMP-3 values was also identified. Elevation of COMP may reflect joint damage that is dependent on the synovial inflammatory process in early-stage RA.

Bone and Cartilage Turnover Markers, Bone Mineral Density, and Radiographic Damage in Men with Ankylosing Spondylitis

PurposeTo determine the levels of bone and cartilage turnover markers in men with ankylosing spondylitis (AS) and to investigate their associations with disease activity, bone mineral density, and radiographic damage of the spine.Patients and MethodsThis cross-sectional study enrolled 35 men with newly diagnosed AS. The bone mineral densities (BMD) of their lumbar spines and proximal femurs, Bath AS Disease Activity Index (BASDAI), and Bath AS Radiographic Index (BASRI) were evaluated. Urinary C-terminal telopeptide fragments of type I collagen (CTX-I) and type II collagen (CTX-II) levels were determined by enzyme-linked immunosorbent assay, and serum levels of bone-specific alkaline phosphatase (BALP) and osteocalcin were determined by an enzyme immunoassay. Levels of biochemical markers were compared with those of 70 age-matched healthy men.ResultsPatients with AS had significantly higher mean urinary CTX-I and CTX-II levels than control subjects (p < 0.05). Elevated urinary CTX-I levels correlated well with BASDAI, femoral BMD, and femoral T score (p < 0.05), and elevated urinary CTX-II levels correlated well with spinal BASRI (p < 0.05) in patients with AS. Mean serum BALP and osteocalcin levels did not differ between patients and controls and did not show any significant correlations with BMD, BASDAI, or BASRI in men with AS.ConclusionsElevated CTX-I reflects disease activity and loss of femoral BMD while elevated CTX-II levels correlate well with radiographic damage of the spine, suggesting the usefulness of these markers for monitoring disease activity, loss of BMD, and radiographic damage in men with AS.

Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis

Background:Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation under the control of pro-inflammatory cytokines, including tumour necrosis factor α (TNFα). Therefore, we tested...