Skip to main content
SpringerLink
Log in

Efficacy of intra-articular hyaluronic acid injections and exercise-based rehabilitation programme, administered as isolated or integrated therapeutic regimens for the treatment of knee osteoarthritis

  • Knee
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

To assess the efficacy of intra-articular hyaluronic acid (HA) injections and exercise-based rehabilitation (EBR) programme, administered as isolated or integrated for the treatment of knee osteoarthritis.

Methods

One hundred sixty-five patients affected by moderate degrees of knee OA were randomly divided into three groups. Group 1 (HA) underwent three HA injections (one every 2 weeks); group 2 (EBR) underwent 20 treatment sessions in a month of an individualized programme; and group 3 (HA + EBR) received both treatments simultaneously. Primary outcome was the Italian version of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; secondary outcome was the evaluation of active range of movement (AROM). All patients were evaluated before and 1, 3 and 6 months after treatment. Significance was set at p < 0.05.

Results

Two patients in each group were lost to follow-up. No adverse events occurred. All groups experienced improvements at 1-month follow-up. No further improvements could be detected within groups over time. At 1-month follow-up, WOMAC pain subscale showed significant improvement in group 3 compared to group 1 (p = 0.043). WOMAC pain, stiffness and function subscales showed that group 2 significantly worsened between 1 and 6 months after treatment (p = 0.004, p = 0.026 and p = 0.025, respectively). AROM revealed no significant differences between and within groups over time.

Conclusions

Intra-articular HA injections and individualized rehabilitation programmes administered in isolation or in combination are effective in improving knee function and pain relief. The combined treatment showed the greatest pain relief at 1-month follow-up compared to either in isolation. Compared to the previous studies, this is the first study, which proposed an EBR programme tailored to the compartment of the knee joint most involved in the degenerative process.

Level of evidence

I.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Altman RD, Schemitsch E, Bedi A (2015) Assessment of clinical practice guideline methodology for the treatment of knee osteoarthritis with intra-articular hyaluronic acid. Semin Arthritis Rheum 45:132–139

    Article  CAS  PubMed  Google Scholar 

  2. Arden N, Nevitt MC (2006) Osteoarthritis: epidemiology. Best Pract Res Clin Rheumatol 20:3–25

    Article  PubMed  Google Scholar 

  3. Ayhan E, Kesmezacar H, Akgun I (2014) Intraarticular injections (corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis. World J Orthop 5:351–361

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G (2006) Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev 2:CD005321

    PubMed  Google Scholar 

  5. Bruyère O, Cooper C, Pelletier J-P, Branco J, Luisa Brandi M, Guillemin F, Hochberg MC, Kanis JA, Kvien TK, Martel-Pelletier J, Rizzoli R, Silverman S, Reginster J-Y (2014) An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum 44:253–263

    Article  PubMed  Google Scholar 

  6. Campbell KA, Erickson BJ, Saltzman BM, Mascarenhas R, Bach BR, Cole BJ, Verma NN (2015) Is local viscosupplementation injection clinically superior to other therapies in the treatment of osteoarthritis of the knee: a systematic review of overlapping meta-analyses. Arthroscopy 31(2036–2045):e14

    PubMed  Google Scholar 

  7. Campbell KA, Saltzman BM, Mascarenhas R, Khair MM, Verma NN, Bach BR, Cole BJ (2015) Does intra-articular platelet-rich plasma injection provide clinically superior outcomes compared with other therapies in the treatment of knee osteoarthritis? A systematic review of overlapping meta-analyses. Arthroscopy 31:2213–2221

    Article  PubMed  Google Scholar 

  8. Chareancholvanich K, Pornrattanamaneewong C, Narkbunnam R (2014) Increased cartilage volume after injection of hyaluronic acid in osteoarthritis knee patients who underwent high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc 22:1415–1423

    Article  PubMed  PubMed Central  Google Scholar 

  9. Christensen R, Bartels EM, Astrup A, Bliddal H (2007) Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: a systematic review and meta-analysis. Ann Rheum Dis 66:433–439

    Article  PubMed  PubMed Central  Google Scholar 

  10. Colen S, van den Bekerom MPJ, Mulier M, Haverkamp D (2012) Hyaluronic acid in the treatment of knee osteoarthritis: a systematic review and meta-analysis with emphasis on the efficacy of different products. BioDrugs 26:257–268

    Article  CAS  PubMed  Google Scholar 

  11. Fernandes L, Hagen KB, Bijlsma JWJ, Andreassen O, Christensen P, Conaghan PG, Doherty M, Geenen R, Hammond A, Kjeken I, Lohmander LS, Lund H, Mallen CD, Nava T, Oliver S, Pavelka K, Pitsillidou I, da Silva JA, de la Torre J, Zanoli G, Vliet Vlieland TPM, European League Against Rheumatism (EULAR) (2013) EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Ann Rheum Dis 72:1125–1135

    Article  PubMed  Google Scholar 

  12. Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL (2015) Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev 1:CD004376

    PubMed  Google Scholar 

  13. Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P, American College of Rheumatology (2012) American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res 64:465–474

    Article  CAS  Google Scholar 

  14. Huang M-H, Yang R-C, Lee C-L, Chen T-W, Wang M-C (2005) Preliminary results of integrated therapy for patients with knee osteoarthritis. Arthritis Rheum 53:812–820

    Article  PubMed  Google Scholar 

  15. Iwano T, Kurosawa H, Tokuyama H, Hoshikawa Y (1990) Roentgenographic and clinical findings of patellofemoral osteoarthrosis. With special reference to its relationship to femorotibial osteoarthrosis and etiologic factors. Clin Orthop Relat Res 252:190–197

    PubMed  Google Scholar 

  16. Jevsevar DS, Brown GA, Jones DL, Matzkin EG, Manner PA, Mooar P, Schousboe JT, Stovitz S, Sanders JO, Bozic KJ, Goldberg MJ, Martin WR, Cummins DS, Donnelly P, Woznica A, Gross L, AmericanAcademy of Orthopaedic Surgeons (2013) The American Academy of Orthopaedic Surgeons evidence-based guideline on: treatment of osteoarthritis of the knee, 2nd edition. J Bone Joint Surg Am 95:1885–1886

    PubMed  Google Scholar 

  17. Jüni P, Hari R, Rutjes AWS, Fischer R, Silletta MG, Reichenbach S, da Costa BR (2015) Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev 10:CD005328

    PubMed  Google Scholar 

  18. Karatosun V, Unver B, Gocen Z, Sen A, Gunal I (2006) Intra-articular hyaluranic acid compared with progressive knee exercises in osteoarthritis of the knee: a prospective randomized trial with long-term follow-up. Rheumatol Int 26:277–284

    Article  CAS  PubMed  Google Scholar 

  19. Karlsson J, Sjögren LS, Lohmander LS (2002) Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study. Rheumatology (Oxford) 41:1240–1248

    Article  CAS  Google Scholar 

  20. Kawasaki T, Kurosawa H, Ikeda H, Takazawa Y, Ishijima M, Kubota M, Kajihara H, Maruyama Y, Kim S-G, Kanazawa H (2009) Doi T Therapeutic home exercise versus intraarticular hyaluronate injection for osteoarthritis of the knee: 6-month prospective randomized open-labeled trial. J Orthop Sci 14:182–191

    Article  PubMed  Google Scholar 

  21. Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Laudy ABM, Bakker EWP, Rekers M, Moen MH (2015) Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med 49:657–672

    Article  PubMed  Google Scholar 

  23. McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, Hawker GA, Henrotin Y, Hunter DJ, Kawaguchi H, Kwoh K, Lohmander S, Rannou F, Roos EM, Underwood M (2014) OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil 22:363–388

    Article  CAS  PubMed  Google Scholar 

  24. Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD (2015) Efficacy of intra-articular platelet-rich plasma injections in knee Osteoarthritis: a systematic review. Arthroscopy. doi:10.1016/j.arthro.2015.08.005

    PubMed  Google Scholar 

  25. Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, Dragomir A, Kalsbeek WD, Luta G, Jordan JM (2008) Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum 59:1207–1213

    Article  PubMed  PubMed Central  Google Scholar 

  26. National Clinical Guideline Centre (UK) (2014) Osteoarthritis: care and management in adults. National Institute for Health and Care Excellence, London

    Google Scholar 

  27. Petrella RJ, Petrella M (2006) A prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intraarticular hyaluronic acid for osteoarthritis of the knee. J Rheumatol 33:951–956

    CAS  PubMed  Google Scholar 

  28. Rodriguez-Merchan EC (2013) Intraarticular injections of platelet-rich plasma (PRP) in the management of knee osteoarthritis. Arch Bone Jt Surg 1:5–8

    PubMed  PubMed Central  Google Scholar 

  29. Rothstein JM, Miller PJ, Roettger RF (1983) Goniometric reliability in a clinical setting. Elbow and knee measurements. Phys Ther 63:1611–1615

    CAS  PubMed  Google Scholar 

  30. Rutjes AWS, Jüni P, da Costa BR, Trelle S, Nüesch E, Reichenbach S (2012) Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med 157:180–191

    Article  PubMed  Google Scholar 

  31. Salaffi F, Leardini G, Canesi B, Mannoni A, Fioravanti A, Caporali R, Lapadula G, Punzi L, Gonorthrosis and Quality Of Life Assessment (GOQOLA) (2003) Reliability and validity of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index in Italian patients with osteoarthritis of the knee. Osteoarthr Cartil 11:551–560

    Article  CAS  PubMed  Google Scholar 

  32. Schafer JL (1999) Multiple imputation: a primer. Stat Methods Med Res 8:3–15

    Article  CAS  PubMed  Google Scholar 

  33. Stemberger R, Kerschan-Schindl K (2013) Osteoarthritis: physical medicine and rehabilitation—nonpharmacological management. Wien Med Wochenschr 163:228–235

    Article  PubMed  Google Scholar 

  34. Stitik TP, Blacksin MF, Stiskal DM, Kim JH, Foye PM, Schoenherr L, Choi E-S, Chen B, Saunders HJ, Nadler SF (2007) Efficacy and safety of hyaluronan treatment in combination therapy with home exercise for knee osteoarthritis pain. Arch Phys Med Rehabil 88:135–141

    Article  PubMed  Google Scholar 

  35. Strand V, Baraf HSB, Lavin PT, Lim S, Hosokawa H (2012) A multicenter, randomized controlled trial comparing a single intra-articular injection of Gel-200, a new cross-linked formulation of hyaluronic acid, to phosphate buffered saline for treatment of osteoarthritis of the knee. Osteoarthr Cartil 20:350–356

    Article  CAS  PubMed  Google Scholar 

  36. Strand V, McIntyre LF, Beach WR, Miller LE, Block JE (2015) Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials. J Pain Res 8:217–228

    PubMed  PubMed Central  Google Scholar 

  37. Van der Weegen W, Wullems JA, Bos E, Noten H, van Drumpt RAM (2015) No difference between intra-articular injection of hyaluronic acid and placebo for mild to moderate knee osteoarthritis: a randomized, controlled double-blind trial. J Arthroplast 30:754–757

    Article  Google Scholar 

  38. Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P (2007) OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthr Cartil 15:981–1000

    Article  CAS  PubMed  Google Scholar 

  39. Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P (2008) OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil 16:137–162

    Article  CAS  PubMed  Google Scholar 

  40. Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P (2010) OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil 18:476–499

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedics, “A. Gemelli” University Hospital, Catholic University, Largo A. Gemelli 8, 00168, Rome, Italy

    Maristella F. Saccomanno, Fabrizio Donati, Silvia Careri, Matteo Bartoli & Giuseppe Milano

  2. Private Practice, Via A. Baldi 53, Rome, 00136, Italy

    Gabriele Severini

Authors
  1. Maristella F. Saccomanno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fabrizio Donati
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvia Careri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matteo Bartoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gabriele Severini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giuseppe Milano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuseppe Milano.

Appendix: Rehabilitation protocols

Appendix: Rehabilitation protocols

  • Varus knee (medial tibio-femoral compartment)

    • Manual therapy;

    • Stretching of the following muscles: psoas, hip external rotators, medial flexors, biceps femoris and gastrocnemius;

    • Isometric exercises for quadriceps, biceps femoris and tensor fascia lata;

    • Isotonic exercises with elastic resistance (tubing) for quadriceps, biceps femoris and tensor fascia lata;

    • Proprioceptive rehabilitation.

  • Valgus knee (lateral tibio-femoral compartment)

    • Manual therapy;

    • Stretching of the following muscles: psoas, medial flexors, biceps femoris, tensor fascia lata and gastrocnemius;

    • Isometric exercises for quadriceps, hip adductors and medial flexors;

    • Isotonic exercises with elastic resistance (tubing) for quadriceps, hip adductors and medial flexors;

    • Proprioceptive rehabilitation.

  • Patello-femoral osteoarthritis

    • Manual therapy;

    • Stretching of the following muscles: psoas, hip external rotators, medial flexors, biceps femoris, tensor fascia lata and gastrocnemius;

    • Isometric exercises for quadriceps;

    • Isotonic exercises in closed kinetic chain for quadriceps with elastic resistance;

    • Proprioceptive rehabilitation.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saccomanno, M.F., Donati, F., Careri, S. et al. Efficacy of intra-articular hyaluronic acid injections and exercise-based rehabilitation programme, administered as isolated or integrated therapeutic regimens for the treatment of knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 24, 1686–1694 (2016). https://doi.org/10.1007/s00167-015-3917-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00167-015-3917-9

Keywords

Search

Navigation