Current Views on Knee Osteoarthritis: 2nd Edition

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (24 November 2023) | Viewed by 16031

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Guest Editor
Department of Propaedeutics of Internal Diseases, Medical University, 4002 Tsentar, Plovdiv, Bulgaria
Interests: nailfold capillaroscopy; Raynaud’s phenomenon; systemic sclerosis; connective tissue diseases; osteoarthritis
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Special Issue Information

Dear Colleagues,

The first volume of the Special Issue about knee osteoarthritis (OA) (“Knee Osteoarthritis – How Close are We to Disease Modifying Treatment?”) was a successful initiative. (https://www.mdpi.com/topics/osteoarthritis)

OA is a leading cause of disability worldwide and knee OA is among the most common disease localizations. There is evidence about existence of different phenotypes of knee OA. However, personalized approach to these patients is insufficiently applied. Moreover, there is no approved disease-modifying drug for the treatment of OA. Therapeutic approaches directed towards different underlying pathogenic processes in knee OA or administration of a drug combination may slow the disease progression. In a proportion of cases, knee OA is associated with obesity and metabolic syndrome. Increased risk of OA in obese patients was suggested to be not only a consequence of mechanical overload but also related to the effects of adipokines. Obesity-associated knee OA is suggested to represent a distinct phenotype—the so-called metabolic knee OA. A new personalized approach towards patients with knee OA, which aims to retard disease progression, i.e., to possess disease-modifying potential, is more than welcome.

Thus, this special issue aims to summarize the available knowledge on this topic. We invite you to share your research and opinion about current views on pathogenesis and treatment of knee OA.

Dr. Sevdalina Lambova
Guest Editor

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Keywords

  • knee osteoarthritis
  • metabolic syndrome
  • obesity
  • pathogenesis
  • adipokines
  • disease-modifying treatment
  • personalized medicine

Published Papers (8 papers)

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Research

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10 pages, 272 KiB  
Article
A Short Course of Celecoxib Prevents Heterotopic Ossification Following Cementless Total Hip Arthroplasty
by Hamid Al Badi, Michael Tanzer, Anas Nooh, Brandon Hall and Adam Hart
Life 2023, 13(4), 944; https://doi.org/10.3390/life13040944 - 04 Apr 2023
Cited by 1 | Viewed by 2844
Abstract
Heterotopic ossification (HO) is a common complication after total hip arthroplasty (THA) and can result in pain and loss of motion of the hip. This is the first study in the literature to determine if a short course of Celecoxib is effective in [...] Read more.
Heterotopic ossification (HO) is a common complication after total hip arthroplasty (THA) and can result in pain and loss of motion of the hip. This is the first study in the literature to determine if a short course of Celecoxib is effective in the prevention of HO in patients undergoing cementless THA. In this retrospective study of prospectively collected data, consecutive patients undergoing a primary cementless THA were reviewed at a 2-year follow-up. The Control group consisted of 104 hips that did not receive Celecoxib (Control group), while the 208 hips in the Celecoxib group received 100 mg twice daily for 10 days. Radiographs, patient-recorded outcome measures and range of motion (ROM) were evaluated. Overall, there was a significantly decreased incidence of HO in the Celecoxib group (18.7%) than in the Control group (31.7%) (p = 0.01). The odds that a patient developed HO using Celecoxib were 0.4965 times the odds that a patient developed HO without treatment. Clinically, the Celecoxib group demonstrated significantly greater improvement in their mean WOMAC stiffness (0.35 vs. 0.17, p = 0.02) and physical function scores (3.26 vs. 1.83, p = 0.03) compared to those in the Control group, but there was no difference in the ROM between the two groups. This study is the first to demonstrate that the lowest dose of Celecoxib for a short course of only 10 days is a simple and effective prophylactic treatment option that can significantly reduce the incidence of HO following cementless THA. Full article
(This article belongs to the Special Issue Current Views on Knee Osteoarthritis: 2nd Edition)
20 pages, 3998 KiB  
Article
Crocus sativus Extract as a Biological Agent for Disease-Modifying Therapy of Collagenase-Induced Mouse Model of Osteoarthritis
by Blagovesta Boneva, Andrey Marchev, Kristiana Amirova, Petya Ganova, Milen Georgiev, Andrey Tchorbanov and Nikolina Mihaylova
Life 2023, 13(4), 894; https://doi.org/10.3390/life13040894 - 28 Mar 2023
Cited by 4 | Viewed by 1464
Abstract
Objectives: Osteoarthritis (OA) is an age-related joint disease that involves the degeneration of cartilage and is the most prevalent form of arthritis, affecting a large part of the population. OA is a multifactorial disorder, and no single etiological mechanism has been found to [...] Read more.
Objectives: Osteoarthritis (OA) is an age-related joint disease that involves the degeneration of cartilage and is the most prevalent form of arthritis, affecting a large part of the population. OA is a multifactorial disorder, and no single etiological mechanism has been found to be common to all forms of the disease. Currently used therapies for control of the disease are mainly nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroid medications. The aim of this study was to investigate the extract from Crocus sativus as a biological disease-suppressing therapy agent. Methods: Balb/c mice were injected intra-articularly with Clostridium histolyticum type IA for induction of osteoarthritis. The mice were randomized to five groups: control group, I group (CIOA untreated), II group (CIOA + 100 mg/kg/daily saffron), III group (CIOA + 50 mg/kg/daily saffron), IV group (CIOA + 25 mg/kg/daily saffron). Flow-cytometry analysis was used to study the splenocytes’ phenotype isolated from the treated animals. The serum levels of inflammatory and anti-inflammatory cytokines were analyzed with ELISA. The histological assessment was used to analyze the saffron extract effect on histopathological alterations. Results: Saffron treatment significantly decreased osteoarthritis-associated joint histological manifestations and decreased serum TNFα levels. The flow-cytometry analysis showed a decrease in pro-inflammatory immune cell subtypes in the spleen. Conclusions: The results obtained suggest that saffron affected the disease progression and could be a potential therapeutic approach in osteoarthritic patients’ therapy. Full article
(This article belongs to the Special Issue Current Views on Knee Osteoarthritis: 2nd Edition)
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21 pages, 3390 KiB  
Article
Correlation between Bone Mineral Density and Progression of Hip Osteoarthritis in Adult Men and Women in Bulgaria—Results from a 7-Year Study
by Lyubomir Sapundzhiev, Tanya Sapundzhieva, Martin Mitev, Kiril Simitchiev and Anastas Batalov
Life 2023, 13(2), 421; https://doi.org/10.3390/life13020421 - 02 Feb 2023
Cited by 1 | Viewed by 1340
Abstract
Changes in clinical presentation, radiographic progression (RP), bone mineral density (BMD), bone turnover (BT), and cartilage turnover (CT) markers were compared in two groups of patients with hip osteoarthritis (HOA) over a period of 7 years. Each group consisted of 150 patients, including [...] Read more.
Changes in clinical presentation, radiographic progression (RP), bone mineral density (BMD), bone turnover (BT), and cartilage turnover (CT) markers were compared in two groups of patients with hip osteoarthritis (HOA) over a period of 7 years. Each group consisted of 150 patients, including a control group on standard-of-care therapy (SC) with simple analgesics and physical exercises, and a study group (SG) on standard-of-care therapy supplemented by vitamin D3 and intravenous administration of zoledronic acid (5 mg) yearly for 3 consecutive years. Patient groups were homogenized regarding the following: (1) radiographic grade (RG), including 75 patients with hip OA RG II according to the Kellgren–Lawrence grading system (K/L), and 75 with RG III on K/L; (2) radiographic model (RM), as each of the K/L grades was subdivided into three subgroups consisting of 25 patients of different RMs: atrophic (‘A’), intermediate (‘I’), and hypertrophic (‘H’); (3) gender-equal ratio of men and women in each subgroup (Female/Male = 15/10). The following parameters were assessed: (1) clinical parameters (CP), pain at walking (WP-VAS 100 mm), functional ability (WOMAC-C), and time to total hip replacement (tTHR); (2) radiographic indicators(RI)—joint space width (JSW) and speed of joint space narrowing (JSN), changes in BMD (DXA), including proximal femur (PF-BMD), lumbar spine (LS-BMD), and total body (TB-BMD); (3) laboratory parameters (LP)—vitamin D3 levels and levels of BT/CT markers. RV were assessed every 12 months, whereas CV/LV were assessed every 6 months. Results: Cross-sectional analysis (CsA) at baseline showed statistically significant differences (SSD) at p < 0.05 in CP (WP, WOMAC-C); BMD of all sites and levels of CT/BT markers between the ‘A’ and ‘H’ RM groups in all patients. Longitudinal analysis (LtA) showed SSD (p < 0.05) between CG and SG in all CP (WP, WOMAC-C, tTHR) parameters of RP (mJSW, JSN), BMD of all sites, and levels of CT/BT markers for all ‘A’ models and in 30% of ‘I’-RMs (those with elevated markers for BT/CT at baseline and during the observation period). Conclusion: The presence of SSD at baseline (‘A’ vs. ‘H’) supported the thesis that at least two different subgroups of HOA exist: one associated with ‘A’ and the other with ‘H’ models. D3 supplementation and the intravenous administration of bisphosphonate were the treatment strategies that slowed down RP and postponed tTHR by over 12 months in the ‘A’ and ‘I’ RM with elevated BT/CT markers. Full article
(This article belongs to the Special Issue Current Views on Knee Osteoarthritis: 2nd Edition)
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15 pages, 5698 KiB  
Article
Collagenase-Induced Mouse Model of Osteoarthritis—A Thorough Flow Cytometry Analysis
by Blagovesta Boneva, Nikola Ralchev, Petya Ganova, Andrey Tchorbanov and Nikolina Mihaylova
Life 2022, 12(11), 1938; https://doi.org/10.3390/life12111938 - 21 Nov 2022
Cited by 3 | Viewed by 1890
Abstract
Objectives: Osteoarthritis (OA) is a chronic degenerative disorder of the joint characterized by cartilage breakdown and synovial inflammation. A number of different cells of innate and adaptive immunity contribute to joint pathology during OA inflammation. The interaction between the local synovial and systemic [...] Read more.
Objectives: Osteoarthritis (OA) is a chronic degenerative disorder of the joint characterized by cartilage breakdown and synovial inflammation. A number of different cells of innate and adaptive immunity contribute to joint pathology during OA inflammation. The interaction between the local synovial and systemic inflammatory cellular response and the structural changes in the joint is still unknown. The objective of this study was to investigate the role of the different types of immune cells in the development of OA. Methods: Collagenase-induced osteoarthritis was induced in Balb/c mice; flow cytometry analysis; and histopathological damages were assessed in histological sections stained with H&E, Toluidine blue, and Safranin O. Results: Flow cytometry analysis showed B lymphocyte infiltration in the active phase of inflammation and an increase in the effector T cell population into the synovium. An increased activation state of cytotoxic T cells and of NK cell populations in the spleen and synovium was also found. The differentiation of NK cells from a cytotoxic phenotype in early OA to cells with an effector phenotype in the chronic phase of the disease followed. Conclusions: A number of different cells contribute to inflammatory processes in OA. The correlation between their phenotype and the inflammatory pathophysiology could result in the development of novel approaches to suppress destructive changes in the joint. Full article
(This article belongs to the Special Issue Current Views on Knee Osteoarthritis: 2nd Edition)
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Review

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13 pages, 313 KiB  
Review
Obesity-Related Knee Osteoarthritis—Current Concepts
by Russka Shumnalieva, Georgi Kotov and Simeon Monov
Life 2023, 13(8), 1650; https://doi.org/10.3390/life13081650 - 28 Jul 2023
Cited by 7 | Viewed by 2194
Abstract
The knee is the joint most frequently involved in osteoarthritis and represents a significant contributor to patient morbidity and impaired functional status. Major risk factors include genetics, age, sex, mechanical load and obesity/metabolic syndrome. Recent studies highlighted the role of obesity and metabolic [...] Read more.
The knee is the joint most frequently involved in osteoarthritis and represents a significant contributor to patient morbidity and impaired functional status. Major risk factors include genetics, age, sex, mechanical load and obesity/metabolic syndrome. Recent studies highlighted the role of obesity and metabolic syndrome in the pathogenesis of knee osteoarthritis not simply through increased mechanical loading but the systemic effects of obesity-induced inflammation. The current concept of knee osteoarthritis is that of a ‘whole joint disease’, which highlights the involvement not only of articular cartilage but also the synovium, subchondral bone, ligaments and muscles. Obesity and metabolic syndrome are associated with higher levels of pro-inflammatory cytokines, increased production of adipokines with both protective and destructive effects on articular cartilage, an up-regulation of proteolytic enzymes such as matrix metalloproteinases and aggrecanases and an increase in free fatty acids and reactive oxygen species induced by dyslipidemia. These findings underscore that the adequate management of knee osteoarthritis needs to include an optimization of body weight and a beneficial mobility regimen. The possible introduction of pharmacological therapy targeting specific molecules involved in the pathogenesis of obesity-related osteoarthritis will likely also be considered in future therapeutic strategies, including personalized treatment approaches. Full article
(This article belongs to the Special Issue Current Views on Knee Osteoarthritis: 2nd Edition)
12 pages, 1263 KiB  
Review
Research Advances in the Application of AI for Preoperative Measurements in Total Knee Arthroplasty
by Wei Li, Sheng-Ming Xu, De-Bao Zhang, Huang-Yi Bi and Gui-Shan Gu
Life 2023, 13(2), 451; https://doi.org/10.3390/life13020451 - 06 Feb 2023
Cited by 3 | Viewed by 1543
Abstract
Total knee arthroplasty (TKA) is widely used in clinical practice as an effective treatment for end-stage knee joint lesions. It can effectively correct joint deformities, relieve painful symptoms, and improve joint function. The reconstruction of lower extremity joint lines and soft tissue balance [...] Read more.
Total knee arthroplasty (TKA) is widely used in clinical practice as an effective treatment for end-stage knee joint lesions. It can effectively correct joint deformities, relieve painful symptoms, and improve joint function. The reconstruction of lower extremity joint lines and soft tissue balance are important factors related to the durability of the implant; therefore, it is especially important to measure the joint lines and associated angles before TKA. In this article, we review the technological progress in the preoperative measurement of TKA. Full article
(This article belongs to the Special Issue Current Views on Knee Osteoarthritis: 2nd Edition)
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12 pages, 457 KiB  
Review
Pleiotropic Effects of Metformin in Osteoarthritis
by Sevdalina Nikolova Lambova
Life 2023, 13(2), 437; https://doi.org/10.3390/life13020437 - 03 Feb 2023
Cited by 1 | Viewed by 2832
Abstract
The involvement of the knee joint is the most common localization of the pathological process in osteoarthritis (OA), which is associated with obesity in over 50% of the patients and is mediated by mechanical, inflammatory, and metabolic mechanisms. Obesity and the associated conditions [...] Read more.
The involvement of the knee joint is the most common localization of the pathological process in osteoarthritis (OA), which is associated with obesity in over 50% of the patients and is mediated by mechanical, inflammatory, and metabolic mechanisms. Obesity and the associated conditions (hyperglycemia, dyslipidemia, and hypertension) have been found to be risk factors for the development of knee OA, which has led to the emerging concept of the existence of a distinct phenotype, i.e., metabolic knee OA. Combined assessment of markers derived from dysfunctional adipose tissue, markers of bone and cartilage metabolism, as well as high-sensitivity inflammatory markers and imaging, might reveal prognostic signs for metabolic knee OA. Interestingly, it has been suggested that drugs used for the treatment of other components of the metabolic syndrome may also affect the clinical course and retard the progression of metabolic-associated knee OA. In this regard, significant amounts of new data are accumulating about the role of metformin—a drug, commonly used in clinical practice with suggested multiple pleiotropic effects. The aim of the current review is to analyze the current views about the potential pleiotropic effects of metformin in OA. Upon the analysis of the different effects of metformin, major mechanisms that might be involved in OA are the influence of inflammation, oxidative stress, autophagy, adipokine levels, and microbiome modulation. There is an increasing amount of evidence from in vitro studies, animal models, and clinical trials that metformin can slow OA progression by modulating inflammatory and metabolic factors that are summarized in the current up-to-date review. Considering the contemporary concept about the existence of metabolic type knee OA, in which the accompanying obesity and systemic low-grade inflammation are suggested to influence disease course, metformin could be considered as a useful and safe component of the personalized therapeutic approach in knee OA patients with accompanying type II diabetes or obesity. Full article
(This article belongs to the Special Issue Current Views on Knee Osteoarthritis: 2nd Edition)
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Other

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21 pages, 1461 KiB  
Systematic Review
Epigenetics in Knee Osteoarthritis: A 2020–2023 Update Systematic Review
by Davide Caldo, Eugenia Massarini, Massimiliano Rucci, Silvia Deaglio and Riccardo Ferracini
Life 2024, 14(2), 269; https://doi.org/10.3390/life14020269 - 17 Feb 2024
Cited by 1 | Viewed by 942
Abstract
Osteoarthritis is a leading cause of disability in the world. The scientific literature highlights the critical importance of epigenetic regulatory effects, intertwined with biomechanical and biochemical peculiar conditions within each musculoskeletal district. While the contribution of genetic and epigenetic factors to knee OA [...] Read more.
Osteoarthritis is a leading cause of disability in the world. The scientific literature highlights the critical importance of epigenetic regulatory effects, intertwined with biomechanical and biochemical peculiar conditions within each musculoskeletal district. While the contribution of genetic and epigenetic factors to knee OA is well-recognized, their precise role in disease management remains an area of active research. Such a field is particularly heterogeneous, calling for regular analysis and summarizing of the data that constantly emerge in the scientific literature, often sparse and scant of integration. The aim of this study was to systematically identify and synthesize all new evidence that emerged in human and animal model studies published between 2020 and 2023. This was necessary because, to the best of our knowledge, articles published before 2019 (and partly 2020) had already been included in systematic reviews that allowed to identify the ones concerning the knee joint. The review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only peer-reviewed articles were considered for inclusion. A total of 40 studies were identified, showing promising results in terms either of biomarker identification, new insight in mechanism of action or potential therapeutic targets for knee OA. DNA methylation, histone modification and ncRNA were all mechanisms involved in epigenetic regulation of the knee. Most recent evidence suggests that epigenetics is a most promising field with the long-term goal of improving understanding and management of knee OA, but a variety of research approaches need greater consolidation. Full article
(This article belongs to the Special Issue Current Views on Knee Osteoarthritis: 2nd Edition)
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