Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis.

OBJECTIVES: To evaluate changes in bone mineral density (BMD) in the hands, hip and spine after 1 and 2 years of follow-up, in relation to antirheumatic and antiresorptive therapies and disease and demographic variables in patients with recent-onset rheumatoid arthritis (RA). METHODS: Changes in BMD measured in metacarpals 2-4 by digital x-ray radiogrammetry and in the hip and spine by dual energy x-ray absorptiometry were assessed at baseline and after 1 and 2 years of follow-up in 218 patients with recent-onset RA from the BeSt study, who received one of four treatment strategies: sequential monotherapy (group 1); step-up combination therapy (group 2); initial combination therapy with tapered high-dose prednisone (group 3); or initial combination therapy with infliximab (group 4). RESULTS: After 1 and 2 years, there was significant BMD loss in all locations, with significantly greater BMD loss in the hands than generalised BMD loss in the hip and spine. Initial combination therapy with prednisone or infliximab were associated with less hand BMD loss compared with initial monotherapy after 1 and 2 years (-0.9 and -1.6%, -0.6 and -1.4%, -1.7 and -3.3%, and -2.6 and -3.6% for group 4-1 after 1 and 2 years, overall p = 0.001 and p = 0.014, respectively). Progression in erosions was independently associated with increased BMD loss both in the hands and hip after 1 year. The use of bisphosphonates protected only against generalised BMD loss in the hip and spine. CONCLUSIONS: The association between joint damage progression and both hand and generalised BMD loss in RA suggests common pathways between these processes, with hand BMD loss occurring earlier in the disease course than generalised BMD loss.

Technetium-99m labelled human immunoglobulin scintigraphy predicts rheumatoid arthritis in patients with arthralgia.

The ability of 99mTc-IgG scintigraphy to predict the development of rheumatoid arthritis (RA) in 47 patients with arthralgia was investigated. 99mTc-IgG scintigraphy and the serum test for rheumatoid factor (RF), measured at the beginning of a year long study, were compared for their ability to predict RA. During the study 8 patients developed RA. The specificity and positive predictive values of RF in predicting RA were 79% and 50% respectively; and for 99mTc-IgG scintigraphy 97% and 88%. The sensitivity and negative predictive values of RF were 100% and of 99mTc-IgG-scintigraphy 88% and 97% respectively. In conclusion, 99mTc-IgG scintigraphy has additional value to RF with respect to the prediction of the development of RA in patients with arthralgia.

99Tcm-HIG accumulates in the synovial tissue of rats with adjuvant arthritis by binding to extracellular matrix proteins.

Our objective was to investigate the mechanism of accumulation of 99Tcm-labelled non-specific polyclonal human immunoglobulin (99Tcm-HIG) in inflamed synovial tissue (ST) in an experimental animal model of arthritis. Following 99Tcm-HIG scintigraphy, the in vivo localization of 99Tcm-HIG in the ST of knee joints of rats with adjuvant arthritis was studied using immunohistochemical techniques. In addition, the in vitro binding of 99Tcm-HIG to extracellular matrix proteins was analysed by means of immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). After 99Tcm-HIG scintigraphy, 99Tcm-HI was detected in the ST of rats with adjuvant arthritis. 99Tcm-HIG was diffusely distributed and not bound to cells. In vitro incubation of 99Tcm-HIG on the ST of rats with adjuvant arthritis revealed binding of 99Tcm-HIG to inflamed, but not to non-inflamed, ST. In addition, specific binding of 99Tcm-HIG to fibronectin, fibrin, collagen type I and III was demonstrated by ELISA. We conclude that the accumulation of 99Tcm-HIG in inflamed ST can be explained by the binding of 99Tcm-HIG to extracellular matrix proteins.

New agents for scintigraphy in rheumatoid arthritis.

Radiopharmaceuticals have been used as investigative tools for the detection and treatment of arthritis activity in rheumatoid arthritis (RA) since the 1950s. Against the background of the pathophysiology of RA, the current status of joint scintigraphy and possible future developments are reviewed. Both non-specific (radiolabelled leucocytes and technetium-99m labelled human immunoglobulin) and specific targeting radiopharmaceuticals (including radiolabelled antibodies) are considered. The use of radiopharmaceuticals in the detection of arthritis activity has the advantages of allowing direct imaging of joints by means of whole-body scintigraphy and of joints that are difficult to assess clinically or radiographically. Promising results have been obtained with radiolabelled anti-CD4 and anti-E-selectin antibodies and with somatostatin receptor imaging, but more data are available regarding 99mTc-IgG scintigraphy, which differentiates between the various degrees of arthritis activity and thus facilitates the choice of antirheumatic drug. Newer promising approaches to the imaging of RA include the use of radiolabelled J001 and cytokines, though studies on these are limited at present.

Technetium-99m labelled polyclonal human IgG scintigraphy before and 26 weeks after initiation of parenteral gold treatment in patients with rheumatoid arthritis.

OBJECTIVE: To determine effectiveness of technetium-99m labelled polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to monitor variation in arthritis activity in patients with rheumatoid arthritis (RA). METHODS: The results of semiquantitative 99mTc-IgG scintigraphy were compared with those of examination before and 26 weeks after initiation of parenteral gold treatment in 19 patients with RA. RESULTS: Clinical and laboratory variables of arthritis activity as well as the scores of 99mTc-IgG scintigraphy were significantly lower after gold treatment compared to the scores before treatment. However, the difference between the mean scores of 99mTc-IgG scintigraphy before and after treatment was statistically significant for more joints than such difference in scores for joint pain and joint swelling. CONCLUSION: 99mTc-IgG scintigraphy is able to reflect variations in arthritis activity in patients with RA.

Joint scintigraphy for quantification of synovitis with 99mTc-labelled human immunoglobulin G compared to histological examination.

OBJECTIVE: This study addressed the following questions: How does 99mTc-IgG scintigraphy compare to physical examination in the detection of synovitis as determined histologically, and is 99mTc-IgG scintigraphy a sensitive detector of histologically documented synovitis activity in the absence of clinically detectable knee joint swelling? METHODS: The results of measuring synovitis activity by physical examination and by scintigraphy with technetium-99m labelled polyclonal human immunoglobulin G (99mTc-IgG) were compared with the results of histological examination of synovial biopsies taken from the knee joints of patients with rheumatoid arthritis (n = 21), osteoarthritis (n = 9) and various other rheumatic diseases (n = 10). RESULTS: The sensitivity of 99mTc-IgG scintigraphy in detecting synovitis activity, as determined histologically (85%), was higher than the sensitivity of joint swelling (65%). In the absence of clinically detectable knee joint swelling the sensitivity of 99mTc-IgG scintigraphy was 83%. CONCLUSION: This study shows that 99mTc-IgG scintigraphy is a more sensitive method than physical examination in detecting histologically documented synovitis activity.

Value of 99mTc-IgG scintigraphy in the prediction of joint destruction in patients with rheumatoid arthritis of recent onset.

The ability of technetium-99m-labelled polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to predict joint destruction in patients with rheumatoid arthritis (RA) was investigated in this study. The progression of radiographically determined joint destruction in wrists, hands and feet was compared with the results of physical and laboratory examination, as well as 99mTc-IgG scintigraphy, measured at the beginning of a year-long study on 30 patients with RA of recent onset. The sensitivity of joint swelling in predicting the progression of radiographically determined joint destruction ranged between 57% and 74%. The sensitivity of 99mTc-IgG scintigraphy ranged between 71% and 100%. The specificity and positive predictive value both of joint swelling and 99mTc-IgG scintigraphy were low. Multiple regression analysis showed that for the total joint score, and for the metacarpophalangeal and forefeet joints, progression of radiographically determined joint destruction was primarily predicted by 99mTc-IgG scintigraphy. Joint swelling, ESR and IgM rheumatoid factor did not contribute to this prediction. We concluded that 99mTc-IgG scintigraphy is superior to conventional clinical and laboratory measurements in RA with respect to prediction of joint destruction.

Joint scintigraphy for quantification of synovitis with 99mTc-labelled human immunoglobulin G compared to late phase scintigraphy with 99mTc-labelled diphosphonate.

The ability of scintigraphy with technetium 99m-labelled polyclonal human immunoglobulin G (99mTc-IgG) to detect and quantify arthritis activity was studied in 24 patients with RA and in 10 patients with OA. The results of 99mTc-IgG scintigraphy were compared with those of scintigraphy with 99mTc-labelled hydroxymethylene-diphosphonate (HDP). The mean joint scores of 99mTc-IgG scintigraphy in RA patients with active disease were significantly higher (P < 0.001) than the mean scores in patients with inactive disease. The mean joint scores were also higher in patients with erosions compared to those in patients without erosions (P < 0.05). For 99mTc-HDP scintigraphy no significant differences were found between the mean joint scores of these patient groups. Comparison of scintigraphic results between patients with RA and OA revealed that the mean joint score of 99mTc-IgG scintigraphy was significantly (P < 0.001) higher in the patients with RA than in patients with OA, whereas for 99mTc-HDP scintigraphy this difference was not significant. These results show that 99mTc-IgG scintigraphy, when compared to 99mTc-HDP scintigraphy, is a more specific method of detecting synovitis and, also, shows differentiation between different degrees of arthritis activity in RA.

99Tcm-labelled polyclonal human immunoglobulin G scintigraphy before and after intra-articular knee injection of triamcinolone hexacetonide in patients with rheumatoid arthritis.

The ability of 99Tcm-labelled polyclonal human immunoglobulin G (99Tcm-IgG) scintigraphy to monitor intra-individual variation in arthritis activity was studied in seven patients with rheumatoid arthritis (RA). These patients were treated with an intra-articular injection of 20 mg triamcinolone hexacetonide. The results of semiquantitative 99Tcm-IgG scintigraphy were compared with the degree of joint swelling and the histological changes observed in synovial biopsies before and 14 days after the injection. In all seven patients the local treatment resulted in a decreased arthritis activity of the treated knee as measured clinically or histologically. This decrease was parallelled, in all patients except one, by a lower uptake of 99Tcm-IgG after the injection when compared to uptake prior to treatment. This study shows that 99Tcm-IgG scintigraphy is able to reflect intra-individual variations in arthritis activity in patients with RA.

99mTc human immunoglobulin scintigraphy--a reliable method to detect joint activity in rheumatoid arthritis.

The ability of 99mtechnetium labelled nonspecific, polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to depict and quantify synovial inflammation was studied in 30 patients with rheumatoid arthritis (RA). All patients were injected with 350 MBq 99mTc-IgG and imaging was performed 4 h later. This resulted in excellent images of inflamed synovium. Scores for 99mTc-IgG joint scintigraphy correlated highly with scores for joint swelling and C-reactive protein levels, weakly with pain scores and not with radiographic scores of joint destruction. These results suggest that 99mTc-IgG joint scintigraphy may provide an objective test to detect synovitis and measure the activity of the disease.