The effect of infliximab on bone metabolism markers in patients with rheumatoid arthritis

OBJECTIVE: The aim of this study was to evaluate urinary excretion of N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD), markers of bone resorption, and serum bone alkaline phosphatase (BAP) level, a marker of bone formation and an early marker of osteoblast differentiation, in patients with rheumatoid arthritis (RA) treated with infliximab. METHODS: Seventeen male and female patients (age 60.7+/-2.53 yr; mean disease duration 12.9+/-3.01 yr; Steinbrocker's class II-IV) with RA, diagnosed according to the criteria of the American College of Rheumatology (ACR), took part in the study between March 2003 and January 2005. None of the patients had a history of oestrogen replacement therapy. All patients were treated with infliximab combined with methotrexate. Infliximab was infused intravenously at 3 mg/kg at baseline, 2 and 6 weeks, then every 8 weeks. To evaluate disease activity, ESR, CRP, the numbers of swollen and tender joints, modified Stanford Health Assessment Questionnaire (mHAQ) score and ACR score were measured. Levels of NTX and DPD in urine and BAP in serum were measured in all patients. RESULTS: ESR, CRP, the number of swollen joints and tender joints, and mHAQ score had decreased significantly 6 weeks after initial treatment and were still low 6 months after initial treatment. NTX levels had decreased significantly 6 weeks after the initial treatment and were still low 6 months after initial treatment. DPD levels had decreased 6 months after initial infusion. Mean serum BAP level did not differ significantly among the three time points. NTX levels were statistically corresponding with the number of swollen joints and mHAQ scores. DPD levels were statistically lower corresponding with ESR. CONCLUSION: Infliximab therapy may inhibit generalized bone loss in patients with RA. NTX is a more sensitive marker than DPD.     

High serum and synovial fluid granulocyte colony stimulating factor (G-CSF) concentrations in patients with rheumatoid arthritis

OBJECTIVE: To determine the relationship between serum G-CSF, RA disease activity and the levels of inflammatory cytokines. METHODS: Sixty-one patients (5 men and 56 women; mean age; 56.1 +/- 11.4 [+/- SD] years, range, 22-70 years) who were selected at random and met the American College of Rheumatology criteria for RA were examined. Granulocyte-colony stimulating factor (G-CSF) levels in sera and synovial fluid were measured by solid-phase radioimmunoassay (RIA). We also measured various indices of RA disease activity and serum levels of IL-1 beta, IL-6 and TNF-alpha by ELISA. RESULTS: The morning stiffness, number of tender or swollen joints, ESR, Lansbury index and serum G-CSF levels in patients with active RA were significantly higher than the corresponding levels in patients with inactive RA. Serum G-CSF levels correlated significantly with morning stiffness, the number of tender or swollen joints and the Lansbury index. However, there was no correlation between serum G-CSF and ESR. High levels of IL-1 beta, IL-6 and TNF-alpha were detected in RA patients. The number of tender or swollen joints, ESR, Lansbury index, and IL-1 beta were significantly higher in G-CSF-positive RA patients than in G-CSF-negative RA patients. CONCLUSION: Our results suggest that G-CSF produced by synovial cells stimulated by inflammatory cytokines might contribute to inflammatory arthritis in RA patients.     

Comparison of intramuscular methotrexate and gold sodium thiomalate in the treatment of early erosive rheumatoid arthritis: 12 month data of a double-blind parallel study of 174 patients

The objective was to compare the safety and efficacy of methotrexate (MTX) and gold sodium thiomalate (GSTM) in patients with early erosive rheumatoid arthritis (RA). A total of 174 patients with active early erosive RA without deformities were enrolled in a 12 month, two-centre double-blind randomized trial. They received a weekly i.m. dose of 15 mg MTX (n = 87) or 50 mg GSTM (n = 87), respectively. Clinical and laboratory evaluations were carried out every 3 months in all patients, including the withdrawals. Ten patients (11.5%) in the MTX group and 21 patients (24.1%) in the GSTM group achieved a clinical remission of the disease [no swollen joints, erythrocyte sedimentation rate (ESR) < 20 mm, no steroids] within the study period (P < 0.05). An at least marked improvement (> 50% reduction of the number of swollen and tender joints and the ESR) was assessed in 59/87 (68%) and 66/87 (76%) patients treated with MTX or GSTM, respectively (P > 0.05). Significantly more patients in the GSTM group were withdrawn due to toxicity (six MTX/32 GSTM). A total of 126 patients (73 on MTX and 53 on GSTM) completed 12 months on their original medication. In the completers, a significant improvement of > 50% compared to baseline was noted in all six clinical variables [morning stiffness, joint count of swollen and tender joints, Lansbury index, grip strength and activities of daily living (ADL) score], the ESR and the C-reactive protein, without intergroup differences. The number of patients taking prednisone was reduced from 21 to 7% in the MTX group and from 15 to 4% in the GSTM group. While significantly more patients achieved a clinical remission with GSTM treatment, tolerability was significantly better with MTX.      

Ileum-targeted steroid therapy in rheumatoid arthritis: double-blind,placebo-controlled trial of controlled-release budesonide

In order to determine whether budesonide, which is believed to exert most of its anti-inflammatory effects in the intestinal tract, has a beneficial effect on disease activity in rheumatoid arthritis (RA), we treated 26 patients with active RA in double-blind fashion with either controlled ileal-release budesonide (9 mg by mouth) ( n=14) or placebo ( n=12). All patients remained on their existing disease-modifying antirheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Paracetamol was used for escape analgesia. Evaluations were performed at 0, 2, and 4 weeks and included tender and swollen joint counts, duration of morning stiffness, visual analogue scale for pain (VAS) on a 100-mm horizontal scale, grip strength using a vigorimeter (lb/in(2)), haemoglobin, erythrocyte sedimentation rate (ESR) (Westergren method, mm/1st h), plasma viscosity (PV) in cP (normal range 1.5-1.72), C-reactive protein (CRP) (normal upper level 1 mg/dl), random plasma cortisol (nmol/l) drawn between 10 a.m. and 2 p.m., and blood pressure. Disease activity scores based on 28 joints (DAS 28) were also derived at all time points. Within-group comparisons revealed significant improvement in the budesonide-treated but not the placebo group with respect to numbers of tender and swollen joints, duration of morning stiffness, grip strength, pain, ESR, PV, and DAS 28. Between-group comparisons showed significant differences for ESR, PV, pain, and random plasma cortisol (drawn between 10 a.m. and 2 p.m.). There were no significant side effects in either group.     

Additive combination of actarit and methotrexate in the treatment of refractory rheumatoid arthritis

The objective of this study was to evaluate the efficacy and safety of an additive combination of a disease-modifying antirheumatic drug (DMARD) actarit and low-dose methotrexate (MTX) in patients with active rheumatoid arthritis (RA) unresponsive to MTX. Thirty-four patients with active RA, who had been unsuccessfully treated with MTX for at least 3 months were enrolled on a 24-week course of actarit (300 mg/day) and MTX (2.5–10 mg/week). Disease activity was evaluated by physical global assessments using conventional measures (Japan Rheumatism Association), and the American College of Rheumatology (ACR) criteria of improvements in RA. Thirty-two patients completed this study. No severe adverse drug reactions were seen. Patients whose RA did not respond to MTX alone responded to the combination therapy, with a significant improvement in the duration of morning stiffness, grip strength, swollen joint counts, patient's articular pain score, modified health assessment questionnaire (M-HAQ) score, score of both patient's and physician's global assessments, and C-reactive proteins (CRP). Sixteen patients (50.0%) and 9 patients (31.0%) showed a significant improvement in overall conventional measures, and ACR response criteria, respectively, and 60.0% of RA patients who received MTX for more than 1 year showed improvement in ACR definition. Patients who responded to the combination treatment within the first 12 weeks showed persistent improvement for the remaining part of the 24 week period. Our results indicate that the additive combination of actarit and MTX is safe, and without serious adverse effects, and has an excellent efficacy in patients with active and refractory RA. Received: July 28, 1999 / Accepted: January 28, 2000     

Usefulness of actarit in elderly rheumatoid arthritis

 Many elderly patients with rheumatoid arthritis (RA) who have decreased physiological functions due to aging may also have symptoms of other complications. Therefore, attention must be paid not only to the efficacy, but also to any possible adverse reactions, when selecting disease-modifying antirheumatic drugs (DMARDs). In this study, we examined the efficacy and safety of actarit for elderly patients with mildly to moderately active rheumatism. Twenty patients with elderly rheumatoid arthritis were enrolled on a 48-week course of actarit (300 mg/day). In the overall evaluation, 14 out of 20 patients (70%) met the criteria for a 20% improvement in the American College of Rheumatology (ACR) core set, and seven out of 20 patients (35%) met the criteria for a 50% improvement. In the evaluation parameters, a significant improvement was shown in the number of swollen joints, the patient's evaluation of pain, the patient's evaluation of chronic arthritis activity, the doctor's evaluation of chronic arthritis activity, erythrocyte sedimentation rate, C-reactive protein (CRP), and Lansbury's activity index after 48 weeks. A particularly remarkable improvement was shown in tender and swollen joints in the small joint category in elderly onset RA. No adverse reactions and no aggravation of complications were observed in this study. From these results, it was concluded that actarit was a safe and highly effective drug for use with elderly patients. Received: March 29, 2001 / Accepted: November 28, 2001     

血清高迁移率族蛋白1水平与类风湿关节炎临床指标的相关性

目的通过检测活动性类风湿关节炎(rheumatoid arthritis,RA)患者血清高迁移率族蛋白1(high mobility group box protein 1,HMGB1)表达水平,探讨HMGB1与RA患者疾病活动性、自身抗体及临床指标的相关性。方法采用双抗体夹心酶联免疫吸附试验测定67例活动性RA患者和21位健康对照者血清HMGB1水平。收集RA患者的同期临床资料并测定相关实验室指标:疼痛视觉模拟评分(visual analog scale,VAS)、疲乏VAS、肿胀关节数、压痛关节数、患者对疾病总体状况的VAS(patient′s global assessment,PGA)、健康评估问卷(health assessment questionnaire,HAQ)、疾病活动评分28(dise aseactivity score28,DAS28)、血沉、C-反应蛋白、类风湿因子-IgM、抗环瓜氨酸肽抗体等,分析以上指标与血清HMGB1的相关性。结果活动性RA组血清HMGB1中位数为8.7ng/ml,四分位间距为16.59ng/ml;健康对照组血清HMGB1中位数为3.47ng/ml,四分位间距为7.43ng/ml,活动性RA组血清HMGB1表达水平显著高于健康对照组,两组间比较差异有统计学意义(P0.01)。活动性RA患者血清HMGB1表达水平与类风湿因子呈正相关(P0.01),与疼痛VAS评分、疲乏VAS评分、肿胀关节数、压痛关节数、PGA、HAQ、DAS28评分及血沉、C-反应蛋白、抗环瓜氨酸肽抗体无相关性(P0.05)。结论活动性RA患者血清HMGB1表达水平较健康对照组显著升高,但可能与疾病活动无关。     

Improvement in rheumatoid arthritis following application of an extracorporeal granulotrap column,G-1

Patients with rheumatoid arthritis (RA) showed significantly (P<0.01) increased numbers of granulocytes in their peripheral blood compared with normal donors and patients with osteoarthritis, and this finding correlated with interleukin-6 and C-reactive protein levels and active joint score. Then, 17 patients with RA were treated eight times in 4 weeks with a newly developed extracorporeal granulotrap column containing cellulose acetate beads (G-1 column). This column reduced granulocytes in the outflow blood by 50.2% compared with inflow counts. To evaluate the efficacy of G-1 therapy, 17 patients were followed for 12 weeks from the beginning of this therapy. The modified Lansbury index (LI) for monitoring RA activity significantly improved from a pretretament mean score of 60.8% to a posttreatment score of 51.3%. The lowered scores were maintained up to 12 weeks after the initiation of therapy. Of the four LI items, tender and swollen joint scores showed the most significant improvement, with the tender joint score showing a particularly significant decrease throughout the study period. No serious side-effects were observed. These findings suggested that G-1 therapy was effective for RA.     

Measurement of disease activity in psoriatic arthritis. Extended report

OBJECTIVE: To determine whether activity indices, generally accepted in rheumatoid arthritis (RA) are useful and valid to measure disease activity in psoriatic arthritis (PsA) patients with peripheral arthritis. METHODS: 38 PsA patients were studied before and after a one year DMARD treatment. Extended and reduced tender and swollen joint counts, Ritchie articular index, Health Assessment Questionnaire HAQ) score, erythrocyte sedimentation rate (ESR) morning stiffness, the patient's and the assessor's global assessment (PGA and AGA) were recorded. Disease activity scores, EULAR, ACR and Clegg improvement criteria were calculated. RESULTS: All indices correlated well before and after treatment with AGA (r > 0.337, p < 0.042), except morning stiffness and tender joint counts. After treatment, PGA correlated well only with the 68 and 28 tender joint counts, ESR and HAQ (r > 0.340, p < 0.05). The response to DMARD treatment was well characterized with the changes in the number of tender and swollen joint counts, and DAS4, DAS3, DAS28. The changes correlated with the PGA and AGA. The level of agreement between Clegg and the EULAR improvement criteria with both extended and reduced joint count was comparable (p < 0.01). CONCLUSION: The well-known activity indices generally accepted in RA, as tender and swollen joint count, DAS3, DAS4, DAS28, are useful and valid indices measuring arthritis activity in PsA with peripheral arthritis. The correlation between Clegg and EULAR improvement classification indices were similar. Both seemed to characterize changes authenticated during DMARD treatment.     

The two-year follow-up of a randomized comparison of in-patient multidisciplinary team care and routine out-patient care for active rheumatoid arthritis

The long-term effects of a period of 11 days of in-patient multidisciplinary team care were compared with routine out-patient care in 80 patients with active rheumatoid arthritis (RA). Endpoint measures included swollen and tender joint counts, the patient's assessment of pain, the patient's and the physician's assessments of disease activity, the ESR and the Health Assessment Questionnaire (HAQ). Two years after hospitalization, all 39 patients randomized to the in- patient group and 39 out of 41 patients randomized to the out-patient group were evaluable. At 2 yr, in the in-patient group the improvement according to mean changes from baseline was greater than that in the out-patient group for all endpoint measures except for the HAQ score, the differences not reaching statistical significance. Averaged over the time points 2, 52 and 104 weeks, the improvement was significantly greater in the in-patient group than in the out-patient group, except for the ESR and HAQ score. In conclusion, a short period of in-patient multidisciplinary team care has a beneficial effect on disease activity over a period of 2 yr and should be considered as a useful treatment modality in patients with active RA.      

The relationship between disease activity and depression in Egyptian patients with rheumatoid arthritis

Aim of the workTo estimate the prevalence of depression and its relationship with disease activity parameters in Egyptian patients with RA.Patients and methodsA cross sectional study was conducted on 170 patients with RA. The following values were assessed for each patient: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), swollen and tender joint counts (SJC and TJC), disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), visual analogue scale (VAS) of pain and hospital anxiety and depression scale-depression subscale (HADS-D).ResultsThe prevalence of depression was 15.29% (26 RA patients). In the depressed RA patients, positive significant correlations were found between HADS-D score and age, disease duration, HAQ score, VAS, DAS28 score and CRP. However, no significant correlation was found between HADS-D score and ESR, number of swollen and tender joints. No significant difference (P > 0.05) was found between depressed male and female patients with RA.ConclusionPatients with RA and co-morbid depression have worse health outcomes. RA cases should be monitored for accompanying depression during follow-up. The identification and treatment of depression in RA paramount to the overall management of RA.     

The effect of methotrexate on bone metabolism markers in patients with rheumatoid arthritis

The aim of the present study was to evaluate the influence on urinary excretion levels of N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD) as a useful marker for bone resorption, and on serum-bone alkaline phosphate (BAP) levels as a useful marker for bone formation and an early marker of osteoblast differentiation in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Thirty patients with RA, diagnosed according to the criteria of the American College of Rheumatology, were involved in this study between March 2003 and January 2005. None of the patients had a history of hormone (estrogen) replacement therapy. All patients were treated with MTX. Methotrexate was administered perorally at a dosage of 4–10 mg/week. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, 3 months and 6 months after the initial treatment. Then the levels of NTX and DPD in urine and BAP in serum were measured in all patients. For comparison with the effect of other DMARDs on bone metabolism markers in RA patients, we measured the levels of NTX and DPD in urine and BAP in serum of RA patients, 13 patients treated with salazosulfapyridine (SASP), and 14 patients treated with actarit (ACT). In patients treated with MTX, NTX levels decreased significantly at 3 months after the initial treatment and remained low at 6 months after the initial treatment, and DPD levels significantly decreased at 6 months after the initial treatment. The mean serum BAP levels changed without significant differences from the baseline at 3 months and 6 months. In patients treated with SASP and ACT, all bone metabolism markers had not changed significantly at the three time points. On disease activity erythrocyte sedimentation rate, C-reactive protein, the number of swollen joints and tender joints, and mHAQ score decreased significantly at 3 months after the initial treatment, and remained at low levels at 6 months after the initial treatment with MTX. Methotrexate therapy looks promising in inhibiting generalized bone loss in patients with RA. In addition, NTX is a more sensitive marker than DPD.     

益赛普联合甲氨蝶呤治疗对类风湿关节炎临床及炎性细胞因子的影响

目的 研究类风湿关节炎（RA）患者益赛普（ETA）联合甲氨蝶呤（MTX）治疗后,临床表现及血清肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6）、干扰素-γ（IFN-γ）浓度的变化.方法 选取活动性RA患者25例和正常人18例作为研究对象,研究期间患者均给予甲氨蝶呤10 mg每周1次口服,以及益赛普25 mg每周2次,皮下注射.治疗前及治疗后第6周收集患者血清,检测其TNF-α,IFN-γ、IL-6浓度,并记录肿胀关节数、压痛关节数、疾病活动性评分（DAS）、健康评估问卷评分（HAQ）、血沉（ESR）、C反应蛋白（CRP）和类风湿因子（RF）等,同时收集正常人血清检测上述指标.结果 RA组患者血清IL-6、TNF-α和IFN-γ浓度明显高于正常对照组（P分别＜0.01、0.05、0.05）.治疗后患者DAS28评分降低（P＜0.01）,HAQ、ESR、CRP、肿胀及压痛关节数也明显好转（P＜0.01）,血清RF、IL-6和TNF-α浓度也明显下降（P分别＜0.05,0.01,0.05）,治疗后血清IFN-γ浓度较前下降,但无显著性差异.结论 血清IL-6、TNF-α和IFN-γ浓度增高以及ESR、CRP、RF增加可作为RA病情活动指标.益赛普和甲氨蝶呤联合治疗能快速缓解患者关节炎症,并改善关节功能.     

Effect of actarit combination therapy in patients with active rheumatoid arthritis resistant to gold agents]

We investigated the utility of combination therapy of actarit with gold agents in patients with active rheumatoid arthritis resistant to gold agents even after the administration of gold agents for longer than 24 weeks in principle. 1. In the final global improvement rate by the combination therapy of actarit with gold agents, the ratio of "improved" and/or better was 30.8% (12/39). 2. The clinical evaluation items which showed significant improvement were grip strength, ESR, number of painful joints, number of swollen joints, active joint count, duration of morning stiffness and Lansbury's activity index. 3. ADRs were observed in 6 patients per 75 patients (8.0%), but there was no serious ADR.     

Functional disability and health-related quality of life in South Africans with rheumatoid arthritis and systemic lupus erythematosus

There is a paucity of data on the impact of chronic rheumatic diseases on functional disability and overall health-related quality of life (HRQOL) in Africans. Materials and methods: We compared Black South Africans (BSA) with rheumatoid arthritis (RA) (n=50) and systemic lupus erythematosus (SLE) (n=50) to geographically and ethnically matched controls cared for at a tertiary care facility. The modified health assessment questionnaire (mHAQ) and Medical Outcome Study short-form 36 (SF-36) scores and indices of disease activity and organ damage were collected from each group. Results: Compared to the controls, both the RA and SLE groups fared significantly worse in respect of all the domains and summary scales of the SF-36. Compared to the SLE group, the RA group scored significantly worse with respect to the mHAQ disability index (mHAQ-DI), physical function and bodily pain (BP) SF-36 subscales, and SF-36 summary physical component score (SF-PCS). In the RA group, both the mHAQ-DI and SF-PCS correlated strongly (p<0.005) with the tender joint count, patient global assessment, 28-joint composite disease activity score, physician global assessment, and pain score. The SF-PCS showed only a weak inverse correlation with the swollen joint count (r=−0.29, p<0.05). In the SLE group, the systemic lupus erythematosus disease activity index correlated inversely best with the SF-36 general health subscale (r=−0.56, p<0.0001) and, to a lesser extent, with the mental health, BP, and vitality subscales, and SF-PCS and SF-mental component summary scores. Conclusion: Both RA and SLE have profound effects on HRQOL in BSA, with BP and physical disability particularly worse in RA patients. Disease activity, rather than organ damage or sociodemographic characteristics, correlates best with certain aspects of functional disability and HRQOL in both RA and SLE. Further longitudinal studies are needed to assess the clinical utility of measures of functional disability and HRQOL in this population.     

Immediate and delayed effects of treatment at the Dead Sea in patients with psoriatic arthritis

The purpose of this study was to evaluate the immediate and delayed effects of balneotherapy at the Dead Sea on patients with psoriatic arthritis (PsA). A total of 42 patients with PsA were treated at the Dead Sea for 4 weeks. Patients were randomly allocated into two groups: group 1 (23 patients) and group 2 (19 patients). Both groups received daily exposure to sun ultraviolet rays and regular bathing at the Dead Sea. Group 1 was also treated with mud packs and sulfur baths. Patients were assessed by a dermatologist and a rheumatologist 3 days before arrival, at the end of treatment, and at weeks 8, 16, and 28 from the start of treatment. The clinical indices assessed were morning stiffness, right and left hand grip, number of tender joints, number of swollen joints, Schober test, distance from finger to floor when bending forward, patient's self-assessment of disease severity, inflammatory neck and back pain and psoriasis area and severity index (PASI) score. Comparison between groups disclosed a similar statistically significant improvement for variables such as PASI, morning stiffness, patient self-assessment, right and left grip, Schober test and distance from finger to floor when bending forward. For variables such as tender and swollen joints, and inflammatory neck and back pain, improvement over time was statistically significant in group 1. Addition of mud packs and sulfur baths to sun ultraviolet exposure and Dead Sea baths seems to prolong beneficial effects and improves inflammatory back pain. Received: 27 April 1999 / Accepted: 23 September 1999     

血清抗角蛋白抗体抗环瓜氨酸肽抗体和类风湿因子在类风湿关节炎中的意义

目的 评价抗角蛋白抗体(AKA)、抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)在类风湿关节炎(RA)中的意义.方法 收集82例RA患者及56例非RA患者,测定其抗CCP抗体、AKA和RF水平,评价对RA诊断的敏感性、特异性,比较RA患者中抗CCP抗体、AKA阳性组和阴性组的压痛关节数、肿胀关节数、红细胞沉降率(ESR)、C反应蛋白(CRP)、疾病活动指数(DAS)、Ritchie's指数(RAI).结果 单独检测AKA、抗CCP抗体、RF及联合检测的曲线下面积都较高(P<0.05).抗CCP抗体、AKA的特异度分别为92.9%、91.1%,联合检测AKA、抗CCP抗体和RF有任何一种及以上阳性的灵敏度最高,为95.1%.抗CCP抗体阳性组与阴性组的关节肿胀数、关节压痛数、ESR、CRP、DAS、RAI差异有统计学意义(P<0.05);AKA阳性组与阴性组的关节肿胀数、ESR、DSA差异均有统计学意义(P<0.05).结论 联合检测抗CCP抗体、RF、AKA对诊断RA有意义,抗CCP抗体、AKA可能与RA的活动度相关.     

The effect of methotrexate on bone metabolism markers in patients with rheumatoid arthritis

Abstract

The aim of the present study was to evaluate the influence on urinary excretion levels of N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD) as a useful marker for bone resorption, and on serum-bone alkaline phosphate (BAP) levels as a useful marker for bone formation and an early marker of osteoblast differentiation in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Thirty patients with RA, diagnosed according to the criteria of the American College of Rheumatology, were involved in this study between March 2003 and January 2005. None of the patients had a history of hormone (estrogen) replacement therapy. All patients were treated with MTX. Methotrexate was administered perorally at a dosage of 4–10?mg/week. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, 3 months and 6 months after the initial treatment. Then the levels of NTX and DPD in urine and BAP in serum were measured in all patients. For comparison with the effect of other DMARDs on bone metabolism markers in RA patients, we measured the levels of NTX and DPD in urine and BAP in serum of RA patients, 13 patients treated with salazosulfapyridine (SASP), and 14 patients treated with actarit (ACT). In patients treated with MTX, NTX levels decreased significantly at 3 months after the initial treatment and remained low at 6 months after the initial treatment, and DPD levels significantly decreased at 6 months after the initial treatment. The mean serum BAP levels changed without significant differences from the baseline at 3 months and 6 months. In patients treated with SASP and ACT, all bone metabolism markers had not changed significantly at the three time points. On disease activity erythrocyte sedimentation rate, C-reactive protein, the number of swollen joints and tender joints, and mHAQ score decreased significantly at 3 months after the initial treatment, and remained at low levels at 6 months after the initial treatment with MTX. Methotrexate therapy looks promising in inhibiting generalized bone loss in patients with RA. In addition, NTX is a more sensitive marker than DPD.     

Bone resorption and inflammatory inhibition efficacy of intermittent cyclical etidronate therapy in rheumatoid arthritis

OBJECTIVE: Osteoclast activation or cartilage and bone destruction are developed in patients with rheumatoid arthritis (RA). The efficacy of etidronate with respect to osteoporosis, inhibition of bone resorption and destruction, and antiinflammation in RA was examined for 72 weeks. METHODS: Sixty-three patients with RA (56 women, 7 men) were divided into a group that received intermittent cyclical etidronate therapy (ICET) (31 patients) and a non-ICET group (32 patients). Over a 72 week followup period, the urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), bone mineral density (BMD), Larsen damage score, Lansbury activity index, and concentrations of serum C-reactive protein (CRP) and serum interleukin 6 (IL-6) of the 2 groups were compared. RESULTS: In the non-ICET group, a significant decrease in BMD and a significant increase in the Larsen damage score were observed. In the ICET group, the level of DPD started to decrease 12 weeks after etidronate administration and progression of the Larsen damage score was significantly inhibited. IL-6 concentration was significantly decreased 72 weeks after etidronate administration. Concentrations of BAP and CRP and the Lansbury activity index were not significantly different between the ICET and the non-ICET groups. A significant correlation between the IL-6 and DPD concentrations was observed. CONCLUSION: Etidronate was effective at inhibiting bone resorption and destruction in study patients with RA, while not increasing BAP concentrations; and a correlation was observed between the concentration of DPD and IL-6, indicating the antiinflammatory effect of etidronate.     

Pain and joint mobility explain individual subdimensions of the health assessment questionnaire (HAQ) disability index in patients with rheumatoid arthritis

OBJECTIVE: To explore the associations between individual subdimensions of the health assessment questionnaire (HAQ) and clinical variables in patients with rheumatoid arthritis. METHODS: 304 patients with rheumatoid arthritis (73% female, mean (SD) age, 58 (13) years; disease duration 6 (9) years, 69% rheumatoid factor positive) completed the HAQ for functional capacity (0-3) and a 100 mm visual analogue scale for pain. Grip strength, range of motion of the large joints, Larsen score for radiographic damage of hand and foot joints, and the number of tender and swollen joints were recorded. A logit regression model was used to study associations between subdimensions of the HAQ and other variables. RESULTS: Mean (range) total HAQ score was 0.92 (0 to 2.88) and varied from 0.73 to 1.04 in the subdimensions. Disability was lowest in the "walking" and highest in the "reach" subdimension. Pain was an explanatory variable in all individual subdimensions. Decreased grip strength, limitation of shoulder and wrist motion, and a larger number of swollen and tender joints in the upper extremities were related to several subdimensions. A higher pain score and swollen joint count in the upper extremities, decreased grip strength, and limited motion of wrist, shoulder, and knee joints explained increased disability (higher total HAQ scores). CONCLUSIONS: In patients with rheumatoid arthritis, pain and range of movements of joints have the greatest impact on individual subdimensions of the HAQ. Extent of radiographic damage in peripheral joints and the number of swollen and tender joints are of lesser importance for function.