Biomarkers Of Cartilage Degradation Research Articles

Association of Serum Biochemical Biomarker Profiles of Joint Tissue Inflammation and Cartilage Metabolism With Posttraumatic Osteoarthritis-Related Symptoms at 12 Months After ACLR

Background: Anterior cruciate ligament injury and anterior cruciate ligament reconstruction (ACLR) are risk factors for symptomatic posttraumatic osteoarthritis (PTOA). After ACLR, individuals demonstrate altered joint tissue metabolism indicative of increased inflammation and cartilage breakdown. Serum biomarker changes have been associated with tibiofemoral cartilage composition indicative of worse knee joint health but not with PTOA-related symptoms. Purpose/Hypothesis: The purpose of this study was to determine associations between changes in serum biomarker profiles from the preoperative sample collection to 6 months after ACLR and clinically relevant knee PTOA symptoms at 12 months after ACLR. It was hypothesized that increases in biomarkers of inflammation, cartilage metabolism, and cartilage degradation would be associated with clinically relevant PTOA symptoms after ACLR. Study Design: Case-control study; Level of evidence, 3. Methods: Individuals undergoing primary ACLR were included (N = 30). Serum samples collected preoperatively and 6 months after ACLR were processed to measure markers indicative of changes in inflammation (ie, monocyte chemoattract protein 1 [MCP-1]) and cartilage breakdown (ie, cartilage oligomeric matrix protein [COMP], matrix metalloproteinase 3, ratio of type II collagen breakdown to type II collagen synthesis). Knee injury and Osteoarthritis Outcome Score surveys were completed at 12 months after ACLR and used to identify participants with and without clinically relevant PTOA-related symptoms. K-means cluster analyses were used to determine serum biomarker profiles. One-way analyses of variance and logistic regressions were used to assess differences in Knee injury and Osteoarthritis Outcome Score subscale scores and clinically relevant PTOA-related symptoms between biomarker profiles. Results: Two profiles were identified and characterized based on decreases (profile 1: 67% female; age, 21.4 ± 5.1 years; body mass index, 24.4 ± 2.4) and increases (profile 2: 33% female; age, 21.3 ± 3.2 years; body mass index, 23.4 ± 2.6) in sMCP-1 and sCOMP preoperatively to 6 months after ACLR. Participants with profile 2 did not demonstrate differences in knee pain, symptoms, activities of daily living, sports function, or quality of life at 12 months after ACLR compared to those with profile 1 (P = .56-.81; η2 = 0.002-0.012). No statistically significant associations were noted between biomarker profiles and clinically relevant PTOA-related symptoms (odds ratio, 1.30; 95% CI, 0.23-6.33). Conclusion: Serum biomarker changes in MCP-1 and sCOMP within the first 6 months after ACLR were not associated with clinically relevant PTOA-related symptoms.

S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation.

Osteoarthritis (OA) is a chronic degenerative disease leading to articular cartilage destruction. Menopausal and postmenopausal women are susceptible to both OA and osteoporosis. S-equol, a soy isoflavone-derived molecule, is known to reduce osteoporosis in estrogen-deficient mice, but its role in OA remains unknown. This study aimed to explore the effect of S-equol on different degrees of menopausal OA in female Sprague-Dawley (SD) rats induced by estrogen deficiency caused by bilateral ovariectomy (OVX) combined with intra-articular injection of mono-iodoacetate (MIA). Knee joint histopathological change; serum biomarkers of bone turnover, including N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX-I) and N-terminal telopeptide of type I collagen (NTX-I); the cartilage degradation biomarkers hyaluronic acid (HA) and N-terminal propeptide of type II procollagen (PIINP); and the matrix-degrading enzymes matrix metalloproteinases (MMP)-1, MMP-3 and MMP-13, as well as the oxidative stress-inducing molecules nitric oxide (NO) and hydrogen peroxide (H2O2), were assessed for evaluation of OA progression after S-equol supplementation for 8 weeks. The results showed that OVX without or with MIA injection induced various severity levels of menopausal OA by increasing pathological damage, oxidative stress, and cartilage matrix degradation to various degrees. Moreover, S-equol supplementation could significantly reduce these increased biomarkers in different severity levels of OA. This indicates that S-equol can lessen menopausal OA progression by reducing oxidative stress and the matrix-degrading enzymes involved in cartilage degradation.

Open-label, single-center, clinical study evaluating the safety, tolerability and clinical effects of pentosan polysulfate sodium in subjects with mucopolysaccharidosis I.

Lysosomal enzyme deficiency in mucopolysaccharidosis (MPS) I results in glycosaminoglycan (GAG) accumulation leading to pain and limited physical function. Disease-modifying treatments for MPS I, enzyme replacement, and hematopoietic stem cell therapy (HSCT), do not completely resolve MPS I symptoms, particularly skeletal manifestations. The GAG reduction, anti-inflammatory, analgesic, and tissue remodeling properties of pentosan polysulfate sodium (PPS) may provide disease-modifying treatment for musculoskeletal symptoms and joint inflammation in MPS I following ERT and/or HSCT. The safety and efficacy of PPS were evaluated in four subjects with MPS I aged 14-19 years, previously treated with ERT and/or HSCT. Subjects received doses of 0.75 mg/kg or 1.5 mg/kg PPS via subcutaneous injections weekly for 12 weeks, then every 2 weeks for up to 72 weeks. PPS was well tolerated at both doses with no serious adverse events. MPS I GAG fragment (UA-HNAc [1S]) levels decreased at 73 weeks. Cartilage degradation biomarkers serum C-telopeptide of crosslinked collagen (CTX) type I (CTX-I) and type II (CTX-II) and urine CTX-II decreased in all subjects through 73 weeks. PROMIS scores for pain interference, pain behavior, and fatigue decreased in all subjects through 73 weeks. Physical function, measured by walking distance and dominant hand function, improved at 49 and 73 weeks. Decreased GAG fragments and cartilage degradation biomarkers, and positive PROMIS outcomes support continued study of PPS as a potential disease-modifying treatment for MPS I with improved pain and function outcomes.

Increased Effusion Synovitis for Those With a Dysregulated Inflammatory Response After an Anterior Cruciate Ligament Injury.

Introduction The progression to posttraumatic osteoarthritis (PTOA) after an anterior cruciate ligament (ACL) injury is likely multifactorial, involving biological, mechanical, and psychosocial factors. Following acute joint trauma, there appears to be a subset of patients that demonstrate a dysregulated inflammatory response. This pro-inflammatory phenotype, or "Inflamma-type," is characterized by an amplified pro-inflammatory response combined with a lack of attendant anti-inflammatory responseand has been observed following both an ACL injury and an intra-articular fracture. The aims of this study were to: 1) compare magnetic resonance imaging (MRI)-measured effusion synovitis between those with vs. without a dysregulated inflammatory response, and 2) assess the correlations between effusion synovitis and synovial fluid concentrations of proinflammatory cytokines, degradative enzymes, and synovial fluid biomarkers of cartilage degradation. Methods A cluster analysis was previously performed with synovial fluid concentrations of biomarkers of inflammation and cartilage degradation from 35 patients with acute ACL injuries. Patients were then categorized into two groups: a pro-inflammatory phenotype ("Inflamma-type") and those with a more normal inflammatory response to injury (NORM). Effusion synovitis measured from each patient's preoperative clinical MRI scan was compared between the Inflamma-type and NORM groups using an independent, two-tailed t-test. In addition, Spearman's rho non-parametric correlations were calculated to evaluate the relationship between effusion synovitis and each of the synovial fluid concentrations of pro-inflammatory cytokines, degradative enzymes, and biomarkers of cartilage degradation and bony remodeling. Results Effusion synovitis was significantly greater for the Inflamma-type (10.9±3.8 mm) than the NORM group (7.4±4.4 mm, p=0.04, Cohen's d=0.82). Effusion synovitis significantly correlated with matrix metalloproteinase-3 (rho=0.63, p<0.001), matrix metalloproteinase-1 (rho=0.50, p=0.003), and sulfated glycosaminoglycan (rho=0.42, p=0.01). No other significant correlations were present. Conclusion Effusion synovitis was significantly greater for those that demonstrated a dysregulated inflammatory response after acute ACL injury than those with a more normal response to injury. Effusion synovitis was also found to significantly correlate with synovial fluid concentrations of degradative enzymes and a biomarker of early cartilage degradation. Future work is needed to determine if non-invasive methods, such as MRI or ultrasound, may accurately identify patients within this pro-inflammatory phenotypeand whether this subset is more prone to more rapid PTOA changes after injury.

Serial intraarticular injections of growth factor concentrate in knee osteoarthritis: A placebo controlled randomized study

ObjectiveTo evaluate and compare clinical efficacy and effect on specific serum biomarker with serial injections of growth factor concentrate (GFC) for knee osteoarthritis (KOA) in a randomized triple blinded placebo controlled interventional study. MethodsFinal assessment was done on 58 patients. Patients with Kellgren-Lawrence grade II, III knee osteoarthritis were administered monthly intraarticular injections(3 injections) of GFC(n = 31) or saline(n = 27) and evaluated clinically with visual analogue scale(VAS) and Western Ontario and McMaster Universities Arthritis Index(WOMAC) at 3,6 and 12 months post therapy. Biochemical analysis was done with serum biomarker of cartilage degeneration, Collagen 2-1 (Coll2-1), estimated at baseline and at final follow up. ResultsBoth the groups exhibited statistically significant improvements (P < 0.05) in VAS at 3,6 and 12 months. WOMAC improvement reached statistical significance for GFC group at every evaluation (P < 0.001) but only at 12 months in NS group (P = 0.029). The improvements were clinically meaningful only in GFC group throughout follow up (Minimal clinically important differences >12% of baseline in WOMAC and >2 cm difference in mean for VAS). Intergroup comparison revealed GFC to be much better for both scores at every evaluation (95% CI of 0.2–1.5,[P = 0.008], 1.4–2.9,[P < 0.0001], and 2.7–4.2,[P < 0.0001] for VAS, 7.3–16.0 [P < 0.001], 11.6–21.9 [P < 0.001] and 18.1–31.1[P < 0.001] for WOMAC). Statistically significant decrease in serum Coll2-1 levels were observed for GFC group only. No serious complications were seen. ConclusionSerial(three) monthly GFC injections result in clinically meaningful improvement of subjective pain and function outcome scores, sustaining up to 12 months in KOA grade II and III. GFC also lead to significant reduction in serum levels of cartilage degradation biomarker coll2-1.

Effectiveness of a Cucumber Extract Supplement on Articular Pain in Patients with Knee Osteoarthritis: A Randomized Double-Blind Controlled Clinical Trial

This 8-week randomized double-blind placebo-controlled study aimed to assess the effectiveness of supplementation with an extract of Cucumis sativus L. (20 mg/day) on pain and other variables in patients with knee osteoarthritis (OA) over 40 years. The change in pain intensity using a 1–10 cm visual analog scale (VAS) was the primary endpoint. Fifty-five patients (mean age 50.6 ± 8.6 years) were included (experimental group, n = 29; placebo, n = 26). VAS scores for pain decreased significantly in both study groups, but decreases were higher in the experimental group (between-group p = 0.013). Improvements in pain, stiffness, and physical function according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were also significantly higher in the experimental group. The Timed Up and Go test result also decreased significantly in the experimental group. An improvement in muscle function was associated with significant increases in isokinetic and isometric dynamometry variables, particularly for isometric 60°·s−1 and 180°·s−1 knee flexion exercises in the experimental group. Plasma levels of interleukin-1-beta (IL-1β) and matrix metalloproteinase-3 (MMP-3) also decreased significantly in the experimental group. Based on the beneficial effects of cucumber on symptomatology and inflammatory and cartilage degradation biomarkers in knee OA, cucumber extract supplementation may a useful natural approach to maintain healthy joints.

Periostin regulation and cartilage degradation early after anterior cruciate ligament reconstruction.

The purpose of this study was to explore pathological processes during the first 4weeks after anterior cruciate ligament reconstruction (ACLR). Sixteen ACL-injured patients (8 females/8 males, mean age = 19.1, mean BMI = 28.6). Arthrocentesis wasperformed 1 and 4weeks after ACLR. Proteins in the synovial fluid were identified using nanoLC-ESI-MS/MS. Differentially up- or down-regulated proteins were identified and quantified, and a pathway analysis was performed. All identified proteins were mapped into a protein-protein interaction (PPI) network, and networks of PPIs with a combined score > 0.9 were then visualized. Seven pathways were upregulated after ACLR:PI3K-AKT signaling pathway, extracellular matrix (ECM)-receptor interaction, focal adhesion, protein digestion and absorption, ameobiasis, and platelet activation. Network analyses identified 8 proteins that were differentially upregulated with strong PPI interactions (periostin and 7 collagen-related proteins). Increases in periostin moderately correlated with increases in a synovial fluid biomarker of type II cartilage degradation (ρ = 0.51, p = 0.06). Pro-inflammatory pathways and periostin were upregulated after ACLR. Periostin demonstrated strong network connections with markers of collagen breakdown, and future work is needed to determine whether periostin may offer a biomarker of early cartilage degradation after ACLR and/or play an active role in early post-traumatic osteoarthritis (PTOA) progression.

The alarmins high mobility group box protein 1 and S100A8/A9 display different inflammatory profiles after acute knee injury

To compare the concentrations of high mobility group box 1 protein (HMGB1) and S100A8/A9 in synovial fluid between patients with knee injuries and osteoarthritis (OA), and knee healthy subjects. To investigate associations of alarmin levels with different joint injuries and with biomarkers of inflammation, Wnt signaling, complement system, bone and cartilage degradation. HMGB1 and S100A8/A9 were measured in synovial fluid by immunoassays in patients with knee injuries, with OA and from knee healthy subjects, and were related to time from injury and with biomarkers obtained from previous studies. Hierarchical cluster and enrichment analyses of biomarkers associated to HMGB1 and S100A8/A9 were performed. The synovial fluid HMGB1 and S100A8/A9 concentrations were increased early after knee injury; S100A8/A9 levels were negatively associated to time after injury and was lower in the old compared to recent injury group, while HMGB1 was not associated to time after injury. The S100A8/A9 levels were also increased in OA. The initial inflammatory response was similar between the alarmins, and HMGB1 and S100A8/A9 shared 9 out of 20 enriched pathways. The alarmins displayed distinct response profiles, HMGB1 being associated to cartilage biomarkers while S100A8/A9 was associated to proinflammatory cytokines. HMGB1 and S100A8/A9 are increased as an immediate response to knee trauma. While they share many features in inflammatory and immunoregulatory mechanisms, S100A8/A9 and HMGB1 are associated to different downstream responses, which may have impact on the OA progression after acute knee injuries.

Biological Effects of High Tibial Osteotomy on Spontaneous Osteonecrosis of the Knee.

ObjectiveThe purpose of this study was to evaluate the postoperative status of spontaneous osteonecrosis of the knee (SONK) after high tibial osteotomy (HTO) with concomitant bone marrow stimulation (BMS) using synovial fluid (SF) biomarkers.DesignTwenty patients with SONK who underwent opening wedge HTO were enrolled. Paired SF samples from the affected knee were collected at the time of HTO surgery and at the time of plate removal. SF concentrations of interleukin (IL)-6, IL-8, and matrix metalloproteinase (MMP)-13 were measured by enzyme-linked immunosorbent assays. The Knee Society Score (KSS) and hip-knee-ankle (HKA) angle were assessed before and 2 years after HTO.ResultsThe KSS knee and function scores were significantly improved after HTO (mean changes of 33.8 and 29.4, respectively). The mean HKA angle was changed from mechanical varus (−8.6°) to valgus (5.2°). Concentrations of IL-6, IL-8, and MMP-13 were significantly decreased after HTO (mean changes of −73.7%, −32.4%, and −47.9% from preoperative baseline, respectively). Significant correlations were found between lesion size and concentrations of biomarkers, except for preoperative MMP-13.ConclusionsSF levels of biomarkers of inflammation and cartilage degradation were reduced after HTO with a concomitant BMS procedure, suggesting a biological improvement in SONK.

Effect of moderate forced physical activity on behaviour, lameness and osteochondrosis in growing pigs from two divergent lines selected for feed efficiency

In pig farming, physical constraints and genetic selection for high production are risk factors for the development of leg disorders, such as degraded locomotor activity. Interactions between both factors need to be explored. The study was carried out on two replicates of 80 pure-bred Large White growing-finishing pigs from the 8th generation of two divergent lines selected for low and high residual feed intake (LRFI, HRFI). Each replicate included 40 LRFI pigs and 40 HRFI pigs, housed on partly slatted flooring in a room equipped with a sorter allowing access to electronic self-feeders during two replicates. Ear tags determined the side of the room to which the pigs were oriented after the sorter exit and the distance back to the sorter (short: spontaneous activity, long: forced activity (FA)). Lameness was assessed individually weekly using visual gait scoring. At slaughter (weight of 100 kg), postmortem quantification of osteochondrosis (OC) lesions was performed on both the proximal and distal extremities of the humerus and femur. Low RFI pigs showed a lower feed conversion ratio (P < 0.001). They also showed lower individual numbers of sorter crossings per day and a lower proportion of standing pigs, which confirmed their lower physical activity. Forced activity clearly increased the number of sorter crossings/d/pig (P < 0.001), and the magnitude of the effect of FA was clearly lower in LRFI pigs than in HRFI pigs. The occurrence of gait was low (less than 9% of recorded scores). The proportion of scores classified as stiffness was higher for LRFI pigs than in HRFI pigs (P < 0.0001). The average lameness score was also higher for LRFI pigs and lower with FA (P < 0.05). The pigs of the LRFI line showed higher OC scores on both the proximal humerus and femur (P < 0.001) and lower OC scores on the distal humerus with surface evaluation (P < 0.05). The carcasses of LRFI pigs were heavier with a higher lean meat percentage (P < 0.001). Most OC scores were unaffected by FA. Only the OC scores of the distal femur (slice method) were higher with increased activity in LRFI pigs, whereas they were lower in HRFI pigs (P < 0.05). Seric biomarkers of cartilage synthesis and degradation were higher for pigs from the LRFI line, but no correlation could be observed between individual OC scores and cartilage biomarker contents.

MOntelukast as a potential CHondroprotective treatment following Anterior cruciate ligament reconstruction (MOCHA Trial): study protocol for a double-blind, randomized, placebo-controlled clinical trial

BackgroundAfter anterior cruciate ligament (ACL) reconstruction, patient-reported outcomes are improved 10 years post-surgery; however, cytokine concentrations remain elevated years after surgery with over 80% of those with combined ACL and meniscus injuries having posttraumatic osteoarthritis (PTOA) within 10–15 years. The purpose of this multicenter, randomized, placebo-controlled trial is to assess whether a 6-month course of oral montelukast after ACL reconstruction reduces systemic markers of inflammation and biochemical and imaging biomarkers of cartilage degradation.MethodsWe will enroll 30 individuals undergoing primary ACL reconstruction to participate in this IRB-approved multicenter clinical trial. This trial will target those at greatest risk of a more rapid PTOA onset (age range 25–50 with concomitant meniscus injury). Patients will be randomly assigned to a group instructed to take 10 mg of montelukast daily for 6 months following ACL reconstruction or placebo. Patients will be assessed prior to surgery and 1, 6, and 12 months following surgery. To determine if montelukast alters systemic inflammation following surgery, we will compare systemic concentrations of prostaglandin E2, monocyte chemoattractant protein-1, and pro-inflammatory cytokines between groups. We will also compare degradative changes on magnetic resonance imaging (MRI) collected 1 and 12 months following surgery between groups with reductions in early biomarkers of cartilage degradation assessed with urinary biomarkers of type II collagen breakdown and bony remodeling.DiscussionThere is a complex interplay between the pro-inflammatory intra-articular environment, underlying bone remodeling, and progressive cartilage degradation. PTOA affects multiple tissues and appears to be more similar to rheumatoid arthritis than osteoarthritis with respect to inflammation. There is currently no treatment to delay or prevent PTOA after ACL injury. Since there is a larger and more persistent inflammatory response after ACL reconstruction than the initial insult of injury, treatment may need to be initiated after surgery, sustained over a period of time, and target multiple mechanisms in order to successfully alter the disease process. This study will assess whether a 6-month postoperative course of oral montelukast affects multiple PTOA mechanisms. Because montelukast administration can be safely sustained for long durations and offers a low-cost treatment option, should it be proven effective in the current trial, these results can be immediately incorporated into clinical practice.Trial registrationClinicalTrials.govNCT04572256. Registered on October 1, 2020.

Cartilage Degradation Biomarkers are Elevated in Younger Adults with Patellofemoral Pain Syndrome

Cartilage Degradation Biomarkers are Elevated in Younger Adults with Patellofemoral Pain Syndrome

Prophylactic Treatment with Rurioctocog Alfa Pegol Results in a Dose-Dependent Normalization of Biomarkers of Joint Health in Severe Hemophilia a: An Exploratory Analysis from the Propel Study

Prophylactic Treatment with Rurioctocog Alfa Pegol Results in a Dose-Dependent Normalization of Biomarkers of Joint Health in Severe Hemophilia a: An Exploratory Analysis from the Propel Study

The Efficacy and Safety of Multiple Dose Regimens of Kudzu (Pueraria lobata) Root Extract on Bone and Cartilage Turnover and Menopausal Symptoms.

Background: Menopause is associated with detrimental changes in turnover of bone and cartilage and a variety of symptoms with negative impact on the quality of life. Naturally occurring isoflavones from Radix Pueraria lobata, Kudzu root, may possess chondroprotective and symptom-relieving properties, but efficacy and safety of dosing and dose frequencies required for pharmacological action is unclear. Purpose: This clinical trial evaluates the efficacy on bone and cartilage turnover, menopausal symptoms, and safety of five dose regimens of Kudzu root extract administered either once, twice or three times daily in women with at least mild menopausal symptoms. Materials and Methods: Fifty postmenopausal women were randomized equally into five different dose regimen groups of Kudzu root extract in a four-week, parallel group, open-label, single-center, exploratory study design. Biomarkers CTX-I and CTX-II reflecting bone and cartilage degradation, respectively, were assessed in blood samples and 24-h urine samples. Change from baseline in the Menopause Rating Scale (MRS) and subscales was evaluated. Safety endpoints were frequency of adverse events, changes in hematology and safety chemistry data, vital signs and electrocardiogram. Results: Fifty women (Age 54.2 years, SD: 2.9) were randomized. After 4 weeks of treatment, biomarkers of bone resorption and cartilage degradation were statistically significantly reduced from baseline levels in the group receiving two capsules three times a day, serum/urine CTX-I (−18.4%, 95% CI: −8.1 to −27.5, p = 0.001/−34.2%, 95% CI: −21.6 to −44.7, p < 0.0001), urine CTX-II (−17.4% 95% CI: −2.5 to −30.0, p = 0.02). The observed effects were consistent across study groups but appeared to favour three times daily dosing. Four weeks of treatment led to statistically significant reductions in the MRS Total Score (p < 0.0001–0.03) in four out of five treatment groups. Kudzu root extract was well tolerated in all dose regimens, and no serious adverse events were reported. Conclusion: The results indicate that Kudzu extract may possess beneficial effects on bone and cartilage health and may be a promising natural alternative to existing treatments for menopausal symptoms. Kudzu root extract was well tolerated for short-term treatment of mild to severe menopausal symptoms in women in all tested doses and dose frequencies.

Biomarkers in axial spondyloarthritis and low back pain: a comprehensive review.

The spectrum of axial spondyloarthritis (AxSpA) (including both non-radiographic and radiographic AxSpA), also known as ankylosing spondylitis AS, has achieved growing recognition. With the development of treatments not only effective in controlling disease activity but also in slowing radiographic progression, and given the cost and risk profiles of these novel treatments and the limitations of current clinical criteria, imaging and peripheral blood biomarkers (C-reactive protein, HLA-B27 testing), the need for better biomarkers has never been greater. The purpose of this review is to present up-to-date information on the biomarkers for the diagnosis for assessing disease diagnosis, activity, treatment response, and radiographic progression of AxSpA, and entails multiple search strings used to identify articles of interest published in PubMed and the Cochrane database up to May 1, 2021. We present the current status of research in serologic biomarkers such as cytokines, adipokines, matrix metalloproteinases, calprotectin, CD74, antibodies, bone turnover markers, and circulating protein fragments of cartilage and connective tissue degradation and other biomarkers. Despite a great deal of work, most serologicresults have been disappointing and to date none perform better than CRP. Recent promising preliminary data for some has been published, but require further confirmation. Transcriptomic biomarkers such as micro-RNAs and genetic biomarkers also show promise to assist in diagnosis and possibly for radiographic severity, including a recently developed panel of genetic risk markers used in a polygenic risk score instrument in AS diagnosis. These need further confirmation and application in AS as well as in nr-AxSpA.

Effects of photobiomodulation and a physical exercise program on the expression of inflammatory and cartilage degradation biomarkers and functional capacity in women with knee osteoarthritis: a randomized blinded study

BackgroundThe knee osteoarthritis (OA) is a joint disease characterized by degradation of articular cartilage that leads to chronic inflammation. Exercise programs and photobiomodulation (PBM) are capable of modulating the inflammatory process of minimizing functional disability related to knee OA. However, their association on the concentration of biomarkers related to OA development has not been studied yet. The aim of the present study is to investigate the effects of PBM (via cluster) with a physical exercise program in functional capacity, serum inflammatory and cartilage degradation biomarkers in patients with knee OA.MethodsForty-two patients were randomly allocated in 3 groups: ESP: exercise + sham PBM; EAP: exercise + PBM and CG: control group. Six patients were excluded before finished the experimental period. The analyzed outcomes in baseline and 8-week were: the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and the evaluation of serum biomarkers concentration (IL-1β, IL-6, IL-8, IL-10 e TNF-α, and CTX-II).ResultsAn increase in the functional capacity was observed in the WOMAC total score for both treated groups (p < 0.001) and ESP presents a lower value compared to CG (p < 0.05) the 8-week post-treatment. In addition, there was a significant increase in IL-10 concentration of EAP (p < 0.05) and higher value compared to CG (p < 0.001) the 8-week post-treatment. Moreover, an increase in IL-1β concentration was observed for CG (p < 0.05). No other difference was observed comparing the other groups.ConclusionOur data suggest that the physical exercise therapy could be a strategy for increasing functional capacity and in association with PBM for increasing IL-10 levels in OA knee individuals.Trial registration: ReBEC (RBR-7t6nzr).

The effect of choline-stabilized orthosilicic acid in patients with peri-implantitis: an exploratory randomized, double-blind, placebo controlled study

BackgroundCholine-stabilized orthosilicic acid (CS-OSA) was previously found to stimulate bone collagen formation in osteopenia and to improve biomarkers of cartilage degradation in knee osteoarthritis. The aim of the present study was to investigate the effect of oral administration of CS-OSA on clinical symptoms of peri-implantitis and the associated bone loss.MethodsTwenty-one patients with peri-implantitis were randomized in CS-OSA or placebo groups. After initial clinical and cone beam computed tomography (CBCT) measurements [probing pocket depth (PPD), bleeding on probing (BOP), mucosal recession (REC), distance from implant shoulder to alveolar crest (IS-AC) and distance from implant shoulder to first bone-to-implant contact (IS-BIC)], flap operations were performed at the peri-implantitis sites. All patients were instructed to use either placebo or CS-OSA capsules twice a day for 1 year. Measurements were repeated 6 and 12 months after randomization.ResultsThe data of 18 patients (36 implants) were used in the per protocol analysis. PPD and BOP improved significantly (p < 0.05) compared to baseline for both groups after 6 and 12 months. However, REC significantly increased in the placebo group but not in the CS-OSA group. The change in REC over 6 and 12 months was significantly different between groups (p < 0.01). IS-BIC and IS-AC measurements remained stable in the CS-OSA group whereas in the placebo group, both parameters increased significantly after 6 and 12 months. The change in IS-BIC over 12 months was significantly different between groups (p < 0.05).ConclusionThe results of this preliminary study suggest that CS-OSA may stabilize and even prevent further bone loss after surgical peri-implantitis treatment and support mucosal tissue healing.Trial registrationThe trial was retrospectively registered at ISRCTN registry, registration number: ISRCTN14348802, registration date: 24/06/2020.

A serological type II collagen neoepitope biomarker reflects cartilage breakdown in patients with osteoarthritis

ObjectivesThere is an unmet medical need for biomarkers in OA which can be applied in clinical drug development trials. The present study describes the development of a specific and robust assay measuring type II collagen degradation (T2CM) and discusses its potential as a noninvasive translational biomarker. MethodsA type II collagen specific neoepitope (T2CM) was identified by mass spectrometry and monoclonal antibodies were raised towards the epitope, employed in a chemiluminescence immunoassay. T2CM was assessed in bovine cartilage explants with or without MMP-13 inhibitor, and explant supernatants were analyzed by Western blot. T2CM was measured in plasma samples from one study (n ​= ​48 patients) where OA patients were referred to total knee replacement (TKR). Additionally, T2CM was quantified in serum from OA patients receiving salmon calcitonin treatment (sCT) (n ​= ​50) compared to placebo (n ​= ​57). ResultsThe T2CM assay was technically robust (13/4 ​% inter/intra-variation) and specific for the type II collagen fragment cleaved by MMP-1 and -13. The MMP-13 inhibitor reduced the T2CM release from bovine cartilage explants receiving catabolic treatment. These results were confirmed by Western blot. In human end-stage OA patients (scheduled for TKR), the T2CM levels were elevated compared to moderate OA (p<0.004). The OA patients receiving sCT had lower levels of T2CM compared to placebo group after 1, 6, and 24 months of treatment (p ​= ​0.0285, p ​= ​0.0484, p ​= ​0.0035). ConclusionsTo our knowledge, T2CM is the first technically robust serological biomarker assay which has shown biological relevance in ex vivo models and OA cohorts. This suggests that T2CM may have potential as a translational biomarker for cartilage degradation.

The Effect of a Lower Body Positive Pressure Supported Treadmill Exercise Regime on Systemic Biomarkers of Inflammation and Cartilage Degradation in Individuals with Knee Osteoarthritis: A Pilot Study

Background: Knee osteoarthritis (OA) has been linked to a chronic low-grade inflammatory response and altered metabolic activity of articular cartilage. Objective: The purpose of this investigation was to evaluate the effectiveness of a 12-week (3 times/week) lower body positive pressure (LBPP) treadmill walking regime on knee pain and systemic biomarkers of inflammation and cartilage degradation. Methods: Sixteen overweight (BMI &gt; 25 kg/m2) knee OA patients were randomized to a LBPP treadmill walking exercise group (N = 7) or non-exercise control group (N = 9). Baseline and 12-week follow-up assessments evaluated the following dependent variables: acute knee pain during full weight bearing treadmill walking; inflammatory biomarkers (C-reactive protein, interleukin-1β, interleukin-6, s100A8/A9, and tumor necrosis factor-α), and catabolic metabolism of articular cartilage (sCOMP). Results: Knee pain at baseline and follow-up remained unchanged for the non-exercise control group (P &gt; 0.05). However, knee pain for the LBPP exercise group was significantly decreased at follow-up (P ≤ 0.05). No differences in the biomarkers of inflammation and cartilage degradation were observed for between and within group comparisons (all P &gt; 0.05). Conclusions: Data suggested that the LBPP supported walking regime could be effectively used to promote regular weight bearing exercise without exacerbation of knee joint pain and did not increase levels of systemic inflammation or catabolic activity of articular cartilage in overweight knee OA patients. This pilot investigation offers important insight regarding the potential role that the LBPP technology could play in facilitating investigations examining the disease modifying effect of exercise on knee OA pathogenesis.

Cartilage Biomarkers Coll2-1 and Coll2-1NO2 Are Associated with Knee OA MRI Features and Are Helpful in Identifying Patients at Risk of Disease Worsening.

To assess the cross-sectional association between serum levels of Coll2-1 and Coll2-1NO2, two cartilage degradation biomarkers; the burden of magnetic resonance imaging (MRI) features and clinical outcomes; and to evaluate the predictive value of these biomarkers on progression. A total of 121 subjects with knee osteoarthritis (OA) were followed during 1 year with pain, function, and MRI assessment (PRODIGE study). Type II collagen-specific biomarker Coll2-1 and its nitrated form Coll2-1NO2 were directly measured in serum using immunoassays at baseline and after 3-, 6-, and 12-month follow-up. Serum Coll2-1 and Coll2-1NO2 were correlated with several baseline knee features quantified with Whole-Organ Magnetic Resonance Imaging Score (WORMS). Coll2-1 was significantly correlated with periarticular cysts/bursitis (ρ = 0.29, P < 0.01), subarticular bone attrition (ρ = 0.25, P = 0.01), subarticular cysts (ρ = 0.24, P = 0.02), and articular cartilage integrity (ρ = 0.23, P = 0.03) WORMS subscores for the whole joint as well as with the medial femorotibial joint sum score (ρ = 0.26, P = 0.01) and medial femorotibial joint cartilage (ρ = 0.23, P = 0.02). Coll2-1NO2 correlated with WORMS total score (ρ = 0.23, P = 0.02), WORMS scores in the patellofemoral (ρ = 0.23, P = 0.02) and medial femorotibial compartments (ρ = 0.21, P = 0.03), with osteophytes scores (ρ = 0.27, P < 0.01), subarticular cysts (ρ = 0.24, P = 0.019), and intraarticular loose bodies (ρ = 0.27, P = 0.007). Baseline Coll2-1NO2 was higher in subjects with a pain worsening (426.4 pg/mL [278.04-566.95]) as compared to non-progressors (306.84 pg/mL [200.37-427.84]) over 1 year (AUC = 0.655, P = 0.015). Serum cartilage biomarkers Coll2-1 and Coll2-1NO2 are associated with several knee OA features quantified with WORMS. Our study also shows that the baseline value of Coll2-1NO2 is positively associated with pain worsening.