Circulating miRNAs in hand osteoarthritis.

OBJECTIVE: Hand osteoarthritis (OA) is a frequent musculoskeletal disorder with an increasing prevalence during ageing. This study aimed to evaluate circulating microRNAs (miRNAs) in the plasma of patients with hand OA compared with age- and sex-matched healthy control subjects. METHODS: In total, 238 participants (96 with erosive and 73 with non-erosive hand OA patients and 69 healthy control subjects) were included in this study. All patients underwent clinical examinations, including self-reported measures (AUSCAN and Algofunctional index). Radiographs of both hands were scored with the Kallman scale. The profile of miRNAs in plasma was screened using TaqMan™ Low-Density Array, and candidate miRNAs were validated on two quantitative real-time PCR (qRT-PCR) systems (QuantStudio and SmartChip). RESULTS: Of all the 754 miRNAs, 40 miRNAs were different between hand OA patients and healthy control subjects in the screening cohort. Following the two-phase validation process, three miRNAs (miR-23a-3p, miR-146a-5p, and miR-652-3p) were increased in patients with hand OA compared with healthy control subjects and were associated with the AUSCAN sum score and AUSCAN pain. Furthermore, an inverse correlation of miR-222-3p with the Kallman radiographic score was found. The expression of miRNAs did not differ between erosive and non-erosive hand OA. CONCLUSION: The profile of circulating miRNAs could unveil candidate biomarkers associated with hand OA symptoms. Longitudinal studies are required to determine the role of miRNAs in hand OA.

Relation of IL-6, IL-13 and IL-15 gene polymorphisms to the rheumatoid factors, anti-CCP and other measures of rheumatoid arthritis activity.

The aim of the study was to examine the relation between polymorphisms and serum levels of selected cytokines (IL-6, IL-13 and IL-15), production of autoantibodies and factors describing rheumatoid arthritis (RA), such as DAS28 and Total Sharp Score. A total of 156 patients with RA according to the ACR criteria, and 200 control subjects were recruited into the study. The measurements of CRP, anti-CCP, the presence of rheumatoid factors (RFs), radiographs of both hands with calculation of Total Sharp Score (TSS) and DAS28 were obtained from all patients with RA. In total, five polymorphisms in genes coding cytokines (IL-6, IL-13 and IL-15) were detected. The levels of these selected cytokines were measured in serum using ELISA method. A significant difference in allele frequencies between patients with RA and controls was observed for IL-15 -267C/T polymorphism. A higher prevalence of heterozygote variants of IL-15 polymorphisms (14035A/T and -267C/T) in the RF IgG- and RF IgA-negative subgroups was observed. Furthermore, the association of polymorphisms in gene for IL-15 with circulating level of IL-15 (14035A/T and 367G/A) and with total RF and Ig-specific RFs (-267C/T) was found. The relation of IL-15 to RFs IgA, IgM, IgG and the measure of DAS28 was proved. The frequency of the T allele of the IL-13 polymorphism -1112C/T was higher in subgroup with faster progression of the disease (TSS/month ≥ 0.1). In conclusion, we present an association of IL-15 gene polymorphisms with the RFs including subtypes (RF, IgG, IgA) underlined by the relation of increased IL-15 levels in circulation to RFs.

Low circulating Dickkopf-1 and its link with severity of spinal involvement in diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: Dickkopf-1 (DKK-1) is an inhibitor of osteoblastogenesis, and its lower levels are linked to new bone formation. The aim of this study was therefore to explore serum levels of DKK-1 and to evaluate DKK-1's association with the severity of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Serum levels of total and functional DKK-1 and C-reactive protein (CRP) were measured in 37 patients with DISH and 22 healthy age and sex-matched controls. Plain radiographs of the cervical and thoracic spine were performed, and the diagnosis of DISH was defined using the Resnick criteria. Patients were divided into three groups based on spinal involvement. Bone mineral density (BMD) and bone turnover markers were evaluated in patients with DISH. RESULTS: The levels of total serum DKK-1 were significantly lower in patients with DISH than in healthy controls (p<0.0001). Importantly, low serum levels of DKK-1 were associated with more severe spinal involvement in DISH, independent of age, sex, disease duration, CRP, bone turnover markers or BMD. However, these findings were less significant for functional DKK-1. CONCLUSION: These observations indicate that DKK-1 may play a significant role in bone formation during DISH.

Elevated prolactin levels in patients with rheumatoid arthritis: association with disease activity and structural damage.

OBJECTIVES: Prolactin (PRL) is a hormone with cytokine-like activities that has been demonstrated to be involved in immune responses. However, there are inconsistent results related to the role of PRL in rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the levels of PRL in serum and synovial fluid in patients with RA and osteoarthritis (OA) and examine whether PRL might be associated with laboratory and clinical disease activity of RA. METHODS: A total of 29 patients with RA and 26 patients with OA were included in the study. The concentration of PRL in the serum and synovial fluid was measured by immunoradiometric assays, and the levels of serum anti-citrullinated protein/peptide autoantibodies (ACPA) and IgM rheumatoid factor (IgM-RF) were analysed by ELISA. Disease activity score (DAS 28) and radiological (Larsen) score were assessed. RESULTS: The levels of PRL in serum (299.55±27.28 vs. 230.59±16.61 mIU/l, p=0.041) as well as in synovial fluid (338.85±33.49 vs. 245.97±21.88 mIU/l, p=0.024) were significantly higher in patients with RA than in patients with OA. A moderate correlation was found between disease activity of RA and levels of PRL in synovial fluid (r=0.485, p=0.010) and the serum PRL levels correlated significantly with the total Larsen score (r=0.484, p=0.014). CONCLUSIONS: The findings of increased prolactin levels in patients with RA lead to the assumption that prolactin may play a role in disease severity and the process of joint damage in RA.

Serum hyaluronic acid as a potential marker with a predictive value for further radiographic progression of hand osteoarthritis.

OBJECTIVE: To compare serum levels of hyaluronic acid (HA) between patients with erosive and non-erosive hand osteoarthritis (HOA), and investigate its association with morphological changes and radiographic progression over 2 years. METHODS: Fifty-five women with erosive and 33 women with non-erosive HOA were included in this study. All underwent clinical examination, which included assessment of pain, swelling, deformity and deviation of small hand joints and completed health assessment questionnaires. Serum levels of HA were measured by ELISA. Three-phase bone scintigraphy was performed at baseline. Radiographs of both hands were performed at baseline and after 2 years and scored according Kallman grading scale. RESULTS: Serum levels of HA were significantly higher in patients with erosive than with non-erosive HOA (P<0.01). It correlated significantly with the number of hand joints with deviations and deformities. HA adjusted for age and disease duration significantly correlated with radiographs at baseline and after 2 years in all patients with HOA (r=0.560 and r=0.542, P<0.01 for both correlations). Although there was an association between HA and radiographic score in erosive disease, after adjustment for confounders it remained no longer significant. HA adjusted for confounders correlated significantly with the late phase in all patients with HOA (r=0.412, P<0.01) and in patients with erosive disease (r=0.320, P<0.05). CONCLUSION: HA is increased in patients with erosive HOA and could be proposed as a surrogate marker with a predictive value for further radiographic progression of HOA in general. Further investigation is necessary to confirm these results.

The lack of correlation between the increased frequency of allele IL-1RN*2 of interleukin-1 receptor antagonist gene in Czech patients with knee osteoarthritis and the markers of cartilage degradation.

Primary OA is a common multifactorial disease with not fully clarified molecular factors influencing the development of the disease. Among factors disturbing the cartilage integrity are cytokines, such as IL-1, which can stimulate proteinases, resulting in the cartilage destruction. In this regard, IL-1RA competing with IL-1 for binding to its receptor may act as an inhibitor of cartilage breakdown. Because of the possible functional implications, we tested VNTR polymorphism in the second intron of the IL-1RN gene as a putative factor of susceptibility to knee OA. Fifty patients with primary knee OA (diagnosed according to ACR criteria) and 170 healthy controls were included into the study. PCR using primers flanking the VNTR region containing variable numbers of an 86-bp tandem repeat was employed to test the hypothesis. An increased frequency and carriage rate of the IL-1RN*2 allele was found in OA patients in comparison with controls (28 % vs. 15 %, P = 0.0013, OR = 2.97; 95% CI 1.55-5.68 for frequency; 52.5 % vs. 25.3 %, P = 0.0019, OR = 2.95; 95% CI 1.54-5.68 for carriage rate). In addition, a higher frequency of genotype IL-1RN*1/*2 in OA patients was observed as compared with controls (42 % vs. 20.6 %, P = 0.0032, OR = 2.79; 95% CI 1.42-5.48). These results suggest that the IL-1RN*2 allele might represent a factor of susceptibility to OA; however, no correlation between this allele and the markers of cartilage degradation was found.

Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials.

OBJECTIVE: To assess the incidence of Total Joint Replacement (TJR) during the long-term follow-up of patients with knee osteoarthritis (OA) formerly receiving treatment with glucosamine sulphate or placebo. METHODS: Knee OA patients participating in two previous randomised, placebo-controlled, double-blind, 3-year trials of glucosamine sulphate and receiving treatment for at least 12 months, were systematically contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement. RESULTS: Out of 340 patients with at least 12 months of treatment, 275 (i.e., 81%) could be retrieved and interviewed for the present evaluation: 131 formerly on placebo and 144 on glucosamine sulphate. There were no differences in baseline disease characteristics between groups or with the patients lost to follow-up. The mean duration of follow-up was approximately 5 years after trial termination and treatment discontinuation, making up a total of 2178 patient-years of observation (including treatment and follow-up). Total knee replacement had occurred in over twice as many patients from the placebo group, 19/131 (14.5%), than in those formerly receiving glucosamine sulphate, 9/144 (6.3%) (P=0.024, chi-square test), with a Relative Risk that was therefore 0.43 (95% confidence interval (CI): 0.20-0.92), i.e., a 57% decrease compared with placebo. The Kaplan Meier/Log-Rank test survival analysis confirmed a significantly decreased (P=0.026) cumulative incidence of total knee replacements in patients who had received glucosamine sulphate. A pharmacoeconomic analysis in a subgroup of subjects suggested that patients formerly on glucosamine sulphate had recurred to less symptomatic medications and use of other health resources than those from the placebo group during the last year of follow-up. CONCLUSIONS: Treatment of knee OA with glucosamine sulphate for at least 12 months and up to 3 years may prevent TJR in an average follow-up of 5 years after drug discontinuation.

Radiographic progression of rheumatoid arthritis in patients from the Czech National Registry receiving infliximab treatment.

OBJECTIVE: To evaluate the clinical status and radiographic progression in patients with rheumatoid arthritis (RA) being followed by the Czech National Registry of biological treatments. METHODS: Patients who failed at least two disease-modifying antirheumatic drugs and had high disease activity (DAS28 > 5.1) were treated with infliximab. Radiographic progression was measured with a modified version of the Sharp score (TSS) after 54 weeks of treatment. RESULTS: Ninety-nine patients with an average disease duration of 13.7 years were enrolled. The DAS28 dropped from 6.66 to 4.07 (p < 0.001). Before treatment the mean TSS was 90.1 and the mean estimated yearly disease progression was 8.56. After 54 weeks of infliximab, radiographic progression was 4.15 times slower than the estimated rate before treatment and 63 patients did not show any radiographic progression at all. In the remaining 36 patients, the progression rate slowed to 3.8 +/- 0.9 from the estimated TSS of 10.9 +/- 6.9 before the initiation of treatment (p = 0.011). CONCLUSION: Data derived from the Czech National Registry, which reflect general clinical practice, show a significant retardation of radiographic progression in patients treated with anti-TNF and the magnitude of the improvement seen is similar to results from clinical trials.

Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein.

BACKGROUND: Pentosidine, an advanced glycation end product, increasingly accumulates in articular cartilage with age, and contributes to the pathogenesis of osteoarthritis (OA). Increased pentosidine concentrations are associated with inflammatory disorders-for example, rheumatoid arthritis. OBJECTIVE: To compare pentosidine serum concentrations in patients with knee OA and in healthy volunteers and to determine a relationship between pentosidine and cartilage oligomeric matrix protein (COMP)-a marker of articular cartilage destruction. METHODS: Paired serum and synovial fluid samples were obtained by arthrocentesis from 38 patients with knee OA and from 38 healthy volunteers. Pentosidine concentration was measured by reverse phase high performance liquid chromatography with fluorescent detection and COMP was determined by sandwich ELISA. RESULTS: Significantly increased serum pentosidine (p<0.01) and COMP (p<0.05) levels were detected in the patients with OA compared with the control group. Serum pentosidine correlated significantly with synovial fluid pentosidine (p<0.001). Pentosidine in synovial fluid (p<0.05) and in serum (p<0.05) correlated significantly with synovial fluid COMP. Pentosidine and COMP concentrations did not correlate significantly with the radiological stage of the disease. CONCLUSION: Increased pentosidine serum concentration in patients with OA and its correlation with the cartilage destruction marker COMP in synovial fluid suggests that pentosidine may be important in OA pathology and is a new potential OA marker.

Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis.

STUDY OBJECTIVES: To study prognostic value of different biochemical markers for morphological progression of early knee osteoarthritis. DESIGN: A total of 89 patients with knee osteoarthritis (OA) were enroled into the study. The follow-up period was 2 years. Radiological OA progression was evaluated by measuring joint space width. Pentosidine was detected using the HPLC method described earlier, cartilage oligomeric matrix protein (COMP) using the method published by our team. MMP-9, tissue inhibitors of metalloproteinases (TIMP), YKL-40 and hyaluronic acid were detected using commercially available kits. RESULTS: In the group of patients suffering from knee OA, higher serum levels of pentosidine (P=0.04), MMP-9 (P=0.02), TIMP (P=0.04) and COMP (P=0.05) were detected compared with healthy control subjects. Using a correlation analysis method, it has been found that the patients with higher basic serum levels of hyaluronic acid had a faster radiological progression (r=0.56, P<0.005), as well as the patients with higher basic serum pentosidine levels (r=0.30, P<0.005). Other biochemical markers had no statistically significant prognostic value. CONCLUSIONS: In our study, serum levels of hyaluronic acid and pentosidine had a predictive value for further development of knee OA in that further joint space narrowing was detected in the patients with knee OA in the next 2 years.

Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis.

OBJECTIVE: To evaluate a contribution of selected laboratory parameters for a prediction of progressive and erosive development in patients with early rheumatoid arthritis (RA). METHODS: In a prospective study baseline levels of antibodies to cyclic citrullinated peptide (anti-CCP), IgM, IgA, and IgG rheumatoid factors (RFs) were measured by enzyme linked immunosorbent assay (ELISA) in 104 patients with RA with disease duration <2 years. Antikeratin antibodies (AKA) and antiperinuclear factor (APF) were detected by indirect immunofluorescence. Patients were divided into two groups based either on the presence or absence of erosions or according to progression of Larsen score at the end of the 24 months' follow up. RESULTS: Sixty seven (64%) patients developed radiographic erosions, 49 (47%) had progression in Larsen score, and 36 (35%) progressed by more than 10 Larsen units. Significant differences in erosions and progression between the two groups were detected for anti-CCP, AKA, APF, IgM RF, IgA RF, and IgG RF. Baseline Larsen score correlated significantly with anti-CCP, IgM RF, and IgA RF levels, and all measured antibodies correlated with the progression >10 units. The combination of anti-CCP and IgM RF increased the ability to predict erosive and progressive disease. CONCLUSION: The data confirmed that measurement of anti-CCP, AKA, APF, and individual isotypes of RFs was useful for prediction of structural damage early in the disease course. Combined analysis of anti-CCP and IgM RF provides the most accurate prediction.

Seronegative Lyme arthritis caused by Borrelia garinii.

A case of a female patient suffering from Lyme arthritis (LA) without elevated antibody levels to Borrelia burgdorferi sensu lato is reported. Seronegative Lyme arthritis was diagnosed based on the classic clinical manifestations and DNA-detected Borrelia garinii in blood and synovial fluid of the patient, after all other possible causes of the disease had been ruled out. The disease was resistant to the first treatment with antibacterial agents. Six months after the therapy, arthritis still persisted and DNA of Borrelia garinii was repeatedly detected in the synovial fluid and the tissue of the patient. At the same time, antigens or parts of spirochaetes were detected by electron microscopy in the synovial fluid, the tissue and the blood of the patient. The patient was then repeatedly treated by antibiotics and synovectomy has been performed.

Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis.

OBJECTIVE: To evaluate the prognostic utility of serum COMP level measured with a new sandwich ELISA, by correlating COMP level with outcome measures of osteoarthritis (OA) progression. DESIGN: Patients (N=48) had symptomatic primary knee OA of Kellgren-Lawrence (K-L) grade I-III and met ACR criteria. These patients were evaluated prospectively as part of a double-blind drug trial of 3 years' duration and represented the placebo arm of the study. Serum COMP levels were measured by sandwich ELISA with monoclonal antibodies 16-F12 and 17-C10 at baseline and at study end and levels were correlated with changes in (1) joint space width (JSW), (2) K-L grade, (3) Lequesne, and (4) WOMAC indices, over 3 years. RESULTS: The change in JSW over 3 years, summed for both knees, correlated positively with serum COMP level at baseline as well as at study end. Patients were sorted by level of progression based upon a change in K-L grade summed for both knees over 3 years; patients who progressed by two K-L grades were shown to have had significantly higher COMP levels at baseline as well as at study end. Baseline and study end COMP levels did not correlate with the change of Lequesne or WOMAC indices. Baseline COMP levels correlated strongly with end serum COMP levels. CONCLUSION: Serum COMP has the potential to be a prognostic marker of disease progression. High COMP levels, persisting over the 3-year study period in the patients with radiographic progression, indicated differences in disease activity detectable throughout the entire follow-up interval.

Serum cartilage oligomeric matrix protein reflects the presence of clinically diagnosed synovitis in patients with knee osteoarthritis.

OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a component of articular cartilage whose serum levels show a strong correlation with radiographic osteoarthritis (OA) status. It has recently been found, however, that COMP is also produced in synovium. To assess the hypothesis that synovitis affects serum COMP levels in patients with knee OA, we collected sera for COMP simultaneous with a clinical examination for synovitis. DESIGN: Sera were collected from OA patients who fulfilled the American College of Rheumatology criteria for knee OA. Radiographs were classified according to the grading system of Kellgren and Lawrence. Synovitis was diagnosed clinically by joint tenderness plus swelling and/or increased warmth over the joint. COMP levels in sera were measured by inhibition ELISA with monoclonal antibody (mAb) 17-C10. RESULTS: Serum COMP levels were significantly correlated with age, synovitis and an interaction of synovitis and OA severity. Synovitis showed the strongest effect on COMP levels (R=0.1587, P< 0.01), in contrast to C-reactive protein, duration of OA and OA severity score which showed no significant effect on COMP levels. Individual signs of synovitis, namely, joint tenderness and warmth had a significant effect on serum COMP levels while swelling alone did not. CONCLUSION: Synovitis exerts a significant effect on serum COMP levels measured with mAb 17-C10 in OA patients. These findings underscore the importance of the clinical joint examination to assess for synovitis, when attempting to apply objective measures, such as COMP, to the clinical setting.

A 5-year randomized controlled, double-blind study of glycosaminoglycan polysulphuric acid complex (Rumalon) as a structure modifying therapy in osteoarthritis of the hip and knee.

OBJECTIVE: To determine the structure (disease) modifying effect of a glycosaminoglycan polypeptide association complex (GP-C; Rumalon) in patients with knee and hip osteoarthritis (OA). METHODS: Double-blind, randomized, placebo-controlled five-year study. Primary assessment criterion was change in radiographic joint space width between baseline and follow-up at 5 years. Secondary outcome criteria included Lequesne algofunctional index (LAI), pain on passive motion and consumption of non-steroidal antiinflammatory drugs (NSAIDs). The patients received 10 courses of injections of placebo or GP-C 2 ml intramuscularly in 5 years (two courses each year). Each course included 15 injections administered twice weekly. RESULTS: There were 277 patients with knee OA and 117 patients with hip OA. Control and GP-C treated groups were comparable as to sex, age, duration of disease, body weight, X-ray stage and value of LAI at the baseline. Knee joint space at 5 years decreased 0.37+/-0.08 (mean+/-standard deviation) mm for GP-C and 0.42+/-0.08 mm for placebo groups (P=0.68). Hip joint space at 5 years decreased 0.21+/-0.08 mm for GP-C and 0.22+/-0.08 mm for placebo groups (P=0.53). In a subset of patients with hip OA, Kellgren-Lawrence> or =2 and JSW> or =1 mm, there was a trend in favor of GPC for lower joint space narrowing in 5 years (P=0.11). In addition, there were no statistical differences between the treatment groups in LAI, pain on passive motion and consumption of NSAIDs. Side-effects after GP-C (14.5%) were rare, mild and not more frequent than in the placebo group (15%). CONCLUSION: We were not able to demonstrate a structure modifying effect of GP-C in OA of the hip or knee. Radiographic progression of OA in both knee and hip OA was lower than expected in both study groups.

Radiographic progression of knee osteoarthritis in a Czech cohort.

OBJECTIVE: To determine the 5-year radiographic progression of osteoarthritis (OA) of the knee in a Czech cohort. METHODS: 139 patients with idiopathic OA were followed for 5 years, receiving only physical therapy and non-steroidal antiinflammatory drugs as needed. Weight-bearing radiographs of both knees were performed at the initial and final evaluation by a single technician using the same instrument and a standardized procedure. Radiographs were evaluated using the Kellgren-Lawrence scale (KL). Joint space width (JSW) was determined by 2 independent trained readers, and discrepancies re-reviewed. RESULTS: JSW decreased 0.39 +/- 0.95 mm in 5 years, or 0.078 +/- 0.19 annually. The reduction of JSW was greatest in the KL grade III radiographs (0.099 +/- 0.18 mm). The smallest reduction in JSW was seen in those with KL grade I (0.044 +/- 0.14 mm). However, only 25% of those with KL stage II or stage III demonstrated any change in JSW over the 5-year period. The reduction in JSW was not constant, being most rapid in the first year and then much slower. The coefficient of variation (CV) of the method was good (intra- and inter-observer CV 3.6%). CONCLUSION: This 5-year follow up of Czech patients with OA of the knee demonstrated a low rate of radiographic progression of JSW. The most rapid progression appeared in KL stage III. The progression was most rapid in the first year.

Comparison of clinical, laboratory, radiographic, and scintigraphic findings in erosive and nonerosive hand osteoarthritis. Results of a two-year study.

OBJECTIVES: The primary objective was to compare the clinical, radiologic, laboratory, and scintigraphic features in 28 patients with erosive hand osteoarthritis and in 24 with non-erosive hand osteoarthritis. Other objectives were to evaluate clinical, radiographic, and scintigraphic progression in the two groups over a two-year period and to estimate the value of bone scintigraphy for predicting clinical and radiographic progression. METHOD: Prospective two-year study of 52 patients with hand osteoarthritis, of whom 28 had at least three subchondral erosions and 24 patients had no erosions. RESULTS: The group with erosive disease had higher serum immunoglobulin G levels (14.53 +/- 3.79 mg/L vs. 12.03 +/- 4.01 mg/L; P < 0.05) and a higher radiographic index (91.81 +/- 3.67 vs. 25.88 +/- 12.81; P < 0.001), whereas the group with non-erosive disease had a higher rate of paresthesia (66.7% vs. 39.3%; P < 0.05) and higher values for the erythrocyte sedimentation rate (25.21 +/- 20.86 vs. 13.21 +/- 12.85; P < 0.05) and serum C-reactive protein level (8.82 +/- 6.08 vs. 3.25 +/- 6.92; P < 0.01). None of the other study parameters showed any significant differences, and both age and sex distribution were also similar in the two groups. At completion of the two-year follow-up, no changes versus baseline were found in any of the study parameters in the overall study population or in either of the two groups. The baseline scintigraphic index was significantly correlated with the radiographic index at baseline (r = 0.497; P < 0.01) and at study completion (r = 0.550; P < 0.001). Joints with a positive baseline scintigram were significantly more likely to show radiographic progression (21.09%, vs 6.68% in negative joints; P < 0.001) and joint tenderness exacerbation (21.22% vs. 13.73%; P < 0.001). CONCLUSION: These data suggest that bone scintigraphy may be useful for predicting clinical and radiographic progression of hand osteoarthritis with or without erosions.

Glycosaminoglycan polysulfuric acid (GAGPS) in osteoarthritis of the knee.

We studied the efficacy and tolerability of glycosaminoglycan polysulfuric acid (GAGPS) in 80 patients with osteoarthritis (OA) of the knee. Patients received two series of five intra-articular injections, at 1-week intervals, of 25 mg (0.5 ml) GAGPS into the knee in a double-blind, parallel, randomized, placebo-controlled trial. There was an immediate decrease in pain after the injections of 43% with GAGPS and 33% with placebo (P = 0.047) (Jezek pain index). Pain relief of GAGPS vs placebo was not different at other intervals (10, 14, 22, 26 weeks after start of treatment). At 6 weeks the Lequesne index decreased 20% after GAGPS and 9% after placebo (P = 0.17). At 10 weeks the Lequesne index decreased 24% after GAGPS and 13% after placebo (P = 0.20). The decrease in Lequesne index at 14 weeks was 31% after GAGPS and 15% after placebo (P = 0.06). The other measured parameters tended to be more favorably influenced by GAGPS than placebo. GAGPS was well tolerated, with associated mild adverse reactions in 8% of cases. GAGPS may have a role as a symptomatic slow acting drug for OA. Further study appears appropriate.

Combination therapy with hydroxychloroquine and methotrexate in rheumatoid arthritis.

The aim of the study was to compare the efficacy of hydroxychloroquine (HCQ) alone and in combination with methotrexate (MTX) in a randomized placebo-controlled study lasting 6 months. Forty patients with rheumatoid arthritis participated in the study and were randomly assigned to two groups--20 patients were treated with HCQ (200 mg daily) and placebo, 20 patients with HCQ and MTX (7.5 mg) once a week. Patients were assessed at regular intervals of 1 month up to 6 months using six clinical and five laboratory tests and one radiological measure. All six clinical variables and two laboratory variables were favorably influenced by combination therapy during the 6-month period. HCQ alone significantly influenced only three clinical variables and none of the laboratory parameters. There was a greater number of patients without radiological progression in the combination group. There was one drop-out in combination group due to general allergic reaction; otherwise the treatment was well tolerated. The results suggest that a combination of HCQ and MTX is more potent than HCQ alone.