• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

骨关节炎疾病改善型药物研究进展

苏博雅, 许元生, 王华, 汤宇晴, 张时群, 宋燕

苏博雅, 许元生, 王华, 汤宇晴, 张时群, 宋燕. 骨关节炎疾病改善型药物研究进展[J]. 中国药科大学学报, 2021, 52(2): 253-260. DOI: 10.11665/j.issn.1000-5048.20210215
引用本文: 苏博雅, 许元生, 王华, 汤宇晴, 张时群, 宋燕. 骨关节炎疾病改善型药物研究进展[J]. 中国药科大学学报, 2021, 52(2): 253-260. DOI: 10.11665/j.issn.1000-5048.20210215
SU Boya, XU Yuansheng, WANG Hua, TANG Yuqing, ZHANG Shiqun, SONG Yan. Progress of research on disease-modifying osteoarthritis drugs[J]. Journal of China Pharmaceutical University, 2021, 52(2): 253-260. DOI: 10.11665/j.issn.1000-5048.20210215
Citation: SU Boya, XU Yuansheng, WANG Hua, TANG Yuqing, ZHANG Shiqun, SONG Yan. Progress of research on disease-modifying osteoarthritis drugs[J]. Journal of China Pharmaceutical University, 2021, 52(2): 253-260. DOI: 10.11665/j.issn.1000-5048.20210215

骨关节炎疾病改善型药物研究进展

基金项目: 2017年广州开发区创业领军人才资助项目(No.2020-L042)

Progress of research on disease-modifying osteoarthritis drugs

Funds: This study was supported by the 2017 Entrepreneurial Leading Talents Project of Guangzhou Development District(No.2020-L042)
  • 摘要: 骨关节炎(OA)是一种常见的慢性关节疾病,主要的病理改变为关节软骨的退化和继发性骨质增生。现有的药物治疗方式存在明显的局限性,仅从镇痛角度治疗或行关节置换术,二者均不能从根本上改善关节软骨的病变。因此,抑制OA疾病进展的药物(DMOAD)应运而生。DMOAD通过参与调节软骨代谢平衡、参与软骨下骨重塑和控制局部炎症等机制从根本上抑制关节软骨结构性退变,从而使OA患者得到疼痛及功能的症状改善,延缓做人工关节置换术的时间,提高患者生活质量。目前全球范围内尚无DMOAD类药物上市,本文从DMOAD药物的研发背景、作用机制以及各类机制下在研代表药物的研发进展进行综述,为今后的研究提供参考。
    Abstract: Osteoarthritis (OA) is a common chronic joint disease,whose main pathological changes are the degeneration of articular cartilage and secondary bone hyperplasia.The limitation of current treatment methods including pain relief and joint replacement surgery is that they cannot fundamentally improve the damage of articular cartilage.The emergence of disease-modifying osteoarthritis drugs (DMOAD) may break the above limitations.They fundamentally inhibit the structural degeneration of articular cartilage by participating in the regulation of cartilage metabolic balance, regulation of subchondral bone remodeling,and control of local inflammation.Thereby,OA patients will get symptom improvement including pain relief and joint function restoration,delay the artificial joint replacement surgery, and improve the quality of life. There are still no DMOAD drugs widely available on the market worldwide.This paper reviews the background of R&D,the classification of mechanisms of action and research progress of representative drugs under different inechanisms so as to provide reference for future research.
  • [1] . Chin J Orthop(中华骨科杂志),2018,38(12):705–715.
    [2] European Medicines Agency. Guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis[R]. London:European Medicines Agency,2010.
    [3] Food and Drug Administration. Osteoarthritis:structural endpoints for the development of drugs,devices,and biological products for treatment guidance for industry[R]. Rockville:U. S. Department of Health and Human Services, 2018.
    [4] Guilak F. Biomechanical factors in osteoarthritis[J]. Best Pract Res Clin Rheumatol, 2011, 25(6): 815-823.
    [5] Jotanovic Z, Mihelic R, Sestan B, et al. Emerging pathways and promising agents with possible disease modifying effect in osteoarthritis treatment[J]. Curr Drug Targets, 2014, 15(6): 635-661.
    [6] Deveza LA, Nelson AE, Loeser RF. Phenotypes of osteoarthritis: current state and future implications[J]. Clin Exp Rheumatol, 2019, 37(5): 64-72.
    [7] Karsdal MA, Bay-Jensen AC, Lories RJ, et al. The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments[J]? Ann Rheum Dis, 2014, 73(2): 336-348.
    [8] Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)[J]. Osteoarthr Cartil, 2013, 21(1): 16-21.
    [9] Oo WM, Yu SP, Daniel MS, et al. Disease-modifying drugs in osteoarthritis: current understanding and future therapeutics[J]. Expert Opin Emerg Drugs, 2018, 23(4): 331-347.
    [10] Muchedzi TA, Roberts SB. A systematic review of the effects of platelet rich plasma on outcomes for patients with knee osteoarthritis and following total knee arthroplasty[J]. Surgeon, 2018, 16(4): 250-258.
    [11] Eckstein F, Wirth W, Guermazi A, et al. Brief report: intraarticular sprifermin not only increases cartilage thickness, but also reduces cartilage loss: location-independent post hoc analysis using magnetic resonance imaging[J]. Arthritis Rheumatol, 2015, 67(11): 2916-2922.
    [12] Hochberg MC, Guermazi A, Guehring H, et al. Effect of intra-articular sprifermin vs placebo on femorotibial joint cartilage thickness in patients with osteoarthritis: the FORWARD randomized clinical trial[J]. JAMA, 2019, 322(14): 1360-1370.
    [13] Chubinskaya S, Hurtig M, Rueger DC. OP-1/BMP-7 in cartilage repair[J]. Int Orthop, 2007, 31(6): 773-781.
    [14] Hunter DJ, Pike MC, Jonas BL, et al. Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis[J]. BMC Musculoskelet Disord, 2010, 11: 232.
    [15] Dhillon RS, Schwarz EM, Maloney MD. Platelet-rich plasma therapy — future or trend[J]? Arthritis Res Ther, 2012, 14(4): 219.
    [16] Jevotovsky DS, Alfonso AR, Einhorn TA, et al. Osteoarthritis and stem cell therapy in humans: a systematic review[J]. Osteoarthritis Cartilage, 2018, 26(6): 711-729.
    [17] Lee WY, Wang B. Cartilage repair by mesenchymal stem cells: clinical trial update and perspectives[J]. J Orthop Translat, 2017, 9: 76-88.
    [18] Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis[J]. Front Biosci, 2006, 11: 529-543.
    [19] Verma P, Dalal K. ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis[J]. J Cell Biochem, 2011, 112(12): 3507-3514.
    [20] Wu LH, Huang XH, Li LF, et al. Insights on biology and pathology of HIF-1α/-2α, TGFβ/BMP, Wnt/β-catenin, and NF-κB pathways in osteoarthritis[J]. Curr Pharm Des, 2012, 18(22): 3293-3312.
    [21] Tonge DP, Pearson MJ, Jones SW. The hallmarks of osteoarthritis and the potential to develop personalised disease-modifying pharmacological therapeutics[J]. Osteoarthritis Cartilage, 2014, 22(5): 609-621.
    [22] Wang MN, Sampson ER, Jin HT, et al. MMP13 is a critical target gene during the progression of osteoarthritis[J]. Arthritis Res Ther, 2013, 15(1): R5.
    [23] Ge XP, Ma XC, Meng JH, et al. Role of Wnt-5A in interleukin-1beta-induced matrix metalloproteinase expression in rabbit temporomandibular joint condylar chondrocytes[J]. Arthritis Rheum, 2009, 60(9): 2714-2722.
    [24] Yazici Y, McAlindon TE, Gibofsky A, et al. Results from a 52-week randomized, double-blind, placebo-controlled, phase 2 study of a novel, intra-articular wnt pathway inhibitor (SM04690) for the treatment of knee osteoarthritis[J]. Osteoarthr Cartil, 2018, 26: S293-S294.
    [25] Malekipour F, Whitton C, Oetomo D, et al. Shock absorbing ability of articular cartilage and subchondral bone under impact compression[J]. J Mech Behav Biomed Mater, 2013, 26: 127-135.
    [26] Li GY, Yin JM, Gao JJ, et al. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes[J]. Arthritis Res Ther, 2013, 15(6): 223.
    [27] Burr DB, Gallant MA. Bone remodelling in osteoarthritis[J]. Nat Rev Rheumatol, 2012, 8(11): 665-673.
    [28] Alliston T, Hernandez CJ, Findlay DM, et al. Bone marrow lesions in osteoarthritis: What lies beneath[J]. J Orthop Res, 2018, 36(7): 1818-1825.
    [29] van Spil WE, Kubassova O, Boesen M, et al. Osteoarthritis phenotypes and novel therapeutic targets[J]. Biochem Pharmacol, 2019, 165: 41-48.
    [30] Vaysbrot EE, Osani MC, Musetti MC, et al. Are bisphosphonates efficacious in knee osteoarthritis?A meta-analysis of randomized controlled trials[J]. Osteoarthritis Cartilage, 2018, 26(2): 154-164.
    [31] Deveza LA, Bierma-Zeinstra SMA, van Spil WE, et al. Efficacy of bisphosphonates in specific knee osteoarthritis subpopulations: protocol for an OA Trial Bank systematic review and individual patient data meta-analysis[J]. BMJ Open, 2018, 8(12): e023889.
    [32] Sondergaard BC, Madsen SH, Segovia-Silvestre T, et al. Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes[J]. BMC Musculoskelet Disord, 2010, 11: 62.
    [33] Chen CH, Ho ML, Chang LH, et al. Parathyroid hormone-( 1-34) ameliorated knee osteoarthritis in rats via autophagy[J]. J Appl Physiol (1985), 2018, 124(5): 1177-1185.
    [34] Lindstr?m E, Rizoska B, Tunblad K, et al. The selective cathepsin K inhibitor MIV-711 attenuates joint pathology in experimental animal models of osteoarthritis[J]. J Transl Med, 2018, 16(1): 56.
    [35] Karsdal MA, Michaelis M, Ladel C, et al. Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future[J]. Osteoarthritis Cartilage, 2016, 24(12): 2013-2021.
    [36] Conaghan PG, Bowes MA, Kingsbury SR, et al. Disease-modifying effects of a novel cathepsin K inhibitor in osteoarthritis: a randomized controlled trial[J]. Ann Intern Med, 2020, 172(2): 86-95.
    [37] Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications[J]. Arthritis Res Ther, 2017, 19(1): 18.
    [38] Pelletier JP, Martel-Pelletier J, Rannou F, et al. Efficacy and safety of oral NSAIDs and analgesics in the management of osteoarthritis: evidence from real-life setting trials and surveys[J]. Semin Arthritis Rheum, 2016, 45(4 Suppl): S22-S27.
    [39] Savvidou O, Milonaki M, Goumenos S, et al. Glucocorticoid signaling and osteoarthritis[J]. Mol Cell Endocrinol, 2019, 480: 153-166.
    [40] Cohen SB, Proudman S, Kivitz AJ, et al. A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee[J]. Arthritis Res Ther, 2011, 13(4): R125.
    [41] Wang SX, Abramson SB, Attur M, et al. Safety, tolerability, and pharmacodynamics of an anti-interleukin-1α/β dual variable domain immunoglobulin in patients with osteoarthritis of the knee: a randomized phase 1 study[J]. Osteoarthritis Cartilage, 2017, 25(12): 1952-1961.
    [42] Fleischmann RM, Bliddal H, Blanco FJ, et al. A phase II trial of lutikizumab, an anti-interleukin-1α/β dual variable domain immunoglobulin, in knee osteoarthritis patients with synovitis[J]. Arthritis Rheumatol, 2019, 71(7): 1056-1069.
    [43] Verbruggen G, Wittoek R, Vander Cruyssen B, et al. Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification[J]. Ann Rheum Dis, 2012, 71(6): 891-898.
    [44] Magnano MD, Chakravarty EF, Broudy C, et al. A pilot study of tumor necrosis factor inhibition in erosive/inflammatory osteoarthritis of the hands[J]. J Rheumatol, 2007, 34(6): 1323-1327.
    [45] Chevalier X, Ravaud P, Maheu E, et al. Adalimumab in patients with hand osteoarthritis refractory to analgesics and NSAIDs: a randomised, multicentre, double-blind, placebo-controlled trial[J]. Ann Rheum Dis, 2015, 74(9): 1697-1705.
    [46] Fioravanti A, Fabbroni M, Cerase A, et al. Treatment of erosive osteoarthritis of the hands by intra-articular infliximab injections: a pilot study[J]. Rheumatol Int, 2009, 29(8): 961-965.
    [47] Kawasaki T, Kawai T. Toll-like receptor signaling pathways[J]. Front Immunol, 2014, 5: 461.
    [48] Maudens P, Seemayer CA, Pfefferlé F, et al. Nanocrystals of a potent p38 MAPK inhibitor embedded in microparticles: Therapeutic effects in inflammatory and mechanistic murine models of osteoarthritis[J]. J Control Release, 2018, 276: 102-112.
    [49] Grothe K, Flechsenhar K, Paehler T, et al. IκB kinase inhibition as a potential treatment of osteoarthritis — results of a clinical proof-of-concept study[J]. Osteoarthritis Cartilage, 2017, 25(1): 46-52.
    [50] Hellio le Graverand MP, Clemmer RS, Redifer P, et al. A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee[J]. Ann Rheum Dis, 2013, 72(2): 187-195.
计量
  • 文章访问数:  359
  • HTML全文浏览量:  15
  • PDF下载量:  880
  • 被引次数: 0
出版历程
  • 收稿日期:  2020-10-21
  • 修回日期:  2021-03-04
  • 刊出日期:  2021-04-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭