Clinically Relevant Molecular Biomarkers for Use in Human Knee Osteoarthritis: A Systematic Review.

OBJECTIVE: Biomarkers in osteoarthritis (OA) could serve as objective clinical indicators for various disease parameters, and act as surrogate endpoints in clinical trials for disease-modifying drugs. The aim of this systematic review was to produce a comprehensive list of candidate molecular biomarkers for knee OA after the 2013 ESCEO review and discern whether any have been studied in sufficient detail for use in clinical settings. DESIGN: MEDLINE and Embase databases were searched between August 2013 and May 2018 using the keywords "knee osteoarthritis," "osteoarthritis," and "biomarker." Studies were screened by title, abstract, and full text. Human studies on knee OA that were published in the English language were included. Excluded were studies on genetic/imaging/cellular markers, studies on participants with secondary OA, and publications that were review/abstract-only. Study quality and bias were assessed. Statistically significant data regarding the relationship between a biomarker and a disease parameter were extracted. RESULTS: A total of 80 studies were included in the final review and 89 statistically significant individual molecular biomarkers were identified. C-telopeptide of type II collagen (CTXII) was shown to predict progression of knee OA in urine and serum in multiple studies. Synovial fluid vascular endothelial growth factor concentration was reported by 2 studies to be predictive of knee OA progression. CONCLUSION: Despite the clear need for biomarkers of OA, the lack of coordination in current research has led to incompatible results. As such, there is yet to be a suitable biomarker to be used in a clinical setting.

Immunodetection of urinary C-terminal telopeptide fragment of type II collagen: An osteoarthritis biomarker analysis.

The urinary C-terminal telopeptide fragment of type II collagen (uCTX-II) has been reported as the efficient blood-based biomarker for osteoarthritis, which affects knees, hands, spine, and hips. This study reports a sensing strategy with antibody-conjugated gold nanoparticles (GNP) on an interdigitated electrode (IDE) to determine uCTX-II. The GNP-antibody complex was chemically immobilized on the IDE surface through the amine linker. uCTX-II was determined by monitoring the alteration in current upon interacting the GNP-complexed antibody. This strategy was improved the detection by attracting higher uCTX-II molecules, and the detection limit falls in the range of 10-100 pM with an acceptable regression value [y = 0.6254x - 0.4073, R² = 0.9787]. The sensitivity of the detection was recognized at 10 pM. Additionally, upon increasing the uCTX-II concentration, the current changes were increased in a linear fashion. Control detection with nonimmune antibody and control protein do not increase the current level, confirming the specific detection of uCTX-II. This method of detection helps in diagnosing osteoarthritis and its follow-up treatment.

Multivariable logistic and linear regression models for identification of clinically useful biomarkers for osteoarthritis.

Osteoarthritis (OA) is the most common chronic degenerative joint disease which causes substantial joint pain, deformity and loss of activities of daily living. Currently, there are over 500 million OA cases worldwide, and there is an urgent need to identify biomarkers for early detection, and monitoring disease progression in patients without obvious radiographic damage to the joint. We have used regression modelling to describe the association of 19 of the currently available biomarkers (predictors) with key radiographic and clinical features of OA (outcomes) in one of the largest and best characterised OA cohort (NIH Osteoarthritis Initiative). We demonstrate that of the 19 currently available biomarkers only 4 (serum Coll2-1 NO2, CS846, COMP and urinary CTXII) were consistently associated with established radiographic and/or clinical features of OA. These biomarkers are independent of one another and provide additional predictive power over, and above established predictors of OA such as age, gender, BMI and race. We also show that that urinary CTXII had the strongest and consistent associations with clinical symptoms of OA as well as radiographic evidence of joint damage. Accordingly, urinary CTXII may aid in early diagnosis of OA in symptomatic patients without radiographic evidence of OA.

[Biochemical predictors of cartilaginous tissue metabolic disorders for early osteoarthrosis evidence diagnostics.]

The complete laboratory and clinical instrumental examination was conducted, it included serum COMP test, circadian excretion of type II collagen C-terminal telopeptides Urine CartiLaps (СТХ II) and Т2 relaxometry in 29 patients of both sexes of the main group with early (0-I) X-ray osteoarthrosis stages, 30 subjects of comparison group with no X-ray osteoarthrosis evidences aged 44.7±5.9 years and 25 healthy subjects aged 26.3±2.6 years of the control group. The increase (р<0,05) of COMP and Urine CartiLaps levels as well as the increase of Т2 relaxation signal was found at early osteoarthrosis evidences. It was proven that there was (р<0.01) a connection (R=0.8) between COMP and Urine CTX II levels as well as (р<0.05) results of Т2 relaxometry (R=0.8). It was proven that collagen anisotropy and formation of chondromalacia areas as Т2 relaxometry showed in patients with early OA evidences were connected with accumulation of serum COMP and increase of type II collagen circadian renal excretion. The combination of laboratory and radiological methods of articular hyaline cartilage assessment may be used for finding early osteoarthrosis stages.

The cartilage degradation marker, urinary CTX-II, is associated with the risk of incident total joint replacement in postmenopausal women. A 18 year evaluation of the OFELY prospective cohort.

OBJECTIVE: Identifying objective risk-indicators for total joint replacement (TJR) is useful to enrich population at high risk in OA clinical trials. We investigate the association of urinary CTX-II, a biochemical marker of cartilage breakdown, with the risk of TJR. METHOD: 478 postmenopausal women (mean age 65.5 ± 7.5 yr) from the OFELY cohort were studied. CTX-II, serum CTX-I (bone resorption) and PINP (bone formation), were measured at baseline. Association between CTX-II and incidence of TJR was assessed by Cox Hazard Regression. RESULTS: During a median (95%CI) 17.8 (15.0-18.1) years follow-up, 38 women sustained a TJR, including hip (n = 29) or knee (n = 9) replacement. CTX-II -but not CTX-I or PINP- was higher in patients with TJR (+34%, P = 0.001 vs women with no TJR). Increased baseline CTX-II levels were associated with a higher risk of TJR with a Hazard Ratio (HR) (95 CI) of 1.45 (1.13-1.85) per 1 SD increase after adjustment for age, BMI and total hip BMD. CTX-II remained significantly associated with the risk of TJR after further adjustment for total WOMAC, prevalent knee OA (KL ≥ 2) and self-reported hip OA [HR (95 CI): 1.31 (1.01-1.71), P = 0,04]. When women were categorized as low and high CTX-II (lower and above the 95 percentile of healthy premenopausal women, respectively), subjects with high levels had an age-BMI-hip BMD adjusted HR (95 CI) of 3.00 (1.54-5.85) compared to women with low levels which remained significant after further adjustment for WOMAC, knee and/or hip OA [HR (95 CI): 2.45 (1.25-4.89), P = 0.01]. CONCLUSION: CTX-II is an independent risk indicator of TJR in postmenopausal women suggesting that it may be useful to identify subjects at high risk of TJR.

Analysis of Polymorphisms in the MATN3 and DOT1L Genes and CTX-II Urinary Levels in Patients with Knee Osteoarthritis in a Northeast Mexican-Mestizo Population.

Aims: To investigate the possible roles of the single nucleotide polymorphisms (SNPs) MATN3 (rs77245812) and DOT1L (rs12982744) with susceptibility to knee osteoarthritis (KOA) among mestizos from the northeast region of Mexico. In addition, we analyzed the relationship of their urinary levels of carboxy terminal telopeptide of collagen type II (CTX-II) and the radiological grade of disease. Materials and Methods: A total of 223 individuals from a Northeast Mexico Mestizo population were included in this study: 110 patients with primary KOA and 113 healthy controls. Genotyping of the MATN3 (rs77245812) and DOT1L (rs12982744) SNPs was performed by real-time polymerase chain reaction. Results: No association was found between the polymorphisms MATN3 (rs77245812), DOT1L (rs12982744), and the risk of developing KOA (odds ratio [OR] = 1.33, 95% confidence interval [CI] = 0.42-6.48, p = 0.621) (OR = 2.03, 95% CI = 0.35-11.5, p = 0.422). However, urinary CTX-II levels were considerably higher by radiographic grade. Conclusions: An increase in CTX-II per radiographic grade was observed in the case group, but no association was found between MATN3 and DOT1L genes and the risk of KOA in Mexican mestizos.

Rapid Progression of Knee Pain and Osteoarthritis Biomarkers Greatest for Patients with Combined Obesity and Depression: Data from the Osteoarthritis Initiative.

OBJECTIVE: To compare the progression of biochemical biomarkers of osteoarthritis (OA), knee pain, and function between nonobese patients (NON), obese patients without depression (OBESE), and obese patients with comorbid depression (O + D). DESIGN: Utilizing the FNIH OA Biomarkers Consortium dataset, we categorized knee OA patients into NON, OBESE, and O + D groups based on body mass index and Center for Epidemiological Studies-Depression (CES-D) scores. Subjective symptoms (Knee injury and Osteoarthritis Outcome Score Quality of Life subscale (KOOS QOL), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function scores, and the Short Form-12 (SF-12) Physical Component Score [PCS]) and objective measures of cartilage degradation and bone remodeling (urinary CTXII and CTXIα) were compared among groups at baseline and 2-year follow-up. RESULTS: Of the 600 patients, 282 (47%) were NON, 285 (47.5%) OBESE, and 33 (5.5%) O + D. The O + D group had significantly worse pain and function both at baseline and 2-year follow-up (P < 0.001 for all comparisons) as evidenced by self-reported measures on KOOS QOL, WOMAC Pain, WOMAC Physical Function, and SF-12 PCS. The O + D group also demonstrated significant increases in CTXII (P = 0.01) and CTXIα (P = 0.005), whereas the NON and OBESE groups did not. CONCLUSIONS: The combination of inferior knee pain, physical function, and significantly greater increases in biomarkers of cartilage degradation and bony remodelling suggest a more rapid progression for obese OA patients with comorbid depression. The link between systemic disease, inflammatory burden, and progressive cartilage degradation is in line with increasing concerns about a degenerative synovial environment in early osteoarthritic knees that progress to treatment failure with biologic restoration procedures.

C-Terminal Cross-Linked Telopeptides of Type II Collagen as Biomarker for Radiological Knee Osteoarthritis: A Meta-Analysis.

BACKGROUND: C-terminal cross-linked telopeptides of type II collagen (CTX-II) are one of the most frequently assessed markers for osteoarthritis (OA) diagnosis. The aim of this meta-analysis was to confirm the diagnostic value of urinary CTX-II in knee OA. MATERIALS AND METHODS: PubMed, ScienceDirect, and EMBASE were searched for studies measured urinary CTX-II in patients with knee OA and in healthy controls. Urinary CTX-II levels were compared between knee OA patients and controls. Differences between groups were expressed as standardized mean differences (SMD) when individual outcomes were measured with different scales. Otherwise, outcomes were presented as mean differences (MD). Subgroup analyses were also conducted to compare efficiency of urinary CTX-II between Kellgren-Lawrence (KL) classification, genders, ethnicities, and study size. RESULTS: Thirteen studies involved a total of 2856 participants were included. Pooled SMD showed that urinary CTX-II levels were significantly elevated in knee OA group compared to controls (SMD 0.82; 95% CI 0.41-1.24; P < 0.0001). For KL 3 to 4 versus KL 2, higher urinary CTX-II levels were found in severe knee OA patients. Subgroup analyses revealed that urinary CTX-II performed better in females as compared with males and in European subjects as compared with Asian population. Also, study size did not influence the statistic results. CONCLUSION: This is the largest scale meta-analysis assessing the diagnostic performance of urinary CTX-II levels as biomarker for knee OA. According to our findings, urinary CTX-II levels have a potential to distinguish knee OA patients from healthy controls which can serve as biomarker for knee OA.

Correlation Analysis of C-terminal telopeptide of collagen type II and Interleukin-1ß for Early Diagnosis of Knee Osteoarthritis.

OBJECTIVE: To analyze the correlation between the Kellgren-Lawrence (K-L) score of knee osteoarthritis (KOA) patients with different degrees and their urine concentration of C-terminal telopeptide of collagen type II (CTX-II) and interleukin-1ß (IL-1ß), and to further evaluate the diagnostic value of CTX-II and IL-1ß during the pathological process by producing an experimental osteoarthritis (OA) model in rabbits. METHODS: From 1 January 2017 to 31 December 2018, a total of 34 subjects (7 mild, 9 moderate, 9 severe arthritis patients, and 9 healthy individuals) comprising 16 men and 18 women were included in this study. Patients were diagnosed according to the American College of Rheumatology (ACR) criteria. The urine of all subjects was collected to detect the concentration of CTX-II and IL-1ß. The rabbits in the KOA group were subjected to protease (control group with saline) injection into the articular cavity of their right knees and immobilization with gypsum. We used radiological and histological examination to identify the KOA model. ELISA was applied to investigate the concentrations of CTX-II and IL-1ß in urine and serum, and Spearman's rank correlation analysis was used to analyze the correlation. RESULTS: There was no significant difference in the mean ages and body mass index (BMI) between groups. The mean ages of mild, moderate, and severe arthritis patients and healthy individuals were 54.29 ± 5.76, 58.44 ± 6.44, 59.89 ± 6.75, and 56.67 ± 4.18 years, respectively. The mean BMI of mild, moderate, and severe arthritis patients and healthy individuals were 23.59 ± 1.56, 23.57 ± 2.06, 24.46 ± 1.64, and 23.42 ± 1.35 kg/m2 , respectively. The Kellgren-Lawrence (K-L) score was higher with the aggravation of KOA. The K-L scores of mild, moderate, and severe KOA patients were 1.14 ± 0.38, 2.56 ± 0.53, and 3.63 ± 0.52, respectively. The KOA symptoms of patients became more severe, with not only increased K-L scores but also elevated concentrations of CTX-II and IL-1ß. Moreover, there was a positive correlation between CTX-II and IL-1ß of all subjects (r = 0.974, P < 0.001), between K-L score and urine concentration of CTX-II (r = 0.900, P < 0.001), and between K-L score and IL-1ß (r = 0.813, P < 0.001) of all subjects. Both were significantly increased in KOA group rabbits at all time points after surgery. The serum concentration of CTX-II and IL-1ß was elevated as early as in the 2nd week (3.69 and 4.25 times) and reached a peak (5.41 and 7.23 times) in the 4th week after surgery. Then, until 12 weeks after surgery, the CTX-II and IL-1ß concentrations in the KOA group were slightly reduced and remained around 4.5 and 6.3 times that in the control group. Moreover, there was a positive correlation between the serum concentration of IL-1ß and CTX-II (r = 0.967, P < 0.001). CONCLUSION: CTX-II and IL-1ß, which were significantly increased during the process of KOA, can be used as biomolecular markers to provide guidelines for early diagnosis and treatment of KOA.

Smartphone-integrated urinary CTX-II immunosensor based on wavelength filtering from chromogenic reaction.

The integration of smart IT devices and biochemical assays with optical biosensing technology facilitates the development of efficacious optical biosensors for many practical diagnostic fields, owing to their minimized use of high-technical electronic components and simple operation. Herein, we introduced a simple optical biosensing system based on the specific wavelength filtering principle and count-based analysis method. The developed system uses a smartphone with a paper-based signal guide and a biosensing channel. The paper-based signal guide was prepared by printing red patterns of various brightness on a black background. Given that a blue product is generated as a result of horseradish peroxidase (HRP)-based enzymatic reaction in the biosensing channel, the channel could be used as a blue filter that absorbs red light. When red light reflected from the red pattern is absorbed by the channel, the pattern appears black. As such, the color of the patterns is assimilated with the black background, so it seems to disappear. Consequently, the amount of blue product relative to the concentration of the target analyte can be measured by counting the number of observed patterns on the paper-based signal guide. In this study, the concentration of urinary C-telopeptide fragment of type II collagen (uCTX-II, 0-10 ng/mL) was measured using the developed system without complicated equipment. In addition, the quantitative analysis of uCTX-II in the real urine sample was successfully performed. Therefore, we expect that the developed optical transducing system could be practically used for point-of-care testing (POCT) diagnosis under resource-limited environmental conditions.

The urinary levels of CTX-II, C2C, PYD, and Helix-II increased among adults with KBD: a cross-sectional study.

BACKGROUND: Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and its pathogenesis is still not entirely clear. Pathologically, many KBD changes are similar to those of osteoarthritis (OA). Therefore, this study aimed to identify changes in the levels of potential urinary biomarkers for OA, including C-telopeptide of type II collagen (uCTX-II), type II collagen cleavage neoepitope (uC2C), pyridinoline (uPYD), and uHelix-II, among adults with KBD. METHODS: Urinary samples of 83 external control (EC) subjects, 91 KBD patients, and 86 internal control (IC) subjects were tested by ELISA after the subjects completed a questionnaire and X-ray examination. RESULTS: The medians of the four markers in the KBD group were higher than those in the EC group and those in the IC group. The medians in the grade II KBD group were higher than those in the grade I group but were not statistically significant (P = 0.301, P = 0.408, P = 0.204, and P = 0.898 for uCTX-II, uC2C, uPYD, and uHelix-II, respectively). The area under the curve (AUC) of uCTX-II (0.775) was higher than that of the others (0.672, 0.639, and 0.628 for uC2C, uPYD, and uHelix-II, respectively). CONCLUSION: The levels of uCTX-II, uC2C, uPYD, and uHelix-II were elevated in adults with KBD and showed an increasing trend as the severity of KBD increased. The prediction accuracy of uCTX-II was more useful than that of the others for assisting in the diagnosis of KBD.

Protein biomarkers in serum and urine for determining presence or absence of hip dysplasia in a canine model.

This study compares serum and urine concentrations of relevant protein biomarkers among adult dogs with or without radiographic canine hip dysplasia (CHD). Adult (≥2 years of age), client-owned dogs (n = 74) radiographically categorized as having at least "good" hips (n = 49) or having "mild," "moderate," or "severe" hip dysplasia (n = 25) by the Orthopedic Foundation for Animals (OFA). Urine and serum samples were obtained from each dog at a single time-point and processed and analyzed for relevant protein biomarkers. Urinary concentrations of CTX-II (p < 0.001) and TIMP-1 (p = 0.002) were significantly lower in dogs with CHD compared to dogs with no CHD. ROC curve analyses were successful in establishing a panel of four biomarkers (urinary CTX-I and II, serum MMP-9, and serum PIICP) with high discriminatory capability for the presence or absence of hip dysplasia in adult dogs (AUC = 0.89). Urine and serum biomarkers can distinguish adult dogs with radiographic CHD from those with no CHD with a sensitivity of 0.95 and specificity of 0.77 using ROC analysis with AUC 0.89. Clinical Significance: This finding suggests that this simple, minimally invasive diagnostic technique has potential for discriminating dysplastic dogs from dogs with normal hips, with possible translational application to humans based on similar etiopathogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-5, 2019.

The levels of urine CTX-II, C2C, and PYD in children patients with Kashin-Beck disease in Qinghai Province of China.

BACKGROUND: Kashin-Beck disease (KBD) is an endemic and chronic osteoarthropathy. At present, the diagnosis of KBD mainly depends on the X-ray examination and which could not reflect early damage of cartilage sensitively. So, the aim of this study was to find effective and sensitive biomarkers for early diagnosis of pediatric KBD. METHODS: A total of 122 children aged 7-15 years old from 3 villages of Qinghai Province were eligible for the study. Thirty-one, 41, and 50 children were assigned in case, internal, and external control groups, respectively. The levels of CTX-II, C2C, and PYD in urine were measured by using ELISA and compared statistically. In addition, the receiver operating characteristic curve (ROC) analysis was used to assess the performance of diagnostic biomarkers. RESULTS: There were significant differences in levels of CTX-II, C2C, and PYD in urine of subjects among three groups. The levels of CTX-II and PYD in the case group were significantly higher than those in external and internal control groups. On the contrary, the level of C2C in the case group was lower than that in the external control group. Compared to the external control group, the area under the curve (AUC) of CTX-II, C2C, and PYD were 0.857, 0.837, and 0.79, and the AUC of CTX-II significantly higher than that of PYD. Compared to the internal control group, the AUC of CTX-II, C2C, and PYD were 0.911, 0.875, and 0.839, and there were no significant differences in the AUC among three indicators. CONCLUSION: Both CTX-II and PYD in urine could be used as biomarkers for early diagnosis of pediatric KBD, and the prediction accuracy of CTX-II was relatively superior.

Combination therapy of curcumin and alendronate modulates bone turnover markers and enhances bone mineral density in postmenopausal women with osteoporosis.

OBJECTIVE: This study evaluated the effects of combination therapy of curcumin and alendronate on BMD and bone turnover markers in postmenopausal women with osteoporosis. SUBJECTS AND METHODS: In a randomized, double-blind trial study, 60 postmenopausal women were divided into three groups: control, alendronate, and alendronate + curcumin. Each group included 20 patients. Total body, total hip, lumbar spine and femoral neck BMDs were measured by dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months of therapy. Bone turnover markers such as bone-specific alkaline phosphatase (BALP), osteocalcin and C-terminal cross-linking telopeptide of type I collagen (CTx) were measured at the outset and 6 months later. RESULTS: Patients in the control group suffered a significant decrease in BMD and increased bone turnover markers at the end of study. The group treated with only alendronate showed significantly decreased levels of BALP and CTx and increased levels of osteocalcin compared to the control group. The alendronate group also showed significant increases in the total body, total hip, lumbar spine and femoral neck BMDs at the end of study compared to the control group. In the curcumin + alendronate group, BALP and CTx levels decreased and osteocalcin levels increased significantly at the end of study compared to the control and alendronate groups. BMD indexes also increased in four areas significantly at the end of study compared to the control and alendronate groups. CONCLUSION: The combination of curcumin and alendronate has beneficial effects on BMD and bone turnover markers among postmenopausal women with osteoporosis. Arch Endocrinol Metab. 2018;62(4):438-45.

Combination therapy of curcumin and alendronate modulates bone turnover markers and enhances bone mineral density in postmenopausal women with osteoporosis

ABSTRACT Objective: This study evaluated the effects of combination therapy of curcumin and alendronate on BMD and bone turnover markers in postmenopausal women with osteoporosis. Subjects and methods: In a randomized, double-blind trial study, 60 postmenopausal women were divided into three groups: control, alendronate, and alendronate + curcumin. Each group included 20 patients. Total body, total hip, lumbar spine and femoral neck BMDs were measured by dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months of therapy. Bone turnover markers such as bone-specific alkaline phosphatase (BALP), osteocalcin and C-terminal cross-linking telopeptide of type I collagen (CTx) were measured at the outset and 6 months later. Results: Patients in the control group suffered a significant decrease in BMD and increased bone turnover markers at the end of study. The group treated with only alendronate showed significantly decreased levels of BALP and CTx and increased levels of osteocalcin compared to the control group. The alendronate group also showed significant increases in the total body, total hip, lumbar spine and femoral neck BMDs at the end of study compared to the control group. In the curcumin + alendronate group, BALP and CTx levels decreased and osteocalcin levels increased significantly at the end of study compared to the control and alendronate groups. BMD indexes also increased in four areas significantly at the end of study compared to the control and alendronate groups. Conclusion: The combination of curcumin and alendronate has beneficial effects on BMD and bone turnover markers among postmenopausal women with osteoporosis. Arch Endocrinol Metab. 2018;62(4):438-45

Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative.

OBJECTIVE: The purpose of this study was to assess the associations between serum/urine biomarkers for osteoarthritis and magnetic resonance (MR) imaging measures of cartilage composition and joint structure (cartilage, meniscus, and bone marrow), using MR imaging data from the Osteoarthritis Initiative (OAI). DESIGN: 141 subjects with Kellgren Lawrence (KL) grades 0-3 in the right knee and with available serum/urine biomarker assays were selected from the OAI. Cartilage magnetic resonance imaging (MRI) T2 measurements were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. Compartment-specific knee morphologic grading [whole-organ magnetic resonance imaging score (WORMS)] in the cartilage, meniscus, and bone marrow was also performed. We focused on associations of serum hyaluronan (sHA), serum cartilage oligomeric matrix protein (sCOMP), serum matrix metalloproteinase-3 (sMMP3), and Urine Carboxy-Terminal Telepeptides of Type II Collagen (uCtX-II)) with MRI parameters (T2, WORMS), assessed using partial correlations adjusted for age, gender, body mass index (BMI), KL grade in both knees, and diabetes status. RESULTS: Higher levels of sHA, sMMP3 and sCOMP were correlated (P < 0.05) with T2 of the lateral femur (r = 0.18 to 0.32) and lateral tibia (r = 0.17 to 0.23), and with average T2 of all knee regions (r = 0.23). uCTXII was correlated with patellar T2 (r = 0.19, P = 0.04). Among the morphologic measures, sHA and sMMP3 was positively correlated (r = 0.17 to 0.21, P < 0.05) with meniscal damage. CONCLUSIONS: This study suggests weak, but statistically significant, correlations between serum biomarkers of OA (sHA, sCOMP, and sMMP3) and MRI T2 measures of cartilage extra-cellular matrix degeneration.

Cartilage turnover and intra-articular corticosteroid injections in knee osteoarthritis.

Intra-articular corticosteroid injections (IACI) are commonly used interventions for pain relief in patients with knee osteoarthritis (OA). Biomarkers may be helpful in further elucidating how IACI exert their effect. The aim of this study is to look at the response of biomarkers of cartilage and bone metabolism after IACI in knee OA. Eighty subjects with symptomatic knee OA [45% male, mean age (SD) 64 (11) years] underwent routine knee joint injection with 40 mg triamcinolone acetonide and 4 ml 1% lignocaine. Knee pain (as pain subscale of WOMAC VAS) and biomarkers [C-telopeptides of type-II collagen (uCTX-II), and N-telopeptides of type-I collagen in urine; cartilage oligomeric matrix protein (COMP), hyaluronic acid, N-terminal propeptide of type-IIA collagen, and human cartilage glycoprotein-39 (YKL-40) in serum] were measured at baseline and 3 weeks after IACI. Radiographic severity of disease was evaluated using knee radiographs. Median uCTX-II, a cartilage degradation marker, was lower at 3 weeks post IACI compared with baseline: 306.3 and 349.9 ng/mmol, respectively (p < 0.01), which remained significant after Bonferroni correction. Apart from a weak trend of lower sCOMP post IACI (p = 0.089), other biomarkers showed no change after IACI. Both baseline uCTX-II values and the change in uCTX-II from baseline to 3 weeks post injection correlated with radiographic severity of joint space narrowing, but not osteophyte grade. No association between uCTX-II and pain was observed. This observational study suggests that IACI in knee OA may reduce cartilage degradation in the short term.

Concentrations of CTX I, CTX II, DPD, and PYD in the urine as a biomarker for the diagnosis of temporomandibular joint osteoarthritis: A preliminary study.

OBJECTIVES: The aim of this study was to identify a marker for temporomandibular joint (TMJ) osteoarthritis (OA) diagnosis by comparing the concentrations of urinary pyridinoline (PYD), deoxypyridinoline (DPD), and C-terminal telopeptides type I collagen (CTX-I), and CTX-II of TMJ OA patients with those of a non-symptomatic group. METHODS: PYD, DPD, CTX-I, and CTX-II concentrations in the urine of 36 non-symptomatic subjects and 31 TMJ OA subjects were analyzed. RESULTS: The differences for only PYD and DPD were significant. In ROC analysis, PYD and DPD showed higher sensitivity and specificity than CTX-I and CTX-II. PYD and DPD concentrations in urine were significantly increased in TMJ OA patients and can therefore be used as a biomarker in the supplementary clinical diagnosis of TMJ OA. DISCUSSION: The findings suggest that measurement of their concentration can be a supplementary method for clinical diagnosis of TMJ OA.

Comparative study of CTX-II, Zn2+, and Ca2+ from the urine for knee osteoarthritis patients and healthy individuals.

The aim of the study was to explore the relationship between the concentration of C-telopeptide fragments of type II collagen (CTX-II), Zn, and Ca in urine and knee osteoarthritis (KOA).Eighty-two patients with KOA and 20 healthy volunteers were enrolled. Anteroposterior and lateral position x-rays of knee joints were collected. The images were classified according to Kellgren-Lawrence radiographic grading criterion. The patients were divided into group grade I, group grade II, group grade III, and grade IV. The concentration of CTX-II in the urine was detected by enzyme-linked immunosorbent assay. The concentration of Zn and Ca in urine was detected by inductively coupled plasma atomic emission spectrometry.Compared with the healthy individuals, the concentration of CTX-II was significantly higher in KOA patients. The concentration of CTX-II in KOA patients from high to low was as follows: group IV, group III, group II, and group I. There was no significant difference between group I and healthy individuals. The concentration of Zn and Ca in urine of KOA patients was higher than that in healthy individuals. There was no difference in each KOA group.The concentration of CTX-II is instrumental to diagnose the progress of KOA. The concentration of Zn and Ca in urine is helpful for early diagnosis of KOA.