- Email: [email protected]
Glucosaminoglycan-polysulfate (GAGPS) influences the anatomical progression of osteoarthritis (OA) of the finger joints
Osteoarthritis and Cartilage Vol. 1 No. 1
69
G l u c o s a m i n o g l y c a n - p o l y s u l f a t e (GAGPS) i n f l u e n c e s the a n a t o m i c a l p r o g r e s s i o n o f o s t e o a r t h r i t i s (OA) o f the finger joints G. VERBRUGGENAND E. M. VEYS Department of Rheumatology, University Hospital, Ghent, Belgium Ninety-two patients with OA of the finger joints were included in a randomized double-blind, placebocontrolled study. They were followed over a 3-year period and 68 of them were followed over a 5-year period. The aim of the study was to show the long-term effects of GAGPS (Arteparon ®) on the progression of the disease. The patients received 45 injections yearly (three series of 15 intramuscularly (i.m.) injections, given twice weekly, every 4th month), 46 patients were injected with GAGPS (50 mg) and 46 of them received 'placebo' (50 pg of GAGPS) during 3 years. Thirty-two patients were injected with GAGPS (50 mg) and 36 of them received ~placebo' (50 #g of GAGPS) during 5 years. Antero-posterior X-ray pictures of distal interphalangeal (DIP), proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints were taken at the start of the study and after each year. Consecutive rSntgenograms allowed us to study: (1)
the number of normal joints that became osteoarthritic within 5 years, and (2) the progression of the anatomical lesions in the OA joints over a 5-year period. GAGPS possibly prevented OA to occur in joints that were normal at the start of the study. However, GAGPS did significantly lower the scores of anatomical progression in finger joints with OA. As observed in one or more finger joints of approximately 40~/o of our patients, OA progressed following characteristic sequences: a stationary phase (osteophytes, discrete narrowing of the joint space) preceeded 'erosive' OA (disappearance of the joint space, subchongral plate eroded by subchondral cysts), and was followed by remodeling of the joint. GAGPS prevented the onset of ~erosive' OA in the affected joints. We may conclude that GAGPS can retard the anatomical progression of OA in finger joints. Stimulation of extracellular matrix synthesis and inhibition of matrix breakdown may contribute to this result.
Influence o f i n t r a - a r t i c u l a r injection o f h y a l u r o n i c acid (HA) on s y n o v i a l fluid (SF) i n f l a m m a t i o n S. TODESCO AND L. PUNZI
Division of Rheumatology, University of Padova, Italy HA represents the major nonproteinaceous, nonaqueous component of SF. In several arthropathies SF is found to contain HA at a.concentration and molecular weight (MW) lower than normal. Good clinical results have been reported after intra-articular injection of exogenous HA (HAI) in osteoarthritis. Several studies demonstrated an anti-inflammatory effect of HA both in vitro a n d ' i n experimental models. However, few investigations on this topic have been performed in man. We studied the effect of HAI (20 mg/2 ml, Hyalgan, Fidia) on some inflammatory indices of SF obtained from different patients with arthropathies. In a study, following one HAI, in comparison with untreated patients, there was a significant reduction in the degree of SF effusion, reduced PGE2 concentration, increase of cAMP and no influence o n white blood cell number (WBC), total protein, total complement and beta-2microglobulin concentration. In another study of patients with rhematoid arthritis we investigated the effects of a course of 4 HAI Hyalgan injections (20 rag/weekly) on SF volume and some inflammatory indices such as WBC, acid phosphatase (AP), lysozyme (LZ) and interleukin-lfl (IL-lfl). We observed an increase in IL-fl 1 week after the first HAI and a further increase
1 week after the second HAI (respectively 61.8, 40.7 and 81.0, 63.0 vs basal value of 52.3, 35.2 pg/ml). One week after the third HAI injection, a decrease in IL-lfl was observed (75.0, 84.7 pg/ml) and a further decrease was evident a week after the fourth HAI injection (24.6, 7.9 pg/ml). The later value of IL-lfl was lower than the basal value (P = 0.048). No significant variations of the other parameters were observed except for SF volume (final: 18.3, 8.8 vs basal: 31.6, 14.5 ml; P = 0.044). This study seems to indicate that HA may exert different antiinflammatory effects on cells and various substances of SF. In the case of IL-lfl it is possible that the initial stimulating and final inhibitory effects are derived from a cytomodulation. The first injected HA is probably quickly cleaved and the resulting low MW may stimulate the cells to produce IL-lfl. Subsequent injected HA, on f~ie other hand, may cause synovial synthesis of a ~good' (higher MW?) HA which in turn could inhibit the production of IL-lfl. These studies suggest that HA may have a ~nontraditional' anti-inflammatory effect on SF, depending on many factors such as the degree of inflammation, the HA concentration and MW, and the frequency of HA injections.
69
G l u c o s a m i n o g l y c a n - p o l y s u l f a t e (GAGPS) i n f l u e n c e s the a n a t o m i c a l p r o g r e s s i o n o f o s t e o a r t h r i t i s (OA) o f the finger joints G. VERBRUGGENAND E. M. VEYS Department of Rheumatology, University Hospital, Ghent, Belgium Ninety-two patients with OA of the finger joints were included in a randomized double-blind, placebocontrolled study. They were followed over a 3-year period and 68 of them were followed over a 5-year period. The aim of the study was to show the long-term effects of GAGPS (Arteparon ®) on the progression of the disease. The patients received 45 injections yearly (three series of 15 intramuscularly (i.m.) injections, given twice weekly, every 4th month), 46 patients were injected with GAGPS (50 mg) and 46 of them received 'placebo' (50 pg of GAGPS) during 3 years. Thirty-two patients were injected with GAGPS (50 mg) and 36 of them received ~placebo' (50 #g of GAGPS) during 5 years. Antero-posterior X-ray pictures of distal interphalangeal (DIP), proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints were taken at the start of the study and after each year. Consecutive rSntgenograms allowed us to study: (1)
the number of normal joints that became osteoarthritic within 5 years, and (2) the progression of the anatomical lesions in the OA joints over a 5-year period. GAGPS possibly prevented OA to occur in joints that were normal at the start of the study. However, GAGPS did significantly lower the scores of anatomical progression in finger joints with OA. As observed in one or more finger joints of approximately 40~/o of our patients, OA progressed following characteristic sequences: a stationary phase (osteophytes, discrete narrowing of the joint space) preceeded 'erosive' OA (disappearance of the joint space, subchongral plate eroded by subchondral cysts), and was followed by remodeling of the joint. GAGPS prevented the onset of ~erosive' OA in the affected joints. We may conclude that GAGPS can retard the anatomical progression of OA in finger joints. Stimulation of extracellular matrix synthesis and inhibition of matrix breakdown may contribute to this result.
Influence o f i n t r a - a r t i c u l a r injection o f h y a l u r o n i c acid (HA) on s y n o v i a l fluid (SF) i n f l a m m a t i o n S. TODESCO AND L. PUNZI
Division of Rheumatology, University of Padova, Italy HA represents the major nonproteinaceous, nonaqueous component of SF. In several arthropathies SF is found to contain HA at a.concentration and molecular weight (MW) lower than normal. Good clinical results have been reported after intra-articular injection of exogenous HA (HAI) in osteoarthritis. Several studies demonstrated an anti-inflammatory effect of HA both in vitro a n d ' i n experimental models. However, few investigations on this topic have been performed in man. We studied the effect of HAI (20 mg/2 ml, Hyalgan, Fidia) on some inflammatory indices of SF obtained from different patients with arthropathies. In a study, following one HAI, in comparison with untreated patients, there was a significant reduction in the degree of SF effusion, reduced PGE2 concentration, increase of cAMP and no influence o n white blood cell number (WBC), total protein, total complement and beta-2microglobulin concentration. In another study of patients with rhematoid arthritis we investigated the effects of a course of 4 HAI Hyalgan injections (20 rag/weekly) on SF volume and some inflammatory indices such as WBC, acid phosphatase (AP), lysozyme (LZ) and interleukin-lfl (IL-lfl). We observed an increase in IL-fl 1 week after the first HAI and a further increase
1 week after the second HAI (respectively 61.8, 40.7 and 81.0, 63.0 vs basal value of 52.3, 35.2 pg/ml). One week after the third HAI injection, a decrease in IL-lfl was observed (75.0, 84.7 pg/ml) and a further decrease was evident a week after the fourth HAI injection (24.6, 7.9 pg/ml). The later value of IL-lfl was lower than the basal value (P = 0.048). No significant variations of the other parameters were observed except for SF volume (final: 18.3, 8.8 vs basal: 31.6, 14.5 ml; P = 0.044). This study seems to indicate that HA may exert different antiinflammatory effects on cells and various substances of SF. In the case of IL-lfl it is possible that the initial stimulating and final inhibitory effects are derived from a cytomodulation. The first injected HA is probably quickly cleaved and the resulting low MW may stimulate the cells to produce IL-lfl. Subsequent injected HA, on f~ie other hand, may cause synovial synthesis of a ~good' (higher MW?) HA which in turn could inhibit the production of IL-lfl. These studies suggest that HA may have a ~nontraditional' anti-inflammatory effect on SF, depending on many factors such as the degree of inflammation, the HA concentration and MW, and the frequency of HA injections.