title: Differences among Branded Hyaluronic Acids in Italy, Part 1: Data from In Vitro and Animal Studies and Instructions for Use.
abstract: BACKGROUND
  The use of hyaluronic acid (HA) for intra-articular (IA) injection is widespread around the world for patients affected by osteoarthritis.
  
  
  OBJECTIVE
  The aim of this study is to identify scientific evidence from in vitro and in vivo studies supporting the use of IA HAs marketed in Italy. We also evaluated the accuracy of indications and contraindications reported in the leaflets of such HAs compared with the available scientific evidence.
  
  
  METHODS
  An extensive literature search was performed to identify all in vitro and in vivo model studies reporting on the effects of various HAs marketed in Italy for IA use. Data reported in the leaflets of different HA-based products for IA use were extracted and analyzed alongside evidence from in vitro and in vivo model studies.
  
  
  RESULTS
  Nine in vitro studies and 11 studies on animal models were examined. Comparing results with what is reported in the leaflets of HAs marketed in Italy, it was observed that many branded formulations are introduced in the market without any reporting of basic scientific evidence. Only 12.82% and 17.95% of branded products had been shown to be effective with scientific evidence from in vitro and in vivo studies, respectively. The rationale of use of these products is based on their nature, as if a class effect existed such that all HAs would yield similar effects.
  
  
  CONCLUSIONS
  Data on HAs deriving from in vitro and in vivo studies are scarce and relate to only a small percentage of products marketed in Italy. Many indications and contraindications are arbitrarily reported in Italian HA leaflets without the support of scientific evidence. Larger and brand-specific studies are necessary and should be reported in the leaflets to guide clinicians in making an appropriate choice regarding HA-based IA therapy.
authors.affiliation: Operative Unit of Rheumatology, S. Pietro Fatebenefratelli Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Migliore
authors.affiliation: Operative Unit of Rheumatology, S. Pietro Fatebenefratelli Hospital, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bizzi
authors.affiliation: Division and Chair of Rheumatology, Gaetano Pini Institute, Milan, Italy.
authors.forename: O
authors.initials: O
authors.lastname: De Lucia
authors.affiliation: Rheumatology Unit, University of Pisa, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Delle Sedie
authors.affiliation: Rheumatology Provincial Network Coordinator, ASP 7, Scicli Hospital, Ragusa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bentivegna
authors.affiliation: Physical Medicine, Rheumatology and Rehabilitation Department, Ain Shams University, Cairo, Egypt.; Physical and Rehabilitation Medicine, Tor Vergata University, Rome, Italy.
authors.forename: Asmaa
authors.initials: A
authors.lastname: Mahmoud
authors.affiliation: Physical and Rehabilitation Medicine, Clinical Sciences and Translational Medicine Department, Tor Vergata University, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Foti
keywords: animal; hyaluronic acid; hylan G-F 20; in vitro; osteoarthritis