ARTHRITIS & RHEUMATISM Vol. 48, No. 6, June 2003, pp 1594–1601 DOI 10.1002/art.11023 © 2003, American College of Rheumatology Effects of Antiinflammatory Drugs on Arthritic Cartilage A High-Frequency Quantitative Ultrasound Study in Rats Britta Jaffre ´, 1 Astrid Watrin, 2 Damien Loeuille, 2 Pierre Gillet, 2 Patrick Netter, 2 Pascal Laugier, 1 and Amena Saı ¨ed 1 Objective. To evaluate the ability of 55-MHz quantitative ultrasound (US) to detect the in vivo effects of experimental arthritis, as well as those of two antiin- flammatory drugs, naproxen (NPX) and dexamethasone (DEX), on cartilage and subchondral bone. Methods. Arthritis was induced in both knees of 108 rats by intraarticular injection of zymosan (ZYM). Two groups of arthritic rats (n  36 per group) were treated daily with either NPX (10 mg/kg/day) or DEX (0.1 mg/kg/day). Using a 3-dimensional US microscope, patellae were explored in vitro on days 5, 14, and 21 after injections. US assessment included the analysis of quantitative indices of local modifications involving cartilage and bone: integrated reflection coefficient (IRC) from the cartilage surface and apparent inte- grated backscatter from the cartilage internal structure (cartilage matrix) (AIB cartilage ) and the cartilage–bone interface (AIB bone ). Results. ZYM induced articular surface fibrilla- tion that resulted in a decrease in IRC at all times (P < 0.02) and in an increase in AIB bone on days 5 and 14 (P < 0.005). Fibrillation was not changed by NPX admin- istration, while it disappeared following DEX treatment. Cartilage–bone interface alterations were prevented by DEX and partially compensated for by NPX. Cartilage matrix echogenicity decreased with time in all groups due to maturation (P < 0.05), except in DEX-treated rats. Conclusion. Quantitative 55 MHz US allowed detection of early cartilage and bone lesions due to experimental arthritis, and also allowed detection of the effects of antiinflammatory drugs. NPX seemed to have an effect on subchondral bone lesions, but not on cartilage. DEX appeared to repair articular surface and bone, but prevented animal growth and cartilage matu- ration. In rheumatoid arthritis (RA), synovial inflamma- tion and pannus releasing matrix metalloproteinases, oxygen-derived free radicals, cytokines, and prostaglan- dins degrade articular cartilage. These mediators pro- voke proteoglycan (PG) synthesis inhibition, cartilage destruction, bone erosions, and ancillary progressive articular loss of function (1,2). They are also responsible for the swelling and pain in arthritic joints. Nonsteroidal antiinflammatory drugs (NSAIDs) and oral steroids reduce the RA symptoms of joint pain and swelling. However, evidence in clinics and from in vitro studies that NSAIDs and steroids can prevent the progression of chronic, destructive arthritis is both sparse and contro- versial (3–7). Furthermore, most in vitro studies rely on destructive techniques (e.g., histology and biochemis- try), and the criteria for determining cartilage degrada- tion remain qualitative. There is increasing interest in the use of ultra- sonography in rheumatology, since ultrasound (US) is noninvasive, safe, more accurate than clinical evaluation of synovitis and cartilage thickness in small joints, and can be used repeatedly in RA patients (8). Recent research suggests that high-frequency US may also serve ex vivo as a useful means for the investigation of cartilage matrix structural changes occurring under var- Supported in part by a grant from the Groupement de Recherche 2237 du Centre National de la Recherche Scientifique (CNRS). 1 Britta Jaffre ´, MSc, Pascal Laugier, PhD, Amena Saı ¨ed, PhD: LIP, Unite ´ Mixte de Recherches (UMR) 7623 CNRS–Universite ´ Paris VI, Paris, France; 2 Astrid Watrin, PhD, Damien Loeuille, MD, PhD, Pierre Gillet, MD, PhD, Patrick Netter, MD, PhD: LPPA, UMR 7561 CNRS–Universite ´ Nancy I, Nancy, France. Address correspondence and reprint requests to Amena Saı ¨ed, PhD, Laboratoire d’Imagerie Parame ´trique, UMR 7623 CNRS–Universite ´ Paris VI, 15 rue de l’Ecole de Me ´decine, 75006 Paris, France. E-mail: Amena.Saied@lip.bhdc.jussieu.fr. Submitted for publication July 17, 2002; accepted in revised form February 19, 2003. 1594