R E V I E W Intra-articular use of hyaluronic acid in the treatment of osteoarthritis Alberto Migliore1,2 Mauro Granata3 1UOS of Rheumatology S. Pietro Fatebenefratelli Hospital, Rome, Italy; 2AFaR Research Center, S. Pietro, Rome, Italy; 3UOS of Rheumatology S. Filippo Neri Hospital, Rome, Italy Correspondence:Alberto Migliore UOS of Rheumatology, S.Pietro Fatebenefratelli Hospital,Via Cassia 600, Rome, Italy Tel +39 06 3358 2145 Fax +39 06 3358 Email alberto.migliore@tin.it Abstract: Osteoarthritis is one of the leading causes of disability in the elderly. The changes in the lubricating properties of synovial ﬂuid lead to signiﬁcant pain and loss of function. More than ten years have passed from the ﬁrst studies. Up till now many authors have supported intra-articular hyaluronan (HA) therapy as not only a symptom-modifying therapy but also a treatment which may signiﬁcantly decrease the rate of deterioration of joint structure. In this review we report data relative to knee and hip treatment. The ongoing studies continue to further our understanding of the fundamental mechanisms that likely underlie the therapeutic beneﬁts of this treatment but, despite recent progress, many unresolved issues require further study. Large scale double blind controlled studies must be carried out to conﬁrm these promising data and produce meaningful guidelines. Keywords: osteoarthritis, hyaluronan, intra-articular injections, ultrasound-guided, visco- supplementation Introduction Osteoarthritis is one of the leading causes of disability in the elderly. The changes in the lubricating properties of synovial ﬂuid lead to signiﬁcant pain and loss of function. Viscosupplementation, the injection of hyaluronic acid (HA) into the joints, improves the biochemical properties of synovial ﬂuid into osteoarthritis joints. The clinical effect is pain relief and disease modifying activity (Balazs and Denlinger 1993; Pelletier and Martel-Pelletier 1993). Although there are many nonsurgical therapies available for the treatment of pain associated with osteoarthritis (OA), their long-term use and safety have not been systematically followed. Intra-articular (IA) hyaluronan therapy has been used in the treatment of symptoms associated with OA of the knee with a very favorable safety proﬁle (Pagnano and Westrich 2005). In this connection, the physiological and phar- macological characteristics of HA have recently been reviewed. The high concentration of HA in spinal ﬂuid (SF) is essential for normal joint function. The altered proper- ties of the synovial ﬂuid in OA, the decrease in molecular size and concentration of HA leads to reduced rheologic properties, which affect the lubrication and protection mechanism of action of IA hyaluronan and is probably more complex than previously thought (Maneiro et al 2004). The hypothesis that HA could bind to speciﬁc receptors is now widely accepted. The cluster determinant 44 (CD44), the intracellular adhesion molecule-1 (ICAM-1) and the receptor for hyaluronate-mediated motility (RHAMM) expressed in many cells, are some of those implicated in the process (Hodge-Dufour et al 1997; Siegelman et al 1999). The binding of HA with its speciﬁc receptors has been reported to trigger various intracellular signal events such as cytokine release and stimulation of cell cycle proteins. The consequences of these interactions is to stimulate cell functional activities such as cell migration and proliferation (Cao et al 2004). Clinical Interventions in Aging 2008:3(2) 365–369 © 2008 Dove Medical Press Limited. All rights reserved 365