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.
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.
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.
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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price includes VAT (USA)
Tax calculation will be finalised during checkout.
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) 68:1743–1750
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 34:172–180
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 58:26–35
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 98:1429–1435
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 174:1702–1704
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 3:213–225
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 16:441–449
Laurent TC, Fraser JR (1992) Hyaluronan. FASEB J 6:2397–2404
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 12:75–82
Moreland LW (2003) Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action. Arthritis Res Ther 5:54–67
Peyron JG (1993) A new approach to the treatment of osteoarthritis: viscosupplementation. Osteoarthr Cartil 1:85–87
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 80:25–32
Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502
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 15:1833–1840
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 28:88–96
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 17:45–56
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 12:389–399
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 157:180–191
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 172:1039–1043
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 97:2047–2060
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:538–545
Bellamy N (2006) Hyaluronic acid and knee osteoarthritis. J Fam Pract 55:967–968
Lo GH, LaValley M, McAlindon T, Felson DT (2003) Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA 290:3115–3121
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, Rockville
Johal H, Devji T, Schemitsch EH, Bhandari M (2016) Viscosupplementation in knee osteoarthritis: evidence revisited. JBJS Rev 4:e11–e111
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 95:1885–1886
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
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) 64:465–474
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 22:363–388
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 26:1–11
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:S3–11
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 7:229–237
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 29:564–570
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:e0145776
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 31:1667–1673
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 55:424–431
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 20:410–423
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) 68:1260–1267
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 67:1716–1723
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 1:363546516680607
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 19:611–619
Puttick MP, Wade JP, Chalmers A, Connell DG, Rangno KK (1995) Acute local reactions after intraarticular hylan for osteoarthritis of the knee. J Rheumatol 22:1311–1314
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 6:57–63
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 162:46–54
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 31:2036–2045
This study received no financial assistance or incentives from pharmaceutical or other industry sources. The Campbell Foundation provided US$1300 for patient stipends. No author received direct or indirect financial support related to this study.
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.
About this article
Cite this article
Bowman, E.N., Hallock, J.D., Throckmorton, T.W. et al. Hyaluronic acid injections for osteoarthritis of the knee: predictors of successful treatment. International Orthopaedics (SICOT) 42, 733–740 (2018). https://doi.org/10.1007/s00264-017-3731-8
- Hyaluronic acid