Short-term treatment with a gonadotropin-releasing hormone antagonist, cetrorelix, in rheumatoid arthritis (AGRA): a randomized, double-blind, placebo-controlled study.

OBJECTIVES: Gonadotropin-releasing hormone (GnRH) stimulates immune responses; therefore, antagonizing GnRH with cetrorelix may have anti-inflammatory effects. The aim of this study was to assess short-term cetrorelix therapy in rheumatoid arthritis (RA) patients. METHOD: In this proof-of-concept, randomized, double-blind study involving 99 patients with active, long-standing RA, 48 patients received subcutaneous cetrorelix (5 mg/day on days 1 and 2; 3 mg/day on days 3-5) and 51 received placebo. The primary end-point was the change in the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) by day 5, when the greatest GnRH suppression was anticipated. Secondary end-points included the change in tumour necrosis factor (TNF)-α, and achievement of American College of Rheumatology (ACR) responses and DAS28-CRP < 2.6 by day 5. Patients were followed up on days 10 and 15. RESULTS: By day 5, DAS28-CRP was non-significantly reduced by 0.82 in the cetrorelix group compared to a 0.57 reduction in the placebo group (p = 0.091), TNF-α (log pg/mL) was significantly reduced in the cetrorelix group compared with the placebo group [0.55, 95% confidence interval (CI) 0.08-1.01, p = 0.023], and more patients on cetrorelix achieved ACR20 responses (40% vs. 18%, p = 0.015) and DAS28-CRP < 2.6 (13% vs. 0%, p = 0.009). Inflammatory markers increased towards baseline levels after withdrawal of treatment. Rates of adverse events were similar in both groups. CONCLUSIONS: Although there was no significant difference in the primary end-point between groups, antagonizing GnRH led to significant improvements in key secondary end-points. Thus, GnRH antagonists may have rapid anti-inflammatory effects in RA, already occurring within 5 days. The data suggest a novel mode of action for TNF-α inhibition in RA, and potentially in other autoimmune diseases.

The association of luteinizing hormone and follicle-stimulating hormone with cytokines and markers of disease activity in rheumatoid arthritis: a case-control study.

OBJECTIVES: Disease activity in rheumatoid arthritis (RA) varies substantially during periods when luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels change, for example during pregnancy, postpartum, and menopause. We wanted to investigate whether small fluctuations in these hormones could be associated with similar fluctuations in cytokines and disease activity in RA. METHODS: Disease activity markers, serum LH, FSH, and 24 cytokines were assessed on days 1 and 8 in 20 RA patients (median age 58 years, six males) and 19 controls (median age 56 years, six males). RESULTS: Percentage changes in LH and FSH correlated positively with percentage changes in key proinflammatory cytokines such as tumour necrosis factor (TNF)alpha (LH r = 0.737, p = 0.0007; FSH r = 0.680, p = 0.001) and interleukin (IL)-1beta (LH r = 0.515, p = 0.050; FSH r = 0.749, p = 0.0008). Similar correlations were observed with IL-2, IL-2R, IL-8, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and eotaxin, but not with the anti-inflammatory cytokine IL-10, in RA and not in controls. Percentage changes in LH, FSH, and cytokines were not correlated with percentage changes of several disease activity markers but were correlated positively with cross-sectional levels of disease activity markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Visual Analogue Scale (VAS) pain, VAS global (physician/patient), and the modified Health Assessment Questionnaire (MHAQ)]. CONCLUSIONS: The significant associations between percentage changes in LH and FSH and percentage changes in key cytokines and several cross-sectional markers of disease activity may indicate that LH and FSH influence crucial points of the cytokine cascade in RA. This may help to explain, partially, why disease activity initiates or worsens during periods of increased LH and FSH, such as the postpartum period and the menopause.

Low-energy distal radius fractures in middle-aged and elderly men and women--the burden of osteoporosis and fracture risk : A study of 1794 consecutive patients.

UNLABELLED: One third of 218 men and half of 1,576 women with low-energy distal radius fractures met the bone mineral density (BMD) criteria for osteoporosis treatment. A large proportion of patients with increased fracture risk did not have osteoporosis. Thus, all distal radius fracture patients >or=50 years should be referred to bone densitometry. INTRODUCTION: Main objectives were to determine the prevalence of patients with a low-energy distal radius fracture in need of osteoporosis treatment according to existing guidelines using T-score or=50 years were included. BMD was assessed by dual energy X-ray absorptiometry (DXA) at femoral neck, total hip, and lumbar spine (L2-L4). The WHO fracture risk assessment tool (FRAX(R)) was applied to calculate the 10-year fracture risk. RESULTS: T-scores or=50 years should be referred to bone densitometry, and if indicated, offered medical treatment.

[Myalgia and high sedimentation rate in adults]. / Myalgi og høy senkning hos voksne.

The polymyalgic syndrome may be the presenting clinical feature for several diseases such as polymyalgia rheumatica, temporal arteritis, malignancy, rheumatoid arthritis, virus infections, connective tissue diseases, and myositis. In this review we present the various diagnostic options seen from a rheumatological point of view, with emphasis on polymyalgia rheumatica, temporal arteritis and the paraneoplastic syndrome. We are of the opinion that polymyalgia rheumatica is overdiagnosed in general practice, and steroid treatment may delay diagnosis and treatment of other differential diagnosis presenting as the polymyalgic syndrome. Several recently published Norwegian epidemiological studies offer new information on various aspects of the polymyalgic syndrome, which will be discussed.