Histological study of effects of colloidal 90 yttrium on knee joint tissues of rabbits.

Objective: To explore whether pretreatment features of synovial tissue in patients with gonarthritis could predict the clinical effect of radiation synovectomy with yttrium-90 ( 90 Y) and glucocorticoids or with intraarticular glucocorticoids alone. Methods: A synovial biopsy was carried out blindly 2 weeks before treatment in 66 patients with persistent gonarthritis, who were randomised to treatment either with 90 Y and triamcinolone or with placebo and triamcinolone. Immunohistochemistry was used to detect T cells, macrophages, B cells, plasma cells, fibroblast-like synoviocytes, adhesion molecules and pro-inflammatory cytokines. Stained sections were evaluated by digital image analysis. Individual patient improvement was expressed using a composite change index (CCI; range 0-12). Successful treatment was defined as CCI >6 after 6 months. Results: Patients with rheumatoid arthritis, psoriatic arthritis, undifferentiated arthritis and other causes of gonarthritis were included. The overall response rate was 47%. Clinical efficacy in both therapeutic groups was similar and not dependent on diagnosis. No significant differences were noted between baseline microscopic features of synovial tissue inflammation in patients with rheumatoid arthritis and in those with non-rheumatoid arthritis (ie, all diagnoses other than rheumatoid arthritis). The number of macrophages in the synovial sublining was significantly higher in responders than in non-responders (p = 0.002), independent of treatment group and diagnosis. The clinical effect was positively correlated with pretreatment total macrophage numbers (r = 0.28; p = 0.03), sublining macrophage numbers (r = 0.34; p = 0.005) and vascular cell adhesion molecule 1 expression (r = 0.25; p = 0.04). Conclusion:The observations support the view that intra-articular treatment either with 90 Y and glucocorticoids or with glucocorticoids alone is especially successful in patients with marked synovial inflammation.

Section: Discussionmentioning

confidence: 99%

Pretreatment macrophage infiltration of the synovium predicts the clinical effect of both radiation synovectomy and intra-articular glucocorticoids

Jahangier

2006

“…3 4 9 16 RSYN was becoming established in the late 1960s but yet little is known about the influence of the radionuclide on other tissues of the target joint, like cartilage. 17 18 Important for our study was that the results of RSYN are most promising when the patients are young or the cartilage of the target joint is still relatively intact. 15 19 20 This makes it more important to determine whether 90 Y also affects cartilage.…”

mentioning

confidence: 99%

Irradiation decreases collagen type II synthesis and increases nitric oxide production and cell death in articular chondrocytes

Ailland

2003

Background: When synovitis is proved, intra-articularly injected b emitting radionuclides like yttrium-90 ( 90 Y) are used to treat the inflamed synovium. Objective: To study the viability, matrix production, and NO production during or after 90 Results: In chondrocyte and synoviocyte monolayer cultures radiation caused a dose dependent increase in cell death and membrane destruction within four days. In alginate and explant cultures, where proliferation is low, no significantly increased LDH activity was seen, and cell viability was ,100% for up to 14 days after irradiation. Collagen type II expression (alginate) and biosynthetic activity (alginate and explants) were decreased dose dependently while there was an increase in NO production. Light and electron microscopy data showed that five weeks after irradiation all cells in alginate and most cells in explants subjected to 3 MBq 90 Y/ml were dead, whereas after lower amounts of irradiation several morphologically intact cells were found. Conclusions: b Irradiation may influence the long term maintenance of cartilage tissue or the aetiology of degenerative joint diseases.

“…Treatment of the rabbit knee with 90 Y showed an increased cellular proliferation of the superficial tangential cells of cartilage with small foci of degeneration in the vicinity of the cruciate ligaments, 16 weeks after RSO. 11 This damage of cartilage was attributed to accumulation of 90 Y in the folds of the cruciate ligaments, or by the thinness of cartilage around the cruciate ligaments. 11 Exposure of normal canine knees to 4 mCi 90 Y led to inhibition of GAG synthesis 24 h after RSO to 37% of the control level of non-irradiated cartilage and to 28% after 5 days, as illustrated by suppressed 35 S uptake by chondrocytes on autoradiography.…”

Section: Discussionmentioning

confidence: 99%

“…11 This damage of cartilage was attributed to accumulation of 90 Y in the folds of the cruciate ligaments, or by the thinness of cartilage around the cruciate ligaments. 11 Exposure of normal canine knees to 4 mCi 90 Y led to inhibition of GAG synthesis 24 h after RSO to 37% of the control level of non-irradiated cartilage and to 28% after 5 days, as illustrated by suppressed 35 S uptake by chondrocytes on autoradiography. 33 Moreover, 4 and 8 h after exposure to 90 Y, the cartilage GAG concentration was only 66% and 54%, respectively, of that before treatment, whereas the corresponding values for control, non-irradiated cartilage were 90% and 87%.…”

Section: Discussionmentioning

confidence: 99%

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

Jahangier

Jacobs²,

Bijlsma³

et al. 2006

Background: It was recently shown that radiation synovectomy with yttrium-90 ( 90 Y) 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 90 Y on human cartilage. Methods: Human cartilage tissue was exposed to 90 Y, glucocorticoids or the combination. 1:2000 to 1:20 dilutions of the clinical dose of 5 mCi/ml 90 Y 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 90 Y or glucocorticoids. Culture supernatants were analysed for cartilage-destructive activity. Results:90 Y, 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 90 Y, an effect that was not changed by addition of glucocorticoids, which had no effect on its own. Proteoglycan content was eventually adversely affected by 90 Y, an effect hardly influenced by glucocorticoids. Neither 90 Y nor glucocorticoids changed the cartilage-destructive properties of synovial tissue. Conclusions:90 Y, but not glucocorticoids, has direct harmful effects on cartilage in vitro. Indirect beneficial effects of 90 Y 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.