Differences in Bone Cell Activity Between Rheumatoid Arthritis and Ankylosing Spondylitis

Objectives:

1. Assess the influence of immune system cells in the modulation of bone turnover in patients with RA, AS and healthy donors (Task 2).
2. Analyze the osteoclast precursors and their differentiation into fully functional osteoclasts in a subgroup of patients with RA, AS and healthy donors (Task 3, 4 and 6).
3. Study osteoblast differentiation potential and activity in a subgroup of patients with RA and AS (Task 5 and 6)
4. Assess the effect of the therapy on bone cell differentiation and function in a subgroup of patients with RA and AS treated with TNF-blockers (Task 2, 3, 4 and 5).

Work program and timetable Starting date: July 2011. Finishing date: July 2013 Task 1 - Patients Patients with RA diagnosis (according to the revised American Rheumatism Association criteria, 1988) and AS diagnosis (according to the European Spondyloarthropathy Study Group criteria, 1991) followed up in the Rheumatology and Bone and Metabolic Diseases Department of Hospital de Santa Maria (HSM) will be recruited for this study. Twenty-five patients with active RA (Disease Activity Score 28 (DAS28)>3.2) and 25 patients with active AS (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)>4) will be included in the study. Fifteen healthy donors, sex and age matched, will be recruited and used as a control group.

Patients will be submitted to a clinical protocol that includes information on sex, age, disease duration, previous therapies, presence of rheumatoid factor and anti cyclic-citrullinated peptide antibodies, Human Leukocyte Antigen (HLA)-B27 status, DAS28 score and Health Assessment Questionnaire - HAQ (Health Assessment Questionnaire, for RA patients), BASDAI, Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Bath Ankylosing Spondylitis Functional Index - BASFI (for AS patients) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Blood will be collected from patients before starting treatment with glucocorticoids and disease-modifying anti-rheumatic drugs (DMARDs: methotrexate, sulphasalazine and leflunomide) and 3 months after reaching a stable dose of these drugs. For those that latter on start TNF-blockers blood samples will be collected after 6 months of starting therapy. Because it is expected that only a minority of this initial cohort will need to be treated with TNF antagonists, a second group of 25 RA and 25 AS patients, selected for starting TNF antagonists, will be assessed before starting the drug and 6 months later.

Written informed consent will be obtained from all patients prior to any protocol-specific procedure and this study will be conducted in accordance with the regulations governing clinical trials such as the Declaration of Helsinki, as amended in Tokyo (2004). This study was approved by HSM Ethics Committee.