Urinary C-terminal Telopeptide Research Articles

Inter-assay variability in the measurement of urinary C-terminal cross-linked telopeptide of type II collagen following anterior cruciate ligament reconstruction.

To compare urinary C-terminal cross-linked telopeptide of type II collagen (u-CTX-II) concentrations and trends as measured by two different commercially available enzyme-linked immunosorbent assays (ELISA) in a cohort of patients in the first year following anterior cruciate ligament (ACL) reconstruction. 22 ACL-injured patients undergoing reconstructive surgery (mean age 25.2 (SD 8.0) years; 12 (54.5​%) male) had urine samples taken on the day of surgery (baseline) and at 6 and 12 months post-operatively. Concentrations of u-CTX-II were measured using the CloudClone® and the CartiLaps® ELISA. u-CTX-II concentrations were normalized to urinary creatinine (Cr). The u-CTX-II concentrations were significantly different between the 2 assays at each timepoint (p​≤​0.01). When measured using the CloudClone® Assay, mean (standard error) u-CTX-II concentrations were 26.5 (2.5) ng/mmol Cr, 29.4 (3.8) ng/mmol Cr and 40.6 (6.9) ng/mmol Cr at the baseline, 6-month and 12-month timepoints respectively. When measured using the CartiLaps® Assay, at the same respective timepoints, u-CTX-II concentrations were 981.2 (256.5) ng/mmol Cr, 867.0 (234.3) ng/mmol Cr and 764.3 (220.3) ng/mmol Cr. Concentrations of u-CTX-II using the CloudClone® Assay increased with time (p​=​0.04). Concentrations of u-CTX-II using the CartiLaps® Assay decreased over time (p​=​0.2). Using two commercially available assays, u-CTX-II differed significantly in terms of both concentration and trends in the first year following ACL reconstruction. The specific assay used is critical to consider when interpreting results and has implications for pooling data and meta-analysis.

Association of biochemical markers with bone marrow lesion changes on imaging—data from the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium

BackgroundTo assess the prognostic value of short-term change in biochemical markers as it relates to bone marrow lesions (BMLs) on MRI in knee osteoarthritis (OA) over 24 months and, furthermore, to assess the relationship between biochemical markers involved with tissue turnover and inflammation and BMLs on MRI.MethodsData from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600) was analyzed. BMLs were measured according to the MRI Osteoarthritis Knee Score (MOAKS) system (0–3), in 15 knee subregions. Serum and urinary biochemical markers assessed were as follows: serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), serum crosslinked N-telopeptide of type I collagen (NTX-I), urinary CTX-Iα and CTX-Iβ, urinary NTX-I, urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), serum matrix metalloproteinase (MMP)-degraded type I, II, and III collagen (C1M, C2M, C3M), serum high sensitivity propeptide of type IIb collagen (hsPRO-C2), and matrix metalloproteinase-generated neoepitope of C-reactive protein (CRPM). The association between change in biochemical markers over 12 months and BMLs over 24 months was examined using regression models adjusted for covariates. The relationship between C1M, C2M, C3M, hsPRO-C2, and CRPM and BMLs at baseline and over 24 months was examined.ResultsIncreases in serum CTX-I and urinary CTX-Iβ over 12 months were associated with increased odds of changes in the number of subregions affected by any BML at 24 months. Increase in hsPRO-C2 was associated with decreased odds of worsening in the number of subregions affected by any BML over 24 months. C1M and C3M were associated with BMLs affected at baseline.ConclusionsShort-term changes in serum CTX-I, hsPRO-C2, and urinary CTX-Iβ hold the potential to be prognostic of BML progression on MRI. The association of C1M and C3M with baseline BMLs on MRI warrants further investigation.

Association between cartilage biomarker level and functional outcome in knee osteoarthritis patients receiving dextrose prolotherapy: a cross-sectional study

Background: Knee osteoarthritis (KOA) is a degenerative joint disease with relatively high prevalence globally and is one of the leading causes of disability in the elderly population. Dextrose prolotherapy (DPT) has been proven effective in improving functional outcomes in knee osteoarthritis. The effect of hypertonic dextrose on cartilage biomarkers has not been evaluated. Purpose: To evaluate the association between a cartilage biomarker and changes in clinical outcomes among patients with KOA who received dextrose prolotherapy (DPT). Patients and methods: This study was conducted with a cross-sectional design. Twenty-six participants received DPT at weeks 1, 5, and 9. Our primary measures were urinary c-terminal telopeptides of type II collagen (uCTX-II), measured by an enzyme-linked immunosorbent assay (ELISA), and the WOMAC score, measured at baseline and week 12. Results: There were significant improvements in all WOMAC subscales and uCTX-II levels after DPT. There is no significant correlation between biomarker levels with the WOMAC score as a functional outcome indicator in KOA after DPT (p > 0.05), but there are positive correlations between pain, functional, total WOMAC score, and uCTX-II. Conclusion: DPT may reduce cartilage degradation and improve functional outcomes in osteoarthritic knees. Significant drops in uCTX-II levels can affect functional outcomes, especially pain, functional and total WOMAC scores.

Evaluation of urinary C-terminal cross-linked telopeptides of type II collagen CTX-II as a biomarker for early diagnosis of osteoarthritis in comparison to routine diagnostic methods

Evaluation of urinary C-terminal cross-linked telopeptides of type II collagen CTX-II as a biomarker for early diagnosis of osteoarthritis in comparison to routine diagnostic methods

Bone turnover in pregnancy, measured by urinary CTX, is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial

The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized. We investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices. MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and β-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann-Whitney Rank Sum test, Spearman's rank correlation, and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes. In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r=0.31) and cholecalciferol (r=0.45) groups (P<0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n=372 total) [placebo (n=188): from 223.6 to 449.7 μg/mmol creatinine; cholecalciferol (n=184): from 222.3 to 419.3 μg/mmol creatinine; P=0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean±SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n=188) than in the cholecalciferol group (n=184) (placebo: 0.16±0.92; cholecalciferol: -0.16±1.06; P-difference<0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g., lumbar spine BMD: β=-0.02g · cm-2 · SD-1 increase in CTX; 95% CI: -0.027, -0.002 g · cm-2 · SD-1; P=0.02, n=283). Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum.This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23.

The inverse association of body adiposity index and bone health in the older adults: A report from a developing country.

The ageing process influences body composition and could be related to bone health. The current study was set out to evaluate the association between body adiposity index (BAI) and bone health in older adults. This is a cross-sectional study performed on 178 elderly persons (51 men and 127 women) with a mean age of 67.04 (range: 60-83) who was referred to the determined 25 health centres in Tehran. The anthropometric measurements were done. Further, serum 25-hydroxy vitamin D (25(OH)D), parathormone (PTH), high-sensitivity C-reactive protein (hs-CRP), osteocalcin and urine C-terminal telopeptide I (CTX-I) were collected. The mean of body mass index (P<.001), body weight (P=.002), body fat (P<.001), waist circumference (P<.001), hip circumference (P<.001), urine CTX-I concentration (P=.011), 25(OH)D (P=.030), was higher in the highest BAI category in comparison with the lowest one. BAI was negatively correlated with urine CTX-I concentration (r=-0.165, P=.028). Moreover, linear regression showed an inverse association between BAI with urine CTX-I (β=-0.165, P=.025) and 25(OH)D (β=-0.039, P=.029). Moreover, the percentage of body fat was positively associated with serum hs-CRP (β=0.026, P=.002). Our study showed a significant inverse association between BAI with urinary CTX-I which shows the effect of obesity on bone health. This study suggests that more clinical and prospective studies for monitoring body fat may have some favourable impacts on bone health.

Changes in levels of cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen in subjects with knee osteoarthritis after dextrose prolotherapy: A randomized controlled trial.

ObjectiveTo assess the effects of dextrose prolotherapy in patients with knee osteoarthritis on the levels of serum cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen, and on the Western Ontario McMaster Universities Index and numerical rating scale score for pain.MethodsA randomized controlled trial, in which participants were randomly allocated into 2 groups, receiving injections of either hyaluronic acid or dextrose prolotherapy. The hyaluronic acid group received 5 injections, 1 each on weeks 1, 2, 3, 4 and 5, and the dextrose prolotherapy group received 3 injections, 1 each on weeks 1, 5 and 9. Serum cartilage oligomeric proteinase, urinary C-terminal telopeptide of type II collagen, Western Ontario McMaster Universities Index score, and numerical rating scale score for pain were measured at baseline and 3 weeks after the last injection. Comparative analysis was conducted using Wilcoxon test within groups and analysis of covariance (ANCOVA) test between groups.ResultsA total of 47 participants (21 allocated to hyaluronic acid, 26 allocated to dextrose prolotherapy) completed the protocol. Both interventions resulted in significant improvements in numerical rating scale scores for pain, total Western Ontario McMaster Universities Index scores, and its subscales score. However, the dextrose prolotherapy outperformed hyaluronic acid in numerical rating scale score for pain and level of urinary C-terminal telopeptide of type II collagen, with score changes differences of 0.93 (p = 0.042) and 0.34 (p = 0.048), respectively. No significant changes in level of serum cartilage oligomeric proteinase were found in either group.ConclusionDextrose prolotherapy is an alternative injection therapy for knee osteoarthritis, which was found to be associated with a significant reduction in urinary C-terminal telopeptide of type II collagen compared with hyaluronic acid injection. Neither injection method resulted in reduced serum cartilage oligomeric proteinase.LAY ABSTRACTKnee osteoarthritis is a common musculoskeletal disorder, which is one of the most frequent causes of disability in elderly people. To improve patients’ quality of life, prolotherapy has been developed as a non-operative treatment option for osteoarthritis. This study compared the effectiveness of dextrose prolotherapy with that of standard therapy using hyaluronic acid injections. Both interventions were effective in terms of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score improvement and numerical rating scale score changes. Cartilage repair was assessed by measuring levels of specific biomarkers of cartilage breakdown: urinary C-terminal telopeptide of type II collagen (uCTX-II) and serum cartilage oligomeric matrix protein (sCOMP). Dextrose prolotherapy was more effective than hyaluronic acid in reducing these biomarkers and decreasing patients’ pain. Dextrose prolotherapy is therefore recommended for use in patients with knee osteoarthritis, since it gives better results, is cost beneficial, and is suitable for use in low-resource settings. Dextrose prolotherapy may help to repair cartilage in knee OA, as it reduces the uCTX-II level.

The correlation between patient reported outcomes and biomarkers for knee osteoarthritis

Background: Novel non-operative treatment modalities, including injections of genetically engineered chondrocytes (GEC), have been developed to target the inflammatory pathways implicated in knee osteoarthritis (OA). Patient reported outcome measures (PROMs) have been the cornerstone of knee OA diagnostics and are frequently used to quantify treatment efficacy but their subjective nature limits their utility. However, inflammatory biomarkers of knee OA provide quantitative data but are less commonly used to assess the severity and progression of OA. Therefore, the purpose of this study was to correlate PROMs with biomarkers in knee OA. Specifically, we compared International Knee Documentation (IKDC) scores with serum C-terminal telopeptide of type I collagen (sCTX-I), urine C-terminal telopeptide of type II collagen (uCTX-II), and joint space width (JSW) in patients receiving GEC injections or placebo injections for knee OA. Methods: A multi-center, double-blinded, randomized, placebo-controlled study was conducted between November 2013 and August 2015. A total of 163 patients were enrolled and randomized to receive GEC injections or placebo injections in a 1:1 ratio of treatment to control. The PROMs assessed were IKDC scores which evaluated three domains: symptoms, sports and daily activity, and difference in knee function. The biomarkers assessed were sCTX-I, uCTX-II, and JSW. Outcomes were measured at baseline as well as at 6, 9, and 12 months after the injections. Scatter plots were created to graphically represent the correlations. Pearson’s correlation coefficients were utilized to determine associations between IKDC scores and each of the three biomarkers. Results: Significant correlations were identified between PROMs and inflammatory biomarkers of knee OA at 6, 9, and 12 months post-treatment with GEC injections. In the GEC cohort, as IKDC scores improved, improvements in sCTX-I levels were also observed. Correlations between IKDC scores and sCTX-I levels were statistically significant at 9 months (r=−0.42, P Conclusions: Newer treatment options for knee OA target the inflammatory pathways that mediate the destruction of bone and cartilage. Inflammatory biomarkers are an objective alternative to assess the severity and progression of OA. This study found significant correlations between an established PROM (IKDC scores) and inflammatory biomarkers in knee OA (sCTX-I, uCTX-II, and JSW). For newer non-operative treatment modalities, such as GEC injections, inflammatory biomarkers of knee OA should be utilized to evaluate the severity and progression of knee OA.

Vertebral fracture assessment (VFA) for monitoring vertebral reshaping in children and adolescents with osteogenesis imperfecta treated with intravenous neridronate.

The study was aimed at monitoring vertebral bodies changes with the use of Vertebral Fracture Assessment (VFA) in children and adolescents affected by osteogenesis imperfecta (OI) during treatment with intravenous neridronate. 60 children and adolescents (35 males and 25 females; age 1-16years) with OI type I, III and IV were included in the study. Intravenous neridronate was administered at the dose of 2mg/kg every 3months in all patients. Lumbar spine (LS) bone mineral density (BMD) and VFA by dual X-ray absorptiometry (DXA) were assessed every 6months up to 24months during treatment. VFA with vertebral morphometry (MXA) was used to calculate the three indices of vertebral deformity: wedging, concavity and crushing. Serum calcium, phosphate, parathyroid hormone (PTH), 25-hydroxy-vitamin D [25(OH)D], total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP) and urinary C-terminal telopeptide of type 1 collagen (CTx) were measured at any time point. Mean LS BMD values significantly increased at 24months compared to baseline (p<0.0001); the corresponding Z-score values were -1.28±1.23 at 24months vs -2.46±1.25 at baseline; corresponding mean Bone Mineral Apparent Density (BMAD) values were 0.335±0.206 vs 0.464±0.216. Mean serum levels of ALP, BALP and CTx significantly decreased from baseline to 24months. By MXA, we observed a significant 19.1% reduction of the mean wedging index of vertebral reshaping at 12months, and 38.4% at 24months (p<0.0001) and of the mean concavity index (16.3% at 12months and 35.9% at 24months; p<0.0001). Vertebral reshaping was achieved for 66/88 (75%) wedge fractures and 59/70 (84%) concave fractures, but there were 4 incident mild fractures. Finally, VF rate was reduced at 24months compared to baseline: 37/710 (5.2%) vs 158/710 (22.2%). Our study demonstrates the utility of VFA as a safe and alternative methodology in the follow-up of children and adolescents with OI.

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.

Can urinary CTX-II be a biomarker for knee osteoarthritis?

BackgroundEarly diagnosis of knee osteoarthritis (OA) remains a diagnostic challenge. Urinary C-terminal cross-linked telopeptide of type II collagen (urinary CTX-II) is one of the potential OA biomarkers. However, conclusive evidence regarding the use of this biomarker as a tool for early diagnosis is still lacking. The purposes of this study were to compare urinary CTX-II levels in patients with knee OA and in healthy controls, to evaluate the correlation between urinary CTX-II levels, radiographic severity of OA, and patient-reported outcomes and to evaluate the effect of age and gender on urinary CTX-II levels in the Asian populations.MethodsTwo groups were studied. The OA group included 78 patients with knee OA aged > 40 years who met the diagnostic criteria for knee OA described by the American College of Rheumatology (ACR). The control group consisted of 51 healthy participants age > 40 years without clinical or radiographic evidence of knee OA. Bilateral knee radiographs were taken and classified according to the Kellgren and Lawrence (KL) grading system. Urinary CTX-II was measured using a competitive ELISA test and Western Ontario and Mcmaster Universities Arthritis Index (WOMAC) was also recorded in all participants.ResultsUrinary CTX-II was significantly higher in the OA group than in the control group (p < 0.001). The severe knee OA group (KL grade 3 and 4) had higher urinary CTX-II levels than mild knee OA group (KL grade 2) but the difference did not reach statistical significance (p = 0.2). There was a moderate correlation between urinary CTX-II levels and KL grades (r = 0.405, p < 0.001) and a weak correlation between urinary CTX-II levels and WOMAC index scores (r = 0.367, p < 0.001). Multiple regression analysis showed that urinary CTX-II was independently associated with KL grades. Whereas age, gender, and WOMAC index had no statistically significant influence on the urinary CTX-II levels.ConclusionsPatients with knee OA had higher urinary CTX-II levels than healthy controls. Moreover, levels of urinary CTX-II were independently correlated with radiographic severity of knee OA. Age, gender, and patient-reported outcomes exerted no effect on the urinary CTX-II levels.Level of evidenceDiagnostic Level III.

O29 Bone turnover in pregnancy, measured by urinary C-terminal telopeptide of type I collagen (CTX), is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the MAVIDOS trial

Background: the pattern of change in maternal bone turnover throughout pregnancy is poorly characterized.Objective: we investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices. Design: the Maternal Vitamin D Osteoporosis Study (MAVIDOS) is a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol vs placebo from 14 weeks’ gestation to birth. Maternal second void urinary α- and β-CTX were measured (Enzyme Linked Immunosorbent Assay, ELISA) at 14 and 34 weeks’ gestation; DXA was performed within 2 weeks post-partum. Mann-Whitney rank sum, Spearman's rank correlation and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes. Results: 372 women had CTX and 25(OH)-vitamin D measured in early and late pregnancy. CTX at 14 and 34 weeks’ gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P Conclusions: maternal urinary CTX, a bone resorption marker, rises through pregnancy, though to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass post-partum.

The correlation between patient reported outcomes and biomarkers for knee osteoarthritis

Background: Novel non-operative treatment modalities, including injections of genetically engineered chondrocytes (GEC), have been developed to target the inflammatory pathways implicated in knee osteoarthritis (OA). Patient reported outcome measures (PROMs) have been the cornerstone of knee OA diagnostics and are frequently used to quantify treatment efficacy but their subjective nature limits their utility. However, inflammatory biomarkers of knee OA provide quantitative data but are less commonly used to assess the severity and progression of OA. Therefore, the purpose of this study was to correlate PROMs with biomarkers in knee OA. Specifically, we compared International Knee Documentation (IKDC) scores with serum C-terminal telopeptide of type I collagen (sCTX-I), urine C-terminal telopeptide of type II collagen (uCTX-II), and joint space width (JSW) in patients receiving GEC injections or placebo injections for knee OA. Methods: A multi-center, double-blinded, randomized, placebo-controlled study was conducted between November 2013 and August 2015. A total of 163 patients were enrolled and randomized to receive GEC injections or placebo injections in a 1:1 ratio of treatment to control. The PROMs assessed were IKDC scores which evaluated three domains: symptoms, sports and daily activity, and difference in knee function. The biomarkers assessed were sCTX-I, uCTX-II, and JSW. Outcomes were measured at baseline as well as at 6, 9, and 12 months after the injections. Scatter plots were created to graphically represent the correlations. Pearson’s correlation coefficients were utilized to determine associations between IKDC scores and each of the three biomarkers. Results: Significant correlations were identified between PROMs and inflammatory biomarkers of knee OA at 6, 9, and 12 months post-treatment with GEC injections. In the GEC cohort, as IKDC scores improved, improvements in sCTX-I levels were also observed. Correlations between IKDC scores and sCTX-I levels were statistically significant at 9 months (r=−0.42, P Conclusions: Newer treatment options for knee OA target the inflammatory pathways that mediate the destruction of bone and cartilage. Inflammatory biomarkers are an objective alternative to assess the severity and progression of OA. This study found significant correlations between an established PROM (IKDC scores) and inflammatory biomarkers in knee OA (sCTX-I, uCTX-II, and JSW). For newer non-operative treatment modalities, such as GEC injections, inflammatory biomarkers of knee OA should be utilized to evaluate the severity and progression of knee OA.

Association between US and MRI scores and correlations with urinary C-terminal telopeptide Type II collagen levels for early detection of hemophilic arthropathy of the knee

Assessment of knee hemophilic arthropathy (HA) requires objective measures. There is no consensus on a preferable ultrasonography (US) scoring system, whereas a reliable scoring system for magnetic resonance imaging (MRI) was developed by the International Prophylaxis Study Group of the World Federation of Hemophilia (IPSG-WFH). In this crosssectional study, a new US scoring system for early detection of knee HA was developed based on 25 peer-reviewed articles published between 1999 and 2015; furthermore, its associations with the MRI scoring system and urinary C-terminal telopeptide type II collagen (CTX-II) levels were investigated. In total, 27 children with severe hemophilia A were recruited. Early HA was confirmed using radiography as Arnold-Hilgartner stages 0–II. Knee MRI and US were scored using the MRI IPSG-WFH and new US scoring systems; urinary CTX-II levels were measured using enzyme-linked immunosorbent assay. Correlations were identified using Spearman test. The US scoring system included joint effusion, synovial hypertrophy and hypervascularization on power Doppler US, hemosiderin deposition, and cartilage damage. The US and MRI scores showed a moderate correlation; the US score and urinary CTX-II levels showed no correlation. The new US score can be used as an alternative to MRI for assessing early-stage kne HA.

Development of IoT-Based Impedometric Biosensor for Point-of-Care Monitoring of Bone Loss

Early detection of disease is essential for an efficient treatment. Bone loss can be detected and monitored by regular measurement of serum or urine C-terminal telopeptide of type 1 collagen (CTx-1). Therefore, rapid, portable, and low-cost point-of-care devices are highly desirable. In this paper, we have reported an Internet of Things (IoT)-based selective, sensitive, quick, and inexpensive device for the quantification of CTx-1 levels in serum. A capacitive interdigital sensor was coated with artificial antibodies, prepared by molecular imprinting technology. Electrochemical impedance spectroscopy was used to evaluate the resistive and capacitive properties of the sample solutions. A microcontroller-based system was developed for the measurement of the level of CTx-1 in serum and for data transmission to an IoT-based cloud server. The data can be provided to the medical practitioner and a detailed investigation can start for early detection and treatment. The developed sensing system responded linearly in a range of 0.1 to 2.5 ppb, which covers the normal reference range of CTx-1 in serum, with a limit of detection of 0.09 ppb. The results demonstrated that the proposed portable biosensing system could provide a rapid, simple, and selective approach for CTx-1 measurement in serum. Sheep serum samples were tested using the proposed system and the validation of the results was done using an enzyme-linked immunosorbent assay kit.

The Effects of Well-Rounded Exercise Program on Systemic Biomarkers Related to Cartilage Metabolism.

Nonsurgical treatment such as exercise is the preferred method for management of knee osteoarthritis (OA). A combination of aerobic, muscle strengthening, and flexibility exercises is recommended for older adults. However, effects of the exercise intervention on cartilage metabolism remain unclear. This study used biomarkers to investigate the effects of well-rounded exercise program on cartilage metabolism in 42 women (mean age: 59 years). Participants started a weekly supervised exercise program and continued for 12 weeks. Before and after the program, we measured physical performance on the Timed Up-and-Go Test, 3-Minute Walk Test, and 30-Second Chair Stand Test. We collected serum and urine samples at the start of the program until 24 weeks and measured the concentrations of 4 biomarkers related to type II collagen metabolism: serum cartilage type II procollagen carboxy propeptide (sPIICP), urine C-terminal telopeptide of collagen type II (uCTX-II), urine cleavage of type II collagen by collagenases (uC2C), and serum cartilage oligomeric matrix protein (sCOMP). Participants were divided into pre-OA and OA groups based on X-ray findings. The pre-OA group showed significant increases and decreases in sPIICP and uCTX-II concentrations with improved physical performance, respectively. sCOMP concentrations significantly increased in both groups. The exercise also improved physical performance with no detrimental effect on type II collagen metabolism in the OA group. Thus, well-rounded exercise may not only improve physical capacity but also have beneficial effects on type II collagen metabolism, especially in people without radiological OA.

Fibulin-3 and other cartilage metabolism biomarkers in relationship to calprotectin (MRP8/14) and disease activity in rheumatoid arthritis patients treated with anti-TNF therapy.

Fibulin-3 (Fib-3) is a new potential biomarker of articular cartilage metabolism. The aim of the study was to evaluate the effect of anti-TNF therapy on serum fibulin-3, cartilage oligomeric matrix protein (COMP), procollagen II C-propeptide (PIICP), and urinary C-terminal telopeptide of type II collagen (CTX-II) levels in relation to calprotectin (MRP8/14) and disease activity in rheumatoid arthritis patients. In the study, 35 female patients with rheumatoid arthritis (RA) were investigated. The concentration of fibulin-3, COMP, PIICP, MRP8/14, and urinary CTX-II in serum was measured before and after anti-TNF therapy. Ten healthy women were investigated as the controls. The concentration of fibulin-3 in RA patients before treatment did not differ significantly from the concentration of fibulin-3 in the control group. A significantly higher concentration of fibulin-3 was noted prior to treatment in the group of women with a worse response to the therapy (non-responders) compared to the concentration of fibulin-3 in the healthy women. During the anti-TNF therapy, the serum fibulin-3 level decreased in patients. The fibulin-3 level correlated with CRP and ESR after anti-TNF treatment. Significant lowering of MRP8/14 was noted in the patients after anti-TNF therapy. No correlation between fibulin-3 and MRP8/14 was observed in the study group or in the control group. During the anti-TNF therapy, the serum fibulin-3 level decreased in RA patients. Serum MRP8/14 concentration also decreased. No correlation between fibulin-3 and MRP8/14 was observed in the study group before and after the treatment. We found a poor correlation between serum fibulin-3 and other cartilage metabolism biomarkers after anti-TNF therapy.

Development of a prediction model for future risk of radiographic hip osteoarthritis

To develop and validate a prognostic model for incident radiologic hip osteoarthritis (HOA) and determine the value of previously identified predictive factors. We first validated previously reported predictive factors for HOA by performing univariate and multivariate analyses for all predictors in three large prospective cohorts (total sample size of 4548 with 653 incident cases). The prognostic model was developed in 2327 individuals followed for 10 years from the Rotterdam Study-I (RS-I) cohort. External validation of the model was tested on discrimination in two other cohorts: RS-II (n=1435) and the Cohort Hip and Cohort Knee (CHECK) study (n=786). From the total number of 28 previously reported predictive factors, we were able to replicate 13 factors, while 15 factors were not significantly predictive in a meta-analysis of the three cohorts. The basic model including the demographic, questionnaire, and clinical examination variables (area under the receiver-operating characteristic curve (AUC)=0.67) or genetic markers (AUC=0.55) or urinary C-terminal cross-linked telopeptide of type II collagen (uCTX-II) levels (AUC=0.67) alone were poor predictors of HOA in all cohorts. Imaging factors showed the highest predictive value for the development of HOA (AUC=0.74). Addition of imaging variables to the basic model led to substantial improvement in the discriminative ability of the model (AUC=0.78) compared with uCTX-II (AUC=0.74) or genetic markers (AUC=0.68). Applying external validation, similar results were observed in the RS-II and the CHECK cohort. The developed prediction model included demographic, a limited number of questionnaire, and imaging risk factors seems promising for prediction of HOA.

Effect of colchicine treatment on primary knee osteoarthritic patients

Background and Aim: It was hypothesized that cartilage degradation in osteoarthritis (OA) facilitates monosodium urate crystals nucleation which by its turn contribute to progression of OA. The aim of the current study is to assess the efficacy of oral colchicine treatment in patients having primary Knee OA (KOA). Patients and Methods: This clinical trial included 40 patients with KOA. After baseline evaluation, patients received oral colchicine 0.5 mg twice daily for 16-weeks period. The outcome measures (knee pain and WOMAC scale) and human urinary C-terminal telopeptide of type II collagen (uCTX-II) were evaluated at inclusion and at the end of study. Results: Colchicine had significantly improved frequency of knee effusion (from 62.5% to 40.0%, p=0.044), tenderness score (from 1.9 ± 0.8 to 1.3 ± 0.6, p<0.001), VAS-pain score (from 60.2 ± 11.7 to 48.6 ± 11.5, p<0.001) and the total WOMAC score (from 48.2 ± 6.4 to 42.8 ± 9.2, p=0.003). The uCTX-II was reduced from 447.4 ± 63.4 ng/mmol at baseline evaluation to 428.9 ± 106.7 ng/mmol at the end of treatment but this difference was not significant. Only one patient complained of gastrointestinal side effect in the form of diarrhea. Conclusion: Colchicine appears to be an effective and safe option treatment in primary KOA. Colchicine reduced pain and stiffness and improves functionality with good safety profile

Meta-analysis of urinary C-terminal telopeptide of type II collagen as a biomarker in osteoarthritis diagnosis

SummaryObjectiveThis study aims to discover that the urinary C-terminal telopeptide of type II collagen (uCTX-II) levels differ between osteoarthritis (OA) patients and healthy individuals (controls). According to this difference, we may conclude that uCTX-II can be a biomarker for OA diagnosis.MethodsWe searched MEDLINE and EMBASE databases updated to 2014 to find literature on OA biomarkers. We retrieved the publications that met the required criterion. Literature quality was assessed according to the Newcastle–Ottawa Scale. Publication bias was assessed by Begg's test and Egger's test with the software STATA version 12.0. The weighted mean difference (WMD) was calculated, and the subgroup analysis was completed using STATA 12.0.ResultsSix publications were included in our analysis. The WMD for OA patients versus the controls was 83.05, which was within the 95% confidence interval. For subgroup analysis, the WMD of patients with severe OA was 119.92, whereas that of patients with mild OA was 28.07.ConclusionsuCTX-II levels were higher in OA patients than in controls, subgroup analysis revealed that the uCTX-II levels rised with the OA severity, the heterogeneity originated from different levels of OA severity, These results showed that uCTX-II would be a promising clinical biomarker in OA diagnosis.