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

Objectives The aim of this work was to evaluate in a randomised double-blind prospecti ve study the effect of pamidronate on intracellular monocytic cytokine prof iles (IL-1, IL-6, TNF-alpha) and bone density in rheumatoid arthritis patie nts. Methods Twenty rheumatoid arthritis patients were treated for one year with methotr exate and a low dose of prednisolone. Double blind randomisation was perfor med 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-alpha), disease activity and bone mass measurements. The human monoc ytic cell line THP-I 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 the spine after 12 months of therapy. In vitro a dose-relat ed increase in pamidronate induced apoptosis was found in THP-I cells. Conclusions This prospective double-blind randomised study demonstrated that pamidronat e therapy resulted in an increase of bone density despite treatment with st eroids. This rise is associated with a suppression of interleukin-1 beta pr oduction in monocytes of patients treated with pamidronate. Our in vitro ex periments suggest that this anti-inflammatory effect could be due to an inc rease in the apoptosis of monocytic cells.