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


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Ferraccioli
G
G
Department of Internal Medicine, School of Medicine, University of Udine, Italy.
Casatta
L
L
Bartoli
E
E
D000209:Acute-Phase Proteins / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D015519:Bone Density / Q000187:drug effects*; D002097:C-Reactive Protein / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007596:Joints / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood*; D019233:Retreatment
D000209:Acute-Phase Proteins; D015675:Osteocalcin; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I; D016572:Cyclosporine; D002097:C-Reactive Protein; D008727:Methotrexate