Sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis - An open clinical trial-

BACKGROUND: Pentosan polysulfate sodium (pentosan) is a semi-synthetic drug manufactured from beech-wood hemicellulose by sulfate esterification of the xylopyranose hydroxyl groups. From in vitro and animal model studies, pentosan has been proposed as a disease modifying osteoarthritis drug (DMOAD). The objective of this study was to assess the efficacy, safety, and patient satisfaction in patients with mild radiographic knee osteoarthritis (OA) findings and OA-associated symptoms and signs. METHODS: Twenty patients were assessed clinically at Nagasaki University Hospital. The radiographic indications of OA were grade 1 to 3 using the Kellgren-Lawrence Grading System (K/L grade). Pentosan used in this study was manufactured and supplied in sterile injectable vials (100 mg/ml) by bene GmbH, Munich, Germany. The study was a single-center, open-label trial. Treatment consisted of 6 weekly subcutaneous injections (sc) of pentosan (2 mg/kg). Patients were clinically assessed at entry and 1 to 8, 11, 15, 24 & 52 weeks post treatment. The results were analyzed using one way ANOVA and Dunnett's method. RESULTS: Hydrarthroses were reduced quickly in all cases. The clinical assessments, i.e., knee flexion, pain while walking, pain after climbing up and down stairs, etc, were improved significantly and these clinical improvements continued for almost one year. The dose used in this study affected the blood coagulation test, but was within safe levels. Slightly abnormal findings were noted in serum triglycerides. CONCLUSIONS: Pentosan treatment in twenty patients with mild knee OA seemed to provide improvements in clinical assessments and C2C level of cartilage metabolism

Viscosupplementation for the treatment of osteoarthritis. The contribution of EUROVISCO group

Viscosupplementation (VS) is a symptomatic treatment for knee and other joint osteoarthritis (OA). Despite a long history of use, conflicting opinions remain on the best clinical indications and the most appropriate patients to be treated with intra-articular hyaluronic acid (IA-HA), the optimal dosing regimen and the modalities of retreatment. A multidisciplinary committee of European experts on OA (EUROVISCO) was constituted to formulate recommendations, aimed at helping physicians in the decision-making and the optimal achievement of VS. Before each session members were tasked to collate an exhaustive literature review. Level of evidence and strength of recommendation were based on the level of agreement for each item according to the Delphi method. In 2015, a consensus position was proposed for 24 statements. Among those that obtained a consensual agreement, the working group stressed that VS is effective in mild/moderate knee OA but is not an alternative to surgery in advanced OA, and that dosing regimen must be supported by controlled trials. In 2018, two decision algorithms for the retreatment with IA-HA in knee OA were published. Among the key recommendations, the experts recommended to re-treat every year patients with high risk of OA progression, even if not symptomatic. In 2020, EUROVISCO published two sets of recommendations for the design of clinical trials on the disease-modifying effect of VS and for optimizing the results of VS. The working group underlined that an accurate analysis of radiological features and symptoms and a careful clinical examination may improve the chances of success of VS, as well as good technique of injection and the use of imaging guidance. Based on the exhaustive analysis of the literature and their own clinical experience, the EUROVISCO experts offer a wide range of recommendations intended to help practitioners, particularly in certain cases where the specific characteristics of the patients make the therapeutic decision difficult. © The Author(s), 2021

Effects of Hylan G-F 20 supplementation on cartilage preservation detected by magnetic resonance imaging in osteoarthritis of the knee: a two-year single-blind clinical trial

<p>Abstract</p> <p>Background</p> <p>Although viscosupplementation is an effective symptomatic treatment for knee osteoarthritis (OA), the effect of longer term administration on articular cartilage has not been fully explored. We examined the effect of viscosupplementation with Hylan G-F 20 on knee cartilage over 2 years in patients with knee OA.</p> <p>Methods</p> <p>In this prospective, single-blind, parallel control group pilot study, 78 patients with symptomatic knee OA (Kellgren-Lawrence grade II and III) were assigned to either intervention group (n = 39 receiving 4 courses of 3 × 2.0 ml of intra-articular Hylan G-F 20 injections at 6 month intervals) or control group (n = 39 receiving usual care for knee OA without injections). Magnetic resonance imaging of the study knee was performed at baseline, 12 and 24 months. Cartilage volume and defects were assessed using validated methods.</p> <p>Results</p> <p>Fifty-five subjects (71%) completed 24 month follow up. Over 24 months, the intervention group had a reduced annual percentage rate of medial and lateral tibial cartilage volume loss (mean ± SD, -0.3 ± 2.7% and -1.4 ± 4.3%) compared with the control group (2.3 ± 2.6% and 1.4 ± 2.6%, P = 0.001 and 0.005 for difference, respectively). The intervention group also showed reduced cartilage defect score increment in the medial tibiofemoral compartment (0.1 ± 1.3) compared with the control group (0.8 ± 1.5, P = 0.05).</p> <p>Conclusions</p> <p>Six monthly intra-articular injections of Hylan G-F 20 administered to patients with symptomatic knee OA have a beneficial effect on knee cartilage preservation measured by both cartilage volume and cartilage defects. Hylan G-F 20 warrants further evaluation in larger clinical trials as a possible disease-modifying agent in the treatment of knee OA.</p> <p>Trial Registration</p> <p>The study was registered with ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00393393">NCT00393393</a>).</p

A Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Effect of Calcium Fructoborate on Systemic Inflammation and Dyslipidemia Markers for Middle-Aged People with Primary Osteoarthritis

The objective of this pilot study was to determine whether 15 days of dietary supplementation with calcium fructoborate could acutely modulate inflammatory and lipid blood markers in individuals diagnosed with primary osteoarthritis. During 2 weeks, a placebo-controlled, randomized, double-blind study was conducted on 116 subjects that were initially recruited. Seventy-two subjects started the study, being divided into four groups, and only 60 completed the study as designed. The aim was to compare the effects of calcium fructoborate to placebo on subjects diagnosed with knee primary osteoarthritis. The obtained outcomes were inflammation biomarkers (C-reactive protein, fibrinogen, and erythrocyte sedimentation rate) and lipid markers (triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol). No serious adverse events were reported. The calcium fructoborate showed beneficial effect on the inflammatory markers for all groups subjected to the treatment when compared with the placebo group and slight changes in the lipid metabolism. This study suggests that short-term (2 weeks) calcium fructoborate supplementation in patients with osteoarthritis symptoms has a favorable prognosis on inflammation diseases

Hyaluronic acid as a treatment for ankle osteoarthritis

Viscosupplementation refers to the concept of synovial fluid replacement with intra-articular injections of hyaluronic acid (HA) for the relief of pain associated with osteoarthritis (OA). Intra-articular viscosupplementation was approved by the Food and Drug Administration (FDA) in 1997. It is currently indicated only for the treatment of pain associated with knee OA. However, OA can occur in several of the weight-bearing joints of the foot and ankle. Ankle OA produces chronic disability that directly impacts the quality of life. There is only limited published literature relating to the use of HA in the ankle. This paper will review the authors’ experience, indications, clinical outcomes, and complications of viscosupplementation therapy in patients with ankle OA

Minimum joint space width and tibial cartilage morphology in the knees of healthy individuals: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The clinical use of minimum joint space width (mJSW) and cartilage volume and thickness has been limited to the longitudinal measurement of disease progression (i.e. change over time) rather than the diagnosis of OA in which values are compared to a standard. This is primarily due to lack of establishment of normative values of joint space width and cartilage morphometry as has been done with bone density values in diagnosing osteoporosis. Thus, the purpose of this pilot study is to estimate reference values of medial joint space width and cartilage morphometry in healthy individuals of all ages using standard radiography and peripheral magnetic resonance imaging.</p> <p>Design</p> <p>For this cross-sectional study, healthy volunteers underwent a fixed-flexion knee X-ray and a peripheral MR (pMR) scan of the same knee using a 1T machine (ONI OrthOne™, Wilmington, MA). Radiographs were digitized and analyzed for medial mJSW using an automated algorithm. Only knees scoring ≤1 on the Kellgren-Lawrence scale (no radiographic evidence of knee OA) were included in the analyses. All 3D SPGRE fat-sat sagittal pMR scans were analyzed for medial tibial cartilage morphometry using a proprietary software program (Chondrometrics GmbH).</p> <p>Results</p> <p>Of 119 healthy participants, 73 were female and 47 were male; mean (SD) age 38.2 (13.2) years, mean BMI 25.0 (4.4) kg/m². Minimum JSW values were calculated for each sex and decade of life. Analyses revealed mJSW did not significantly decrease with increasing decade (p > 0.05) in either sex. Females had a mean (SD) medial mJSW of 4.8 (0.7) mm compared to males with corresponding larger value of 5.7 (0.8) mm. Cartilage morphometry results showed similar trends with mean (SD) tibial cartilage volume and thickness in females of 1.50 (0.19) μL/mm²and 1.45 (0.19) mm, respectively, and 1.77 (0.24) μL/mm²and 1.71 (0.24) mm, respectively, in males.</p> <p>Conclusion</p> <p>These data suggest that medial mJSW values do not decrease with aging in healthy individuals but remain fairly constant throughout the lifespan with "healthy" values of 4.8 mm for females and 5.7 mm for males. Similar trends were seen for cartilage morphology. Results suggest there may be no need to differentiate a t-score and a z-score in OA diagnosis because cartilage thickness and JSW remain constant throughout life in the absence of OA.</p