OSTEOARTHRITIS CARTILAGE - Crespine Gel

154 Listrat et al.: Hyaluronân in osteoarthritis of the kneeIocal anesthesia with a small arthroscope; (2) thequantification of chondropathic severity wasfeasible using either the physician's overallassessment with a 100 mm visual analog scale(VAS) or the scoring systems proposed by theFrench Society of Arthroscopy which are compositeindices taking into account the three maincharacteristics of chondropathy, i.e., localization,depth and size [11.12]. Previous studies haveshown that this method fulfills some of the guidelinesproposed for outcome measures: validity,reproducibility and clinical relevance [10-12].Hyaluronan (hyaluronic acid) forms the centralaxis of the various proteoglycan aggregatesnecessary for the functional integrity of cartilageand other extracellular matrices [13]. Hyaluronicacid is responsible for the unique viscoelasticproperties of the synovial fluid [1a-16] and isthought to play an important role in biologicalactivities as diverse as cell proliferation andactivation 117-201.'Its clinical use was suggestedby the finding thàt hyaluronic acid was reducedin concentration and in chain length in thesynovial fluids of arthritic patients [14]. The'viscosupplementation'termhas been used todescribe the effects of high-molecular-weighthyaluronan [21]. However, this concept is basedonly on the mechanical properties of the moleculewhile there is a considerable body of evidencethat the therapeutic efficacy of hyaluronan isdue to a combination of both physicochemicaland pharmacological properties [22].Several studies with various preparations ofhyaluronan of different molecular weights havebeen conducted [23-25 and reviewed in 26], andthere has been a broad consensus in the studiespublished that this treatment is well-tolerated andresults in sustained relief of pain and functionaldisability of patients suffering from knee osteoarthritis.This clinical improvement is usuallyobserved after three to five injections performed atl-week intervals. Moreover, a carry-over effect forat ieast 3 months after discontinuation has beensuggested.Animal model studies suggest that hyaluronanaffects the progression of chondral lesions [27,28].To our knowledge, no data have been published inthe literature suggesting that intra-articularinjections of hyaluronic acid might interfere withthe natural course ofthe cartilage lesions observedin knee osteoarthritis in humans. Therefore, itseemed interesting to conduct the following pilotstudy in order to evaiuate, by arthroscopy, theeffects of repeated intra-articular injections ofhyaluronan.Patients and MethodsPATIENTSPatients suffering from knee osteoarthritisfulfilling the American College of Rheumatologycriteria [29] were enrolled in the study. Otherinclusion criteria were the following:(1) primary osteoarthritis as defined by theAmerican College of Rheumatology [29];(2) clinical involvement of the medial compartment(pain localized at the medial part of theknee);(3) active disease (pain and disability) justifyinglocal therapy (lavage) at entry (based on theopinion of the investigator);(4) absence of contraindication of arthroscopy(anti-coagulant therapy, cutaneous lesion of theknee, allergy to lidocaine);(5) absence of advanced disease defined by aradiological grade fV according to the classificationproposed by Kellgren and Lawrence [30];(6) presence of chondropathy of the medialcompartment at arthroscopy defined by thepresence of chondropathy at least grade IIaccording to the classification proposed by Beguinand Locker [31] and observed on at least 10% oftheevaluated surface.Patients were not included in the study if (1) anyintra-articular surgery was performed during thepast 5 years (including any arthroscopic procedure).(2) Any intra-articular treatment wasprescribed i.e., lavage, intra-articular injection ofcort costeroids during the past 3 months. Anyconcurrent symptomatic treatment, i.e., analgesics,nonsteroidal anti-inflammatory drugs(NSAIDs), physiotherapy had to be stable for atIeast 1 month before the studv.STUDY MEDICATIONHyalgan@, supplied by Fidia S.p.A., is aconcentrated (20 mg12 ml) solution of 500-230 kDamolecular weight, highly-purified sodiumhyaluronate extracted from rooster combs.STUDY DESIGNThe study was a single-center, prospective,randomized, controlled study of l-year durationapproved by the ethics committee of CochinHospital, Paris. All patients underwent kneearthroscopy during which lavage (2 I saline.serum)was performed. After the arthroscopy procédure,and after written informed consent was obtained,the patients entered one of the two study groups :