ab1901

Influence of cyclic intravenous pamidronate on proinflammatory monocytic cytokine profiles and bone density in rheumatoid arthritis treated with low dose prednisolone and methotrexate

J.F. Van Offel, A.J. Schuerwegh, C.H. Bridts, P.G. Bracke¹, W.J. Stevens, L.S. De Clerck

Department of Immunology, Allergology and Rheumatology; ¹Department of Radiology, University of Antwerp, Belgium

ABSTRACT
Objectives
The aim of this work was to evaluate in a randomised double-blind prospective study the effect of pamidronate on intracellular monocytic cytokine profiles (IL-1, IL-6, TNF-a) and bone density in rheumatoid arthritis patients.

Methods
Twenty rheumatoid arthritis patients were treated for one year with methotrexate and a low dose of prednisolone. Double blind randomisation was performed for either IV pamidronate (at 3-month intervals) or placebo. The effect of pamidronate was evaluated on intracellular cytokine profiles (IL-1, IL-6, TNF-a), disease activity and bone mass measurements. The human monocytic cell line THP-1 was used to evaluate in vitro apoptosis by pamidronate.

Results
Spontaneous production of interleukin-1b by patient blood monocytes was lower in the pamidronate group and was associated with an increase in bone density of the spine after 12 months of therapy. In vitro a dose-related increase in pamidronate induced apoptosis was found in THP-1 cells.

Conclusions
This prospective double-blind randomised study demonstrated that pamidronate therapy resulted in an increase of bone density despite treatment with steroids. This rise is associated with a suppression of interleukin-1b production in monocytes of patients treated with pamidronate. Our in vitro experiments suggest that this anti-inflammatory effect could be due to an increase in the apoptosis of monocytic cells.

Key words
Rheumatoid arthritis, bisphosphonates, pamidronate, inflammation, osteoporosis, cytokines, monocytes, apoptosis, necrosis.

Please address correspondence and reprint requests to: Wim J. Stevens, PhD, University Hospital of Antwerp, Department of Immunology, Allergology and Rheumatology, Wilrijkstraat 10, B2650 Edegem, Belgium.
E–mail: stevens@uia.ua.ac.be