62nd National Congress of the Italian Society of Rheumatology Open access

PO:09:134 | The impact of intra-articular hyaluronic acid injections on osteoarthritis synovitis: a study on synovial tissue of total knee arthroplasty patients

Orazio De Lucia1, Laura Giudice1|2, Carolina Artusi1, Luca Ingrao1|2, Giorgia Trignani1|2, Matteo Ferrito1, Andrea Amati1|2, Marta Arese1|2, Camilla Riboldi1|2, Isabella Scotti1, Antonella Murgo1, Ennio Giulio Favalli1|2, Antonina Parafioriti3, Elisabetta Armiraglio3, Andrea Di Bernardo3, Filippo Calanna4, Chiara Fossati4, Pietro Simone Randelli4|5, Roberto Felice Caporali1|2 | 1Dipartimento di Reumatologia e Scienze Mediche,ʁSST Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO, Milano; 2Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano; 3UOC Anatomia Patologica, ASST Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO, Milano; 4UOC 1° Clinica Ortopedica, ASST Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO, Milano; 5Università degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute, Milano, Italy

Authors

Published
25 November 2025
Section
62nd National Congress of the Italian Society of Rheumatology

Abstract

Background. Intra-articular hyaluronic acid injections (IA-HA) represent a therapeutic strategy widely used to manage knee osteoarthritis, aiming to reduce pain and to improve joints’ range of movement. However, the effect of this treatment on histological synovial inflammation is still quite unexplored. Krenn’s score is a validated semi-quantitative histopathological scoring system to evaluate synovitis and it is particularly useful in identifying inflammation in advanced osteoarthritis patients.

Objective. Evaluating the correlation between IA-HA treatment and synovial inflammation, which was measured by Krenn’s score, in total knee arthroplasty (TKA) patients.

 

Methods. We included 108 patients affected by knee osteoarthritis who had undertaken TKA. 48 patients, who had been treated with steroid intra-articular injections, were excluded from the analysis to avoid confounding factors. Out of the remaining 60 patients, 45/60 had been treated with IA-HA in the pre-operative period and 15/60 had not been treated with IA-HA. We then calculated the mean time from knee osteoarthritis diagnosis and TKA (yearsOATKA) and we analysed the bivariate correlation between total number of intra-articular hyaluronic acid injections (NHAinj) and the time from diagnosis to surgery. During the surgical procedure of 36 patients, it was taken a sample of synovial membrane for histopathological analysis and Krenn’s score evaluation. Statistical analysis included the evaluation of the correlation between Krenn’s score and the number of intra-articular injections, as well as the comparison between groups (IA-HA vs non-IA-HA) to identify differences in synovial inflammation.

 

Results. Patients treated with IA-HA (n=45) had a mean time from diagnosis to TKA of 10,91 years (SD: 8,96), in comparison to those non treated with IA-HA (n=15), whose mean time was 5,33 years (SD: 3,94). Mean Krenn’s score in IA-HA patients (n=26) was 3,0 (SD: 1,88), while in non-IA-HA patients (n=10) was 2,4 (SD: 0,84). The bivariate correlation analysis between total number of intra-articular injections and time to TKA, using Spearman’s coefficient (since the variables had a non-normal distribution), showed a statistically significant result (p=0,006) (Figure 1). However, the correlation between total number of intra-articular injections and Krenn’s score classes was not statically significant (p > 0,05 for all analyses). It is important to recognise that the sample size and the unbalanced distribution between Krenn’s classes reduce the power of statistical analysis (Figure 2).

 

Conclusions. Our study confirms that patients treated with hyaluronic acid have a longer mean time from diagnosis to TKA, which, despite already being known in literature, suggests that performing IA-HA helps delaying surgery. On the other hand, we did not find a significant association between intra-articular hyaluronic acid injections and a reduction in synovial inflammation, the latter one histologically measured by Krenn’s score. These results suggest a possibly modulating role for IA-HA on synovitis, even in an advanced stage of osteoarthritis, yet there is a need for further studies considering the phenotypic variance of osteoarthritis and the episodic nature of inflammation in this disease.

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