Download PDF
J Knee Surg 2020; 33(11): 1078-1087
DOI: 10.1055/s-0040-1713813
Special Focus Section

Nonsurgical Management of Cartilage Defects of the Knee: Who, When, Why, and How?

Chad Hanaoka
1   Department of Physical Medicine and Rehabilitation, Shirley Ryan AbilityLab, Chicago, Illinois
,
Cameron Fausett
1   Department of Physical Medicine and Rehabilitation, Shirley Ryan AbilityLab, Chicago, Illinois
2   Department of Physical Medicine and Rehabilitation, McGaw Medical Center of Northwestern University, Chicago, Illinois
,
Prakash Jayabalan
1   Department of Physical Medicine and Rehabilitation, Shirley Ryan AbilityLab, Chicago, Illinois
3   Department of Physical Medicine and Rehabilitation, Northwestern Feinberg School of Medicine, Chicago, Illinois
› Author Affiliations Funding The author is supported by a grant from the National Center for Advancing Translational Sciences (2KL2TR001424-05A1).
› Further Information
    Permissions and Reprints

Abstract

The nonoperative practitioner managing individuals with cartilage defects should use a patient-centered, multifaceted approach that aims to individualize treatment to provide optimal benefit. These include addressing modifiable risk factors for disease progression and instituting interventions such as weight loss, nutrition, physical activity, and potentially regenerative medicine strategies. This review will focus on these nonoperative treatment strategies with a focus on when treatments are necessary, who will benefit from these approaches, why they are specifically appropriate, and, finally, how these treatments directly modify the structure of a patient's cartilage and resulting symptoms.

Keywords

cartilage - osteoarthritis - knee


Publication History

Received: 07 April 2020

Accepted: 24 May 2020

Article published online:
14 July 2020

Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.

 

  • References

  • 1 Cross M, Smith E, Hoy D. et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014; 73 (07) 1323-1330
    CrossrefPubMedGoogle Scholar
  • 2 Briggs AM, Cross MJ, Hoy DG. et al. Musculoskeletal health conditions represent a global threat to healthy aging: a report for the 2015 World Health Organization World Report on Ageing and Health. Gerontologist 2016; 56 (Suppl. 02) S243-S255
    CrossrefPubMedGoogle Scholar
  • 3 Blagojevic M, Jinks C, Jeffery A, Jordan KP. Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage 2010; 18 (01) 24-33
    CrossrefPubMedGoogle Scholar
  • 4 Silverwood V, Blagojevic-Bucknall M, Jinks C, Jordan JL, Protheroe J, Jordan KP. Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage 2015; 23 (04) 507-515
    CrossrefPubMedGoogle Scholar
  • 5 Shane Anderson A, Loeser RF. Why is osteoarthritis an age-related disease?. Best Pract Res Clin Rheumatol 2010; 24 (01) 15-26
    CrossrefPubMedGoogle Scholar
  • 6 Hame SL, Alexander RA. Knee osteoarthritis in women. Curr Rev Musculoskelet Med 2013; 6 (02) 182-187
    CrossrefPubMedGoogle Scholar
  • 7 Messier SP, Gutekunst DJ, Davis C, DeVita P. Weight loss reduces knee-joint loads in overweight and obese older adults with knee osteoarthritis. Arthritis Rheum 2005; 52 (07) 2026-2032
    CrossrefPubMedGoogle Scholar
  • 8 Poulsen E, Goncalves GH, Bricca A, Roos EM, Thorlund JB, Juhl CB. Knee osteoarthritis risk is increased 4-6 fold after knee injury - a systematic review and meta-analysis. Br J Sports Med 2019; 53 (23) 1454-1463
    CrossrefPubMedGoogle Scholar
  • 9 Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med 2007; 35 (10) 1756-1769
    CrossrefPubMedGoogle Scholar
  • 10 Bayliss LE, Culliford D, Monk AP. et al. The effect of patient age at intervention on risk of implant revision after total replacement of the hip or knee: a population-based cohort study. Lancet 2017; 389 (10077): 1424-1430
    CrossrefPubMedGoogle Scholar
  • 11 Oliver-Welsh L, Griffin JW, Meyer MA, Gitelis ME, Cole BJ. Deciding how best to treat cartilage defects. Orthopedics 2016; 39 (06) 343-350
    CrossrefPubMedGoogle Scholar
  • 12 Braun HJ, Gold GE. Diagnosis of osteoarthritis: imaging. Bone 2012; 51 (02) 278-288
    CrossrefPubMedGoogle Scholar
  • 13 Schonberg MA, Marcantonio ER, Hamel MB. Perceptions of physician recommendations for joint replacement surgery in older patients with severe hip or knee osteoarthritis. J Am Geriatr Soc 2009; 57 (01) 82-88
    CrossrefPubMedGoogle Scholar
  • 14 Hunter DJ, March L, Sambrook PN. The association of cartilage volume with knee pain. Osteoarthritis Cartilage 2003; 11 (10) 725-729
    CrossrefPubMedGoogle Scholar
  • 15 McAlindon TE, LaValley MP, Harvey WF. et al. Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial. JAMA 2017; 317 (19) 1967-1975
    CrossrefPubMedGoogle Scholar
  • 16 Grotle M, Hagen KB, Natvig B, Dahl FA, Kvien TK. Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet Disord 2008; 9: 132
    CrossrefPubMedGoogle Scholar
  • 17 Zheng H, Chen C. Body mass index and risk of knee osteoarthritis: systematic review and meta-analysis of prospective studies. BMJ Open 2015; 5 (12) e007568
    CrossrefPubMedGoogle Scholar
  • 18 Coggon D, Reading I, Croft P, McLaren M, Barrett D, Cooper C. Knee osteoarthritis and obesity. Int J Obes Relat Metab Disord 2001; 25 (05) 622-627
    CrossrefPubMedGoogle Scholar
  • 19 Messier SP, Loeser RF, Miller GD. et al. Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: the Arthritis, Diet, and Activity Promotion Trial. Arthritis Rheum 2004; 50 (05) 1501-1510
    CrossrefPubMedGoogle Scholar
  • 20 Hurwitz DE, Ryals AB, Case JP, Block JA, Andriacchi TP. The knee adduction moment during gait in subjects with knee osteoarthritis is more closely correlated with static alignment than radiographic disease severity, toe out angle and pain. J Orthop Res 2002; 20 (01) 101-107
    CrossrefPubMedGoogle Scholar
  • 21 Chang AH, Moisio KC, Chmiel JS. et al. External knee adduction and flexion moments during gait and medial tibiofemoral disease progression in knee osteoarthritis. Osteoarthritis Cartilage 2015; 23 (07) 1099-1106
    CrossrefPubMedGoogle Scholar
  • 22 Thijssen E, van Caam A, van der Kraan PM. Obesity and osteoarthritis, more than just wear and tear: pivotal roles for inflamed adipose tissue and dyslipidaemia in obesity-induced osteoarthritis. Rheumatology (Oxford) 2015; 54 (04) 588-600
    CrossrefPubMedGoogle Scholar
  • 23 Thomas S, Browne H, Mobasheri A, Rayman MP. What is the evidence for a role for diet and nutrition in osteoarthritis?. Rheumatology (Oxford) 2018; 57 (04) (Suppl. 04) iv61-iv74
    CrossrefPubMedGoogle Scholar
  • 24 Berenbaum F, Eymard F, Houard X. Osteoarthritis, inflammation and obesity. Curr Opin Rheumatol 2013; 25 (01) 114-118
    CrossrefPubMedGoogle Scholar
  • 25 Messier SP, Mihalko SL, Legault C. et al. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA 2013; 310 (12) 1263-1273
    CrossrefPubMedGoogle Scholar
  • 26 Messier SP, Beavers DP, Loeser RF. et al. Knee joint loading in knee osteoarthritis: influence of abdominal and thigh fat. Med Sci Sports Exerc 2014; 46 (09) 1677-1683
    CrossrefPubMedGoogle Scholar
  • 27 Messier SP, Resnik AE, Beavers DP. et al. Intentional weight loss in overweight and obese patients with knee osteoarthritis: is more better?. Arthritis Care Res (Hoboken) 2018; 70 (11) 1569-1575
    CrossrefPubMedGoogle Scholar
  • 28 Eckstein F, Hudelmaier M, Putz R. The effects of exercise on human articular cartilage. J Anat 2006; 208 (04) 491-512
    CrossrefPubMedGoogle Scholar
  • 29 Guermazi A, Alizai H, Crema MD, Trattnig S, Regatte RR, Roemer FW. Compositional MRI techniques for evaluation of cartilage degeneration in osteoarthritis. Osteoarthritis Cartilage 2015; 23 (10) 1639-1653
    CrossrefPubMedGoogle Scholar
  • 30 Gersing AS, Solka M, Joseph GB. et al. Progression of cartilage degeneration and clinical symptoms in obese and overweight individuals is dependent on the amount of weight loss: 48-month data from the Osteoarthritis Initiative. Osteoarthritis Cartilage 2016; 24 (07) 1126-1134
    CrossrefPubMedGoogle Scholar
  • 31 Lotz M, Martel-Pelletier J, Christiansen C. et al. Value of biomarkers in osteoarthritis: current status and perspectives. Ann Rheum Dis 2013; 72 (11) 1756-1763
    CrossrefPubMedGoogle Scholar
  • 32 Loeser RF, Beavers DP, Bay-Jensen AC. et al. Effects of dietary weight loss with and without exercise on interstitial matrix turnover and tissue inflammation biomarkers in adults with knee osteoarthritis: the Intensive Diet and Exercise for Arthritis trial (IDEA). Osteoarthritis Cartilage 2017; 25 (11) 1822-1828
    CrossrefPubMedGoogle Scholar
  • 33 Siebuhr AS, Petersen KK, Arendt-Nielsen L. et al. Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover. Osteoarthritis Cartilage 2014; 22 (01) 44-50
    CrossrefPubMedGoogle Scholar
  • 34 Lu B, Driban JB, Xu C, Lapane KL, McAlindon TE, Eaton CB. Dietary fat intake and radiographic progression of knee osteoarthritis: data from the Osteoarthritis Initiative. Arthritis Care Res (Hoboken) 2017; 69 (03) 368-375
    CrossrefPubMedGoogle Scholar
  • 35 Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 2006; 83 (6, Suppl): 1505S-1519S
    CrossrefPubMedGoogle Scholar
  • 36 Schell J, Scofield RH, Barrett JR. et al. Strawberries improve pain and inflammation in obese adults with radiographic evidence of knee osteoarthritis. Nutrients 2017; 9 (09) E949
    CrossrefPubMedGoogle Scholar
  • 37 Basu A, Kurien BT, Tran H. et al. Strawberries decrease circulating levels of tumor necrosis factor and lipid peroxides in obese adults with knee osteoarthritis. Food Funct 2018; 9 (12) 6218-6226
    CrossrefPubMedGoogle Scholar
  • 38 Csaki C, Keshishzadeh N, Fischer K, Shakibaei M. Regulation of inflammation signalling by resveratrol in human chondrocytes in vitro. Biochem Pharmacol 2008; 75 (03) 677-687
    CrossrefPubMedGoogle Scholar
  • 39 Bach-Faig A, Berry EM, Lairon D. , et al; Mediterranean Diet Foundation Expert Group. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr 2011; 14 (12A): 2274-2284
    CrossrefPubMedGoogle Scholar
  • 40 Musumeci G, Trovato FM, Pichler K, Weinberg AM, Loreto C, Castrogiovanni P. Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model: an in vivo and in vitro study on lubricin expression. J Nutr Biochem 2013; 24 (12) 2064-2075
    CrossrefPubMedGoogle Scholar
  • 41 Dyer J, Davison G, Marcora SM, Mauger AR. Effect of a Mediterranean type diet on inflammatory and cartilage degradation biomarkers in patients with osteoarthritis. J Nutr Health Aging 2017; 21 (05) 562-566
    CrossrefPubMedGoogle Scholar
  • 42 Veronese N, Stubbs B, Noale M, Solmi M, Luchini C, Maggi S. Adherence to the Mediterranean diet is associated with better quality of life: data from the Osteoarthritis Initiative. Am J Clin Nutr 2016; 104 (05) 1403-1409
    CrossrefPubMedGoogle Scholar
  • 43 Vasiliadis HS, Tsikopoulos K. Glucosamine and chondroitin for the treatment of osteoarthritis. World J Orthop 2017; 8 (01) 1-11
    CrossrefPubMedGoogle Scholar
  • 44 Calamia V, Ruiz-Romero C, Rocha B. et al. Pharmacoproteomic study of the effects of chondroitin and glucosamine sulfate on human articular chondrocytes. Arthritis Res Ther 2010; 12 (04) R138
    CrossrefPubMedGoogle Scholar
  • 45 Lippiello L. Glucosamine and chondroitin sulfate: biological response modifiers of chondrocytes under simulated conditions of joint stress. Osteoarthritis Cartilage 2003; 11 (05) 335-342
    CrossrefPubMedGoogle Scholar
  • 46 Sawitzke AD, Shi H, Finco MF. et al. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial. Arthritis Rheum 2008; 58 (10) 3183-3191
    CrossrefPubMedGoogle Scholar
  • 47 Sawitzke AD, Shi H, Finco MF. et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis 2010; 69 (08) 1459-1464
    CrossrefPubMedGoogle Scholar
  • 48 Gallagher B, Tjoumakaris FP, Harwood MI, Good RP, Ciccotti MG, Freedman KB. Chondroprotection and the prevention of osteoarthritis progression of the knee: a systematic review of treatment agents. Am J Sports Med 2015; 43 (03) 734-744
    CrossrefPubMedGoogle Scholar
  • 49 Buddhachat K, Siengdee P, Chomdej S, Soontornvipart K, Nganvongpanit K. Effects of different omega-3 sources, fish oil, krill oil, and green-lipped mussel against cytokine-mediated canine cartilage degradation. In Vitro Cell Dev Biol Anim 2017; 53 (05) 448-457
    CrossrefPubMedGoogle Scholar
  • 50 Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB. Effect of fish oil on heart rate in humans: a meta-analysis of randomized controlled trials. Circulation 2005; 112 (13) 1945-1952
    CrossrefPubMedGoogle Scholar
  • 51 Weitz D, Weintraub H, Fisher E, Schwartzbard AZ. Fish oil for the treatment of cardiovascular disease. Cardiol Rev 2010; 18 (05) 258-263
    CrossrefPubMedGoogle Scholar
  • 52 Curtis CL, Hughes CE, Flannery CR, Little CB, Harwood JL, Caterson B. n-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. J Biol Chem 2000; 275 (02) 721-724
    CrossrefPubMedGoogle Scholar
  • 53 Zainal Z, Longman AJ, Hurst S. et al. Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis. Osteoarthritis Cartilage 2009; 17 (07) 896-905
    CrossrefPubMedGoogle Scholar
  • 54 Knott L, Avery NC, Hollander AP, Tarlton JF. Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease. Osteoarthritis Cartilage 2011; 19 (09) 1150-1157
    CrossrefPubMedGoogle Scholar
  • 55 Wann AKT, Mistry J, Blain EJ, Michael-Titus AT, Knight MM. Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation. Arthritis Res Ther 2010; 12 (06) R207
    CrossrefPubMedGoogle Scholar
  • 56 Hill CL, March LM, Aitken D. et al. Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose. Ann Rheum Dis 2016; 75 (01) 23-29
    CrossrefPubMedGoogle Scholar
  • 57 Akbar U, Yang M, Kurian D, Mohan C. Omega-3 fatty acids in rheumatic diseases: a critical review. J Clin Rheumatol 2017; 23 (06) 330-339
    CrossrefPubMedGoogle Scholar
  • 58 Juhl C, Christensen R, Roos EM, Zhang W, Lund H. Impact of exercise type and dose on pain and disability in knee osteoarthritis: a systematic review and meta-regression analysis of randomized controlled trials. Arthritis Rheumatol 2014; 66 (03) 622-636
    CrossrefPubMedGoogle Scholar
  • 59 Holden MA, Nicholls EE, Young J, Hay EM, Foster NE. Role of exercise for knee pain: what do older adults in the community think?. Arthritis Care Res (Hoboken) 2012; 64 (10) 1554-1564
    CrossrefPubMedGoogle Scholar
  • 60 Darlow B, Brown M, Thompson B. et al. Living with osteoarthritis is a balancing act: an exploration of patients' beliefs about knee pain. BMC Rheumatol 2018; 2: 15
    CrossrefPubMedGoogle Scholar
  • 61 Vanwanseele B, Eckstein F, Knecht H, Spaepen A, Stüssi E. Longitudinal analysis of cartilage atrophy in the knees of patients with spinal cord injury. Arthritis Rheum 2003; 48 (12) 3377-3381
    CrossrefPubMedGoogle Scholar
  • 62 Bricca A, Struglics A, Larsson S, Steultjens M, Juhl CB, Roos EM. Impact of exercise therapy on molecular biomarkers related to cartilage and inflammation in individuals at risk of, or with established, knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken) 2019; 71 (11) 1504-1515
    CrossrefPubMedGoogle Scholar
  • 63 Hunter DJ, Eckstein F. Exercise and osteoarthritis. J Anat 2009; 214 (02) 197-207
    CrossrefPubMedGoogle Scholar
  • 64 Jayabalan P, Kocherginsky M, Chang AH. et al. Physical activity and worsening of radiographic findings in persons with or at higher risk of knee osteoarthritis. Arthritis Care Res (Hoboken) 2019; 71 (02) 198-206
    CrossrefPubMedGoogle Scholar
  • 65 Munukka M, Waller B, Häkkinen A. et al. Physical activity is related with cartilage quality in women with knee osteoarthritis. Med Sci Sports Exerc 2017; 49 (07) 1323-1330
    CrossrefPubMedGoogle Scholar
  • 66 Multanen J, Nieminen MT, Häkkinen A. et al. Effects of high-impact training on bone and articular cartilage: 12-month randomized controlled quantitative MRI study. J Bone Miner Res 2014; 29 (01) 192-201
    CrossrefPubMedGoogle Scholar
  • 67 Koli J, Multanen J, Kujala UM. et al. Effects of exercise on patellar cartilage in women with mild knee osteoarthritis. Med Sci Sports Exerc 2015; 47 (09) 1767-1774
    CrossrefPubMedGoogle Scholar
  • 68 Castrogiovanni P, Musumeci G. Which is the best physical treatment for osteoarthritis?. J Funct Morphol Kinesiol. 2016; 1 (01) 54-68
    CrossrefPubMedGoogle Scholar
  • 69 Batterham SI, Heywood S, Keating JL. Systematic review and meta-analysis comparing land and aquatic exercise for people with hip or knee arthritis on function, mobility and other health outcomes. BMC Musculoskelet Disord 2011; 12: 123
    CrossrefPubMedGoogle Scholar
  • 70 Kutzner I, Heinlein B, Graichen F. et al. Loading of the knee joint during ergometer cycling: telemetric in vivo data. J Orthop Sports Phys Ther 2012; 42 (12) 1032-1038
    CrossrefPubMedGoogle Scholar
  • 71 Salacinski AJ, Krohn K, Lewis SF, Holland ML, Ireland K, Marchetti G. The effects of group cycling on gait and pain-related disability in individuals with mild-to-moderate knee osteoarthritis: a randomized controlled trial. J Orthop Sports Phys Ther 2012; 42 (12) 985-995
    CrossrefPubMedGoogle Scholar
  • 72 Alkatan M, Baker JR, Machin DR. et al. Improved function and reduced pain after swimming and cycling training in patients with osteoarthritis. J Rheumatol 2016; 43 (03) 666-672
    CrossrefPubMedGoogle Scholar
  • 73 Alkatan M, Machin DR, Baker JR, Akkari AS, Park W, Tanaka H. Effects of swimming and cycling exercise intervention on vascular function in patients with osteoarthritis. Am J Cardiol 2016; 117 (01) 141-145
    CrossrefPubMedGoogle Scholar
  • 74 Munukka M, Waller B, Rantalainen T. et al. Efficacy of progressive aquatic resistance training for tibiofemoral cartilage in postmenopausal women with mild knee osteoarthritis: a randomised controlled trial. Osteoarthritis Cartilage 2016; 24 (10) 1708-1717
    CrossrefPubMedGoogle Scholar
  • 75 Waller B, Munukka M, Rantalainen T. et al. Effects of high intensity resistance aquatic training on body composition and walking speed in women with mild knee osteoarthritis: a 4-month RCT with 12-month follow-up. Osteoarthritis Cartilage 2017; 25 (08) 1238-1246
    CrossrefPubMedGoogle Scholar
  • 76 Roos EM, Dahlberg L. Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: a four-month, randomized, controlled trial in patients at risk of osteoarthritis. Arthritis Rheum 2005; 52 (11) 3507-3514
    CrossrefPubMedGoogle Scholar
  • 77 Jan MH, Lin JJ, Liau JJ, Lin YF, Lin DH. Investigation of clinical effects of high- and low-resistance training for patients with knee osteoarthritis: a randomized controlled trial. Phys Ther 2008; 88 (04) 427-436
    CrossrefPubMedGoogle Scholar
  • 78 Slemenda C, Brandt KD, Heilman DK. et al. Quadriceps weakness and osteoarthritis of the knee. Ann Intern Med 1997; 127 (02) 97-104
    CrossrefPubMedGoogle Scholar
  • 79 Segal NA, Glass NA, Torner J. et al. Quadriceps weakness predicts risk for knee joint space narrowing in women in the MOST cohort. Osteoarthritis Cartilage 2010; 18 (06) 769-775
    CrossrefPubMedGoogle Scholar
  • 80 Amin S, Baker K, Niu J. et al. Quadriceps strength and the risk of cartilage loss and symptom progression in knee osteoarthritis. Arthritis Rheum 2009; 60 (01) 189-198
    CrossrefPubMedGoogle Scholar
  • 81 Helmark IC, Petersen MC, Christensen HE, Kjaer M, Langberg H. Moderate loading of the human osteoarthritic knee joint leads to lowering of intraarticular cartilage oligomeric matrix protein. Rheumatol Int 2012; 32 (04) 1009-1014
    CrossrefPubMedGoogle Scholar
  • 82 Tuna S, Balcı N, Özçakar L. The relationship between femoral cartilage thickness and muscle strength in knee osteoarthritis. Clin Rheumatol 2016; 35 (08) 2073-2077
    CrossrefPubMedGoogle Scholar
  • 83 Miyaguchi M, Kobayashi A, Kadoya Y, Ohashi H, Yamano Y, Takaoka K. Biochemical change in joint fluid after isometric quadriceps exercise for patients with osteoarthritis of the knee. Osteoarthritis Cartilage 2003; 11 (04) 252-259
    CrossrefPubMedGoogle Scholar
  • 84 McIntyre JA, Jones IA, Han B, Vangsness Jr CT. Intra-articular mesenchymal stem cell therapy for the human joint: a systematic review. Am J Sports Med 2018; 46 (14) 3550-3563
    CrossrefPubMedGoogle Scholar
  • 85 Goldberg A, Mitchell K, Soans J, Kim L, Zaidi R. The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review. J Orthop Surg Res 2017; 12 (01) 39
    CrossrefPubMedGoogle Scholar
  • 86 Elik H, Doğu B, Yılmaz F, Begoğlu FA, Kuran B. The efficiency of platelet-rich plasma treatment in patients with knee osteoarthritis. J Back Musculoskeletal Rehabil 2020; 33 (01) 127-138
    CrossrefPubMedGoogle Scholar
  • 87 Hohmann E, Tetsworth K, Glatt V. Is platelet-rich plasma effective for the treatment of knee osteoarthritis? A systematic review and meta-analysis of level 1 and 2 randomized controlled trials. Eur J Orthop Surg Traumatol 2020; (e-pub ahead of print) DOI: 10.1007/s00590-020-02623-4.
    CrossrefPubMedGoogle Scholar
  • 88 Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O'Connor MIA. A prospective, single-blind, placebo-controlled trial of bone marrow aspirate concentrate for knee osteoarthritis. Am J Sports Med 2017; 45 (01) 82-90
    CrossrefPubMedGoogle Scholar
  • 89 Bastos R, Mathias M, Andrade R. et al. Intra-articular injections of expanded mesenchymal stem cells with and without addition of platelet-rich plasma are safe and effective for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2018; 26 (11) 3342-3350
    CrossrefPubMedGoogle Scholar