International Orthopaedics

, Volume 42, Issue 4, pp 733–740 | Cite as

Hyaluronic acid injections for osteoarthritis of the knee: predictors of successful treatment

  • Eric N. Bowman
  • Justin D. Hallock
  • Thomas W. Throckmorton
  • Fredrick M. Azar
Original Paper

Abstract

Purpose

This study aimed to identify patient and treatment factors that predict a favourable response to intra-articular hyaluronic acid (HA) treatment to better guide patient and treatment selection.

Methods

This prospective, observational study evaluated patients with mild-to-moderate (Kellgren–Lawrence grades 1–3) primary knee osteoarthritis treated between March 2013 and May 2016. Patient function and pain scores were assessed by the Western Ontario and McMaster Universities Arthritis Index/Knee Injury and Osteoarthritis Outcome Score (WOMAC/KOOS) and visual analogue scale (VAS) surveys, with response to treatment defined according to the Osteoarthritis Research Society International (OARSI) 2004 criteria. Surveys were completed at each injection and three months post-treatment. Patients were followed an average of 27 months.

Results

Of 102 patients, 57% had a positive response. Those at least twice as likely to respond were patients with grades 1–2 osteoarthritis or a positive response to the first injection and those who were ≥60 years. Gender, race, body mass index (BMI), smoking status, HA brand, and initial VAS and WOMAC/KOOS scores were not significant predictors of success. Mean time to arthroplasty following injection series was 11 months (30% of nonresponders, 12% of responders). The VAS strongly correlated with KOOS pain scores and successful outcomes.

Conclusion

Patients with mild-to-moderate osteoarthritis (grades 1–2) and those responding positively to the first injection were twice as likely to respond positively to the injection series, as were patients ≥60 years. Patients who did not respond positively were more likely to proceed to arthroplasty. The VAS appears to be a reliable method of defining and monitoring treatment success. Judicious patient selection and counseling may improve outcomes associated with intra-articular HA injections.

Keywords

Osteoarthritis Knee Hyaluronic acid Injection Viscosupplementation 

Notes

Compliance with ethical standards

Conflict of interest

Authors Bowman and Hallock declare that they have no conflict of interest. Author Azar has received consultant fees from 98point6, Iovera, and Zimmer and publishing royalties from Elsevier; he serves on the governing/editorial board/committee of the ABOS, Am J Sports Med, Orthop Clin N Am, and St. Jude Children’s Research Hospital. Author Throckmorton has received consultant and speaker fees, IP royalties, and research support from Biomet and Zimmer; he receives publishing royalties from Elsevier, and serves on the governing/editorial board/committee of the AAOS, Am J Orthop, American Shoulder & Elbow Surgeons, J Orthop Trauma, Mid-America Orthop Assoc, Orthop Clin No Am, and Tech in Shoulder & Elbow Surgery.

References

  1. 1.
    Deshpande BR, Katz JN, Solomon DH, Yellin EH, Hunter DJ, Messier SP et al (2016) Number of persons with symptomatic knee osteoarthritis in the US: impact of race and ethnicity, age, sex, and obesity. Arthritis Care Res (Hoboken) 68:1743–1750CrossRefGoogle Scholar
  2. 2.
    Jordan JM, Helmick CG, Renner JB, Luter G, Dragomir AD, Woodard J et al (2007) Prevalence of knee symptoms and radiographic and symptomatic knee osteoarthritis in African Americans and Caucasians: the Johnston County osteoarthritis project. J Rheumatol 34:172–180PubMedGoogle Scholar
  3. 3.
    Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA et al (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 58:26–35CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Weick JW, Bawa HS, Dirschl DR (2016) Hyaluronic acid injections for treatment of advanced osteoarthritis of the knee: utilization and cost in a national population sample. J Bone Joint Surg Am 98:1429–1435CrossRefPubMedGoogle Scholar
  5. 5.
    Schmajuk G, Bozic KJ, Yazdany J (2014) Using Medicare data to understand low-value health care: the case of intra-articular hyaluronic acid injections. JAMA Intern Med 174:1702–1704CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Adams ME, Atkinson MH, Lussier AJ, Schulz JI, Siminovitch KA, Wade JP et al (1995) The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with nonsteroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone. Osteoarthr Cartil 3:213–225CrossRefPubMedGoogle Scholar
  7. 7.
    Frizziero L, Govoni E, Bacchini P (1998) Intra-articular hyaluronic acid in the treatment of osteoarthritis of the knee: clinical and morphological study. Clin Exp Rheumatol 16:441–449PubMedGoogle Scholar
  8. 8.
    Laurent TC, Fraser JR (1992) Hyaluronan. FASEB J 6:2397–2404CrossRefPubMedGoogle Scholar
  9. 9.
    Ghosh P (1994) The role of hyaluronic acid (hyaluronan) in health and disease: interactions with cells, cartilage and components of synovial fluid. Clin Exp Rheumatol 12:75–82PubMedGoogle Scholar
  10. 10.
    Moreland LW (2003) Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action. Arthritis Res Ther 5:54–67CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Peyron JG (1993) A new approach to the treatment of osteoarthritis: viscosupplementation. Osteoarthr Cartil 1:85–87CrossRefPubMedGoogle Scholar
  12. 12.
    Rydell N, Balazs EA (1971) Effect of intra-articular injection of hyaluronic acid on the clinical symptoms of osteoarthritis and on granulation tissue formation. Clin Orthop Relat Res 80:25–32CrossRefPubMedGoogle Scholar
  13. 13.
    Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840PubMedGoogle Scholar
  15. 15.
    Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD (1998) Knee injury and osteoarthritis outcome score (KOOS)--development of a self-administered outcome measure. J Orthop Sports Phys Ther 28:88–96CrossRefPubMedGoogle Scholar
  16. 16.
    Price DD, McGrath PA, Rafii A, Buckingham B (1983) The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain 17:45–56CrossRefPubMedGoogle Scholar
  17. 17.
    Pham T, van der Heijde D, Altman RD, Anderson JJ, Bellamy N, Hochberg M et al (2004) OMERACT-OARSI initiative: osteoarthritis research society international set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthr Cartil 12:389–399CrossRefPubMedGoogle Scholar
  18. 18.
    Rutjes AW, Juni P, da Costa BR, Trelle S, Nuesch E, Reichenbach S (2012) Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med 157:180–191CrossRefPubMedGoogle Scholar
  19. 19.
    Arrich J, Piribauer F, Mad P, Schmid D, Klaushofer K, Mullner M (2005) Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis. CMAJ 172:1039–1043CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Jevsevar D, Donnelly P, Brown GA, Cummins DS (2015) Viscosupplementation for osteoarthritis of the knee: a systematic review of the evidence. J Bone Joint Surg Am 97:2047–2060CrossRefPubMedGoogle Scholar
  21. 21.
    Wang CT, Lin J, Chang CJ, Lin YT, Hou SM (2004) Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomized controlled trials. J Bone Joint Surg Am 86-A:538–545CrossRefPubMedGoogle Scholar
  22. 22.
    Bellamy N (2006) Hyaluronic acid and knee osteoarthritis. J Fam Pract 55:967–968PubMedGoogle Scholar
  23. 23.
    Lo GH, LaValley M, McAlindon T, Felson DT (2003) Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA 290:3115–3121CrossRefPubMedGoogle Scholar
  24. 24.
    Newberry SJ, Fitzgerald JD, Maglione MA, O’Hanlon CE, Booth M, Motala A et al (2015) Systematic review for effectiveness of hyaluronic acid in the treatment of severe degenerative joint disease (DJD) of the knee. AHRQ Technology Assessments, RockvilleGoogle Scholar
  25. 25.
    Johal H, Devji T, Schemitsch EH, Bhandari M (2016) Viscosupplementation in knee osteoarthritis: evidence revisited. JBJS Rev 4:e11–e111CrossRefPubMedGoogle Scholar
  26. 26.
    Jevsevar DS, Brown GA, Jones DL, Matzkin EG, Manner PA, Mooar P et al (2013) The American Academy of Orthopaedic surgeons evidence-based guideline on: treatment of osteoarthritis of the knee, 2nd edition. J Bone Joint Surg Am 95:1885–1886CrossRefPubMedGoogle Scholar
  27. 27.
    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 45:132–139CrossRefPubMedGoogle Scholar
  28. 28.
    Hochberg MC, Altman RD, April KT et al (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 (Hoboken) 64:465–474CrossRefGoogle Scholar
  29. 29.
    McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM et al (2012) OARSI guidelines for the nonsurgical management of knee osteoarthritis. Osteoarthr Cartil 22:363–388CrossRefGoogle Scholar
  30. 30.
    Trojian TH, Concoff AL, Joy SM, Hatzenbuehler JR, Saulsberry WJ, Coleman CI (2016) AMSSM scientific statement concerning viscosupplementation injections for knee osteoarthritis: importance for individual patient outcomes. Clin J Sport Med 26:1–11CrossRefPubMedGoogle Scholar
  31. 31.
    Bruyere O, Cooper C, Pelletier JP, Maheu E, Rannou F, Branco J et al (2016) A consensus statement on the European Society for Clinical and Economic Aspects of osteoporosis and osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-from evidence-based medicine to the real-life setting. Semin Arthritis Rheum 45:S3–11CrossRefPubMedGoogle Scholar
  32. 32.
    Altman RD, Farrokhyar F, Fierlinger A, Niazi F, Rosen J (2016) Analysis for prognostic factors from a database for the intra-articular hyaluronic acid (Euflexxa) treatment for osteoarthritis of the knee. Cartilage 7:229–237CrossRefPubMedGoogle Scholar
  33. 33.
    Altman R, Fredericson M, Bhattacharyya SK, Bisson B, Abbot T, Yadalam S et al (2016) Association between hyaluronic acid injections and time-to-total knee replacement surgery. J Knee Surg 29:564–570CrossRefPubMedGoogle Scholar
  34. 34.
    Altman R, Lim S, Steen RG, Dasa V (2015) Hyaluronic acid injections are associated with delay of total knee replacement surgery in patients with knee osteoarthritis: evidence from a large U.S. health claims database. PLoS One 10:e0145776CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Ong KL, Anderson AF, Niazi F, Fierlinger AL, Kurtz SM, Altman RD (2016) Hyaluronic acid injections in Medicare knee osteoarthritis patients are associated with longer time to knee arthroplasty. J Arthroplast 31:1667–1673CrossRefGoogle Scholar
  36. 36.
    Lohmander LS, Dalen N, Englund G, Hämäläinen M, Jensen EM, Karlsson K et al (1996) Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan multicentre trial group. Ann Rheum Dis 55:424–431CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Wobig M, Dickhut A, Maier R, Vetter G (1998) Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy and safety in the osteoarthritic knee. Clin Ther 20:410–423CrossRefPubMedGoogle Scholar
  38. 38.
    Selten EM, Vriezekolk JE, Geenen R, van der Laan WH, van der Meulen-Dilling RG, Nijhof MW et al (2016) Reasons for treatment choices in knee and hip osteoarthritis: a qualitative study. Arthritis Care Res (Hoboken) 68:1260–1267CrossRefGoogle Scholar
  39. 39.
    Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M (2008) The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis 67:1716–1723CrossRefPubMedGoogle Scholar
  40. 40.
    Saltzman BM, Leroux T, Meyer MA, Basques BA, Chahal J, Bach BR Jr et al (2016) The therapeutic effect of intra-articular normal saline injections for knee osteoarthritis. Am J Sports Med Dec 1:363546516680607Google Scholar
  41. 41.
    Bannuru RR, Natov NS, Dasi UR, Schmid CH, McAlindon TE (2011) Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis. Osteoarthr Cartil 19:611–619CrossRefPubMedGoogle Scholar
  42. 42.
    Puttick MP, Wade JP, Chalmers A, Connell DG, Rangno KK (1995) Acute local reactions after intraarticular hylan for osteoarthritis of the knee. J Rheumatol 22:1311–1314PubMedGoogle Scholar
  43. 43.
    Miller LE, Block JE (2013) US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee steoarthritis: systematic review and meta-analysis of randomized, saline-controlled trials. Clin Med Insights Arthritis Musculoskelet Disord 6:57–63CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE (2015) Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med 162:46–54CrossRefPubMedGoogle Scholar
  45. 45.
    Campbell KA, Erickson BJ, Saltzman BM, MascarenhasR BBR Jr, Cole BJ et al (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 31:2036–2045CrossRefPubMedGoogle Scholar

Copyright information

© SICOT aisbl 2018

Authors and Affiliations

  • Eric N. Bowman
    • 1
  • Justin D. Hallock
    • 1
  • Thomas W. Throckmorton
    • 1
  • Fredrick M. Azar
    • 1
  1. 1.Department of Orthopaedics & Biomedical EngineeringCampbell Clinic – University of TennesseeMemphisUSA

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