Progress of research on disease-modifying osteoarthritis drugs

SU Boya; XU Yuansheng; WANG Hua; TANG Yuqing; ZHANG Shiqun; SONG Yan

doi:10.11665/j.issn.1000-5048.20210215

Journal of China Pharmaceutical University > 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:

PDF (591 KB)

Progress of research on disease-modifying osteoarthritis drugs

Guangzhou Link Health Pharma Co., Ltd., Guangzhou 510663, China

Funds: This study was supported by the 2017 Entrepreneurial Leading Talents Project of Guangzhou Development District(No.2020-L042)

More Information

Received Date: October 21, 2020
Revised Date: March 04, 2021

Graphical Abstract

Abstract

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.
- osteoarthritis,
- disease-modifying of osteoarthritis drug,
- cartilage repair,
- subchondral bone remodeling,
- inflammation

FullText(HTML)

References (50)

References

[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.

[1]	ZHAO Xiujuan, YANG Hengli, WU Jinye, ZHENG Xiaoqi, ZHANG Yaoping, LIN Yuping, HU Chunyan. Synthesis and anti-inflammatory activity of three series of coumarin-based derivatives[J]. Journal of China Pharmaceutical University, 2025, 56(1): 40-48. DOI: 10.11665/j.issn.1000-5048.2024072101
[2]	ZHU Hong, WEI Xiaopeng, JIN Meihua, QIN Nan. Synthesis and inhibition of NO production activities of 1, 6-O, O-diacylbritannilactone derivatives[J]. Journal of China Pharmaceutical University, 2017, 48(4): 440-444. DOI: 10.11665/j.issn.1000-5048.20170408
[3]	MOU Yi, CHEN Tong, HUANG Zhangjian, LAI Yisheng, PENG Sixun, JI Hui, ZHANG Yihua. Design, synthesis and anti-inflammatory evaluation of CDDO-Me ester prodrugs[J]. Journal of China Pharmaceutical University, 2016, 47(6): 661-665. DOI: 10.11665/j.issn.1000-5048.20160605
[4]	XU Guijun, LI Zhijun, WANG Qi, TAN Jiejun, SHI Guoshan, QI Wei, LI Di, WANG Youpeng. Isolation and identification of anti-inflammatory constituents from Houttuynia cordata[J]. Journal of China Pharmaceutical University, 2016, 47(3): 294-298. DOI: 10.11665/j.issn.1000-5048.20160308
[5]	WU Mingming, FANG Lei, GOU Shaohua, CHEN Li. 以2-甲基-2-取代苯氧基丙酸为离去基团的铂(Ⅱ)配合物的合成、表征及细胞毒活性[J]. Journal of China Pharmaceutical University, 2013, 44(4): 303-306. DOI: 10.11665/j.issn.1000-5048.20130403
[6]	HUANG Wen-xing, LAI Yi-sheng, ZHANG Yi-hua, WANG Zhen-guo, ZHANG Zhi-hao, MA Lin, JI Hui. Synthesis and anti-inflammatory activity of p-(sulfamyl)benzylidene-linked heterocyclic ketone derivatives[J]. Journal of China Pharmaceutical University, 2009, 40(6): 497-502.
[7]	AO Gui-zhen, ZHENG Li-ling, XU Guang-lin, LI Jing. Synthesis and anti-inflammatory activity of α-aryl-3，5-dimethoxyphenylpropenamides[J]. Journal of China Pharmaceutical University, 2009, 40(4): 302-305.
[8]	Synthesis and anti-inflammatory activities of aryl alkyl acid NSAIDs tetraacetylated glucoside derivatives[J]. Journal of China Pharmaceutical University, 2009, 40(1): 26-30.
[9]	Synthesis and anti-inflammatory activities of imidazo[1,2-a] pyrimidine derivatives[J]. Journal of China Pharmaceutical University, 2009, 40(1): 16-20.
[10]	Synthesis and Anti-inflammatory Activity of Nitric Oxidedonating α-Substituted p-(Methanesulfonyl)phenylpropenoic Acid Esters[J]. Journal of China Pharmaceutical University, 2004, (3): 6-10.

Cited By

Cited by

Periodical cited type(3)

1.	王苗苗，秦嘉泽，郭佳琪，于天成. 杓唇石斛开花特性与繁育系统研究. 浙江农业学报. 2025(01): 103-114 .
2.	关丽，赵惠茹，高璐，唐潇潇，李伟泽，赵宁，冯锋. 4-羟基-3, 5, 2′-三甲氧基联苄的合成及抑制血管新生活性研究. 化学与生物工程. 2022(10): 16-19 .
3.	刘鹏飞，范蓓，刘湘丹，杨洋，卢聪，佟立涛，孙晶，王凤忠. 铁皮石斛枫斗加工前后差异成分比较. 核农学报. 2022(12): 2412-2418 .

Other cited types(1)

Get Citation

PDF

XML

Article views PDF downloads Cited by(4)

Turn off MathJax

Article Contents

Abstract

References

Progress of research on disease-modifying osteoarthritis drugs

Abstract

References

Related Articles

Cited by

Periodical cited type(3)

Other cited types(1)

Catalog

Progress of research on disease-modifying osteoarthritis drugs

Abstract

References

Related Articles

Cited by

Periodical cited type(3)

Other cited types(1)

Catalog

Export File

Citation

Format

Content