Potential New Treatments for Knee OA: A Prospective Review of Registered Trials

We aimed to evaluate potential new treatments for knee osteoarthritis (OA). The National Institute of Health ClinicalTrials.gov database was searched for “Osteoarthritis, Knee”. We found 565 ongoing interventional studies with a total planned enrollment of 111,276 subjects. Ongoing studies for knee OA represent a very small fraction of the registered clinical trials, but they are over a quarter of all knee trials and over two thirds of all OA studies. The most researched topic was arthroplasty, with aspects such as implant design changes, cementless fixation, robotic guidance, pain management, and fast track recovery. Intraarticular injections focused on cell therapies with mesenchymal stem cells sourced from adipose tissue, bone marrow, or umbilical cord. We could see the introduction of the first disease modifying drugs with an impact on knee OA, as well as new procedures such as geniculate artery embolization and geniculate nerve ablation.

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Early Knee Osteoarthritis Changes Pre- And Post-Anterior Cruciate Ligament Reconstruction Assessed By the Semi-Quantitative MRI Osteoarthritis Knee Score (MOAKS) Case Series and Case-Control Study

10.21203/rs.3.rs-885671/v1 ◽

2021 ◽

Author(s):

Tsuyoshi Hamada ◽

Yusuke Sato ◽

Atsuya Watanabe ◽

Takayuki Sakai ◽

Masahiro Inoue ◽

...

Keyword(s):

Medial Meniscus ◽

Cruciate Ligament ◽

Linear Regression Analysis ◽

Multiple Linear Regression Analysis ◽

Cartilage Loss ◽

Knee Oa ◽

Osteoarthritis Knee ◽

Anterior Cruciate ◽

Injured Knee ◽

Time From Injury

Abstract Background: Semi-quantitative scoring of knee abnormalities on magnetic resonance imaging (MRI) can aid in the diagnosis of early stage knee osteoarthritis (OA). Injuries to the anterior cruciate ligament (ACL) and medial meniscus (MM) can contribute to the development of knee OA, but their relationship to its time of onset is unknown.Purpose: To analyze the factors contributing to early knee OA changes in ACL injured knees using MRI Osteoarthritis Knee Score (MOAKS). Methods: Thirty-four cases status post unilateral ACL reconstruction (ACLR) were included. Knee OA abnormalities were evaluated using MOAKS scores of MRIs performed pre- and post-ACLR. Using multiple linear regression analysis, the MOAKS scores of medial osteophytes, medial cartilage alteration, and patellofemoral cartilage alteration were determined as dependent variables. Age, the presence of a meniscal abnormality, the time from injury to ACLR, and body mass index (BMI) were determined as explanatory variables. MOAKS differences between knees with and without medial meniscus (MM) abnormality were tested for each variable using a 2-way repeated-measures analysis of variance with the factors of preoperative vs. postoperative status and MM abnormality. Results: In the pre-ACLR multiple linear regression analysis, the waiting period was significantly and positively associated with medial cartilage loss, Lateral femorotibial osteophytes, lateral cartilage loss. and BMI were positively associated with MM abnormalities. BMI and lateral meniscus (LM) abnormality were significantly associated with lateral cartilage loss. Age was significantly associated with medial osteophytes. Age and LM abnormality were significantly associated with lateral osteophytes. Age, BMI, and LM abnormality were significantly associated with patellofemoral osteophytes. Conclusion: We found early knee OA changes in most knees a mean of 28.2 ± 52.0 months after ACL injury. The time from injury to ACLR, BMI, and the presence of MM or LM abnormality in the ACL injured knee were associated with early knee OA changes. In the ACL injured knee with MM involvement, prompt ACLR may forestall the development of OA.

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Disease-Modifying Drugs and Stem Cell Therapies for the Treatment of Myelin Degeneration due to Multiple Sclerosis

10.47363/jnrrr/2020(2)106 ◽

2020 ◽

pp. 1-5

Author(s):

Darren Ioos ◽

◽

Vincent Gallicchio ◽

Keyword(s):

Multiple Sclerosis ◽

Nervous System ◽

Stem Cell ◽

Signal Propagation ◽

Stem Cell Therapies ◽

Disease Modifying Drugs ◽

Cell Therapies ◽

Differentiated Cells ◽

Pns Myelin ◽

Magnetic Resonance Imaging Mri

Myelin, a modified plasma membrane wrapped around axons, is an essential part of signal propagation in the nervous system. Formed by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS), myelin lowers the amount of energy needed to send or receive signals. Multiple Sclerosis (MS) is an autoimmune, hyperinflammatory disease that attacks the nervous system, specifically myelin. MS is characterized by three types of lesions in the brain and along the blood brain barrier, making it very difficult to diagnose through conventional magnetic resonance imaging (MRI) and even more difficult to treat. It has an unpredictable pathophysiology that cannot be cured by current drug therapies. Stem cell therapies have been heavily researched in recent years to try to combat the autoimmune disease by stopping demyelination and recovering lost function through the regeneration of differentiated cells

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

Cartilage ◽

10.1177/1947603520941239 ◽

2020 ◽

pp. 194760352094123

Author(s):

James G. Convill ◽

Gwenllian F. Tawy ◽

Anthony J. Freemont ◽

Leela C. Biant

Keyword(s):

Systematic Review ◽

Knee Osteoarthritis ◽

English Language ◽

Type Ii Collagen ◽

Molecular Biomarkers ◽

Keywords Knee ◽

Clinical Indicators ◽

Disease Modifying Drugs ◽

Knee Oa ◽

Cellular Markers

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.

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The Influence of Kinematic Conditions and Variations in Component Positioning on the Severity of Edge Loading and Wear of Ceramic-on-Ceramic Hip Bearings

Ceramics ◽

10.3390/ceramics2030037 ◽

2019 ◽

Vol 2 (3) ◽

pp. 488-501 ◽

Cited By ~ 1

Author(s):

Murat Ali ◽

Mazen Al-Hajjar ◽

John Fisher ◽

Louise M. Jennings

Keyword(s):

Implant Design ◽

Implant Positioning ◽

Direct Edge ◽

Design Changes ◽

Hip Simulator ◽

Edge Loading ◽

Inclination Angles ◽

Elliptical Contact ◽

Hip Joint Simulator ◽

Ceramic On Ceramic

Dynamic separation and direct edge loading of hip replacement bearings can be caused by many factors, including implant positioning, implant design, changes in device over time, surgical variations and patient variations. Such dynamic separation and direct edge loading can lead to increased wear. Different input kinematic conditions have been used for experimental hip simulator studies to produce clinically relevant elliptical contact wear paths between the bearings during gait. The aim of this study was to investigate the influence of input kinematics (two axes of rotation simulation conditions (without abduction/adduction) and three axes of rotation simulation conditions (with abduction/adduction and different loading profiles) and variations in component positioning (different levels of medial-lateral translational mismatch at standard and steep cup inclination angles) on the occurrence, severity of edge loading, dynamic separation and wear of size 36 mm ceramic-on-ceramic hip bearings on an electromechanical hip joint simulator. The results showed that, overall, either of the two axes or three axes input profiles were equally valid in providing a suitable preclinical testing method for assessing the occurrence and severity of edge loading and wear under edge loading conditions. In terms of component positioning, as cup inclination and medial-lateral translational mismatch increased, so did dynamic separation, axial load at the rim, severity of edge loading and wear.

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Chronic Collection of Cerebrospinal Fluid from Rhesus Macaques (Macaca mulatta) with Cisterna Magna Ports: Update on Refinements

Comparative Medicine ◽

10.30802/aalas-cm-21-000060 ◽

2021 ◽

Author(s):

David B Gilberto ◽

Maria S Michener ◽

Brad E Smith ◽

Peter J Szczerba ◽

Marie A Holahan ◽

...

Keyword(s):

Animal Model ◽

Cerebrospinal Fluid ◽

Animal Models ◽

Macaca Mulatta ◽

Rhesus Macaques ◽

Implant Design ◽

Cisterna Magna ◽

Chronic Models ◽

New Procedures ◽

Green Monkeys

More than 20 y ago, we developed an animal model for chronic and continuous collection of cerebrospinal fluid (CSF) from conscious rhesus macaques. Since our previous publication in 2003, we have successfully implanted 168 rhesus macaquesusing this approach. Our experience enables us to provide up-to-date information regarding the model, including refinementsto our implant design, reductions in maintenance, and new procedures for dealing with contamination. The results of our experiences have reduced the number of surgeries required and helped to increase the longevity of the implant, with some functioning for more than 18 y. Building on our success in rhesus macaques, we attempted to develop similar animal models in the African green monkeys and dogs but have been unable to develop reliable chronic models for CSF collection in these species.

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Can Computed Tomography Perfusion Predict Treatment Response After Prostate Artery Embolization: A Feasibility Study

Diagnostics ◽

10.3390/diagnostics10050304 ◽

2020 ◽

Vol 10 (5) ◽

pp. 304

Author(s):

Brian Malling ◽

Martin Andreas Røder ◽

Carsten Lauridsen ◽

Lars Lönn

Keyword(s):

Computed Tomography ◽

Treatment Response ◽

Patient Selection ◽

Specific Antigen ◽

Strongly Correlated ◽

Artery Embolization ◽

Computed Tomography Perfusion ◽

Prostate Artery Embolization ◽

New Treatments ◽

Post Hoc

Prostate artery embolization (PAE) is an emerging therapy for benign prostatic hyperplasia (BPH). Optimal patient selection is an important step when introducing new treatments and several characteristics associated with a good clinical outcome has previously been proposed. However, no prognostic tool is yet available for PAE. Computed tomography perfusion is an imaging technique that provides hemodynamic parameters making it possible to estimate the prostatic blood flow (PBF). This study investigated the relationship between PBF and the response to PAE. A post hoc analysis including prostate-specific antigen (PSA) measurements before and 24-h after embolization from two prospective studies on sixteen patients undergoing PAE with BPH or prostate cancer were performed. The primary outcome was the correlation between baseline PBF and the change in PSA as a surrogate measure of treatment response. Prostate volume strongly correlated with treatment response and the response was greater with incremental amounts of injected embolic material. PBF was not associated with elevation in PSA and added no information that could guide patient selection.

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Osteoarthritis-Related Knee Pain Treated With Genicular Artery Embolization: A Systematic Review and Meta-analysis

Orthopaedic Journal of Sports Medicine ◽

10.1177/23259671211021356 ◽

2021 ◽

Vol 9 (7) ◽

pp. 232596712110213

Author(s):

Pooya Torkian ◽

Jafar Golzarian ◽

Majid Chalian ◽

Alexander Clayton ◽

Shahram Rahimi-Dehgolan ◽

...

Keyword(s):

Systematic Review ◽

Polyvinyl Alcohol ◽

Knee Pain ◽

Pain Medication ◽

Current Evidence ◽

Artery Embolization ◽

Knee Oa ◽

Number Of Patients ◽

Significant Difference ◽

Genicular Artery

Background: Genicular artery embolization (GAE) is an innovative technique that has been investigated as a supplementary treatment method for chronic pain secondary to knee osteoarthritis (OA). Purpose: To evaluate the current evidence on the effectiveness and safety of GAE for OA-related knee pain. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic literature search was conducted in the PubMed, Web of Science, EMBASE, and Scopus databases to identify studies related to knee OA treated with GAE. Treatment agents were categorized as Embozene, imipenem/cilastatin, resorbable microspheres, and polyvinyl alcohol. The main outcomes were the mean difference (MD) in pre- and postembolization pain based on the visual analog scale (VAS) or the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores as well as changes in the need for pain medication. Random- and fixed-effects models were applied for data analysis. Results: Of 379 initially inspected publications, 11 (N = 225 patients; 268 knees) were included in the final review. The quality of the studies was fair in 8 and poor in 3—categorized according to the National Institutes of Health quality assessment tool. Overall, 119, 72, 13, and 21 patients were treated with imipenem/cilastatin, Embozene, resorbable microspheres, and polyvinyl alcohol, respectively. Symptomatic improvement was reported in all studies. The pooled effect size, characterized by MD, showed a significant improvement in the VAS and WOMAC pain scores, with better functional status after GAE. Pre- versus postembolization MDs in VAS scores ranged from 32 within the first week to 58 after a 2-year follow-up (equivalent to 54% and 80% improvement, respectively). There was a similar trend in the overall WOMAC scores, with MDs ranging from 28.4 to 36.8 (about 58% and 85% improvement, respectively). GAE resulted in a decreased need for pain medication for knee OA, with a 27%, 65%, and 73% decline in the number of patients who used opioids, nonsteroidal anti-inflammatory drugs, and intra-articular hyaluronic acid injection, respectively ( P < .00001 for all). No significant difference between embolic agents was seen with regard to post-GAE pain reduction. No severe or life-threatening complications were reported. Conclusion: OA treated by GAE using different embolic particles can be considered generally safe, with good efficacy and no reported serious complications.

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Does vitamin D3 supplementation improve medial joint space narrowing in patients with osteoarthritis knee

International Journal of Research in Orthopaedics ◽

10.18203/issn.2455-4510.intjresorthop20211616 ◽

2021 ◽

Vol 7 (3) ◽

pp. 602

Author(s):

Rahul Bharadwaj ◽

Vipin Sharma ◽

Narinder Singh ◽

Rishabh Bansal ◽

Virender Singh

Keyword(s):

Vitamin D3 ◽

Joint Space Narrowing ◽

Joint Space ◽

Control Group ◽

Case Group ◽

Inclusion Criteria ◽

Knee Oa ◽

Osteoarthritis Knee ◽

Vitamin D3 Supplementation ◽

To Receive

Background: Although vitamin D3 levels are known to improve pain and knee function in patients with knee OA, no clear evidence is available regarding relation between improvement in medial joint space with improvement in vitamin D3 levels. The aim of this study was to evaluate effectiveness of vitamin D3 supplements in improving joint space in the patients with OA knee.Methods: 100 patients with OA Knee who fulfilled inclusion criteria and consented to participate were enrolled for study. Patients of OA Knee were blinded and randomized to receive either tablet vitamin D3 or identical placebo tablet. Vitamin D3 Tab was administered in a dose of 60000U/week for 3 months in 12 doses while placebo tablets with identical dosing schedule were used for control group. The patients who received vitamin D3 tablets were allocated to case group while those receiving identical placebo tablets were grouped as controls. The vitamin D3 levels and medial joint space were assessed at baseline, 3 mo, 6mo and 1 year in both the groups.Results: In two groups of patients of OA knee of 50 patients each vitamin D3 supplementation increased levels of vitamin D3 in case group. While no significant improvement in joint space narrowing was noted with vitamin D3 supplementation in case group. Also no significant correlation was observed between vitamin D3 levels and medial joint space narrowing.Conclusions: There was no improvement in medial knee joint space with vitamin D3 supplementation.

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The Stem-Cell Market for the Treatment of Knee Osteoarthritis: A Patient Perspective

The Journal of Knee Surgery ◽

10.1055/s-0037-1604443 ◽

2017 ◽

Vol 31 (06) ◽

pp. 551-556 ◽

Cited By ~ 22

Author(s):

Nicolas Piuzzi ◽

Mitchell Ng ◽

Morad Chughtai ◽

Anton Khlopas ◽

Kenneth Ng ◽

...

Keyword(s):

Stem Cell ◽

Standard Deviation ◽

Knee Osteoarthritis ◽

Clinical Efficacy ◽

Symptomatic Improvement ◽

Stem Cell Therapies ◽

Cell Therapies ◽

Musculoskeletal Conditions ◽

Knee Oa ◽

The Mean

AbstractThe use of stem-cell therapies for the treatment of various musculoskeletal conditions, especially knee osteoarthritis (OA), is rapidly expanding, despite only low-level evidence to support its use. Centers offering these therapies are often marketing and charging patients out-of-pocket costs for such services. Therefore, the purpose of this study was to determine the current marketed: (1) prices and (2) clinical efficacy of stem-cell therapies for knee OA. This was a prospective cross-sectional study which queried 317 U.S. centers that offered direct-to-consumer stem-cell therapies for musculoskeletal conditions. A total of 273 of 317 centers were successfully contacted via phone or e-mail, using a simulated 57-year-old male patient with knee OA. Scripted questions were asked by the simulated patient to determine the marketed prices and clinical efficacy. Centers generally reported the proportion of patients who had “good results” or “symptomatic improvement.” The mean price of a unilateral (same-day) stem-cell knee injection was $5,156 with a standard deviation of $2,446 (95% confidence interval [CI]: $4,550–5,762, n = 65). The mean proportion of claimed clinical efficacy was 82% with a standard deviation of 9.6% (95% CI: 79.0–85.5%, n = 36). Most American stem-cell centers offer therapies for knee OA. The cost of these therapies averages about $5,000 per injection, and centers claim that 80% of the patients had “good results” or “symptomatic improvement,” denoting a gap between what is documented in the published literature and the marketing claims. These findings offer both patients and physicians insight into the current stem-cell market for knee OA. We hope that with this information, providers can more optimally make patients aware of discrepancies between what is being marketed versus the current evidence-based landscape of these therapies for knee OA.

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EVALUATING THE EFFECTIVENESS OF PHONOPHORESIS BY PIROXICAM AND DIMETHYL SULFOXIDE FOR WOMEN’S WITH OSTEOARTHRITIS KNEE JOINT

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i6.24615 ◽

2018 ◽

Vol 11 (6) ◽

pp. 329

Author(s):

Monisha R ◽

Manikumar M ◽

Aparna Krishnakumar

Keyword(s):

Articular Cartilage ◽

Chronic Disease ◽

Pain Relief ◽

Knee Joint ◽

Dimethyl Sulfoxide ◽

Moderate Degree ◽

Knee Oa ◽

Osteoarthritis Knee ◽

Symptomatic Knee ◽

Inflammatory Drugs

Objective: Osteoarthritis (OA) is a progressive chronic disease with the loss of articular cartilage. In managing osteoarthritis, inadequate pain relief often occurs, particularly with a single non-steroidal anti-inflammatory drugs therapy.Methods: A total of 50 participants were randomly allocated into three groups, received phonophoresis with piroxicam, dimethyl sulfoxide (DMSO), and ultrasound (US) therapy with aquasonic gel.Results: On comparing, the baseline phonophoresis group with piroxicam showed significantly more pain reduction than the DMSO and US therapy. Enrolled patients in three groups have completed the study without any drawbacks.Conclusion: This study showed that phonophoresis was superior to conventional US therapy in reducing pain in patients with symptomatic knee OA of a mild to moderate degree.

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