title: Radiation synovectomy with yttrium-90 for persisting arthritis has direct harmful effects on human cartilage that cannot be prevented by co-administration of glucocorticoids: an in vitro study.
abstract: BACKGROUND
  It was recently shown that radiation synovectomy with yttrium-90 (90Y) and glucocorticoids is not superior to intra-articular glucocorticoids alone in the treatment of persistent gonarthritis. In that study, it seemed that in patients treated by radiation synovectomy, progression of radiographic joint damage occurred.
  
  
  OBJECTIVE
  To test in vitro the direct effects of radiation synovectomy with 90Y on human cartilage.
  
  
  METHODS
  Human cartilage tissue was exposed to 90Y, glucocorticoids or the combination. 1:2000 to 1:20 dilutions of the clinical dose of 5 mCi/ml 90Y and 20 mg/ml glucocorticoids were used. After a 4-day exposure and a subsequent 12-day recovery period, proteoglycan synthesis, proteoglycan release and proteoglycan content were measured. In addition, human synovial tissue was cultured for 4 days with 90Y or glucocorticoids. Culture supernatants were analysed for cartilage-destructive activity.
  
  
  RESULTS
  90Y, glucocorticoids and the combination inhibited proteoglycan synthesis considerably and dose dependently, an effect that sustained for at least 12 days. Proteoglycan release was transiently increased by 90Y, an effect that was not changed by addition of glucocorticoids, which had no effect on its own. Proteoglycan content was eventually adversely affected by 90Y, an effect hardly influenced by glucocorticoids. Neither 90Y nor glucocorticoids changed the cartilage-destructive properties of synovial tissue.
  
  
  CONCLUSIONS
  90Y, but not glucocorticoids, has direct harmful effects on cartilage in vitro. Indirect beneficial effects of 90Y via inhibition of cartilage-destructive properties of synovial tissue could not be shown. These observations may explain the possible radiographic joint damage on radiation synovectomy.
authors.affiliation: Department of Rheumatology and Clinical Immunology F02.127, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. njahangier@zhh.nl
authors.forename: Z N
authors.initials: ZN
authors.lastname: Jahangier
authors.forename: K M G
authors.initials: KM
authors.lastname: Jacobs
authors.forename: J W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: F P J G
authors.initials: FP
authors.lastname: Lafeber
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism; D011832:Radiation Injuries / Q000378:metabolism*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D046509:Tissue Culture Techniques; D015021:Yttrium Radioisotopes / Q000633:toxicity*
chemical_list: D005938:Glucocorticoids; D011509:Proteoglycans; D015021:Yttrium Radioisotopes