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Uchio Y, Ishijima M, Ikeuchi M, Ikegawa S, Ishibashi Y, Omori G, Shiba N, Takeuchi R, Tanaka S, Tsumura H, Deie M, Tohyama H, Yoshimura N, Nakashima Y. Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of Osteoarthritis of the knee - Secondary publication. J Orthop Sci 2025; 30:185-257. [PMID: 39127581 DOI: 10.1016/j.jos.2024.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 06/28/2024] [Indexed: 08/12/2024]
Affiliation(s)
- Yuji Uchio
- Department of Orthopaedic Surgery, Shimane University, Izumo, Japan.
| | | | - Masahiko Ikeuchi
- Department of Orthopaedic Surgery, Kochi University, Nankoku, Japan
| | - Shiro Ikegawa
- Laboratory for Bone and Joint Diseases, Center for Integrated Medical Science (IMS), RIKEN, Tokyo, Japan
| | - Yasuyuki Ishibashi
- Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Go Omori
- Department of Health and Sports, Niigata University of Health and Welfare, Niigata, Japan
| | - Naoto Shiba
- Department of Orthopaedics, Kurume University School of Medicine, Fukuoka, Japan
| | - Ryohei Takeuchi
- Department of Joint Surgery Center, Yokohama Sekishinkai Hospital, Yokohama, Japan
| | - Sakae Tanaka
- Department of Orthopaedic Surgery, University of Tokyo, Tokyo, Japan
| | - Hiroshi Tsumura
- Department of Orthopaedic Surgery, Oita University, Oita, Japan
| | - Masataka Deie
- Department of Orthopaedic Surgery, Aichi Medical University, Nagakute, Japan
| | | | - Noriko Yoshimura
- Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, University of Tokyo, Tokyo, Japan
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López-Rodríguez R, Vermetten J, Domínguez L, Fernández-Ruiz V, Cámara M. A critical review of synthetic novel foods within the European regulation: proposed classification, toxicological concerns and potential health claims. Crit Rev Food Sci Nutr 2025:1-21. [PMID: 39810437 DOI: 10.1080/10408398.2024.2449246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
The NF concept was first established by Regulation (EC) 258/97 and includes any food that has not been used to a significant extent for human consumption in the EU before 15 May 1997. Synthetic novel foods (SNF) are a currently undefined group of NF without a universal definition. The objectives of this work are to perform an analysis of those currently authorized in the EU, identify their potential adverse effects and health benefits, and their health claims. For that, an extensive review of the available legislative documents and scientific literature regarding SNF was performed, and a market analysis was performed regarding their commercial availability. This review considers SNF as those that are obtained by chemical synthesis, excluding genetically modified foods. A total of 29 SNF were identified and classified into 9 categories, and their potential risks and benefits were described. All SNF were considered safe and different health benefits were studied and suggested for various categories. Currently, 22 SNF are available on the EU market. This work characterizes a previously unexplored food group and expands the knowledge in a new and promising research area combining health and toxicological perspectives with legislation for more optimal risk management in the EU.
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Affiliation(s)
- Ricardo López-Rodríguez
- Nutrition and Food Science department, Faculty of Pharmacy, University Complutense de Madrid, Madrid, Spain
| | - Johanne Vermetten
- Nutrition and Food Science department, Faculty of Pharmacy, University Complutense de Madrid, Madrid, Spain
| | - Laura Domínguez
- Nutrition and Food Science department, Faculty of Pharmacy, University Complutense de Madrid, Madrid, Spain
| | - Virginia Fernández-Ruiz
- Nutrition and Food Science department, Faculty of Pharmacy, University Complutense de Madrid, Madrid, Spain
| | - Montaña Cámara
- Nutrition and Food Science department, Faculty of Pharmacy, University Complutense de Madrid, Madrid, Spain
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Zhu R, Fang H, Wang J, Ge L, Zhang X, Aitken D, Cai G. Inflammation as a therapeutic target for osteoarthritis: A literature review of clinical trials. Clin Rheumatol 2024; 43:2417-2433. [PMID: 38961031 PMCID: PMC11269414 DOI: 10.1007/s10067-024-07042-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 06/12/2024] [Accepted: 06/24/2024] [Indexed: 07/05/2024]
Abstract
The burden of osteoarthritis (OA) is rapidly increasing with population aging, but there are still no approved disease-modifying drugs available. Accumulating evidence has shown that OA is a heterogeneous disease with multiple phenotypes, and it is unlikely to respond to one-size-fits-all treatments. Inflammation is recognized as an important phenotype of OA and is associated with worse pain and joint deterioration. Therefore, it is believed that anti-inflammatory treatments may be more effective for OA with an inflammatory phenotype. In this review, we summarized clinical trials that evaluated anti-inflammatory treatments for OA and discussed whether these treatments are more effective in inflammatory OA phenotypes compared to general OA patients.
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Affiliation(s)
- Rui Zhu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Haonan Fang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Junjie Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Liru Ge
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Xiaoyue Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Dawn Aitken
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 7000, Australia
| | - Guoqi Cai
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China.
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 7000, Australia.
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Shen Q, Guo Y, Wang K, Zhang C, Ma Y. A Review of Chondroitin Sulfate's Preparation, Properties, Functions, and Applications. Molecules 2023; 28:7093. [PMID: 37894574 PMCID: PMC10609508 DOI: 10.3390/molecules28207093] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/07/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Chondroitin sulfate (CS) is a natural macromolecule polysaccharide that is extensively distributed in a wide variety of organisms. CS is of great interest to researchers due to its many in vitro and in vivo functions. CS production derives from a diverse number of sources, including but not limited to extraction from various animals or fish, bio-synthesis, and fermentation, and its purity and homogeneity can vary greatly. The structural diversity of CS with respect to sulfation and saccharide content endows this molecule with distinct complexity, allowing for functional modification. These multiple functions contribute to the application of CS in medicines, biomaterials, and functional foods. In this article, we discuss the preparation of CS from different sources, the structure of various forms of CS, and its binding to other relevant molecules. Moreover, for the creation of this article, the functions and applications of CS were reviewed, with an emphasis on drug discovery, hydrogel formation, delivery systems, and food supplements. We conclude that analyzing some perspectives on structural modifications and preparation methods could potentially influence future applications of CS in medical and biomaterial research.
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Affiliation(s)
- Qingshan Shen
- Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Changjiang Road 80, Nanyang 473004, China
- Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Yujie Guo
- Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Kangyu Wang
- Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Chunhui Zhang
- Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Yanli Ma
- Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Changjiang Road 80, Nanyang 473004, China
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Lila AM, Alekseeva LI, Baranov AA, Taskina EA, Kashevarova NG, Lapkina NA, Trofimov EA. Chondroitin sulfate and glucosamine combination in patients with knee and hip osteoarthritis: A long-term observational study in Russia. World J Orthop 2023; 14:443-457. [PMID: 37377986 PMCID: PMC10292059 DOI: 10.5312/wjo.v14.i6.443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/19/2023] [Accepted: 05/12/2023] [Indexed: 06/19/2023] Open
Abstract
BACKGROUND Oral treatment of glucosamine (GA) combined with chondroitin sulfate (CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clinical trials. While the effectiveness of GA and CS on both clinical and radiological findings has been demonstrated, only a few high-quality trials exist. Therefore, controversy regarding their effectiveness in real-world clinical practice remains.
AIM To investigate the impact of GA + CS on clinical outcomes of patients with knee and hip osteoarthritis in routine clinical practice.
METHODS A multicenter prospective observational cohort study included 1102 patients of both genders with knee or hip osteoarthritis (Kellgren & Lawrence grades I-III) in 51 clinical centers in the Russian Federation from November 20, 2017, to March 20, 2020, who had started to receive oral capsules of glucosamine hydrochloride 500 mg and CS 400 mg according to the approved patient information leaflet starting from 3 capsules daily for 3 wk, followed by a reduced dosage of 2 capsules daily before study inclusion (minimal recommended treatment duration is 3-6 mo). Changes in subscale scores [Pain, Symptoms, Function, and Quality of Life (QOL)] of the Knee Injury and Osteoarthritis Outcome Score (KOOS)/Hip Disability and Osteoarthritis Outcome Score (HOOS) questionnaires during the observational period (up to 54-64 wk with a total of 4 visits). Patients’ treatment satisfaction, data on the combined oral use of glucosamine hydrochloride and CS, concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs), and adverse events (AEs) were also evaluated.
RESULTS A total of 1102 patients with knee and hip osteoarthritis were included in the study. The mean patient age was 60.4 years, most patients were women (87.8%), and their average body mass index was 29.49 kg/m2. All subscale scores (Pain, Symptoms, Function, and QOL) of the KOOS and HOOS demonstrated clinically and statistically significant improvements. In patients with knee osteoarthritis, the mean score increases from baseline to the end of Week 64 were 22.87, 20.78, 16.60, and 24.87 on Pain, Symptoms, Physical Function (KOOS-PS), and QOL subscales (P < 0.001 for all), respectively. In patients with hip osteoarthritis, the mean score increases were 22.81, 19.93, 18.77, and 22.71 on Pain, Symptoms, Physical Function (HOOS-PS), and QOL subscales (P < 0.001 for all), respectively. The number of patients using any NSAIDs decreased from 43.1% to 13.5% (P < 0.001) at the end of the observation period. Treatment-related AEs occurred in 2.8% of the patients and mainly included gastrointestinal disorders [25 AEs in 24 (2.2%) patients]. Most patients (78.1%) were satisfied with the treatment.
CONCLUSION Long-term oral GA + CS was associated with decreased pain, reduced concomitant NSAID therapy, improved joint function and QOL in patients with knee and hip osteoarthritis in routine clinical practice.
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Affiliation(s)
- Alexander M Lila
- Director, Research Institute of Rheumatology Named after VA Nasonova, Moscow 115522, Moscow, Russia
| | - Lyudmila I Alekseeva
- Bone and Joints Metabolic Diseases Laboratory, Research Institute of Rheumatology Named after VA Nasonova, Moscow 115522, Moscow, Russia
| | - Andrey A Baranov
- Department of Therapy, Clinical Laboratory Diagnostics and Medical Biochemistry, Yaroslavl State Medical University, Yaroslavl 150000, Yaroslavl, Russia
| | - Elena A Taskina
- Bone and Joints Metabolic Diseases Laboratory, Research Institute of Rheumatology Named after VA Nasonova, Moscow 115522, Moscow, Russia
| | - Natalya G Kashevarova
- Bone and Joints Metabolic Diseases Laboratory, Research Institute of Rheumatology Named after VA Nasonova, Moscow 115522, Moscow, Russia
| | - Natalia A Lapkina
- Department of Therapy, Clinical Laboratory Diagnostics and Medical Biochemistry, Yaroslavl State Medical University, Yaroslavl 150000, Yaroslavl, Russia
| | - Evgeny A Trofimov
- Department of Therapy and Rheumatology, North-Western State Medical University named after I.I. Mechnikov, St. Petersburg 191015, St. Petersburg, Russia
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Nowaczyk A, Szwedowski D, Dallo I, Nowaczyk J. Overview of First-Line and Second-Line Pharmacotherapies for Osteoarthritis with Special Focus on Intra-Articular Treatment. Int J Mol Sci 2022; 23:1566. [PMID: 35163488 PMCID: PMC8835883 DOI: 10.3390/ijms23031566] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/19/2022] [Accepted: 01/27/2022] [Indexed: 02/07/2023] Open
Abstract
Osteoarthritis (OA) can be defined as the result of pathological processes of various etiologies leading to damage to the articular structures. Although the mechanism of degenerative changes has become better understood due to the plethora of biochemical and genetic studies, the drug that could stop the degenerative cascade is still unknown. All available forms of OA therapy are based on symptomatic treatment. According to actual guidelines, comprehensive treatment of OA should always include a combination of various therapeutic options aimed at common goals, which are pain relief in the first place, and then the improvement of function. Local treatment has become more common practice, which takes place between rehabilitation and pharmacological treatment in the hierarchy of procedures. Only in the case of no improvement and the presence of advanced lesions visible in imaging tests, should surgery be considered. Currently, an increasing number of studies are being published suggesting that intra-articular injections may be as effective or even more effective than non-steroidal anti-inflammatory drugs (NSAIDs) and result in fewer systemic adverse events. The most commonly used preparations are hyaluronic acid (HA), glucocorticosteroids (GS), and also platelet-rich plasma (PRP) in recent years. This review aims to present the mechanism of action and clinical effectiveness of different pharmacological options in relieving pain and improving functions in OA as well as the emerging approach in intra-articular treatment with PRP.
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Affiliation(s)
- Alicja Nowaczyk
- Department of Organic Chemistry, Faculty of Pharmacy, LudwikRydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 2 dr. A. Jurasza St., 85-094 Bydgoszcz, Poland
| | - Dawid Szwedowski
- Department of Orthopaedics and Trauma Surgery, Provincial Polyclinical Hospital, 87-100 Toruń, Poland;
- Orthopedic Arthroscopic Surgery International (O.A.S.I.) Bioresearch Foundation, Gobbi N.P.O., 20133 Milan, Italy
| | - Ignacio Dallo
- Unit of Biological Therapies, SportMe Medical Center, Department of Orthopaedic Surgery and Sports Medicine, 41013 Seville, Spain;
| | - Jacek Nowaczyk
- Department of Physical Chemistry and Physicochemistry of Polymers, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarina St., 87-100 Toruń, Poland
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Ewald CY. Drug Screening Implicates Chondroitin Sulfate as a Potential Longevity Pill. FRONTIERS IN AGING 2021; 2:741843. [PMID: 35821992 PMCID: PMC9261418 DOI: 10.3389/fragi.2021.741843] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 08/26/2021] [Indexed: 11/13/2022]
Abstract
Discovering compounds that promote health during aging ("geroprotectors") is key to the retardation of age-related pathologies and the prevention of chronic age-related diseases. In in-silico and model organisms' lifespan screens, chondroitin sulfate has emerged as a geroprotective compound. Chondroitin sulfate is a glycosaminoglycan attached to extracellular matrix proteins and is naturally produced by our body. Oral supplementation of chondroitin sulfate shows a high tolerance in humans, preferable pharmacokinetics, a positive correlation with healthy human longevity, and efficacy in deceleration of age-related diseases in randomized clinical trials. We have recently shown that chondroitin sulfate supplementation increases the lifespan of C. elegans. Thus, chondroitin sulfate holds the potential to become a geroprotective strategy to promote health during human aging. This review discusses the two major potential mechanisms of action, extracellular matrix homeostasis and inhibition of inflammation, that counteract age-related pathologies upon chondroitin sulfate supplementation.
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2021 revised algorithm for the management of knee osteoarthritis-the Chinese viewpoint. Aging Clin Exp Res 2021; 33:2141-2147. [PMID: 34189714 PMCID: PMC8302513 DOI: 10.1007/s40520-021-01906-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 06/01/2021] [Indexed: 12/19/2022]
Abstract
AIM The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide from 2014, but in 2019 an update was published. Based on this algorithm, a Working Group (WG), including ESCEO members and Chinese experts, wished to see how the new ESCEO algorithm was perceived by Chinese experts in knee OA and how it was integrated into their clinical practice. METHODS A WG was held between members of the international ESCEO task force and a group of Chinese experts. RESULTS Non-pharmacological approach should be combined with pharmacological interventions. In step 1, symptomatic slow-acting drugs for osteoarthritis (SYSADOA) are the most important background drugs. Evidence, supported by high-quality research, is available only for crystalline glucosamine sulfate (pCGS) and chondroitin sulfate. Topical NSAIDs could be used as an additional option. In step 2, oral NSAIDs could be useful, but cardiovascular/renal/gastrointestinal profiles of the patients should be considered. Intra-articular hyaluronic acid and corticosteroids are alternative to oral NSAIDs, but the evidence is still limited. If steps 1 and 2 are not sufficient, weak opioids could be used. Overall, the conclusions of the ESCEO algorithm are accepted in China for products available in this country. The WG suggests the importance of economic studies, specifically made in China. CONCLUSION This work provides evidence-based advice to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in China.
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Evidence, Efficasy and Safety of the Chondroprotective Parapharmaceuticals in Treatment of the Early Stages of Osteoarthritis. Fam Med 2021. [DOI: 10.30841/2307-5112.2-3.2021.240762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Osteoarthritis (OA) is the most common joint disease that significantly affects the patients’ quality of life and requires significant medical and social investments for treatment and rehabilitation. There are no therapeutic agents which would be able to regenerate lost or damaged hyaline cartilage.
The objective: to assess the efficacy and safety of the chondroprotective parapharmaceutical agent Flexogial in the complex treatment of patients with initial stages of the knee ОА.
Materials and methods. 12-weeks study was conducted with the participation of 60 patients with knee OA aged 53,7±2,9 years, women – 36 (60%), men – 24 (40%) with the initial stages of the disease (I–II radiological stage). The main clinical group consisted of 30 patients who took the chondroprotective complex agent Flexogial 15 ml once a day; the comparison group included 30 patients who were administered glucosamine sulfate 1500 mg in a monopreparation taken once a day. Efficacy of the treatment was evaluated using the VAS scale, Tegner’s scale, Lisholm scale at the beginning of treatment, after 6 and 12 weeks in dynamics with subsequent statistical processing of the results.
Results. The study demonstrated better indicators of functional activity and less pain intensity in the affected joints in patients of the main group who took the parapharmaceutical agent Flexogial compared to the group of patients who took glucosamine monopreparation with the same number of registered adverse events in both groups of patients (5%).
Conclusions. The results of the presented clinical study proved the advantage of use of the combined chondroprotective drinking complex Flexogial in comparison with the monopharmaceutical preparation glucosamine sulfate in the treatment of patients with early stages knee OA in terms of the effect on the intensity of pain and improvement in the parameters of the functional activity of patients after 6 and 12 weeks with the same frequency of registered adverse events.
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2019 revised algorithm for the management of knee osteoarthritis: the Southeast Asian viewpoint. Aging Clin Exp Res 2021; 33:1149-1156. [PMID: 33774784 PMCID: PMC8081679 DOI: 10.1007/s40520-021-01834-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023]
Abstract
Background Since 2014, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide. Aim Based on this document, a Southeast Asia Working Group (SEAWG) wished to see how the new ESCEO algorithm developed in 2019 was perceived by Southeast Asian experts and how it was integrated into their clinical practice. Methods A SEAWG was set up between members of the international ESCEO task force and a group of Southeast Asian experts. Results Non-pharmacological management should always be combined with pharmacological management. In step 1, symptomatic slow-acting drugs for osteoarthritis are the main background therapy, for which high-quality evidence is available only for the formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. In step 2, oral NSAIDs are a useful option, considering the cardiovascular/renal/gastrointestinal profiles of the individual patient. Intra-articular hyaluronic acid and corticosteroids are a possible alternative to oral NSAIDs, but limited evidence is available. If steps 1 and 2 do not give adequate relief of symptoms, tramadol can be used, but its safety is debated. In general, the indications of the ESCEO algorithm are important in Southeast Asian countries, but the reimbursement criteria of local health systems are an important aspect for adherence to the ESCEO algorithm. Conclusion This guidance provides evidence-based and easy-to-follow advice on how to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in Southeast Asian countries.
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Mishra S, Ganguli M. Functions of, and replenishment strategies for, chondroitin sulfate in the human body. Drug Discov Today 2021; 26:1185-1199. [PMID: 33549530 DOI: 10.1016/j.drudis.2021.01.029] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 09/26/2020] [Accepted: 01/28/2021] [Indexed: 02/06/2023]
Abstract
Chondroitin sulfate (CS) belongs to a class of molecules called glycosaminoglycans (GAGs). These are long, linear chains of polysaccharides comprising alternating amino sugars and hexuronic acid. Similar to other GAGs, CS is important in a multitude of biological activities. Alteration of CS levels has been implicated in several pathological conditions, including osteoarthritis (OA) and other inflammatory diseases, as well as physiological conditions, such as aging. Therefore, devising replenishment strategies for this molecule is an important area of research. In this review, we discuss the nature of CS, its function in different organs, and its implications in health and disease. We also describe different methods for the exogenous administration of CS.
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Affiliation(s)
- Sarita Mishra
- CSIR - Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Munia Ganguli
- CSIR - Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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Reginster JY, Veronese N. Highly purified chondroitin sulfate: a literature review on clinical efficacy and pharmacoeconomic aspects in osteoarthritis treatment. Aging Clin Exp Res 2021; 33:37-47. [PMID: 32638342 PMCID: PMC7897612 DOI: 10.1007/s40520-020-01643-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 06/22/2020] [Indexed: 12/12/2022]
Abstract
Osteoarthritis (OA) is the most prevalent musculoskeletal disease and a major cause of negative relevant outcomes, associated with an ever-increasing societal burden. Pharmaceutical-grade chondroitin sulfate (CS) was repeatedly reported to reduce pain and improve function in patients with OA. This article aims to review the evidence for the role of highly purified (hp) CS (Condrosulf®, IBSA) in the treatment of OA. We collected and reported evidence concerning (1) efficacy of hpCS 800 mg/day in the treatment of OA affecting the knee, hand and hip; (2) efficacy and safety of hpCS 1200 mg/day also in the oral gel formulation; (3) the safety profile of hpCS; (4) the difference of hpCS and pharmaceutical-grade formulations versus food supplements; (5) pharmacoeconomic added value of hpCS. The data support that hpCS is an effective and safe treatment of OA, with its effect already evident at 30 days; in addition, its beneficial action is prolonged, being maintained for at least 3 months after the drug is discontinued. Full safety reports’ analyses confirm that CS is safe to use and has almost no side effects, in particular, it showed better gastrointestinal tolerance if compared with non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, the therapeutic strategy has proved to be cost-effective: treatment with CS reduced the use of NSAIDs and their side effects.
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Affiliation(s)
- Jean-Yves Reginster
- Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
- WHO Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, University of Liège, Liège, Belgium.
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
| | - Nicola Veronese
- Geriatric Unit, Department of Internal Medicine and Geriatrics, University of Palermo, 90100, Palermo, Italy
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Yu KE, Alder KD, Morris MT, Munger AM, Lee I, Cahill SV, Kwon HK, Back J, Lee FY. Re-appraising the potential of naringin for natural, novel orthopedic biotherapies. Ther Adv Musculoskelet Dis 2020; 12:1759720X20966135. [PMID: 33343723 PMCID: PMC7727086 DOI: 10.1177/1759720x20966135] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 09/22/2020] [Indexed: 01/03/2023] Open
Abstract
Naringin is a naturally occurring flavonoid found in plants of the Citrus genus that has historically been used in traditional Chinese medical regimens for the treatment of osteoporosis. Naringin modulates signaling through numerous molecular pathways critical to musculoskeletal development, cellular differentiation, and inflammation. Administration of naringin increases in vitro expression of bone morphogenetic proteins (BMPs) and activation of the Wnt/β-catenin and extracellular signal-related kinase (Erk) pathways, thereby promoting osteoblastic proliferation and differentiation from stem cell precursors for bone formation. Naringin also inhibits osteoclastogenesis by both modifying RANK/RANKL interactions and inducing apoptosis in osteoclasts in vitro. In addition, naringin acts on the estrogen receptor in bone to mimic the native bone-preserving effects of estrogen, with few systemic side effects on other estrogen-sensitive tissues. The efficacy of naringin therapy in reducing the osteolysis characteristic of common musculoskeletal pathologies such as osteoporosis, degenerative joint disease, and osteomyelitis, as well as inflammatory conditions affecting bone such as diabetes mellitus, has been extensively demonstrated in vitro and in animal models. Naringin thus represents a naturally abundant, cost-efficient agent whose potential for use in novel musculoskeletal biotherapies warrants re-visiting and further exploration through human studies. Here, we review the cellular mechanisms of action that have been elucidated regarding the action of naringin on bone resident cells and the bone microenvironment, in vivo evidence of naringin’s osteostimulative and chondroprotective properties in the setting of osteolytic bone disease, and current limitations in the development of naringin-containing translational therapies for common musculoskeletal conditions.
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Affiliation(s)
- Kristin E Yu
- Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, 330 Cedar St, TMP 523 PO Box 208071, New Haven, CT 06520-8071, USA
| | - Kareme D Alder
- Department of Orthopædics & Rehabilitation, Yale University, School of Medicine, New Haven, CT, USA
| | - Montana T Morris
- Department of Orthopædics & Rehabilitation, Yale University, School of Medicine, New Haven, CT, USA
| | - Alana M Munger
- Department of Orthopædics & Rehabilitation, Yale University, School of Medicine, New Haven, CT, USA
| | - Inkyu Lee
- Department of Orthopædics & Rehabilitation, Yale University, School of Medicine, New Haven, CT, USA; Department of Life Science, Chung-Ang University, Seoul, Republic of Korea
| | - Sean V Cahill
- Department of Orthopædics & Rehabilitation, Yale University, School of Medicine, New Haven, CT, USA
| | - Hyuk-Kwon Kwon
- Department of Orthopædics & Rehabilitation, Yale University, School of Medicine, New Haven, CT, USA
| | - JungHo Back
- Department of Orthopædics & Rehabilitation, Yale University, School of Medicine, New Haven, CT, USA
| | - Francis Y Lee
- Department of Orthopædics & Rehabilitation, Yale University, School of Medicine, New Haven, CT, USA
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Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol 2020; 17:59-66. [PMID: 33116279 DOI: 10.1038/s41584-020-00523-9] [Citation(s) in RCA: 290] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2020] [Indexed: 11/08/2022]
Abstract
Knee osteoarthritis (OA) is a heterogeneous disease associated with substantial effects on quality of life, and its clinical management is difficult. Among the several available guidelines for the management of knee OA, those from OARSI and ESCEO were updated in 2019. Here, we examine the similarities and differences between these two guidelines and provide a narrative to help guide health-care providers through the complexities of non-surgical management of knee OA. OARSI and ESCEO both recommend education, structured exercise and weight loss as core treatments, topical NSAIDs as first-line treatments and oral NSAIDs and intra-articular injections for persistent pain. Low-dose, short-term acetaminophen, pharmaceutical grade glucosamine and chondroitin sulfate are recommended by ESCEO whereas OARSI strongly recommends against their use (including all glucosamine and chondroitin formulations). Despite this difference, the two guidelines are consistent in the majority of their recommendations and provide useful treatment recommendations for individuals with OA and health-care providers.
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15
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Naumov AV, Khovasova NO, Moroz VI, Tkacheva ON. [The place of chondroitin sulfate and glucosamine sulfate in osteoarthritis pain therapy: a practical view from evidence-based medicine]. Zh Nevrol Psikhiatr Im S S Korsakova 2020; 119:112-117. [PMID: 31626227 DOI: 10.17116/jnevro2019119091112] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Osteoarthritis is one of the leading causes of a chronic pain in elderly people. Old and very old age in itself is a risk factor of a comorbidity, which often limits the therapy specified in clinical recommendations. First of all, it concerns NSAID. In such situations, priority is given to chondroitin sulfate (CS) and glucosamine sulfate (GS) having the anti-inflammatory properties comparable with effects of NSAID. CS and GS also promote the delay in progression of degenerative processes and restoration of the structure of cartilaginous tissue. The drugs of CS and GS groups are Chondroguard and Sustaguard Artro having the considerable evidence-based efficacy and safety and also a polymodality of effects in patients with a combination of osteoarthritis and socially important diseases (atherosclerosis, diabetes mellitus type 2, oncological diseases) and also geriatric syndromes (sarcopenia) and aging in general.
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Affiliation(s)
- A V Naumov
- Pirogov Russian National Research Medical University, Moscow, Russia; Russian Clinical and Research Center of Gerontology Pirogov Russian National Research Medical University), Moscow, Russia ,Abstract
| | - N O Khovasova
- Pirogov Russian National Research Medical University, Moscow, Russia; Russian Clinical and Research Center of Gerontology Pirogov Russian National Research Medical University), Moscow, Russia ,Abstract
| | - V I Moroz
- Russian Clinical and Research Center of Gerontology Pirogov Russian National Research Medical University), Moscow, Russia ,Abstract
| | - O N Tkacheva
- Pirogov Russian National Research Medical University, Moscow, Russia; Russian Clinical and Research Center of Gerontology Pirogov Russian National Research Medical University), Moscow, Russia ,Abstract
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16
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Bruyère O, Honvo G, Veronese N, Arden NK, Branco J, Curtis EM, Al-Daghri NM, Herrero-Beaumont G, Martel-Pelletier J, Pelletier JP, Rannou F, Rizzoli R, Roth R, Uebelhart D, Cooper C, Reginster JY. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum 2019; 49:337-350. [PMID: 31126594 DOI: 10.1016/j.semarthrit.2019.04.008] [Citation(s) in RCA: 338] [Impact Index Per Article: 56.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/31/2019] [Accepted: 04/25/2019] [Indexed: 12/27/2022]
Abstract
OBJECTIVES The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) sought to revisit the 2014 algorithm recommendations for knee osteoarthritis (OA), in light of recent efficacy and safety evidence, in order to develop an updated stepwise algorithm that provides practical guidance for the prescribing physician that is applicable in Europe and internationally. METHODS Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process, a summary of evidence document for each intervention in OA was provided to all members of an ESCEO working group, who were required to evaluate and vote on the strength of recommendation for each intervention. Based on the evidence collected, and on the strength of recommendations afforded by consensus of the working group, the final algorithm was constructed. RESULTS An algorithm for management of knee OA comprising a stepwise approach and incorporating consensus on 15 treatment recommendations was prepared by the ESCEO working group. Both "strong" and "weak" recommendations were afforded to different interventions. The algorithm highlights the continued importance of non-pharmacological interventions throughout the management of OA. Benefits and limitations of different pharmacological treatments are explored in this article, with particular emphasis on safety issues highlighted by recent literature analyses. CONCLUSIONS The updated ESCEO stepwise algorithm, developed by consensus from clinical experts in OA and informed by available evidence for the benefits and harms of various treatments, provides practical, current guidance that will enable clinicians to deliver patient-centric care in OA practice.
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Affiliation(s)
- Olivier Bruyère
- Division of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium; WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium.
| | - Germain Honvo
- Division of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium; WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Nicola Veronese
- Nicola Veronese: National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy
| | - Nigel K Arden
- Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, University of Oxford, Oxford, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
| | - Jaime Branco
- CEDOC, NOVA Medical School, Universidade Nova de Lisboa, Department of Rheumatology, CHLO, Hospital Egas Moniz, Lisbon, Portugal
| | - Elizabeth M Curtis
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
| | - Nasser M Al-Daghri
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Gabriel Herrero-Beaumont
- Department of Rheumatology, Bone and Joint Research Unit, Fundación Jiménez Diaz, Universidad Autonoma, Madrid, Spain
| | - Johanne Martel-Pelletier
- Division of Rheumatology, University of Montreal Hospital Centre (CHUM), Osteoarthritis Research Unit, CHUM Research Centre (CRCHUM), Montreal, Quebec, Canada
| | - Jean-Pierre Pelletier
- Division of Rheumatology, University of Montreal Hospital Centre (CHUM), Osteoarthritis Research Unit, CHUM Research Centre (CRCHUM), Montreal, Quebec, Canada
| | - François Rannou
- Division of Physical Medicine and Rehabilitation, Department of Rheumatology, AP-HP Cochin Hospital, Université Paris Descartes Sorbonne Paris Cité, and INSERM U1124, France
| | - René Rizzoli
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium; Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Roland Roth
- Max-Reger-Strasse 17-19, 45128, Essen-Suedviertel, Germany
| | - Daniel Uebelhart
- Division of Musculoskeletal, Internal Medicine and Oncological Rehabilitation, Department of Orthopaedics and Traumatology, Hôpital du Valais (HVS), Centre Hospitalier du Valais Romand (CHVR), CVP, 3963, Crans-Montana, Switzerland
| | - Cyrus Cooper
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
| | - Jean-Yves Reginster
- Division of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium; WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium; Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
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Update on the role of pharmaceutical-grade chondroitin sulfate in the symptomatic management of knee osteoarthritis. Aging Clin Exp Res 2019; 31:1163-1167. [PMID: 31243744 PMCID: PMC6661017 DOI: 10.1007/s40520-019-01253-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 06/19/2019] [Indexed: 12/13/2022]
Abstract
Osteoarthritis (OA) is the most prevalent musculoskeletal disease and a major cause of negative relevant outcomes, associated with an ever-increasing societal burden. Pharmaceutical-grade chondroitin sulfate (CS) was repeatedly reported to reduce pain and improve function in patients with knee OA. This treatment was also shown to be cost-effective, compared to placebo, up to 24 months. However, controversies still persist regarding the usefulness of CS for patients with knee OA, mainly due to inconsistent reports from various clinical trials. In this literature review, we aimed to summarize the main most recent findings on the efficacy and safety of CS in OA. Based on the results of studies presenting a low risk of bias, the most recent meta-analysis shows that only the pharmaceutical-grade CS may be considered as an appropriate background treatment for the management of knee OA. Evidence from another recent meta-analysis, using data from full safety reports, confirms the good safety profile of CS in OA. This new evidence on efficacy and safety suggests that recommendations for the use of CS in patients with knee OA cannot be extrapolated to other low-grade preparations as generics, nutraceutical-grade or over-the-counter preparations.
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18
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Veronese N, Cooper C, Reginster JY, Hochberg M, Branco J, Bruyère O, Chapurlat R, Al-Daghri N, Dennison E, Herrero-Beaumont G, Kaux JF, Maheu E, Rizzoli R, Roth R, Rovati LC, Uebelhart D, Vlaskovska M, Scheen A. Type 2 diabetes mellitus and osteoarthritis. Semin Arthritis Rheum 2019; 49:9-19. [PMID: 30712918 PMCID: PMC6642878 DOI: 10.1016/j.semarthrit.2019.01.005] [Citation(s) in RCA: 132] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 12/13/2018] [Accepted: 01/08/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are common diseases that frequently co-exist, along with overweight/obesity. While the mechanical impact of excess body weight on joints may explain lower limb OA, we sought to explore whether T2DM is linked to OA outside of excess weight and whether T2DM may play a role in OA pathophysiology. The consequence of T2DM on OA outcomes is a question of research interest. METHODS We conducted a critical review of the literature to explore the association between T2DM and OA, whether any association is site-specific for OA, and whether the presence of T2DM impacts on OA outcomes. We also reviewed the literature to assess the safety of anti-OA treatments in patients with T2DM. RESULTS T2DM has a pathogenic effect on OA through 2 major pathways involving oxidative stress and low-grade chronic inflammation resulting from chronic hyperglycemia and insulin resistance. T2DM is a risk factor for OA progression and has a negative impact on arthroplasty outcomes. Evidence is mounting for safety concerns with some of the most frequently prescribed anti-OA medications, including paracetamol, non-steroidal anti-inflammatory drugs, and corticosteroid injections, while other anti-OA medications may be safely prescribed in OA patients with T2DM, such as glucosamine and intra-articular hyaluronic acid. CONCLUSIONS Future research is needed to better understand whether diabetes control and prevention can modulate OA occurrence and progression. The selection of therapy to treat OA symptoms in patients with T2DM may require careful consideration of the evidence based to avoid untoward safety issues.
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Affiliation(s)
- Nicola Veronese
- National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy.
| | - Cyrus Cooper
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK; WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Jean-Yves Reginster
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium; Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman B23, 4000 Liège, Belgium; Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Marc Hochberg
- Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; Geriatric Research, Education and Clinical Center, Baltimore, MD, USA; Medical Care Clinical Center, VA Maryland Health Care System, Baltimore, MD, USA
| | - Jaime Branco
- CEDOC, NOVA Medical School, Universidade Nova de Lisboa, Department of Rheumatology, CHLO, Hospital Egas Moniz, Lisbon, Portugal
| | - Olivier Bruyère
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium; Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman B23, 4000 Liège, Belgium
| | - Roland Chapurlat
- INSERM UMR 1033, Université de Lyon, Hôpital E Herriot, 69437 Lyon cedex 03, France
| | - Nasser Al-Daghri
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Elaine Dennison
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
| | - Gabriel Herrero-Beaumont
- Department of Rheumatology, Bone and Joint Research Unit, Fundación Jiménez Diaz, Universidad Autonoma, Madrid, Spain
| | - Jean-François Kaux
- Department of Physical & Rehabilitation Medicine and Sports Traumatology, SportS(2), FIFA Medical Centre of Excellence, University and University Hospital of Liège, 4000 Liège, Belgium
| | - Emmanuel Maheu
- Rheumatology Department, AP-HP, Saint-Antoine Hospital, 4 Blvd. Beaumarchais, 75011 Paris, France
| | - René Rizzoli
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium; Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Roland Roth
- Max-Reger-Strasse 17-19, 45128 Essen-Suedviertel, Germany
| | - Lucio C Rovati
- School of Medicine and Surgery, University of Milano - Bicocca, Milan, Italy; Department of Clinical Research, Rottapharm Biotech, Monza, Italy
| | - Daniel Uebelhart
- Division of Musculoskeletal, Internal Medicine and Oncological Rehabilitation, Department of Orthopaedics and Traumatology, Hôpital du Valais (HVS), Centre Hospitalier du Valais Romand (CHVR), CVP, Crans-Montana, Switzerland
| | - Mila Vlaskovska
- Medical University Sofia, Medical Faculty, Department of Pharmacology, 2, Zdrave str., 1431 Sofia, Bulgaria
| | - André Scheen
- Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit, Department of Medicine, University of Liège, CHU Liège, Sart Tilman B35, B-4000 Liège, Belgium
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Honvo G, Bruyère O, Geerinck A, Veronese N, Reginster JY. Efficacy of Chondroitin Sulfate in Patients with Knee Osteoarthritis: A Comprehensive Meta-Analysis Exploring Inconsistencies in Randomized, Placebo-Controlled Trials. Adv Ther 2019; 36:1085-1099. [PMID: 30879253 PMCID: PMC6824370 DOI: 10.1007/s12325-019-00921-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Indexed: 12/12/2022]
Abstract
INTRODUCTION There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results. METHODS We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau2 and I2 statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized mean differences (SMDs), with a 95% confidence interval (CI). Heterogeneity was explored by stratifying the analyses according to pre-specified study-level characteristics and assessing the sources of funnel plot asymmetry. RESULTS The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: - 0.63; 95% CI: - 0.91, - 0.35; I2 = 94%) and improved function (SMD: - 0.82; 95% CI: - 1.31, - 0.33; I2 = 95%). When limiting the analysis to studies with a low risk of bias, the pharmaceutical grade CS of IBSA origin showed a greater reduction in pain (SMD: - 0.25; 95% CI: - 0.34, - 0.16; I2 = 75%) and function (SMD: - 0.33; 95% CI: - 0.47, - 0.20; I2 = 53%, p = 0.07) compared with the other preparations (SMDPain: - 0.08; 95% CI: - 0.19, + 0.02; I2 = 20%; SMDFunction: - 0.18; 95% CI: - 0.36, +0.01; I2 = 0%). Assessing funnel plot asymmetry in the studies with a low risk of bias, we found strong correlations between the treatment effects and study size (pain: rS = 0.93; LI: rS = 0.86; p < 0.05). Ultimately, there was no residual heterogeneity in the CS effects when the smallest studies were removed from the analyses. CONCLUSION This new meta-analysis suggests that CS provides a moderate benefit for pain and has a large effect on function in knee OA, however with large inconsistency. The risks of bias, brand and study size were the factors explaining heterogeneity among the clinical trial results.
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Affiliation(s)
- Germain Honvo
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium.
| | - Olivier Bruyère
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Anton Geerinck
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Nicola Veronese
- National Research Council, Neuroscience Institute, Aging Branch, Padua, Italy
| | - Jean-Yves Reginster
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
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Honvo G, Reginster JY, Rabenda V, Geerinck A, Mkinsi O, Charles A, Rizzoli R, Cooper C, Avouac B, Bruyère O. Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. Drugs Aging 2019; 36:65-99. [PMID: 31073924 PMCID: PMC6509099 DOI: 10.1007/s40266-019-00662-z] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). OBJECTIVE We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. METHODS We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. RESULTS Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58-3.13; I2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02-4.04; I2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36-4.96; I2 = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42-4.31; I2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85-5.47; I2 = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo. CONCLUSIONS GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.
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Affiliation(s)
- Germain Honvo
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Jean-Yves Reginster
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Véronique Rabenda
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Anton Geerinck
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Ouafa Mkinsi
- Rheumatology Department, IBN ROCHD University Hospital, Casablanca, Morocco
| | - Alexia Charles
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Rene Rizzoli
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
- Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Cyrus Cooper
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
- National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
| | - Bernard Avouac
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | - Olivier Bruyère
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
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Istomina EV, Shikhkerimov RK. The possibilities of using chondroitin sulfate in patients with chronic back pain. Zh Nevrol Psikhiatr Im S S Korsakova 2019; 119:12-15. [DOI: 10.17116/jnevro201911903112] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Effect of collagen supplementation on osteoarthritis symptoms: a meta-analysis of randomized placebo-controlled trials. INTERNATIONAL ORTHOPAEDICS 2018; 43:531-538. [DOI: 10.1007/s00264-018-4211-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 10/19/2018] [Indexed: 01/06/2023]
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Simental-Mendía M, Sánchez-García A, Vilchez-Cavazos F, Acosta-Olivo CA, Peña-Martínez VM, Simental-Mendía LE. Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials. Rheumatol Int 2018; 38:1413-1428. [PMID: 29947998 DOI: 10.1007/s00296-018-4077-2] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 06/02/2018] [Indexed: 01/10/2023]
Abstract
Although glucosamine and chondroitin sulfate have showed beneficial effects on joint tissues in osteoarthritis (OA), their therapeutic use in the clinical setting is still debatable. Hence, a systematic review and meta-analysis of randomized placebo-controlled trials was conducted to investigate the efficacy of glucosamine and chondroitin sulfate on knee OA symptoms. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials evaluating the effect of orally administered glucosamine and/or chondroitin sulfate on OA symptoms using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and/or the Visual Analog Scale (VAS). Meta-analysis was conducted using a random-effects model and generic inverse-variance method. Heterogeneity was tested using the I2 statistic index. Treatments with glucosamine and chondroitin were found to significantly reduce pain in VAS [weighted mean difference (WMD) - 7.41 mm, 95% CI - 14.31, - 0.51, p = 0.04 and WMD - 8.35 mm, 95% CI - 11.84, - 4.85, p < 0.00001, respectively]. Their combination did not show this behavior (WMD - 0.28 mm, 95% CI - 8.87, 8.32, p = 0.95). None of the glucosamine, chondroitin or their combination had a significant positive effect on the total WOMAC index and its subscores. Oral supplementation with glucosamine or chondroitin sulfate reduces pain in knee OA. However, there is no additional effect using both therapeutic agents in combination for the management of symptomatic knee OA.
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Affiliation(s)
- Mario Simental-Mendía
- Orthopedics and Traumatology Service, Universidad Autónoma de Nuevo León, University Hospital ''Dr. José Eleuterio González'', Monterrey, Nuevo León, Mexico
| | - Adriana Sánchez-García
- Endocrinology Division, Universidad Autónoma de Nuevo León, University Hospital ''Dr. José Eleuterio González'', Monterrey, Nuevo León, Mexico
| | - Félix Vilchez-Cavazos
- Orthopedics and Traumatology Service, Universidad Autónoma de Nuevo León, University Hospital ''Dr. José Eleuterio González'', Monterrey, Nuevo León, Mexico
| | - Carlos A Acosta-Olivo
- Orthopedics and Traumatology Service, Universidad Autónoma de Nuevo León, University Hospital ''Dr. José Eleuterio González'', Monterrey, Nuevo León, Mexico
| | - Víctor M Peña-Martínez
- Orthopedics and Traumatology Service, Universidad Autónoma de Nuevo León, University Hospital ''Dr. José Eleuterio González'', Monterrey, Nuevo León, Mexico
| | - Luis E Simental-Mendía
- Unidad de Investigación Biomédica, Delegación Durango, Instituto Mexicano del Seguro Social, Canoas 100, Col. Los Angeles, 34067, Durango, DGO, Mexico.
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Zhu X, Sang L, Wu D, Rong J, Jiang L. Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials. J Orthop Surg Res 2018; 13:170. [PMID: 29980200 PMCID: PMC6035477 DOI: 10.1186/s13018-018-0871-5] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 06/25/2018] [Indexed: 12/20/2022] Open
Abstract
Objective To assess the symptomatic effectiveness and safety of oral symptomatic slow-acting drugs (SYSADOAs) on the treatment of knee and/or hip osteoarthritis, such as chondroitin, glucosamine, and combination treatment with chondroitin plus glucosamine. Methods We searched electronic database including PubMed, Embase, Cochrane Library, and the reference lists of relevant articles published from inception to May 22, 2018. An updated meta-analysis was performed to assess the effectiveness of these slow-acting drugs for osteoarthritis. Results Twenty-six articles describing 30 trials met our inclusion criteria and were included in the meta-analysis. The estimates between chondroitin and placebo showed that chondroitin could alleviate pain symptoms and improve function. Compared with placebo, glucosamine proved significant effect only on stiffness improvement. However, the combination therapy did not have enough evidence to be superior to placebo. Additionally, there was no significant difference in the incidence of AEs and discontinuations of AEs when compared with placebo. Conclusions Given the effectiveness of these symptomatic slow-acting drugs, oral chondroitin is more effective than placebo on relieving pain and improving physical function. Glucosamine showed effect on stiffness outcome. Regarding on the limited number of combination therapy, further studies need to investigate the accurate effectiveness. This information accompanied with the tolerability and economic costs of included treatments would be conducive to making decisions for clinicians. Electronic supplementary material The online version of this article (10.1186/s13018-018-0871-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xiaoyue Zhu
- Baoshan Center for Disease Control and Prevention, Shanghai, People's Republic of China
| | - Lingli Sang
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China
| | - Dandong Wu
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China
| | - Jiesheng Rong
- Department of Orthopedics Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China
| | - Liying Jiang
- Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, People's Republic of China.
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Tuncer T, Cay FH, Altan L, Gurer G, Kacar C, Ozcakir S, Atik S, Ayhan F, Durmaz B, Eskiyurt N, Genc H, GokceKutsal Y, Gunaydin R, Hepguler S, Hizmetli S, Kaya T, Kurtais Y, Saridogan M, Sindel D, Sutbeyaz S, Sendur OF, Ugurlu H, Unlu Z. 2017 update of the Turkish League Against Rheumatism (TLAR) evidence-based recommendations for the management of knee osteoarthritis. Rheumatol Int 2018; 38:1315-1331. [PMID: 29777340 DOI: 10.1007/s00296-018-4044-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 05/05/2018] [Indexed: 12/19/2022]
Abstract
In a Turkish League Against Rheumatism (TLAR) project, evidence-based recommendations for the management of knee osteoarthritis (OA) was developed for the first time in our country in 2012 (TLAR-2012). In accordance with developing medical knowledge and scientific evidence, recommendations were updated. The committee was composed of 22 physical medicine and rehabilitation specialists (4 have rheumatology subspeciality also) and an orthopaedic surgeon. Systematic literature search were applied on Pubmed, Embase, Cochrane and Turkish Medical Index for the dates between January the 1st 2012 and January the 29th of 2015. The articles were assessed for quality and classified according to hierarchy for the level of evidence, and the selected ones sent to committee members electronically. They were asked to develop new recommendations. In the meeting in 2015, the format of the recommendations was decided to be patient-based and considering the grade and the severity of the disease. By the discussion of the each item under the light of new evidences, the final recommendations were developed. Each item was voted electronically on a 10-cm visual analogue scale (VAS) and the strength of recommendation (SoR) was calculated. In the light of evidences, totally 11 titles of recommendations were developed; the first 7 were applicable to each patient in every stages of the disease, remaining were for defined specific clinical situations. The mean SoR value of the recommendations was between 7.44 and 9.93. TLAR-2012 recommendations were updated in a new format. We think that, present recommendations will be beneficial for the physicians who manage, as well as the patients who suffer from the disease.
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Affiliation(s)
- Tiraje Tuncer
- School Of Medicine, Physical Medicine Rehabilitation, Akdeniz University, Antalya, Turkey
| | - Fatih Hasan Cay
- Antalya Training and Research Hospital, Physical Medicine Rehabilitation and Rheumatology, University of Health Sciences, Antalya, Turkey.
| | - Lale Altan
- School of Medicine, Physical Medicine Rehabilitation, Uludağ University, Bursa, Turkey
| | - Gulcan Gurer
- School of Medicine, Physical Medicine Rehabilitation and Rheumatology, Adnan Menderes University, Aydın, Turkey
| | - Cahit Kacar
- School Of Medicine, Physical Medicine Rehabilitation and Rheumatology, Akdeniz University, Antalya, Turkey
| | - Suheda Ozcakir
- School of Medicine, Physical Medicine Rehabilitation, Uludağ University, Bursa, Turkey
| | - Sahap Atik
- School of Medicine, Orthopaedics and Traumatology, Gazi University, Ankara, Turkey
| | - Figen Ayhan
- Ankara Training and Research Hospital, Physical Medicine Rehabilitation, University Of Health Sciences, Ankara, Turkey
| | - Berrin Durmaz
- School of Medicine, Physical Medicine Rehabilitation, Ege University, Izmir, Turkey
| | - Nurten Eskiyurt
- Istanbul School of Medicine, Physical Medicine Rehabilitation (Retired), İstanbul University, Istanbul, Turkey
| | - Hakan Genc
- Ankara Training and Research Hospital, Physical Medicine Rehabilitation, University Of Health Sciences, Ankara, Turkey
| | - Yesim GokceKutsal
- School of Medicine, Physical Medicine Rehabilitation, Hacettepe University, Ankara, Turkey
| | - Rezzan Gunaydin
- Physical Medicine Rehabilitation, Medical Park İzmir Hospital, Izmir, Turkey
| | - Simin Hepguler
- School of Medicine, Physical Medicine Rehabilitation, Ege University, Izmir, Turkey
| | - Sami Hizmetli
- School of Medicine, Physical Medicine Rehabilitation and Rheumatology Physical Medicine Rehabilitation, Cumhuriyet University, Sivas, Turkey
| | - Taciser Kaya
- Bozyaka Training and Research Hospital, Physical Medicine Rehabilitation, University of Health Sciences, Izmir, Turkey
| | - Yesim Kurtais
- School of Medicine, Physical Medicine Rehabilitation, Ankara University, Ankara, Turkey
| | - Merih Saridogan
- Cerrahpaşa School of Medicine, Physical Medicine Rehabilitation, İstanbul University, Istanbul, Turkey
| | - Dilsad Sindel
- İstanbul School of Medicine, Physical Medicine Rehabilitation, İstanbul University, Istanbul, Turkey
| | - Serap Sutbeyaz
- Kayseri Training and Research Hospital, Physical Medicine Rehabilitation, University of Health Sciences, Kayseri, Turkey
| | - Omer Faruk Sendur
- School of Medicine, Physical Medicine Rehabilitation, Adnan Menderes University, Aydın, Turkey
| | - Hatice Ugurlu
- School of Medicine, Physical Medicine Rehabilitation, Necmettin Erbakan University, Konya, Turkey
| | - Zeliha Unlu
- School of Medicine, Physical Medicine Rehabilitation, Celal Bayar University, Manisa, Turkey
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Bruyère O, Cooper C, Al-Daghri NM, Dennison EM, Rizzoli R, Reginster JY. Inappropriate claims from non-equivalent medications in osteoarthritis: a position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Aging Clin Exp Res 2018; 30:111-117. [PMID: 29177637 PMCID: PMC5814472 DOI: 10.1007/s40520-017-0861-1] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 11/11/2017] [Indexed: 12/12/2022]
Abstract
Osteoarthritis (OA) is a progressive joint disease, that occurs frequently in the aging population and is a major cause of disability worldwide. Both glucosamine and chondroitin are biologically active molecules that are substrates for proteoglycan, an essential component of the cartilage matrix. Evidence supports the use of glucosamine and chondroitin as symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) with impact on OA symptoms and disease-modifying effects in the long term. Glucosamine and chondroitin are administered in exogenous form as a sulfate salt and multiple formulations of these agents are available, both as prescription-grade products and nutritional supplements. However, while all preparations may claim to deliver a therapeutic level of glucosamine or chondroitin not all are supported by clinical evidence. Only patented crystalline glucosamine sulfate (pCGS) is shown to deliver consistently high glucosamine bioavailability and plasma concentration in humans, which corresponds to demonstrated clinical efficacy. Similarly, clinical evidence supports only the pharmaceutical-grade chondroitin sulfate. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) advocates, through careful consideration of the evidence base, that judicious choice of glucosamine and chondroitin formulation is essential to maximize clinical benefit, patient adherence and satisfaction with treatment. In future, the ESCEO recommends that complex molecules with biological activity such as pCGS may be treated as "biosimilars" akin to the European Medicines Agency guidance on biological medicinal products. It seems likely that for all other complex molecules classed as SYSADOAs, the recommendation to use only formulations clearly supported by the evidence-base should apply.
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Affiliation(s)
- Olivier Bruyère
- Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman B23, 4000, Liège, Belgium
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Cyrus Cooper
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
- NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Nasser M Al-Daghri
- Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Elaine M Dennison
- NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
| | - René Rizzoli
- Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Jean-Yves Reginster
- Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman B23, 4000, Liège, Belgium.
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium.
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Access to Highly Purified Chondroitin Sulfate for Appropriate Treatment of Osteoarthritis: A Review. MEDICINE ACCESS @ POINT OF CARE 2017. [DOI: 10.5301/maapoc.0000022] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Current pharmacological therapies for osteoarthritis are symptom-focused and aimed at controlling pain. However, currently approved symptom-modifying agents do not restore the structure and function of damaged joints. Symptomatic slow-acting drugs in osteoarthritis (SySADOAs), including the sulfated glycosaminoglycan, chondroitin sulfate, have shown promising beneficial effects on the pain and other symptoms of osteoarthritis, and some may also have a positive effect on cartilage, slowing the progression of joint deterioration in osteoarthritis. A highly-purified, standardized, pharmaceutical-grade preparation of chondroitin sulfate has shown activity in osteoarthritis and has become one of the most prescribed SySADOAs. However, in many countries, formulations of chondroitin sulfate of various sources and purity are available as food supplements or nutraceuticals. As the effects of chondroitin sulfate could vary according to the characteristics of the chondroitin sulfate employed, including source, purity, or structural organization, clinical data from well-designed studies of pharmaceutical-grade chondroitin sulfate should not be extrapolated to support clinical efficacy claims of food supplements; nor should results from trials of chondroitin sulfate-containing food supplements be used to draw conclusions about the efficacy of pharmaceutical-grade chondroitin sulfate. This article reviews the evidence for the role of highly-purified pharmaceutical-grade chondroitin sulfate in the treatment of osteoarthritis and examines the efficacy and safety concerns of other formulations of chondroitin sulfate. Highly-purified pharmaceutical-grade chondroitin sulfate has mild-to-moderate efficacy in the treatment of symptomatic osteoarthritis, with clinically meaningful efficacy.
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28
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PANLAR Consensus Recommendations for the Management in Osteoarthritis of Hand, Hip, and Knee. J Clin Rheumatol 2017; 22:345-54. [PMID: 27660931 DOI: 10.1097/rhu.0000000000000449] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE The objective of this consensus is to update the recommendations for the treatment of hand, hip, and knee osteoarthritis (OA) by agreeing on key propositions relating to the management of hand, hip, and knee OA, by identifying and critically appraising research evidence for the effectiveness of the treatments and by generating recommendations based on a combination of the available evidence and expert opinion of 18 countries of America. METHODS Recommendations were developed by a group of 48 specialists of rheumatologists, members of other medical disciplines (orthopedics and physiatrists), and three patients, one for each location of OA. A systematic review of existing articles, meta-analyses, and guidelines for the management of hand, hip, and knee OA published between 2008 and January 2014 was undertaken. The scores for Level of Evidence and Grade of Recommendation were proposed and fully consented within the committee based on The American Heart Association Evidence-Based Scoring System. The level of agreement was established through a variation of Delphi technique. RESULTS Both "strong" and "conditional" recommendations are given for management of hand, hip, and knee OA and nonpharmacological, pharmacological, and surgical modalities of treatment are presented according to the different levels of agreement. CONCLUSIONS These recommendations are based on the consensus of clinical experts from a wide range of disciplines taking available evidence into account while balancing the benefits and risks of nonpharmacological, pharmacological, and surgical treatment modalities, and incorporating their preferences and values. Different backgrounds in terms of patient education or drug availability in different countries were not evaluated but will be important.
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Rojas-Briones V, Harrison-Muñoz S, Irarrázaval S. Is chondroitin sulfate effective for osteoarthritis? Medwave 2017; 17:e6929. [PMID: 28452976 DOI: 10.5867/medwave.2017.6929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 12/30/2016] [Indexed: 11/27/2022] Open
Abstract
Osteoarthritis is the most prevalent chronic articular disease, in which pain is one of the main symptoms and the major determinant of functional loss. Several therapeutic options have been proposed, including chondroitin sulfate, but its actual usefulness has not yet been established. To answer this question we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified 13 systematic reviews including 50 randomized trials overall. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded it is not clear whether the use of chondroitin sulfate leads to an improvement in pain or functionality in osteoarthritis because the certainty of the evidence is very low.
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Affiliation(s)
- Valentina Rojas-Briones
- Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Proyecto Epistemonikos, Santiago, Chile. . Address: Escuela de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Oficina 310, Santiago Centro, Chile
| | - Stephanie Harrison-Muñoz
- Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Proyecto Epistemonikos, Santiago, Chile
| | - Sebastián Irarrázaval
- Proyecto Epistemonikos, Santiago, Chile; Departamento de Traumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
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Roman‐Blas JA, Castañeda S, Sánchez‐Pernaute O, Largo R, Herrero‐Beaumont G, Blanco FJ, Gómez RB, Burlato MC, González CG, Vázquez JLG, Martín‐Mola E, Brancós AIM, Navarro Blasco FJ, Román Ivorra JA, Rosas Gómez de Salazar JC. Combined Treatment With Chondroitin Sulfate and Glucosamine Sulfate Shows No Superiority Over Placebo for Reduction of Joint Pain and Functional Impairment in Patients With Knee Osteoarthritis: A Six‐Month Multicenter, Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial. Arthritis Rheumatol 2016; 69:77-85. [DOI: 10.1002/art.39819] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Accepted: 07/14/2016] [Indexed: 01/21/2023]
Affiliation(s)
| | - Santos Castañeda
- Hospital de La Princesa, Madrid, Spain. Members of the CS/GS Combined Therapy Study Group are shown in Appendix A
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Bishnoi M, Jain A, Hurkat P, Jain SK. Chondroitin sulphate: a focus on osteoarthritis. Glycoconj J 2016; 33:693-705. [PMID: 27194526 DOI: 10.1007/s10719-016-9665-3] [Citation(s) in RCA: 121] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 03/28/2016] [Accepted: 03/29/2016] [Indexed: 01/19/2023]
Abstract
Chondroitin sulfate (CS) being a natural glycosaminoglycan is found in the cartilage and extracellular matrix. It shows clinical benefits in symptomatic osteoarthritis (OA) of the finger, knee, hip joints, low back, facial joints and other diseases due to its anti-inflammatory activity. It also helps in OA by providing resistance to compression, maintaining the structural integrity, homeostasis, slows breakdown and reduces pain in sore muscles. It is most often used in combination with glucosamine to treat OA. CS is a key role player in the regulation of cell development, cell adhesion, proliferation, and differentiation. Its commercial applications have been continuously explored in the engineering of biological tissues and its combination with other biopolymers to formulate scaffolds which promote and accelerate the regeneration of damaged structure. It is approved in the USA as a dietary supplement for OA, while it is used as a symptomatic slow-acting drug (SYSADOA) in Europe and some other countries. Any significant side effects or overdoses of CS have not been reported in clinical trials suggesting its long-term safety. This review highlights the potential of CS, either alone or in combination with other drugs, to attract the scientists engaged in OA treatment and management across the world.
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Affiliation(s)
- Mamta Bishnoi
- Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar, MP, 470 003, India
| | - Ankit Jain
- Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar, MP, 470 003, India
| | - Pooja Hurkat
- Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar, MP, 470 003, India
| | - Sanjay K Jain
- Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar, MP, 470 003, India.
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Marconcin P, Espanha M, Yázigi F, Campos P. The PLE(2)NO self-management and exercise program for knee osteoarthritis: Study Protocol for a Randomized Controlled Trial. BMC Musculoskelet Disord 2016; 17:250. [PMID: 27267755 PMCID: PMC4896008 DOI: 10.1186/s12891-016-1115-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Accepted: 06/02/2016] [Indexed: 11/21/2022] Open
Abstract
Background International recommendations suggest exercise and self-management programs, including non-pharmacological treatments, for knee osteoarthritis (KOA) because they can benefit pain relief and improve function and exercise adherence. The implementation of a combined self-management and exercise program termed PLE2NO may be a good method for controlling KOA symptoms because it encourages the development of self-efficacy to manage the pathology. This study will assess the effects of a self-management and exercise program in comparison to an educational intervention (control program) on symptoms, physical fitness, health-related quality of life, self-management behaviors, self-efficacy, physical activity level and coping strategies. Methods/Design This PLE2NO study is a single-blinded, randomized controlled trial of elderly (aged above 60 yrs old) patients with clinical and radiographic KOA. The patients will be allocated into either an educational group (control) or a self-management and exercise group (experimental). All participants will receive a supplement of chondroitin and glucosamine sulfates. This paper describes the protocol that will be used in the PLE2NO program. Discussion This program has several strengths. First, it involves a combination of self-management and exercise approaches, is available in close proximity to the patients and occurs over a short period of time. The latter two characteristics are crucial for maintaining participant adherence. Exercise components will be implemented using low-cost resources that permit their widespread application. Moreover, the program will provide guidance regarding the effectiveness of using a self-management and exercise program to control KOA symptoms and improve self-efficacy and health-related quality of life. Trial registration NCT02562833 (09/23/2015)
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Affiliation(s)
- Priscila Marconcin
- Universidade de Lisboa, Faculdade de Motricidade Humana, CIPER, LBMF, P-1499-002, Estrada da Costa, 1499-002 Cruz Quebrada, Dafundo, Portugal. .,CAPES Foundation, Ministry of Education of Brazil, Brasília, DF, 70040-020, Brazil.
| | - Margarida Espanha
- Universidade de Lisboa, Faculdade de Motricidade Humana, CIPER, LBMF, P-1499-002, Estrada da Costa, 1499-002 Cruz Quebrada, Dafundo, Portugal
| | - Flávia Yázigi
- Universidade de Lisboa, Faculdade de Motricidade Humana, CIPER, Laboratório de Fisiologia eBioquímica do Exercício, P-1499-002, Estrada da Costa 1499-002 Cruz Quebrada, Dafundo, Portugal
| | - Pedro Campos
- Universidade de Lisboa, Faculdade de Motricidade Humana, CIPER, LBMF, P-1499-002, Estrada da Costa, 1499-002 Cruz Quebrada, Dafundo, Portugal
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Bruyère O, Cooper C, Pelletier JP, Maheu E, Rannou F, Branco J, Luisa Brandi M, Kanis JA, Altman RD, Hochberg MC, Martel-Pelletier J, Reginster JY. A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis—From evidence-based medicine to the real-life setting. Semin Arthritis Rheum 2016; 45:S3-11. [DOI: 10.1016/j.semarthrit.2015.11.010] [Citation(s) in RCA: 166] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Revised: 11/12/2015] [Accepted: 11/25/2015] [Indexed: 01/27/2023]
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Efficacy and safety of glucosamine sulfate in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum 2016; 45:S12-7. [DOI: 10.1016/j.semarthrit.2015.11.011] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Revised: 11/12/2015] [Accepted: 11/25/2015] [Indexed: 12/31/2022]
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Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ, Cochrane Musculoskeletal Group. Chondroitin for osteoarthritis. Cochrane Database Syst Rev 2015; 1:CD005614. [PMID: 25629804 PMCID: PMC4881293 DOI: 10.1002/14651858.cd005614.pub2] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Osteoarthritis, a common joint disorder, is one of the leading causes of disability. Chondroitin has emerged as a new treatment. Previous meta-analyses have shown contradictory results on the efficacy of chondroitin. This, in addition to the publication of more trials, necessitates a systematic review. OBJECTIVES To evaluate the benefit and harm of oral chondroitin for treating osteoarthritis compared with placebo or a comparator oral medication including, but not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, opioids, and glucosamine or other "herbal" medications. SEARCH METHODS We searched seven databases up to November 2013, including the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials. We searched the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) websites for adverse effects. Trial registers were not searched. SELECTION CRITERIA All randomized or quasi-randomized clinical trials lasting longer than two weeks, studying adults with osteoarthritis in any joint, and comparing chondroitin with placebo, an active control such as NSAIDs, or other "herbal" supplements such as glucosamine. DATA COLLECTION AND ANALYSIS Two review authors independently performed all title assessments, data extractions, and risk of bias assessments. MAIN RESULTS Forty-three randomized controlled trials including 4,962 participants treated with chondroitin and 4,148 participants given placebo or another control were included. The majority of trials were in knee OA, with few in hip and hand OA. Trial duration varied from 1 month to 3 years. Participants treated with chondroitin achieved statistically significantly and clinically meaningful better pain scores (0-100) in studies less than 6 months than those given placebo with an absolute risk difference of 10% lower (95% confidence interval (CI), 15% to 6% lower; number needed to treat (NNT) = 5 (95% CI, 3 to 8; n = 8 trials) (level of evidence, low; risk of bias, high); but there was high heterogeneity between the trials (T(2) = 0.07; I(2) = 70%, which was not easily explained by differences in risk of bias or study sample size). In studies longer than 6 months, the absolute risk difference for pain was 9% lower (95% CI 18% lower to 0%); n = 6 trials; T(2) = 0.18; I(2) = 83% ), again with low level of evidence.For the Western Ontario and McMaster Universities Osteoarthritis Index Minimal Clinically Important Improvement (WOMAC MCII Pain subscale) outcome, a reduction in knee pain by 20% was achieved by 53/100 in the chondroitin group versus 47/100 in the placebo group, an absolute risk difference of 6% (95% CI 1% to 11%), (RR 1.12, 95% CI 1.01 to 1.24; T(2) = 0.00; I(2) = 0%) (n = 2 trials, 1253 participants; level of evidence, high; risk of bias, low).Differences in Lequesne's index (composite of pain,function and disability) statistically significantly favoured chondroitin as compared with placebo in studies under six months, with an absolute risk difference of 8% lower (95% CI 12% to 5% lower; T(2)= 0.78; n = 7 trials) (level of evidence, moderate; risk of bias, unclear), also clinically meaningful. Loss of minimum joint space width in the chondroitin group was statistically significantly less than in the placebo group, with a relative risk difference of 4.7% less (95% CI 1.6% to 7.8% less; n = 2 trials) (level of evidence, high; risk of bias, low). Chondroitin was associated with statistically significantly lower odds of serious adverse events compared with placebo with Peto odds ratio of 0.40 (95% CI 0.19 to 0.82; n = 6 trials) (level of evidence, moderate). Chondroitin did not result in statistically significant numbers of adverse events or withdrawals due to adverse events compared with placebo or another drug. Adverse events were reported in a limited fashion, with some studies providing data and others not.Comparisons of chondroitin taken alone or in combination with glucosamine or another supplement showed a statistically significant reduction in pain (0-100) when compared with placebo or an active control, with an absolute risk difference of 10% lower (95% CI 14% to 5% lower); NNT = 4 (95% CI 3 to 6); T(2) = 0.33; I(2) = 91%; n = 17 trials) (level of evidence, low). For physical function, chondroitin in combination with glucosamine or another supplement showed no statistically significant difference from placebo or an active control, with an absolute risk difference of 1% lower (95% CI 6% lower to 3% higher with T(2) = 0.04; n = 5 trials) (level of evidence, moderate). Differences in Lequesne's index statistically significantly favoured chondroitin as compared with placebo, with an absolute risk difference of 8% lower (95% CI, 12% to 4% lower; T(2) = 0.12; n = 10 trials) (level of evidence, moderate). Chondroitin in combination with glucosamine did not result in statistically significant differences in the numbers of adverse events, withdrawals due to adverse events, or in the numbers of serious adverse events compared with placebo or with an active control.The beneficial effects of chondroitin in pain and Lequesne's index persisted when evidence was limited to studies with adequate blinding or studies that used appropriate intention to treat (ITT) analyses. These beneficial effects were uncertain when we limited data to studies with appropriate allocation concealment or a large study sample (> 200) or to studies without pharmaceutical funding. AUTHORS' CONCLUSIONS A review of randomized trials of mostly low quality reveals that chondroitin (alone or in combination with glucosamine) was better than placebo in improving pain in participants with osteoarthritis in short-term studies. The benefit was small to moderate with an 8 point greater improvement in pain (range 0 to 100) and a 2 point greater improvement in Lequesne's index (range 0 to 24), both seeming clinically meaningful. These differences persisted in some sensitivity analyses and not others. Chondroitin had a lower risk of serious adverse events compared with control. More high-quality studies are needed to explore the role of chondroitin in the treatment of osteoarthritis. The combination of some efficacy and low risk associated with chondroitin may explain its popularity among patients as an over-the-counter supplement.
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Affiliation(s)
- Jasvinder A Singh
- Birmingham VA Medical CenterDepartment of MedicineFaculty Office Tower 805B510 20th Street SouthBirminghamALUSA35294
| | - Shahrzad Noorbaloochi
- Minneapolis VA Medical Center and University of MinnesotaDepartment of MedicineOne Veterans DriveMinneapolisMNUSA55417
| | - Roderick MacDonald
- Minneapolis VA Medical CenterGeneral Internal Medicine (111‐0)One Veterans DriveMinneapolisMinnesotaUSA55417
| | - Lara J Maxwell
- Ottawa Hospital Research Institute (OHRI), The Ottawa Hospital ‐ General CampusCentre for Practice‐Changing Research (CPCR)501 Smyth Road, Box 711OttawaONCanadaK1H 8L6
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Bottegoni C, Muzzarelli RA, Giovannini F, Busilacchi A, Gigante A. Oral chondroprotection with nutraceuticals made of chondroitin sulphate plus glucosamine sulphate in osteoarthritis. Carbohydr Polym 2014; 109:126-38. [PMID: 24815409 DOI: 10.1016/j.carbpol.2014.03.033] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2014] [Revised: 03/01/2014] [Accepted: 03/04/2014] [Indexed: 12/13/2022]
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Henrotin Y, Marty M, Mobasheri A. What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis? Maturitas 2014; 78:184-7. [DOI: 10.1016/j.maturitas.2014.04.015] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Accepted: 04/12/2014] [Indexed: 10/25/2022]
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Bruyère O, Cooper C, Pelletier JP, Branco J, Luisa Brandi M, Guillemin F, Hochberg MC, Kanis JA, Kvien TK, Martel-Pelletier J, Rizzoli R, Silverman S, Reginster JY. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum 2014; 44:253-63. [PMID: 24953861 DOI: 10.1016/j.semarthrit.2014.05.014] [Citation(s) in RCA: 309] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 04/24/2014] [Accepted: 05/09/2014] [Indexed: 01/11/2023]
Abstract
OBJECTIVES Existing practice guidelines for osteoarthritis (OA) analyze the evidence behind each proposed treatment but do not prioritize the interventions in a given sequence. The objective was to develop a treatment algorithm recommendation that is easier to interpret for the prescribing physician based on the available evidence and that is applicable in Europe and internationally. The knee was used as the model OA joint. METHODS ESCEO assembled a task force of 13 international experts (rheumatologists, clinical epidemiologists, and clinical scientists). Existing guidelines were reviewed; all interventions listed and recent evidence were retrieved using established databases. A first schematic flow chart with treatment prioritization was discussed in a 1-day meeting and shaped to the treatment algorithm. Fine-tuning occurred by electronic communication and three consultation rounds until consensus. RESULTS Basic principles consist of the need for a combined pharmacological and non-pharmacological treatment with a core set of initial measures, including information access/education, weight loss if overweight, and an appropriate exercise program. Four multimodal steps are then established. Step 1 consists of background therapy, either non-pharmacological (referral to a physical therapist for re-alignment treatment if needed and sequential introduction of further physical interventions initially and at any time thereafter) or pharmacological. The latter consists of chronic Symptomatic Slow-Acting Drugs for OA (e.g., prescription glucosamine sulfate and/or chondroitin sulfate) with paracetamol at-need; topical NSAIDs are added in the still symptomatic patient. Step 2 consists of the advanced pharmacological management in the persistent symptomatic patient and is centered on the use of oral COX-2 selective or non-selective NSAIDs, chosen based on concomitant risk factors, with intra-articular corticosteroids or hyaluronate for further symptom relief if insufficient. In Step 3, the last pharmacological attempts before surgery are represented by weak opioids and other central analgesics. Finally, Step 4 consists of end-stage disease management and surgery, with classical opioids as a difficult-to-manage alternative when surgery is contraindicated. CONCLUSIONS The proposed treatment algorithm may represent a new framework for the development of future guidelines for the management of OA, more easily accessible to physicians.
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Affiliation(s)
- Olivier Bruyère
- Support Unit in Epidemiology and Biostatistics, Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman, 4000 Liège, Belgium.
| | - Cyrus Cooper
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
| | - Jean-Pierre Pelletier
- Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada
| | - Jaime Branco
- CEDOC, Department of Rheumatology, Faculdade de Ciências Médicas, Universidade Nova de Lisboa/CHLO, EPE-Hospital Egas Moniz, Lisbon, Portugal
| | - Maria Luisa Brandi
- Department of Internal Medicine, University of Florence, Florence, Italy
| | | | - Marc C Hochberg
- Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD; Geriatric Research, Education and Clinical Center, Baltimore, MD; Health Care System, Baltimore, MD
| | - John A Kanis
- WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK
| | - Tore K Kvien
- Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
| | - Johanne Martel-Pelletier
- Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada
| | - René Rizzoli
- Service of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Stuart Silverman
- Cedars-Sinai Medical Center, Los Angeles, CA; OMC Clinical Research Center, Beverly Hills, CA
| | - Jean-Yves Reginster
- Support Unit in Epidemiology and Biostatistics, Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman, 4000 Liège, Belgium
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Henrotin Y, Lambert C. Chondroitin and Glucosamine in the Management of Osteoarthritis: An Update. Curr Rheumatol Rep 2013; 15:361. [PMID: 23955063 DOI: 10.1007/s11926-013-0361-z] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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