Influence of cyclic intravenous pamidronate on proinflammatory monocytic cytokine profiles and bone density in rheumatoid arthritis treated with low dose prednisolone and methotrexate.
OBJECTIVE
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-alpha) 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 i.v. pamidronate (at 3-month intervals) or placebo. The effect of pamidronate was evaluated on intracellular cytokine profiles (IL-1, IL-6, TNF-alpha), 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-1 beta 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-1 beta 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.
Van Offel
J F
JF
Department of Immunology, Allergology and Rheumatology, University of Antwerp, Belgium.
Schuerwegh
A J
AJ
Bridts
C H
CH
Bracke
P G
PG
Stevens
W J
WJ
De Clerck
L S
LS
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001799:Blood Sedimentation / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D002097:C-Reactive Protein / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D000077268:Pamidronate; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D011446:Prospective Studies; D011897:Random Allocation
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004164:Diphosphonates; D007166:Immunosuppressive Agents; D002097:C-Reactive Protein; D011239:Prednisolone; D000077268:Pamidronate; D008727:Methotrexate