Increase of bone mineral density and anabolic variables in patients with rheumatoid arthritis resistant to methotrexate after cyclosporin A therapy.

Abstract

To determine the bone mineral density (BMD) and anabolic variables in a cohort of patients with severe, early rheumatoid arthritis (RA) resistant to weekly doses of methotrexate (MTX), after addition of cyclosporin A (CyA) therapy. We studied 10 rheumatoid factor positive patients of 58 with early erosive, aggressive RA with poor response to a 6 month course of MTX (< 20% improvement in the American College of Rheumatology core set of criteria). BMD was assessed at entry, after 6 months of MTX, and after a further 6 months of combination therapy of MTX plus CyA. Bone Gla protein (BGP) dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor-1 (IGF-1, somatomedin C) levels were determined along with clinical variables and acute phase reactants (C-reactive protein, erythrocyte sedimentation rate). An average BMD decline of 4.05 +/- 0.8% (mean, SD) occurred in the first 6 months of MTX treatment, along with a statistically significant decline of IGF-1 (-24.8%), DHEAS (-21.6%), and BGP (-19.7%) levels. After adding CyA 3 mg/kg daily for 6 months, BMD had increased by 3.9 +/- 0.97%, IGF-1 by 42.4%, DHEAS by 34.2%, BGP by +34.3%. These changes mirrored the clinical variables (Health Assessment Questionnaire, morning stiffness, joint count) and acute phase reactants, which improved in a statistically significant manner. Patients with active RA, even in the early phases, lose bone very rapidly. Effective control of systemic inflammation allowed a rapid rescue of BMD, at least in the short term. This happened with a simultaneous increase in some anabolic variables such as IGF-1, BGP, and DHEAS.