International Orthopaedics

, Volume 43, Issue 11, pp 2437–2445 | Cite as

Prevention of post-traumatic osteoarthritis after intra-articular knee fractures using hyaluronic acid: a randomized prospective pilot study

  • Ahmed Samir BarakatEmail author
  • Nour Muhamad Ibrahim
  • Osama Elghobashy
  • Ahmed Maher Sultan
  • Khaled F. M. Abdel-Kader
Original Paper



Based on the irreversible destruction of hyaline cartilage, post-traumatic osteoarthritis (PTOA) is a notorious sequelae after intra-articular knee fractures. This study evaluates the clinical efficacy and applicability of immediate post-operative intra-articular injection of hyaluronic acid (IA HA) into the knee joint with an intra-articular fracture.


Prospective randomized case-control study involving 40 patients (20 in each group) with intra-articular knee fracture with an average follow-up of 23 months (range 18–24 months). Twenty patients with intra-articular distal femoral or intra-articular proximal tibial fractures who met our inclusion criteria received three intra-articular hyaluronic acid injections weekly starting immediately after ORIF. Another 20 patients serving as a control group received no injection after ORIF. Patients were assessed functionally with Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) score. Plain X-rays and when indicated CT scans were used to assess radiological union.


The results showed patients treated with intra-articular hyaluronic acid injection after fixation had significantly less pain (KOOS) (p = 0.01). No significant difference was found between both groups in other KOOS-related outcome measures, complications, functional outcome, or quality of life.


These preliminary results support a direct role for hyaluronic acid in the acute phase of the inflammatory process that follows articular injury and provides initial evidence for the efficacy of IA HA.


Intra-articular injection after trauma Intra-articular hyaluronic acid injection Hyaluronic acid (HA) Post-traumatic osteoarthritis 


Compliance with ethical standards

This work was conducted at Cairo University Hospitals in accordance with the ethical standards of the Helsinki Declaration. All participating patients signed an informed consent regarding the procedure, possible complications, and alternative treatment modalities.

Conflict of interest

The authors declare that there is no conflict of interest.


  1. 1.
    Anderson DD, Chubinskaya S, Guilak F, Martin JA, Oegema TR, Olson SA, Buckwalter JA (2011) Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J Orthop Res 29:802–809. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Rossi R, Bardelli A (2005) Tibial plateau fractures. A review of classifications. MINERVA Ortop E Traumatol 56:457–463Google Scholar
  3. 3.
    Buckwalter JA (2012) The role of mechanical forces in the initiation and progression of osteoarthritis. HSS J 8:37–38. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Anderson DD, Van Hofwegen C, Marsh JL, Brown TD (2011) Is elevated contact stress predictive of post-traumatic osteoarthritis for imprecisely reduced tibial plafond fractures? J Orthop Res 29:33–39. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Martin JA, McCabe D, Walter M, Buckwalter JA, McKinley TO (2009) N-acetylcysteine inhibits post-impact chondrocyte death in osteochondral explants. J Bone Jt Surg Ser A 91:1890–1897. CrossRefGoogle Scholar
  6. 6.
    Nagase H, Kashiwagi M (2003) Aggrecanases and cartilage matrix degradation. Arthritis Res Ther 5:94–103. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Grodzinsky AJ, Wang Y, Kakar S, Vrahas MS, Evans CH (2017) Intra-articular dexamethasone to inhibit the development of post-traumatic osteoarthritis. J Orthop Res 35:406–411CrossRefGoogle Scholar
  8. 8.
    Huang TL, Hsu HC, Yang KC, Yao CH, Lin FH (2010) Effect of different molecular weight hyaluronans on osteoarthritis-related protein production in fibroblast-like synoviocytes from patients with tibia plateau fracture. J Trauma 68:146–152. CrossRefPubMedGoogle Scholar
  9. 9.
    Balazs EA, Denlinger JL (1993) Viscosupplementation: a new concept in the treatment of osteoarthritis. J Rheumatol:3–9Google Scholar
  10. 10.
    Akmal M (2005) The effects of hyaluronic acid on articular chondrocytes. J Bone Joint Surg Br Vol 87-B:1143–1149. CrossRefGoogle Scholar
  11. 11.
    Maytin EV (2016) Hyaluronan: more than just a wrinkle filler. Glycobiology 26:553–559CrossRefGoogle Scholar
  12. 12.
    Olson SA, Furman BD, Kraus VB, Huebner JL, Guilak F (2015) Therapeutic opportunities to prevent post-traumatic arthritis: lessons from the natural history of arthritis after articular fracture. J Orthop Res 33:1266–1277. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Schumacher HR, Chen LX (2005) Injectable corticosteroids in treatment of arthritis of the knee. Am J Med 118:1208–1214CrossRefGoogle Scholar
  14. 14.
    Chen WYJ, Abatangelo G (1999) Functions of hyaluronan in wound repair. Wound Repair Regen 7:79–89CrossRefGoogle Scholar
  15. 15.
    Miller LE, Block JE (2013) US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee osteoarthritis: systematic review and meta-analysis of randomized, saline-controlled trials. Clin Med Insights Arthritis Musculoskelet Disord 6:57–63. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    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 Sport Phys Ther 28:88–96. CrossRefGoogle Scholar
  17. 17.
    Irrgang JJ, Anderson AF, Boland AL, Harner CD, Kurosaka M, Neyret P, Richmond JC, Shelborne KD (2001) Development and validation of the International Knee Documentation Committee Subjective Knee Form. Am J Sports Med 29:600–613. CrossRefPubMedGoogle Scholar
  18. 18.
    Pelletier JP, McCollum R, Cloutier JM, Martel-Pelletier J (1995) Synthesis of metalloproteases and interleukin 6 (IL-6) in human osteoarthritic synovial membrane is an IL-1 mediated process. J Rheumatol 109–114Google Scholar
  19. 19.
    Bowman EN, Hallock JD, Throckmorton TW, Azar FM (2018) Hyaluronic acid injections for osteoarthritis of the knee: predictors of successful treatment. Int Orthop 42:733–740. CrossRefPubMedGoogle Scholar
  20. 20.
    Campos ALS, E Albuquerque RSP, da Silva EB, Fayad SG, Acerbi LD, de Almeida FN, Ooka NHM, Franco JS, Gameiro VS (2017) Viscosupplementation in patients with severe osteoarthritis of the knee: six month follow-up of a randomized, double-blind clinical trial. Int Orthop 41:2273–2280. CrossRefPubMedGoogle Scholar
  21. 21.
    Westrich G, Schaefer S, Walcott-Sapp S, Lyman S (2009) Randomized prospective evaluation of adjuvant hyaluronic acid therapy administered after knee arthroscopy. Am J Orthop (Belle Mead NJ) 38:612–616Google Scholar
  22. 22.
    Roos EM, Lohmander LS (2003) The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes 1:64CrossRefGoogle Scholar
  23. 23.
    Lyman S, Lee YY, McLawhorn AS, Islam W, MacLean CH (2018) What are the minimal and substantial improvements in the HOOS and KOOS and JR versions after total joint replacement? Clin Orthop Relat Res 476:2432–2441. CrossRefPubMedGoogle Scholar
  24. 24.
    Clarke S, Lock V, Duddy J, Sharif M, Newman JH, Kirwan JR (2005) Intra-articular hylan G-F 20 (Synvisc®) in the management of patellofemoral osteoarthritis of the knee (POAK). Knee 12:57–62. CrossRefPubMedGoogle Scholar
  25. 25.
    Huang M-H, Yang R-C, Chou P-H (2007) Preliminary effects of hyaluronic acid on early rehabilitation of patients with isolated anterior cruciate ligament reconstruction. Clin J Sport Med 17:242–250. CrossRefPubMedGoogle Scholar
  26. 26.
    Hempfling H (2007) Intra-articular hyaluronic acid after knee arthroscopy: a two-year study. Knee Surg Sport Traumatol Arthrosc 15:537–546. CrossRefGoogle Scholar
  27. 27.
    Schiavone Panni A, Vasso M, Braile A, Toro G, De Cicco A, Viggiano D, Lepore F (2019) Preliminary results of autologous adipose-derived stem cells in early knee osteoarthritis: identification of a subpopulation with greater response. Int Orthop 43:7–13. CrossRefPubMedGoogle Scholar
  28. 28.
    Hong Z, Chen J, Zhang S, Zhao C, Bi M, Chen X, Bi Q (2019) Intra-articular injection of autologous adipose-derived stromal vascular fractions for knee osteoarthritis: a double-blind randomized self-controlled trial. Int Orthop 43:1123–1134. CrossRefPubMedGoogle Scholar
  29. 29.
    Di Matteo B, Marcacci M, Kon E (2019) Letter to the editor concerning the article: “Intra-articular injection of autologous adipose-derived stromal vascular fractions for knee osteoarthritis: a double-blind randomized self-controlled trial” (Hong et al. International Orthopaedics doi: 10.1007). Int Orthop 43:751–752. CrossRefPubMedGoogle Scholar
  30. 30.
    Hernigou P, Auregan JC, Dubory A, Flouzat-Lachaniette CH, Chevallier N, Rouard H (2018) Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee. Int Orthop 42:2563–2571. CrossRefPubMedGoogle Scholar
  31. 31.
    Krstičević M, Jerić M, Došenović S, Jeličić Kadić A, Puljak L (2017) Proliferative injection therapy for osteoarthritis: a systematic review. Int Orthop 41:671–679CrossRefGoogle Scholar
  32. 32.
    Centeno CJ, Al-Sayegh H, Freeman MD, Smith J, Murrell WD, Bubnov R (2016) A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. Int Orthop 40:1755–1765. CrossRefPubMedGoogle Scholar

Copyright information

© SICOT aisbl 2019

Authors and Affiliations

  1. 1.Orthopedics and Trauma DepartmentCairo UniversityCairoEgypt
  2. 2.Orthopedics DepartmentSligo University HospitalSligoIreland

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