Birgitta Tengstrand

The foot: still the most important reason for walking incapacity in rheumatoid arthritis: Distribution of symptomatic joints in 1,000 RA patients

Background and purpose Our knowledge of frequency of foot involvement in rheumatoid arthritis (RA) is still often based on a study from Finland in 1956. Great changes in the treatment of RA may have led to a different situation. We investigated the distribution of joint involvement in RA patients today, with special attention given to the feet and subjective walking ability. Methods 1,000 RA patients answered a questionnaire concerning joints affected, joint surgery, foot problems, and subjectively experienced reasons for walking incapacity. Results In 45% of the patients, the forefoot was involved at the start of the disease. In 17%, the hindfoot/ankle was involved at the start. Only hand symptoms were commoner. 80% of patients reported current foot problems, 86% in the forefoot and 52% in the hindfoot/ankle. Difficulty in walking due to the feet was reported by 71%. For 41% of patients, the foot was the most important part of the lower extremity causing reduced walking capacity, and for 32% it was the only part. Interpretation After the hand, the foot was the most frequently symptomatic joint complex at the start of the disease, but also during active medical treatment. The foot caused walking disability in three-quarters of the cases and—4 times as often as the knee or the hip—it was the only joint to subjectively impair gait.

Cachexia in rheumatoid arthritis is associated with inflammatory activity, physical disability, and low bioavailable insulin‐like growth factor

Objectives: To examine the impact of inflammation, insulin‐like growth factor (IGF‐1) and its regulating binding protein (IGFBP‐1) on lean body mass (LBM) in patients with rheumatoid arthritis (RA). Methods: In 60 inpatients (50 women), inflammatory activity was measured by Disease Activity Score 28 (DAS28), C‐reactive protein (CRP), and interleukin (IL)‐6, and physical disability by the Health Assessment Questionnaire (HAQ). LBM was assessed by dual‐energy X‐ray absorptiometry (DXA) and fat free mass index (FFMI; kg/m2) and fat mass index (FMI; kg/m2) were calculated. Results: Median age was 65 years and disease duration 13 years. Fifty per cent of the patients had FFMI below the 10th percentile of a reference population and 45% had FMI above the 90th percentile, corresponding to the condition known as rheumatoid cachexia (loss of muscle mass in the presence of stable or increased FM). DAS28, CRP, and IL‐6 correlated negatively with LBM (p = 0.001, 0.001, and 0.018, respectively), as did HAQ (p = 0.001). Mean (confidence interval) IGF‐1 was in the normal range, at 130 (116–143) μg/L. IGFBP‐1 levels were elevated in patients (median 58 µg/L in women and 59 µg/L in men) compared with a normal population (33 µg/L in women and 24 µg/L in men). The ratio IGF‐1/IGFBP‐1, which reflects bioavailable IGF‐1, was low (2.0 µg/L) and was positively correlated with LBM (p = 0.015). In multiple regression analysis, 42% of the LBM variance was explained by IGF‐1/IGFBP‐1, HAQ score, and DAS28. Conclusion: A large proportion of RA inpatients, mainly women, had rheumatoid cachexia. The muscle wasting was explained by inflammatory activity and physical disability as well as low bioavailable IGF‐1.

Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months

IntroductionRheumatoid arthritis (RA) is associated with changes in body composition and bone mineral density (BMD). The purpose of the present study was to evaluate whether anti-TNF treatment in early RA has an impact on body composition and BMD besides that which could be achieved by intensive disease-modifying anti-rheumatic drug (DMARD) combination therapy.MethodsForty patients with early RA who failed treatment with methotrexate up to 20 mg/week for 3 months were randomised to addition of sulphasalazine and hydroxychloroquine (treatment A) or addition of infliximab (treatment B). At 3, 12 and 24 months, body composition and BMD were assessed by total-body dual-energy X-ray absorptiometry. At the same time points, leptin, adiponectin, apolipoproteins, insulin-like growth factor-1 (IGF-1) and markers of bone remodelling were analysed. Compliance to treatment was considered in the analyses. Data were analysed with a mixed, linear model.ResultsPatients treated with anti-TNF had a significant increase in fat mass at 2 years, 3.8 (1.6 to 5.9) kg, in contrast to patients in treatment A, 0.4 (-1.5 to 2.2) kg (P = 0.040), despite similar reduction in disease activity. Both treatment strategies prevented loss of muscle mass and bone. Leptin concentrations increased significantly in both groups at 2 years and adiponectin increased significantly at 2 years in treatment A and at 1 year in treatment B. There were no significant changes in apolipoproteins or IGF-1. The markers of bone resorption decreased at 12 months in both treatment groups with no significant difference between the treatment groups.ConclusionsInfliximab therapy increased body fat mass, an effect that was not achieved with the combination of DMARDs, despite a similar reduction in disease activity, and thus seemed to be drug specific. The increase of fat mass was not associated with an exacerbated atherogenic lipid profile. Leptin and adiponectin concentrations increased in both treatment groups. The increase of adiponectin may partially explain the reduced frequency of cardiovascular diseases found when disease activity is reduced in RA.Trial registrationISRCTN39045408.

Gonadal hormones in men with rheumatoid arthritis--from onset through 2 years.

Objective. To evaluate changes over a 2-year course in the hypothalamic-pituitary-gonadal (HPG) axis in men with early rheumatoid arthritis (RA) from start of treatment with disease modifying antirheumatic drugs. Methods. Forty-one men with early RA and with joint symptoms less than 1 year were studied. Mean age at inclusion was 53 years and mean disease duration 6 months. They were followed prospectively for 2 years for disease activity [Disease Activity Score 28 (DAS28)], physical impairment (Health Assessment Questionnaire), total serum testosterone, non-sex hormone-binding globulin-bound testosterone, and luteinizing hormone (LH). A group of 131 healthy, medicine-free men served as controls for baseline hormone concentrations. Results. The men with RA already had mean testosterone levels lower than controls early in the disease course. Patients older than 50 years also had significantly lower LH levels compared with controls, consistent with mild hypogonadotropic hypogonadism. In patients who responded to treatment at the 2-year followup the testosterone levels increased significantly. A decrease in DAS28 during the 2 years correlated significantly with increased testosterone levels (rs = −0.46, p = 0.006). LH levels were low and stable and did not correlate with disease activity. Conclusion. In early RA, current inflammation seemed to affect the HPG axis, mainly at the gonadal rather than the hypothalamic-pituitary level. Prospective studies are indicated to determine if low HPG activity may be a cause rather than a consequence of a chronic inflammatory state.

Impact of low-dose prednisolone on bone synthesis and resorption in early rheumatoid arthritis: experiences from a two-year randomized study

IntroductionPatients with rheumatoid arthritis (RA) have an increased frequency of osteoporosis, mainly because of increased bone resorption. Reduction of disease activity is suggested to reduce bone remodelling. It might also be possible that prednisolone treatment could cause this effect because prednisolone has been shown to arrest the development of joint destruction in early RA. Therefore, we examined the effects of low-dose prednisolone on serum concentrations of bone remodelling markers and insulin-like growth factor-1 (IGF-1) in RA patients in relation to bone mineral density.MethodsOne hundred and fifty patients, 67% women, with early RA, mean disease duration of six months (95% confidence interval (CI) = three to eight months), who had participated in the BARFOT (Better Anti-Rheumatic FarmacOTherapy) low-dose prednisolone study were included. They had been randomised to either the P-group, who were treated with 7.5 mg prednisolone daily (n = 70, mean age = 51 years, 95% CI 48 to 54 years), or the NoP-group, who received no prednisolone (n = 80, mean age 58 years, 95% CI 56 to 61 years), when they started their first disease-modifying anti-rheumatic drug (DMARD). Serum samples were analysed at baseline, 3 and 12 months for procollagen type I N-terminal propeptide (P1NP), a marker of bone formation, and the C-telopeptide crosslaps of type I collagen (CTX-1) and C-terminal telopeptide of type I collagen (1CTP), markers of bone degradation. IGF-1 was analysed at baseline and after 12 months. Bone mineral density at the lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry at baseline and after 24 months.ResultsLevels of P1NP decreased rapidly in the P-group (p < 0.001). Levels of CTX-1 and 1CTP decreased in both treatment groups, but significantly more in the P-group (differences between groups p < 0.019 and p < 0.001, respectively). IGF-1 increased in the P-group (p < 0.001) but remained stable in the NoP-group. Bone mineral density decreased in the spine in both groups, significantly more in postmenopausal women from the P-group. Femur bone mineral density only decreased in the NoP-group.ConclusionsLow-dose prednisolone in early RA counteracts the negative impact of rheumatoid inflammation on bone tissue in the hip, a juxta-articular localisation. Thus bone mineral density was preserved in the femur in the P-group and 1CTP decreased rapidly. However, the systemic inflammatory consequences on bone could not be prevented in the lumbar spine, especially not in postmenopausal women, probably because of the combined effect of suppression of bone synthesis by prednisolone and the postmenopausal status.

Randomized withdrawal of long‐term prednisolone treatment in rheumatoid arthritis: effects on inflammation and bone mineral density

Objective: Short‐term, low‐dose glucocorticoid (GC) treatment has anti‐inflammatory and disease‐modifying effects in rheumatoid arthritis (RA). However, scientific support for long‐term, low‐dose GC treatment, although widespread, is poor, and information on the effects on bone density is scarce. The aim of this study was to investigate how long‐term GC treatment in RA affects inflammation as well as bone density, and also to investigate the feasibility of withdrawal of GC. Patients and methods: Fifty‐eight patients with RA treated with 5–7.5 mg prednisolone daily for at least 2 years were randomized either to withdraw or to continue GC treatment. The patients were followed prospectively for 2 years with respect to disease activity [using the Disease Activity Score calculated for 28 joints, (DAS28)], functional ability [using the Health Assessment Questionnaire (HAQ) score] and bone mineral density (BMD) of the lumbar spine and hip. Results: Only 11 patients out of 26 randomized to stop GC treatment and available for outcome measures succeeded in stopping the GC medication within 1 year. Fifteen patients failed withdrawal of GC because of increased joint symptoms. A higher mean DAS28 during the study was associated with loss of bone mass in the trochanter. The group that continued with unchanged GC treatment did not deteriorate in BMD during the 2 years but in fact Z‐scores improved significantly. Conclusion: Our results indicate that low‐dose GC treatment after several years has persisting anti‐inflammatory effects in RA and no further negative impact on BMD. It thus seems to be more important to control disease activity than withdraw low‐dose GC treatment in this population considering bone health.

Treatment with low-dose prednisolone is associated with altered body composition but no difference in bone mineral density in rheumatoid arthritis patients: a controlled cross-sectional study

Objectives: To determine whether low-dose prednisolone affects body composition and bone mineral density (BMD) in patients with rheumatoid arthritis (RA), also considering inflammation and physical disability. Methods: This cross-sectional study included 100 patients (50 women) with RA with a median (IQR) disease duration of 8 (4–15) years. Fifty patients had been treated with prednisolone (5–7.5 mg) for at least 2 years (the P-group) and 50 patients matched for gender and age had not (the NoP-group). Body composition and BMD were assessed by dual‐energy X-ray absorptiometry (DXA). Disease activity (28-joint Disease Activity Score, DAS28) and physical disability (Health Assessment Questionnaire, HAQ) were assessed. Results: The total patient group had increased fat mass (FM) and a high trunk:peripheral fat ratio, of which 38% had a fat free mass index (FFMI, kg/m2) below the 10th percentile of a reference population. The P-group had significantly higher FM but similar lean body mass (LBM) and BMD compared with the NoP-group. In multivariate analyses, treatment with prednisolone and a higher HAQ score were significantly and independently associated with higher FM but not with LBM. Higher C-reactive protein (CRP) was independently associated with lower LBM. Higher HAQ score and low weight were significantly and independently associated with lower BMD at femoral neck and lumbar spine. Conclusions: RA patients treated with low-dose prednisolone had significantly higher FM than patients without prednisolone, an effect that was independent of current inflammation. However, there was no association between prednisolone treatment and muscle mass or BMD. Thus, the net effect of prednisolone on body composition and bone is different in inflammatory diseases such as RA.