Emerging and New Treatment Options for Knee Osteoarthritis

Md.   Abu Bakar    Siddiq; Danny       Clegg; Tim    L.   Jansen; Johannes    J.    Rasker
doi:10.2174/1573397117666211116111738
Abstract

Osteoarthritis (OA) is the most prevalent type of arthritis worldwide, resulting in pain and often chronic disability and a significant burden on healthcare systems globally. Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee OA has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, none of them has articular cartilage regenerating potential. Due to a better understanding of osteoarthritis, innovative new treatment options have been developed. In this narrative review, we focus on emerging OA knee treatments, relieving symptoms, and regenerating damaged articular cartilage that includes intra-articular human serum albumin, conventional disease-modifying anti-rheumatic drugs (DMARDs), metformin, lipid-lowering agents (statin), nerve growth factors antagonists, bone morphogenetic protein, fibroblast growth factors, Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSC), exosomes, interleukin-1 blockers, gene-based therapy, and bisphosphonate.
Keywords: Anti-inflammatory agents, analgesics, cartilage, knee, nerve growth factors, osteoarthritis, pain, platelet-rich plasma.
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[1] 
Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage  2013; 21(1): 16-21.
[http://dx.doi.org/10.1016/j.joca.2012.11.012] [PMID: 23194896] 
[2] 
Favero M, Ramonda R, Goldring MB, Goldring SR, Punzi L. Early knee osteoarthritis. RMD Open  2015; 1: e000062.
[http://dx.doi.org/10.1136/rmdopen-2015-000062] [PMID: 26557380] 
[3] 
Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med  2010; 26(3): 355-69.
[http://dx.doi.org/10.1016/j.cger.2010.03.001] [PMID: 20699159] 
[4] 
Chua JR, Jamal S, Riad M, et al. Disease burden in Osteoarthritis (OA) is similar to Rheumatoid Arthritis (RA) at initial rheumatology visit and significantly greater six months later. Arthritis Rheumatol  2019; 71(8): 1276-84.
[http://dx.doi.org/10.1002/art.40869] [PMID: 30891933] 
[5] 
Luyten FP, Bierma-Zeinstra S, Dell’Accio F, et al. Toward classification criteria for early osteoarthritis of the knee. Semin Arthritis Rheum  2018; 47(4): 457-63.
[http://dx.doi.org/10.1016/j.semarthrit.2017.08.006] [PMID: 28917712] 
[6] 
Klement MR, Sharkey PF. The significance of osteoarthritis-associated bone marrow lesions in the knee. J Am Acad Orthop Surg  2019; 27(20): 752-9.
[http://dx.doi.org/10.5435/JAAOS-D-18-00267] [PMID: 30964755] 
[7] 
Sadatsuki R, Ishijima M, Kaneko H, et al. Bone marrow lesion is associated with disability for activities of daily living in patients with early stage knee osteoarthritis. J Bone Miner Metab  2019; 37(3): 529-36.
[http://dx.doi.org/10.1007/s00774-018-0950-z] [PMID: 30187274] 
[8] 
Chu CR, Williams AA, Coyle CH, Bowers ME. Early diagnosis to enable early treatment of pre-osteoarthritis. Arthritis Res Ther  2012; 14(3): 212-22.
[http://dx.doi.org/10.1186/ar3845] [PMID: 22682469] 
[9] 
King LK, Marshall DA, Faris P, et al. BEST-Knee Research Team. Use of recommended non-surgical knee osteoarthritis management in patients prior to total knee arthroplasty: A cross-sectional study. J Rheumatol  2020; 47(8): 1253-60.
[http://dx.doi.org/10.3899/jrheum.190467] [PMID: 31732554] 
[10] 
Hochberg M, Altman RD, April KT, et al. American College of Rheumatology. American College of Rheumatology 2012 Recommendations for the use of non-pharmacological and pharmacological therapies in osteoarthritis of the hand, hip and knee. Arthritis Care Res (Hoboken)  2012; 64(4): 465-74.
[http://dx.doi.org/10.1002/acr.21596] [PMID: 22563589] 
[11] 
Zhang W, Ouyang H, Dass CR, Xu J. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res  2016; 4: 15040.
[http://dx.doi.org/10.1038/boneres.2015.40] [PMID: 26962464] 
[12] 
Dieppe P, Goldingay S, Greville-Harris M. The power and value of placebo and nocebo in painful osteoarthritis. Osteoarthritis Cartilage  2016; 24(11): 1850-7.
[http://dx.doi.org/10.1016/j.joca.2016.06.007] [PMID: 27338671] 
[13] 
Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: Meta-analysis of randomised controlled trials. Ann Rheum Dis  2008; 67(12): 1716-23.
[http://dx.doi.org/10.1136/ard.2008.092015] [PMID: 18541604] 
[14] 
CASP checklists.   Available from: https://casp-uk.net/casp-tools-checklists/
[15] 
Frederick ED, Hausburg MA, Thomas GW, Rael LT, Brody E, Bar-Or D. The low molecular weight fraction of human serum albumin upregulates COX2, prostaglandin E2, and prostaglandin D2 under inflammatory conditions in osteoarthritic knee synovial fibroblasts. Biochem Biophys Rep  2016; 8: 68-74.
[http://dx.doi.org/10.1016/j.bbrep.2016.08.015] [PMID: 28955943] 
[16] 
Bar-Or D, Salottolo KM, Loose H, et al. A randomized clinical trial to evaluate two doses of an intra-articular injection of LMWF-5A in adults with pain due to osteoarthritis of the knee. PLoS One  2014; 9(2): e87910.
[http://dx.doi.org/10.1371/journal.pone.0087910] [PMID: 24498399] 
[17] 
Schwappach J, Dryden SM, Salottolo KM. Preliminary trial of intra-articular LMWF-5A for osteoarthritis of the knee. Orthopedics  2017; 40(1): e49-53.
[http://dx.doi.org/10.3928/01477447-20160926-02] [PMID: 27684085] 
[18] 
Salottolo K, Cole B, Bar-Or D. Intra-articular injection of the anti-inflammatory compound LMWF-5A in adults with severe osteoarthritis: A double-blind prospective randomized controlled multi-center safety and efficacy trial. Patient Saf Surg  2018; 12: 11.
[19] 
Schwappach J, Schultz J, Salottolo K, Bar-Or D. Incidence of total knee replacement subsequent to intra-articular injection of the anti-inflammatory compound LMWF-5A versus saline: A long-term follow-up study to a randomized controlled trial. Patient Saf Surg  2018; 12: 14.
[http://dx.doi.org/10.1186/s13037-018-0162-4] [PMID: 29881459] 
[20] 
Persson MSM, Sarmanova A, Doherty M, Zhang W. Conventional and biologic disease-modifying anti-rheumatic drugs for osteoarthritis: A meta-analysis of randomized controlled trials. Rheumatology (Oxford)  2018; 57(10): 1830-7.
[http://dx.doi.org/10.1093/rheumatology/key131] [PMID: 29917100] 
[21] 
Wenham CY, Grainger AJ, Hensor EM, Caperon AR, Ash ZR, Conaghan PG. Methotrexate for pain relief in knee osteoarthritis: An open-label study. Rheumatology (Oxford)  2013; 52(5): 888-92.
[http://dx.doi.org/10.1093/rheumatology/kes386] [PMID: 23300331] 
[22] 
Enteshari-Moghaddam A, Isazadehfar K, Habibzadeh A, Hemmati M. Efficacy of methotrexate on pain severity reduction and improvement of quality of life in patients with moderate to severe knee osteoarthritis. Anesth Pain Med  2019; 9(3): e89990.
[http://dx.doi.org/10.5812/aapm.89990] [PMID: 31497519] 
[23] 
Kingsbury SR, Tharmanathan P, Keding A, et al. Significant pain reduction with oral methotrexate in knee osteoarthritis; results from a randomised controlled phase III trial of treatment effectiveness. Arthritis Rheumatol  2019; 27(S1): S84-5.
[24] 
Tamura T, Higuchi Y, Kitamura H, et al. Novel hyaluronic acid-methotrexate conjugate suppresses joint inflammation in the rat knee: efficacy and safety evaluation in two rat arthritis models. Arthritis Res Ther  2016; 18: 79.
[http://dx.doi.org/10.1186/s13075-016-0971-8] [PMID: 27039182] 
[25] 
Jokar M, Mirfeizi Z, Keyvanpajouh K. The effect of hydroxychloroquine on symptoms of knee osteoarthritis: A double-blind randomized controlled clinical trial. Iran J Med Sci  2013; 38(3): 221-6.
[PMID: 24174692] 
[26] 
ClinicalTrials.gov Identifier: Genovese, M. Hydroxychloroquine/Atorvastatin in the Treatment of Osteoarthritis (OA) of the Knee. National Library of Medicine (US) NCT01645176, 2017.
[27] 
Lu CH, Chung CH, Lee CH, et al. Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan. PLoS One  2018; 13(1): e0191242.
[http://dx.doi.org/10.1371/journal.pone.0191242] [PMID: 29385156] 
[28] 
Wang Y, Hussain SM, Wluka AE, et al. Association between metformin use and disease progression in obese people with knee osteoarthritis: Data from the osteoarthritis initiative-a prospective cohort study. Arthritis Res Ther  2019; 21(1): 127.
[http://dx.doi.org/10.1186/s13075-019-1915-x] [PMID: 31126352] 
[29] 
Yu SM, Han Y, Kim SJ. Simvastatin induces differentiation in rabbit articular chondrocytes via Wnt/β-catenin pathway. Eur J Pharmacol  2019; 863: 172672.  Available from: https://www.sciencedirect.com/science/article/abs/pii/S0014299919306247?via%3Dihub
[http://dx.doi.org/10.1016/j.ejphar.2019.172672] [PMID: 31542485] 
[30] 
Simopoulou T, Malizos KN, Poultsides L, Tsezou A. Protective effect of atorvastatin in cultured osteoarthritic chondrocytes. J Orthop Res  2010; 28(1): 110-5.
[PMID: 19623662] 
[31] 
Clockaerts S, Van Osch GJ, Bastiaansen-Jenniskens YM, et al. Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study. Ann Rheum Dis  2012; 71(5): 642-7.
[http://dx.doi.org/10.1136/annrheumdis-2011-200092] [PMID: 21989540] 
[32] 
Eymard F, Parsons C, Edwards MH, et al. Statin use and knee osteoarthritis progression: Results from a post-hoc analysis of the SEKOIA trial. Joint Bone Spine  2018; 85(5): 609-14.
[http://dx.doi.org/10.1016/j.jbspin.2017.09.014] [PMID: 29037516] 
[33] 
Michaëlsson K, Lohmander LS, Turkiewicz A, Wolk A, Nilsson P, Englund M. Association between statin use and consultation or surgery for osteoarthritis of the hip or knee: A pooled analysis of four cohort studies. Osteoarthritis Cartilage  2017; 25(11): 1804-13.
[http://dx.doi.org/10.1016/j.joca.2017.07.013] [PMID: 28756279] 
[34] 
Li J, Zhang B, Liu WX, et al. Metformin limits osteoarthritis development and progression through activation of AMPK signalling. Ann Rheum Dis  2020; 79(5): 635-45.
[http://dx.doi.org/10.1136/annrheumdis-2019-216713] [PMID: 32156705] 
[35] 
Park MJ, Moon SJ, Baek JA, et al. Metformin augments anti-inflammatory and chondroprotective properties of mesenchymal stem cells in experimental osteoarthritis. J Immunol  2019; 203(1): 127-36.
[http://dx.doi.org/10.4049/jimmunol.1800006] [PMID: 31142603] 
[36] 
Shang X, Wang Z, Tao H. Mechanism and therapeutic effectiveness of nerve growth factor in osteoarthritis pain. Ther Clin Risk Manag  2017; 13: 951-6.
[http://dx.doi.org/10.2147/TCRM.S139814] [PMID: 28814877] 
[37] 
Lane NE, Schnitzer TJ, Birbara CA, et al. Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med  2010; 363(16): 1521-31.
[http://dx.doi.org/10.1056/NEJMoa0901510] [PMID: 20942668] 
[38] 
Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR. Tanezumab reduces osteoarthritic hip pain: results of a randomized, double-blind, placebo-controlled phase III trial. Arthritis Rheum  2013; 65(7): 1795-803.
[http://dx.doi.org/10.1002/art.37950] [PMID: 23553790] 
[39] 
Miyagi M, Ishikawa T, Kamoda H, et al. Efficacy of nerve growth factor antibody in a knee osteoarthritis pain model in mice. BMC Musculoskelet Disord  2017; 18(1): 428.
[http://dx.doi.org/10.1186/s12891-017-1792-x] [PMID: 29100502] 
[40] 
von Loga IS, El-Turabi A, Jostins L, et al. Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis. Ann Rheum Dis  2019; 78(5): 672-5.
[http://dx.doi.org/10.1136/annrheumdis-2018-214489] [PMID: 30862648] 
[41] 
Miller RE, Malfait AM, Block JA. Current status of nerve growth factor antibodies for the treatment of osteoarthritis pain. Clin Exp Rheumatol  2017; 107(5): 85-7.
[42] 
Berenbaum F, Blanco FJ, Guermazi A, et al. Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period. Ann Rheum Dis  2020; 79(6): 800-10.
[http://dx.doi.org/10.1136/annrheumdis-2019-216296] [PMID: 32234715] 
[43] 
Dakin P, DiMartino SJ, Gao H, et al. The efficacy, tolerability, and joint safety of fasinumab in osteoarthritis pain: A phase IIb/III double-blind, placebo-controlled, randomized clinical trial. Arthritis Rheumatol  2019; 71(11): 1824-34.
[http://dx.doi.org/10.1002/art.41012] [PMID: 31207169] 
[44] 
Chen J, Li J, Li R, et al. Efficacy and safety of tanezumab on osteoarthritis knee and hip pains: A meta-analysis of randomized controlled trials. Pain Med  2017; 18(2): 374-85.
[PMID: 28034979] 
[45] 
Schmelz M, Mantyh P, Malfait AM, et al. Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety. Pain  2019; 160(10): 2210-20.
[http://dx.doi.org/10.1097/j.pain.0000000000001625] [PMID: 31145219] 
[46] 
Deng ZH, Li YS, Gao X, Lei GH, Huard J. Bone morphogenetic proteins for articular cartilage regeneration. Osteoarthritis Cartilage  2018; 26(9): 1153-61.
[http://dx.doi.org/10.1016/j.joca.2018.03.007] [PMID: 29580979] 
[47] 
Liu Y, Hou R, Yin R, Yin W. Correlation of bone morphogenetic protein-2 levels in serum and synovial fluid with disease severity of knee osteoarthritis. Med Sci Monit  2015; 21: 363-70.
[http://dx.doi.org/10.12659/MSM.892160] [PMID: 25644704] 
[48] 
Hunter DJ, Pike MC, Jonas BL, Kissin E, Krop J, McAlindon T. Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis. BMC Musculoskelet Disord  2010; 11: 232.
[http://dx.doi.org/10.1186/1471-2474-11-232] [PMID: 20932341] 
[49] 
Badlani N, Inoue A, Healey R, Coutts R, Amiel D. The protective effect of OP-1 on articular cartilage in the development of osteoarthritis. Osteoarthritis Cartilage  2008; 16(5): 600-6.
[http://dx.doi.org/10.1016/j.joca.2007.09.009] [PMID: 17977753] 
[50] 
Hicks JJ, Rocha JL, Li H, Huard J, Wang Y, Hogan MV. Sustained release of bone morphogenetic protein 2 via coacervate improves muscle derived stem cell mediated cartilage regeneration in MIA-induced osteoarthritis. Orthop J Sports Med  2016; 4: 7.
[http://dx.doi.org/10.1177/2325967116S00152] 
[51] 
BMP-2 bone morphogenetic protein 2 2018. Available from: https://www.ncbi.nlm.nih.gov/gene/650 Accessed on 04/02/2018.
[52] 
Sharma AC, Srivastava RN, Srivastava SR, Agrahari A, Singh A, Parmar D. Evaluation of the association between a single-nucleotide polymorphism of bone morphogenetic proteins 5 gene and risk of knee osteoarthritis. J Postgrad Med  2017; 63: 151-156.
[http://dx.doi.org/10.1177/2040622319825567] [PMID: 30815245] 
[53] 
Gato-Calvo L, Magalhaes J, Ruiz-Romero C, Blanco FJ, Burguera EF. Platelet-rich plasma in osteoarthritis treatment: review of current evidence. Ther Adv Chronic Dis  2019; 10: 2040622319825567.
[http://dx.doi.org/10.1177/2040622319825567] [PMID: 30815245] 
[54] 
Petrera M, De Croos JN, Iu J, Hurtig M, Kandel RA, Theodoropoulos JS. Supplementation with platelet-rich plasma improves the in vitro formation of tissue-engineered cartilage with enhanced mechanical properties. Arthroscopy  2013; 29(10): 1685-92.
[http://dx.doi.org/10.1016/j.arthro.2013.07.259] [PMID: 24075614] 
[55] 
van Buul GM, Koevoet WL, Kops N, et al. Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes. Am J Sports Med  2011; 39(11): 2362-70.
[http://dx.doi.org/10.1177/0363546511419278] [PMID: 21856929] 
[56] 
Burchard R, Huflage H, Soost C, Richter O, Bouillon B, Graw JA. Efficiency of platelet-rich plasma therapy in knee osteoarthritis does not depend on level of cartilage damage. J Orthop Surg Res  2019; 14(1): 153.
[http://dx.doi.org/10.1186/s13018-019-1203-0] [PMID: 31126348] 
[57] 
Raeissadat SA, Ghorbani E, Sanei Taheri M, et al. MRI changes after platelet rich plasma injection in knee osteoarthritis (randomized clinical trial). J Pain Res  2020; 13(1): 65-73.
[http://dx.doi.org/10.2147/JPR.S204788] [PMID: 32021396] 
[58] 
Halpern B, Chaudhury S, Rodeo SA, et al. Clinical and MRI outcomes after platelet-rich plasma treatment for knee osteoarthritis. Clin J Sport Med  2013; 23(3): 238-9.
[http://dx.doi.org/10.1097/JSM.0b013e31827c3846] [PMID: 23238250] 
[59] 
Raeissadat SA, Hosseini GP, Bahrami MH, et al. The Comparison effects of intra-articular injection of Platelet-Rich Plasma (PRP), Plasma Rich in Growth Factor (PRGF), Hyaluronic Acid (HA), and ozone in knee osteoarthritis; A one year randomized clinical trial. Ann Rheum Dis  2020; 79(S1): 1744-5.
[60] 
Di Martino A, Di Matteo B, Papio T, et al. Platelet-rich plasma versus hyaluronic acid injections for the treatment of knee osteoarthritis: Results at 5 years of a double-blind, randomized controlled trial. Am J Sports Med  2019; 47(2): 347-54.
[http://dx.doi.org/10.1177/0363546518814532] [PMID: 30545242] 
[61] 
Karasavvidis T, Totlis T, Gilat R, Cole BJ. Platelet-rich plasma combined with hyaluronic acid improves pain and function compared with hyaluronic acid alone in knee osteoarthritis: A systematic review and meta-analysis. Arthroscopy  2021; 37(4): 1277-1287.e1.
[http://dx.doi.org/10.1016/j.arthro.2020.11.052] [PMID: 33278533] 
[62] 
Altamura SA, Di Martino A, Andriolo L, et al. Platelet-rich plasma for sport-active patients with knee osteoarthritis: Limited return to sport. BioMed Res Int  2020; 2020: 8243865.  Available from: https://www.hindawi.com/journals/bmri/2020/8243865/
[http://dx.doi.org/10.1155/2020/8243865] [PMID: 32076616] 
[63] 
Su K, Bai Y, Wang J, Zhang H, Liu H, Ma S. Comparison of hyaluronic acid and PRP intra-articular injection with combined intra-articular and intraosseous PRP injections to treat patients with knee osteoarthritis. Clin Rheumatol  2018; 37(5): 1341-50.
[http://dx.doi.org/10.1007/s10067-018-3985-6] [PMID: 29388085] 
[64] 
Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JH. Intra-articular injection of platelet-rich plasma is superior to hyaluronic acid or saline solution in the treatment of mild to moderate knee osteoarthritis: A randomized, double-blind, triple-parallel, placebo-controlled clinical trial. Arthroscopy  2019; 35(1): 106-17.
[http://dx.doi.org/10.1016/j.arthro.2018.06.035] [PMID: 30611335] 
[65] 
Rai SK, Raman VP, Rohit V, Wani SS. Combined intra-articular injections (Hyaluronic acid, platelet-rich plasma, and corticosteroid) for osteoarthritis knee, an effective alternative treatment. J Orthop Trauma Rehabil  2018; 10(1): 57-60.
[http://dx.doi.org/10.4103/jotr.jotr_7_17] 
[66] 
Dhillon MS, Patel S, Bansal T. Improvising PRP for use in osteoarthritis knee- upcoming trends and futuristic view. J Clin Orthop Trauma  2019; 10(1): 32-5.
[http://dx.doi.org/10.1016/j.jcot.2018.10.005] [PMID: 30705528] 
[67] 
Mohiuddin AKM, Lewis P, Choudhury KN, Sadiq BU. Clinical outcome of photoactivated platelet-rich plasma in the treatment of knee osteoarthritis. Rheumatol Orthop Med  2018; 4(1): 1-4.
[68] 
Badr ME, Hafez EA, Atif EG, El-Sayed Heba M. Intra-articular injection of platelet-rich plasma and therapeutic exercise in knee osteoarthritis. Egypt Rheumatol Rehabil  2019; 46(1): 1-10.
[http://dx.doi.org/10.4103/err.err_22_18] 
[69] 
O’Connell B, Wragg NM, Wilson SL. The use of PRP injections in the management of knee osteoarthritis. Cell Tissue Res  2019; 376(2): 143-52.
[http://dx.doi.org/10.1007/s00441-019-02996-x] [PMID: 30758709] 
[70] 
Platelet-rich plasma injections for osteoarthritis of the knee, Inc.   Available from: https://www.nice.org.uk/guidance/IPG637
[71] 
Robinson K. EULAR Issues Recommendations for Knee OA Platelet-Rich Plasma Injections. 2020.  Available from: https://www.rheumatologynetwork.com/view/eular-issues-recommendations-knee-oa-platelet-rich-plasma-injections Accessed on 29 June, published on 11 June, 2020.
[72] 
Shahid M, Kundra R. Platelet-Rich Plasma (PRP) for knee disorders. EFORT Open Rev  2017; 2(1): 28-34.
[http://dx.doi.org/10.1302/2058-5241.2.160004] [PMID: 28607768] 
[73] 
Manchikanti L, Centeno CJ, Atluri S, et al. Bone Marrow Concentrate (BMC) therapy in musculoskeletal disorders: evidence-based policy position Statement of American Society of Interventional Pain Physicians (ASIPP). Pain Physician  2020; 23(2): E85-E131.
[PMID: 32214287] 
[74] 
Gong J, Fairley J, Cicuttini FM, et al. Effect of stem cell injections on osteoarthritis-related structural outcomes-a systematic review. J Rheumatol  2021; 48(4): 585-97.
[http://dx.doi.org/10.3899/jrheum.200021] [PMID: 33004537] 
[75] 
Chahal J, Gómez-Aristizábal A, Shestopaloff K, et al. Bone marrow mesenchymal stromal cell treatment in patients with osteoarthritis results in overall improvement in pain and symptoms and reduces synovial inflammation. Stem Cells Transl Med  2019; 8(8): 746-57.
[PMID: 30964245] 
[76] 
Freitag J, Bates D, Wickham J, et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: A randomized controlled trial. Regen Med  2019; 14(3): 213-30.
[http://dx.doi.org/10.2217/rme-2018-0161] [PMID: 30762487] 
[77] 
Gobbi A, Whyte GP. Long-term clinical outcomes of one-stage cartilage repair in the knee with hyaluronic acid-based scaffold embedded with mesenchymal stem cells sourced from bone marrow aspirate concentrate. Am J Sports Med  2019; 47(7): 1621-8.
[http://dx.doi.org/10.1177/0363546519845362] [PMID: 31095402] 
[78] 
Jo CH, Lee YG, Shin WH, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: A proof-of-concept clinical trial. Stem cell  2014; 32(5): 1254-66.
[http://dx.doi.org/10.1002/stem.1634] 
[79] 
Hernigou P, Delambre J, Quiennec S, Poignard A. Human bone marrow mesenchymal stem cell injection in subchondral lesions of knee osteoarthritis: A prospective randomized study versus contralateral arthroplasty at a mean fifteen year follow-up. Int Orthop  2021; 45(2): 365-73.
[http://dx.doi.org/10.1007/s00264-020-04571-4] [PMID: 32322943] 
[80] 
Song JS, Hong KT, Kim NM, et al. Cartilage regeneration in osteoarthritic knees treated with distal femoral osteotomy and intra-lesional implantation of allogenic human umbilical cord blood-derived mesenchymal stem cells: A report of two cases. Knee  2019; 26(6): 1445-50.
[http://dx.doi.org/10.1016/j.knee.2019.07.017] [PMID: 31443940] 
[81] 
Matas J, Orrego M, Amenabar D, et al. Umbilical cord-derived Mesenchymal Stromal Cells (MSCs) for knee osteoarthritis: Repeated MSC dosing is superior to a Single MSC dose and to hyaluronic acid in a controlled randomized phase I/II trial. Stem Cells Transl Med  2019; 8(3): 215-24.
[http://dx.doi.org/10.1002/sctm.18-0053] [PMID: 30592390] 
[82] 
Xing D, Wu J, Wang B, et al. Intra-articular delivery of umbilical cord-derived mesenchymal stem cells temporarily retard the progression of osteoarthritis in a rat model. Int J Rheum Dis  2020; 23(6): 778-87.
[http://dx.doi.org/10.1111/1756-185X.13834] [PMID: 32319197] 
[83] 
Geng Y, Chen J, Alahdal M, et al. Intra-articular injection of hUC-MSCs expressing miR-140-5p induces cartilage self-repairing in the rat osteoarthritis. J Bone Miner Metab  2020; 38(3): 277-88.
[http://dx.doi.org/10.1007/s00774-019-01055-3] [PMID: 31760502] 
[84] 
Zhu Y, Wang Y, Zhao B, et al. Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Res Ther  2017; 8(1): 64.
[http://dx.doi.org/10.1186/s13287-017-0510-9] [PMID: 28279188] 
[85] 
Hsu CC, Cheng JH, Wang CJ, Ko JY, Hsu SL, Hsu TC. Shockwave therapy combined with autologous adipose-derived mesenchymal stem cells is better than with human umbilical cord Wharton’s jelly-derived mesenchymal stem cells on knee osteoarthritis. Int J Mol Sci  2020; 21(4): 1217.
[http://dx.doi.org/10.3390/ijms21041217] [PMID: 32059379] 
[86] 
Jevotovsky DS, Alfonso AR, Einhorn TA, Chiu ES. Osteoarthritis and stem cell therapy in humans: A systematic review. Osteoarthritis Cartilage  2018; 26(6): 711-29.
[http://dx.doi.org/10.1016/j.joca.2018.02.906] [PMID: 29544858] 
[87] 
Songa Y, Zhanga J, Xua H, et al. Mesenchymal stem cells in knee osteoarthritis treatment: A systematic review and meta-analysis. J orthop Transl  2020; 24: 121-30.
[88] 
Ni Z, Zhou S, Li S, et al. Exosomes: Roles and therapeutic potential in osteoarthritis. Bone Res  2020; 8: 25.
[http://dx.doi.org/10.1038/s41413-020-0100-9] 
[89] 
Ni Z, Kuang L, Chen H, et al. The exosome-like vesicles from osteoarthritic chondrocyte enhanced mature IL-1β production of macrophages and aggravated synovitis in osteoarthritis. Cell Death Dis  2019; 10(7): 522.
[http://dx.doi.org/10.1038/s41419-019-1739-2] [PMID: 31285423] 
[90] 
Zhou Q, Cai Y, Jiang Y, Lin X. Exosomes in osteoarthritis and cartilage injury: Advanced development and potential therapeutic strategies. Int J Biol Sci  2020; 16(11): 1811-20.
[http://dx.doi.org/10.7150/ijbs.41637] [PMID: 32398951] 
[91] 
Nummenmaa E, Hamalainen M, Moilanen T, Vuolteenaho K, Moilanen E. Effects of fibroblast growth factor-2 and its receptor antagonists in osteoarthritis. Osteoarthr cartel  2015; 23(S2): A269.
[http://dx.doi.org/10.1016/j.joca.2015.02.490] 
[92] 
Li R, Wang B, He CQ, et al. Upregulation of fibroblast growth factor 1 in the synovial membranes of patients with late stage osteoarthritis. Genet Mol Res  2015; 14(3): 11191-9.
[http://dx.doi.org/10.4238/2015.September.22.13] [PMID: 26400350] 
[93] 
Honsawek S, Yuktanandana P, Tanavalee A, Saetan N, Anomasiri W, Parkpian V. Correlation between plasma and synovial fluid basic fibroblast growth factor with radiographic severity in primary knee osteoarthritis. Int Orthop  2012; 36(5): 981-5.
[http://dx.doi.org/10.1007/s00264-011-1435-z] [PMID: 22173563] 
[94] 
Li ZC, Xiao J, Wang G, et al. Fibroblast growth factor-21 concentration in serum and synovial fluid is associated with radiographic bone loss of knee osteoarthritis. Scand J Clin Lab Invest  2015; 75(2): 121-5.
[http://dx.doi.org/10.3109/00365513.2014.992942] [PMID: 25549692] 
[95] 
Zhu L, Weng Z, Shen P, et al. S100B regulates inflammatory response during osteoarthritis via fibroblast growth factor receptor 1 signaling. Mol Med Rep  2018; 18(6): 4855-64.
[http://dx.doi.org/10.3892/mmr.2018.9523] [PMID: 30280200] 
[96] 
Lohmander LS, Hellot S, Dreher D, et al. Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: A randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol  2014; 66(7): 1820-31.
[http://dx.doi.org/10.1002/art.38614] [PMID: 24740822] 
[97] 
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. JAMA  2019; 322(14): 1360-70.
[http://dx.doi.org/10.1001/jama.2019.14735] [PMID: 31593273] 
[98] 
Zeng N, Chen XY, Yan ZP, Li JT, Liao T, Ni GX. Efficacy and safety of sprifermin injection for knee osteoarthritis treatment: A meta-analysis. Arthritis Res Ther  2021; 23(1): 107.
[http://dx.doi.org/10.1186/s13075-021-02488-w] [PMID: 33836824] 
[99] 
Joosten LA, Helsen MMA, Saxne T, van De Loo FA, Heinegard D, van Den Berg WB. IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-alpha blockade only ameliorates joint inflammation. J Immunol  1999; 163(9): 5049-55.
[PMID: 10528210] 
[100] 
Ismail HM, Miotla-Zarebska J, Troeberg L, et al. JNK-2 controls aggrecan degradation in murine articular cartilage and the development of experimental osteoarthritis. Arthritis Rheumatol  2016; 68(5): 1165-71.
[PMID: 26663140] 
[101] 
Jiang Y, Genant HK, Watt I, et al. A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: Radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum  2000; 43(5): 1001-9.
[http://dx.doi.org/10.1002/1529-0131(200005)43:5<1001::AID-ANR7>3.0.CO;2-P] [PMID: 10817552] 
[102] 
Fraenkel L, Roubenoff R, LaValley M, et al. The association of peripheral monocyte derived interleukin 1beta (IL-1beta), IL-1 receptor antagonist, and tumor necrosis factor-alpha with osteoarthritis in the elderly. J Rheumatol  1998; 25(9): 1820-6.
[PMID: 9733466] 
[103] 
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.
[http://dx.doi.org/10.1186/ar3430] [PMID: 21801403] 
[104] 
Lacy SE, Wu C, Ambrosi DJ, et al. Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig(TM)) molecule that specifically and potently neutralizes both IL-1α and IL-1β. MAbs  2015; 7(3): 605-19.
[http://dx.doi.org/10.1080/19420862.2015.1026501] [PMID: 25764208] 
[105] 
Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med  2017; 377(12): 1119-31.
[http://dx.doi.org/10.1056/NEJMoa1707914] [PMID: 28845751] 
[106] 
Schieker M, Conaghan PG, Mindeholm L, et al. Effects of interleukin-1β inhibition on incident hip and knee replacement: Exploratory analyses from a randomized, double-blind, placebo-controlled trial. Ann Intern Med  2020; 173(7): 509-15.
[http://dx.doi.org/10.7326/M20-0527] [PMID: 32744862] 
[107] 
Marchetti C, Swartzwelter B, Gamboni F, et al. OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proc Natl Acad Sci USA  2018; 115(7): E1530-9.
[http://dx.doi.org/10.1073/pnas.1716095115] [PMID: 29378952] 
[108] 
Vincent TL. IL-1 in osteoarthritis: time for a critical review of the literature. F1000 Res  2019; 8: F1000 Faculty Rev-934.
[http://dx.doi.org/10.12688/f1000research.18831.1] [PMID: 31249675] 
[109] 
Evans CH, Ghivizzani SC, Robbins PD. Arthritis gene therapy approved in Korea. J Am Acad Orthop Surg  2018; 26(2): e36-8.
[http://dx.doi.org/10.5435/JAAOS-D-17-00695] [PMID: 29303924] 
[110] 
Kim MK, Ha CW, In Y, et al. A multicenter, double-blind, phase III clinical trial to evaluate the efficacy and safety of a cell and gene therapy in knee osteoarthritis patients. Hum Gene Ther Clin Dev  2018; 29(1): 48-59.
[http://dx.doi.org/10.1089/humc.2017.249] [PMID: 29641281] 
[111] 
Lee B. INVOSSA, a first-in-class of cell and gene therapy for osteoarthritis treatment: the phase III trial. Osteoarthritis Cartilage  2018; 26(7): S43-4.
[http://dx.doi.org/10.1016/j.joca.2018.02.103] 
[112] 
Saviola G, Ferrari P, Niccolò E, et al. Use of clodronate for painful knee prosthesis in osteoarthritis patients: A 6-month pilot study. Minerva Med  2020; 111(6): 551-9.
[http://dx.doi.org/10.23736/S0026-4806.20.06706-3] [PMID: 32573517] 
[113] 
Hayes KN, Giannakeas V, Wong AKO. Bisphosphonate use is protective of radiographic knee osteoarthritis progression among those with low disease severity and being non-overweight: Data from the osteoarthritis initiative. J Bone Miner Res  2020; 35(12): 2318-26.
[http://dx.doi.org/10.1002/jbmr.4133] [PMID: 32662919] 
[114] 
Xing RL, Zhao LR, Wang PM. Bisphosphonates therapy for osteoarthritis: A meta-analysis of randomized controlled trials. Springerplus  2016; 5(1): 1704.
[http://dx.doi.org/10.1186/s40064-016-3359-y] [PMID: 27757376] 
[115] 
Vaysbrot EE, Osani MC, Musetti MC, McAlindon TE, Bannuru RR. Are bisphosphonates efficacious in knee osteoarthritis? A meta-analysis of randomized controlled trials. Osteoarthritis Cartilage  2018; 26(2): 154-64.
[http://dx.doi.org/10.1016/j.joca.2017.11.013] [PMID: 29222056] 
[116] 
Cai G, Aitken D, Laslett LL, et al. Effect of intravenous zoledronic acid on tibiofemoral cartilage volume among patients with knee osteoarthritis with bone marrow lesions: A randomized clinical trial. JAMA  2020; 323(15): 1456-66.
[http://dx.doi.org/10.1001/jama.2020.2938] [PMID: 32315057] 
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DOI https://dx.doi.org/10.2174/1573397117666211116111738	Print ISSN 1573-3971
Publisher Name Bentham Science Publisher	Online ISSN 1875-6360
Current Rheumatology Reviews

Emerging and New Treatment Options for Knee Osteoarthritis

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