Pharmacological therapy approaches for the treatment of knee osteoarthritis
Keywords:
knee, osteoarthritis, pain, pharmacological treatment, non-steroidal anti-inflammatory drugs (NSAID)
Abstract
To date, no effective treatment has been able to modify the pathological progression of osteoarthritis (OA). Current therapy can be broadly categorized into pharmacological and non-pharmacological approaches before considering surgical interventions. Non-pharmacological methods address lifestyle modifications, weight reduction and physical therapy, all aiming at alleviating mechanical stress on the affected joint. In this article, we focused on pharmacological treatment options, that primarily target pain reduction by reducing joint inflammation or restoring the altered synovial environment to a normal state. In this literature review, the main focus is on approved conservative therapies and examined emerging conservative strategies. Evaluating their advantages and limitations.
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References
References
1. Arendt-Nielsen L. Pain sensitisation in osteoarthritis. Clin Exp Rheumatol. 2017;35 Suppl 107(5):68-74.
2. Hunter DJ, Felson DT. Osteoarthritis. BMJ. 2006; 332(7542) :639-642. doi:10.1136/bmj.332.7542.639
3. Osteoarthritis: Symptoms, Diagnosis, and Treatment | Arthritis Foundation. https://www.arthritis.org/diseases/osteoarthritis. Updated October 9, 2023. Accessed October 9, 2023.
4. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986;29(8):1039-1049. doi:10.1002/art.1780290816.
5. Callahan LF, Cleveland RJ, Allen KD, Golightly Y. Racial/Ethnic, Socioeconomic, and Geographic Disparities in the Epidemiology of Knee and Hip Osteoarthritis. Rheum Dis Clin North Am. 2021;47(1):1-20. doi:10.1016/j.rdc.2020.09.001.
6. Primorac D, Molnar V, Matišić V, et al. Comprehensive Review of Knee Osteoarthritis Pharmacological Treatment and the Latest Professional Societies' Guidelines. Pharmaceuticals (Basel). 2021;14(3):205. Published 2021 Mar 2. doi:10.3390/ph14030205
7. Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthritis Cartilage. 2020;28(5):555-561. doi:10.1016/j.joca.2020.01.007.
8. Molnar V, Matišić V, Kodvanj I, et al. Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis. Int J Mol Sci. 2021;22(17). doi:10.3390/ijms22179208.
9. Hawthorn C. A Narrative Review: The Use of the Topical NSAID Ibuprofen for the Treatment of Knee Osteoarthritis. Supporting Clinician Decision-Making in the First-Line Treatment of Osteoarthritis. Rehabil Process Outcome. 2020; 9:1179572720914945. doi:10.1177/1179572720914945.
10. Ling T, Li JJ, Xu R-J, Wang B, Ge W-H. Topical Diclofenac Solution for Osteoarthritis of the Knee: An Updated Meta-Analysis of Randomized Controlled Trials. Biomed Res Int. 2020;2020:1758071. doi:10.1155/2020/1758071.
11. Global Ibuprofen Market – 360 Market Updates. https://www.360marketupdates.com/global-ibuprofen-market-19870840. Updated October 9, 2023. Accessed October 9, 2023.
12. Garg Y, Singh J, Sohal HS, Gore R, Kumar A. Comparison of Clinical Effectiveness and Safety of Newer Nonsteroidal Anti-inflammatory Drugs in Patients of Osteoarthritis of Knee Joint: A Randomized, Prospective, Open-label Parallel-group Study. Indian J Pharmacol. 2017;49(5):383-389. doi:10.4103/ijp.IJP_245_16.
13. Moss P, Benson HAE, Will R, Wright A. Fourteen days of etoricoxib 60 mg improves pain, hyperalgesia and physical function in individuals with knee osteoarthritis: a randomized controlled trial. Osteoarthritis Cartilage. 2017;25(11):1781-1791. doi:10.1016/j.joca.2017.07.009
14. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2020;72(2):220-233. doi:10.1002/art.41142.
15. Wernecke C, Braun HJ, Dragoo JL. The Effect of Intra-articular Corticosteroids on Articular Cartilage: A Systematic Review. Orthop J Sports Med. 2015;3(5):2325967115581163. doi:10.1177/2325967115581163.
16. Pemmari A, Leppänen T, Hämäläinen M, Moilanen T, Vuolteenaho K, Moilanen E. Widespread regulation of gene expression by glucocorticoids in chondrocytes from patients with osteoarthritis as determined by RNA-Seq. Arthritis Res Ther. 2020;22(1):271. doi:10.1186/s13075-020-02289-7.
17. Paik J, Duggan ST, Keam SJ. Triamcinolone Acetonide Extended-Release: A Review in Osteoarthritis Pain of the Knee. Drugs. 2019;79(4):455-462. doi:10.1007/s40265-019-01083-3.
18. Webner D, Huang Y, Hummer CD. Intraarticular Hyaluronic Acid Preparations for Knee Osteoarthritis: Are Some Better Than Others? Cartilage. 2021;13(1_suppl):1619S-1636S. doi:10.1177/19476035211017320.
19. Raeissadat SA, Rayegani SM, Hassanabadi H, et al. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015;8:1-8. doi:10.4137/CMAMD.S17894.
20. Altman R, Hackel J, Niazi F, Shaw P, Nicholls M. Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: A systematic review. Semin Arthritis Rheum. 2018;48(2):168-175. doi:10.1016/j.semarthrit.2018.01.009.
21. Bansal H, Leon J, Pont JL, et al. Platelet-rich plasma (PRP) in osteoarthritis (OA) knee: Correct dose critical for long term clinical efficacy. Sci Rep. 2021;11(1):3971. doi:10.1038/s41598-021-83025-2.
22. Andia I, Atilano L, Maffulli N. Moving toward targeting the right phenotype with the right platelet-rich plasma (PRP) formulation for knee osteoarthritis. Ther Adv Musculoskelet Dis. 2021;13:1759720X211004336. doi:10.1177/1759720X211004336.
23. Lana JF, Macedo A, Ingrao ILG, Huber SC, Santos GS, Santana MHA. Leukocyte-rich PRP for knee osteoarthritis: Current concepts. J Clin Orthop Trauma. 2019;10(Suppl 1):S179-S182. doi:10.1016/j.jcot.2019.01.011.
24. Assirelli E, Filardo G, Mariani E, et al. Effect of two different preparations of platelet-rich plasma on synoviocytes. Knee Surg Sports Traumatol Arthrosc. 2015;23(9):2690-2703. doi:10.1007/s00167-014-3113-3.
25. 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. Arthritis Rheumatol. 2019;71(7):1056-1069. doi:10.1002/art.40840.
26. 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. Arthritis Res Ther. 2011;13(4):R125. doi:10.1186/ar3430.
27. Maksymowych WP, Russell AS, Chiu P, et al. Targeting tumour necrosis factor alleviates signs and symptoms of inflammatory osteoarthritis of the knee. Arthritis Res Ther. 2012;14(5):R206. doi:10.1186/ar4044.
28. Ohtori S, Orita S, Yamauchi K, et al. Efficacy of Direct Injection of Etanercept into Knee Joints for Pain in Moderate and Severe Knee Osteoarthritis. Yonsei Med J. 2015;56(5):1379-1383. doi:10.3349/ymj.2015.56.5.1379.
29. 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. Osteoarthritis Cartilage. 2017;25(1):46-52. doi:10.1016/j.joca.2016.08.010.
30. Tuure L, Pemmari A, Hämäläinen M, Moilanen T, Moilanen E. Regulation of gene expression by MF63, a selective inhibitor of microsomal PGE synthase 1 (mPGES1) in human osteoarthritic chondrocytes. Br J Pharmacol. 2020;177(18):4134-4146. doi:10.1111/bph.15142.
31. Singh A, Kotlo A, Wang Z, Dissanayaka T, Das S, Antony B. Efficacy and safety of hydroxychloroquine in osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Korean J Intern Med. 2022;37(1):210-221. doi:10.3904/kjim.2020.605.
32. Yazici Y, McAlindon TE, Gibofsky A, et al. A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis. Osteoarthritis Cartilage. 2021;29(5):654-666. doi:10.1016/j.joca.2021.02.004.
33. Lopa S, Colombini A, Moretti M, Girolamo L de. Injective mesenchymal stem cell-based treatments for knee osteoarthritis: from mechanisms of action to current clinical evidences. Knee Surg Sports Traumatol Arthrosc. 2019;27(6):2003-2020. doi:10.1007/s00167-018-5118-9.
34. Cao Z, Liu W, Qu X, et al. miR-296-5p inhibits IL-1β-induced apoptosis and cartilage degradation in human chondrocytes by directly targeting TGF-β1/CTGF/p38MAPK pathway. Cell Cycle. 2020;19(12):1443-1453. doi:10.1080/15384101.2020.1750813.
35. Wei Y, Luo L, Gui T, et al. Targeting cartilage EGFR pathway for osteoarthritis treatment. Sci Transl Med. 2021;13(576). doi:10.1126/scitranslmed.abb3946.
36. Aitken D, Laslett LL, Cai G, et al. A protocol for a multicentre, randomised, double-blind, placebo-controlled trial to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change and knee pain over 24 months in knee osteoarthritis patients - ZAP2. BMC Musculoskelet Disord. 2018;19(1):217. doi:10.1186/s12891-018-2143-2.
37. Fernández-Martín S, González-Cantalapiedra A, Permuy M, García-González M, López-Peña M, Muñoz F. Histomorphometric Quantitative Evaluation of Long-Term Risedronate Use in a Knee Osteoarthritis Rabbit Model. Front Vet Sci. 2021;8:669815. doi:10.3389/fvets.2021.669815.
38. Yu D, Ding H, Mao Y, et al. Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model. Acta Pharmacol Sin. 2013;34(3):393-402. doi:10.1038/aps.2012.167.
39. Nakasa T, Ishikawa M, Takada T, Miyaki S, Ochi M. Attenuation of cartilage degeneration by calcitonin gene-related paptide receptor antagonist via inhibition of subchondral bone sclerosis in osteoarthritis mice. J Orthop Res. 2016;34(7):1177-1184. doi:10.1002/jor.23132.
40. Li J-W, Wang R-L, Xu J, et al. Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1. Acta Pharmacol Sin. 2022;43(2):417-428. doi:10.1038/s41401-021-00646-z.
41. Tian Y, Onodera T, Terkawi MA, et al. Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model. Int J Mol Sci. 2021;22(5). doi:10.3390/ijms22052552.
42. Yamanashi Y, Ohmichi M, Ohmichi Y, et al. Efficacy of Methotrexate on Rat Knee Osteoarthritis Induced by Monosodium Iodoacetate. J Inflamm Res. 2021; 14:3247-3259. doi:10.2147/JIR.S318540.
43. Jin Y, Smith C, Monteith D, et al. CGRP blockade by galcanezumab was not associated with reductions in signs and symptoms of knee osteoarthritis in a randomized clinical trial. Osteoarthritis Cartilage. 2018;26(12):1609-1618. doi:10.1016/j.joca.2018.08.019
44. Rovati LC, Brambilla N, Blicharski T, et al. Efficacy and safety of the first-in-class imidazoline-2 receptor ligand CR4056 in pain from knee osteoarthritis and disease phenotypes: a randomized, double-blind, placebo-controlled phase 2 trial. Osteoarthritis Cartilage. 2020;28(1):22-30. doi:10.1016/j.joca.2019.09.002.
45. Li J, Zhang B, Liu W-X, et al. Metformin limits osteoarthritis development and progression through activation of AMPK signalling. Ann Rheum Dis. 2020;79(5):635-645. doi:10.1136/annrheumdis-2019-216713.
46. Guo H, Ding D, Wang L, Yan J, Ma L, Jin Q. Metformin attenuates osteoclast-mediated abnormal subchondral bone remodeling and alleviates osteoarthritis via AMPK/NF-κB/ERK signaling pathway. PLoS One. 2021;16(12):e0261127. doi:10.1371/journal.pone.0261127.
47. Baker MC, Sheth K, Liu Y, Lu D, Lu R, Robinson WH. Development of Osteoarthritis in Adults With Type 2 Diabetes Treated With Metformin vs a Sulfonylurea. JAMA Netw Open. 2023;6(3):e233646. doi:10.1001/jamanetworkopen.2023.3646
1. Arendt-Nielsen L. Pain sensitisation in osteoarthritis. Clin Exp Rheumatol. 2017;35 Suppl 107(5):68-74.
2. Hunter DJ, Felson DT. Osteoarthritis. BMJ. 2006; 332(7542) :639-642. doi:10.1136/bmj.332.7542.639
3. Osteoarthritis: Symptoms, Diagnosis, and Treatment | Arthritis Foundation. https://www.arthritis.org/diseases/osteoarthritis. Updated October 9, 2023. Accessed October 9, 2023.
4. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986;29(8):1039-1049. doi:10.1002/art.1780290816.
5. Callahan LF, Cleveland RJ, Allen KD, Golightly Y. Racial/Ethnic, Socioeconomic, and Geographic Disparities in the Epidemiology of Knee and Hip Osteoarthritis. Rheum Dis Clin North Am. 2021;47(1):1-20. doi:10.1016/j.rdc.2020.09.001.
6. Primorac D, Molnar V, Matišić V, et al. Comprehensive Review of Knee Osteoarthritis Pharmacological Treatment and the Latest Professional Societies' Guidelines. Pharmaceuticals (Basel). 2021;14(3):205. Published 2021 Mar 2. doi:10.3390/ph14030205
7. Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthritis Cartilage. 2020;28(5):555-561. doi:10.1016/j.joca.2020.01.007.
8. Molnar V, Matišić V, Kodvanj I, et al. Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis. Int J Mol Sci. 2021;22(17). doi:10.3390/ijms22179208.
9. Hawthorn C. A Narrative Review: The Use of the Topical NSAID Ibuprofen for the Treatment of Knee Osteoarthritis. Supporting Clinician Decision-Making in the First-Line Treatment of Osteoarthritis. Rehabil Process Outcome. 2020; 9:1179572720914945. doi:10.1177/1179572720914945.
10. Ling T, Li JJ, Xu R-J, Wang B, Ge W-H. Topical Diclofenac Solution for Osteoarthritis of the Knee: An Updated Meta-Analysis of Randomized Controlled Trials. Biomed Res Int. 2020;2020:1758071. doi:10.1155/2020/1758071.
11. Global Ibuprofen Market – 360 Market Updates. https://www.360marketupdates.com/global-ibuprofen-market-19870840. Updated October 9, 2023. Accessed October 9, 2023.
12. Garg Y, Singh J, Sohal HS, Gore R, Kumar A. Comparison of Clinical Effectiveness and Safety of Newer Nonsteroidal Anti-inflammatory Drugs in Patients of Osteoarthritis of Knee Joint: A Randomized, Prospective, Open-label Parallel-group Study. Indian J Pharmacol. 2017;49(5):383-389. doi:10.4103/ijp.IJP_245_16.
13. Moss P, Benson HAE, Will R, Wright A. Fourteen days of etoricoxib 60 mg improves pain, hyperalgesia and physical function in individuals with knee osteoarthritis: a randomized controlled trial. Osteoarthritis Cartilage. 2017;25(11):1781-1791. doi:10.1016/j.joca.2017.07.009
14. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2020;72(2):220-233. doi:10.1002/art.41142.
15. Wernecke C, Braun HJ, Dragoo JL. The Effect of Intra-articular Corticosteroids on Articular Cartilage: A Systematic Review. Orthop J Sports Med. 2015;3(5):2325967115581163. doi:10.1177/2325967115581163.
16. Pemmari A, Leppänen T, Hämäläinen M, Moilanen T, Vuolteenaho K, Moilanen E. Widespread regulation of gene expression by glucocorticoids in chondrocytes from patients with osteoarthritis as determined by RNA-Seq. Arthritis Res Ther. 2020;22(1):271. doi:10.1186/s13075-020-02289-7.
17. Paik J, Duggan ST, Keam SJ. Triamcinolone Acetonide Extended-Release: A Review in Osteoarthritis Pain of the Knee. Drugs. 2019;79(4):455-462. doi:10.1007/s40265-019-01083-3.
18. Webner D, Huang Y, Hummer CD. Intraarticular Hyaluronic Acid Preparations for Knee Osteoarthritis: Are Some Better Than Others? Cartilage. 2021;13(1_suppl):1619S-1636S. doi:10.1177/19476035211017320.
19. Raeissadat SA, Rayegani SM, Hassanabadi H, et al. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015;8:1-8. doi:10.4137/CMAMD.S17894.
20. Altman R, Hackel J, Niazi F, Shaw P, Nicholls M. Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: A systematic review. Semin Arthritis Rheum. 2018;48(2):168-175. doi:10.1016/j.semarthrit.2018.01.009.
21. Bansal H, Leon J, Pont JL, et al. Platelet-rich plasma (PRP) in osteoarthritis (OA) knee: Correct dose critical for long term clinical efficacy. Sci Rep. 2021;11(1):3971. doi:10.1038/s41598-021-83025-2.
22. Andia I, Atilano L, Maffulli N. Moving toward targeting the right phenotype with the right platelet-rich plasma (PRP) formulation for knee osteoarthritis. Ther Adv Musculoskelet Dis. 2021;13:1759720X211004336. doi:10.1177/1759720X211004336.
23. Lana JF, Macedo A, Ingrao ILG, Huber SC, Santos GS, Santana MHA. Leukocyte-rich PRP for knee osteoarthritis: Current concepts. J Clin Orthop Trauma. 2019;10(Suppl 1):S179-S182. doi:10.1016/j.jcot.2019.01.011.
24. Assirelli E, Filardo G, Mariani E, et al. Effect of two different preparations of platelet-rich plasma on synoviocytes. Knee Surg Sports Traumatol Arthrosc. 2015;23(9):2690-2703. doi:10.1007/s00167-014-3113-3.
25. 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. Arthritis Rheumatol. 2019;71(7):1056-1069. doi:10.1002/art.40840.
26. 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. Arthritis Res Ther. 2011;13(4):R125. doi:10.1186/ar3430.
27. Maksymowych WP, Russell AS, Chiu P, et al. Targeting tumour necrosis factor alleviates signs and symptoms of inflammatory osteoarthritis of the knee. Arthritis Res Ther. 2012;14(5):R206. doi:10.1186/ar4044.
28. Ohtori S, Orita S, Yamauchi K, et al. Efficacy of Direct Injection of Etanercept into Knee Joints for Pain in Moderate and Severe Knee Osteoarthritis. Yonsei Med J. 2015;56(5):1379-1383. doi:10.3349/ymj.2015.56.5.1379.
29. 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. Osteoarthritis Cartilage. 2017;25(1):46-52. doi:10.1016/j.joca.2016.08.010.
30. Tuure L, Pemmari A, Hämäläinen M, Moilanen T, Moilanen E. Regulation of gene expression by MF63, a selective inhibitor of microsomal PGE synthase 1 (mPGES1) in human osteoarthritic chondrocytes. Br J Pharmacol. 2020;177(18):4134-4146. doi:10.1111/bph.15142.
31. Singh A, Kotlo A, Wang Z, Dissanayaka T, Das S, Antony B. Efficacy and safety of hydroxychloroquine in osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Korean J Intern Med. 2022;37(1):210-221. doi:10.3904/kjim.2020.605.
32. Yazici Y, McAlindon TE, Gibofsky A, et al. A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis. Osteoarthritis Cartilage. 2021;29(5):654-666. doi:10.1016/j.joca.2021.02.004.
33. Lopa S, Colombini A, Moretti M, Girolamo L de. Injective mesenchymal stem cell-based treatments for knee osteoarthritis: from mechanisms of action to current clinical evidences. Knee Surg Sports Traumatol Arthrosc. 2019;27(6):2003-2020. doi:10.1007/s00167-018-5118-9.
34. Cao Z, Liu W, Qu X, et al. miR-296-5p inhibits IL-1β-induced apoptosis and cartilage degradation in human chondrocytes by directly targeting TGF-β1/CTGF/p38MAPK pathway. Cell Cycle. 2020;19(12):1443-1453. doi:10.1080/15384101.2020.1750813.
35. Wei Y, Luo L, Gui T, et al. Targeting cartilage EGFR pathway for osteoarthritis treatment. Sci Transl Med. 2021;13(576). doi:10.1126/scitranslmed.abb3946.
36. Aitken D, Laslett LL, Cai G, et al. A protocol for a multicentre, randomised, double-blind, placebo-controlled trial to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change and knee pain over 24 months in knee osteoarthritis patients - ZAP2. BMC Musculoskelet Disord. 2018;19(1):217. doi:10.1186/s12891-018-2143-2.
37. Fernández-Martín S, González-Cantalapiedra A, Permuy M, García-González M, López-Peña M, Muñoz F. Histomorphometric Quantitative Evaluation of Long-Term Risedronate Use in a Knee Osteoarthritis Rabbit Model. Front Vet Sci. 2021;8:669815. doi:10.3389/fvets.2021.669815.
38. Yu D, Ding H, Mao Y, et al. Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model. Acta Pharmacol Sin. 2013;34(3):393-402. doi:10.1038/aps.2012.167.
39. Nakasa T, Ishikawa M, Takada T, Miyaki S, Ochi M. Attenuation of cartilage degeneration by calcitonin gene-related paptide receptor antagonist via inhibition of subchondral bone sclerosis in osteoarthritis mice. J Orthop Res. 2016;34(7):1177-1184. doi:10.1002/jor.23132.
40. Li J-W, Wang R-L, Xu J, et al. Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1. Acta Pharmacol Sin. 2022;43(2):417-428. doi:10.1038/s41401-021-00646-z.
41. Tian Y, Onodera T, Terkawi MA, et al. Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model. Int J Mol Sci. 2021;22(5). doi:10.3390/ijms22052552.
42. Yamanashi Y, Ohmichi M, Ohmichi Y, et al. Efficacy of Methotrexate on Rat Knee Osteoarthritis Induced by Monosodium Iodoacetate. J Inflamm Res. 2021; 14:3247-3259. doi:10.2147/JIR.S318540.
43. Jin Y, Smith C, Monteith D, et al. CGRP blockade by galcanezumab was not associated with reductions in signs and symptoms of knee osteoarthritis in a randomized clinical trial. Osteoarthritis Cartilage. 2018;26(12):1609-1618. doi:10.1016/j.joca.2018.08.019
44. Rovati LC, Brambilla N, Blicharski T, et al. Efficacy and safety of the first-in-class imidazoline-2 receptor ligand CR4056 in pain from knee osteoarthritis and disease phenotypes: a randomized, double-blind, placebo-controlled phase 2 trial. Osteoarthritis Cartilage. 2020;28(1):22-30. doi:10.1016/j.joca.2019.09.002.
45. Li J, Zhang B, Liu W-X, et al. Metformin limits osteoarthritis development and progression through activation of AMPK signalling. Ann Rheum Dis. 2020;79(5):635-645. doi:10.1136/annrheumdis-2019-216713.
46. Guo H, Ding D, Wang L, Yan J, Ma L, Jin Q. Metformin attenuates osteoclast-mediated abnormal subchondral bone remodeling and alleviates osteoarthritis via AMPK/NF-κB/ERK signaling pathway. PLoS One. 2021;16(12):e0261127. doi:10.1371/journal.pone.0261127.
47. Baker MC, Sheth K, Liu Y, Lu D, Lu R, Robinson WH. Development of Osteoarthritis in Adults With Type 2 Diabetes Treated With Metformin vs a Sulfonylurea. JAMA Netw Open. 2023;6(3):e233646. doi:10.1001/jamanetworkopen.2023.3646
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Hofmann M, Studers P, Jakovicka D. Pharmacological therapy approaches for the treatment of knee osteoarthritis . Int J Med Res Rev [Internet]. 2024Feb.19 [cited 2024Nov.22];12(1):1-11. Available from: https://ijmrr.medresearch.in/index.php/ijmrr/article/view/1460
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Copyright (c) 2024 Author (s). Published by Siddharth Health Research and Social Welfare Society
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