Open study to evaluate etidronate influence on bone markers, inflammation and RANKL/OPG system in ankylosing spondylitis (AS) patients with active inflammation.
Effect of etidronate on number and metabolic activity of proinflammatory subpopulation of blood monocytes CD14+CD16+ in AS patients – a pilot study

Objective: The aim of the study was to assess the effect of etidronate (bisphosphonate) on bone markers, inflammatory markers and RANKL/OPG in male subjects with active ankylosing spondylitis (AS). To explore the influence of etidronate on number and metabolic activity of proinflammatory subpopulation of blood monocytes CD14+CD16+ in AS patients.
Material and methods: Etidronate (two 14-days cycles) was administered in a group of 25 men fulfiling New York AS criteria and having elevated ESR and/or CRP values. Osteocalcin (OC, formation marker), telopeptid b-CTx (CTX, resorption marker), soluble receptor activator of nuclear factor kB ligand (sRANKL) and osteoprotegerin (OPG) were assayed before and after each cycle of treatment.
Results: The statistically significant decrease of CTX, OC and CRP, a non statistically significant elevation of OPG and reduction of sRANKL after etidronate treatment were observed. There were no correlation between bone markers and CRP, sRANKL and OPG as well as between CRP and sRANKL and OPG. Statistically significant correlation between sRANKL/OPG ratio before treatment and after 1st and 2nd cycle were found. No difference between number of proinflammatory monocytes (CD14+ CD16+) and classic monocytes (CD14++CD16–) were found before and after etidronate treatment with regard to the true number of cells in blood. Following PHA stimulation the avarage 80-fold increase in IL-10 production and only 40-fold rise in TNF-α were observed after 1. cycle of etidronate in PHA-stimulated peripheral blood mononuclear cells of patients, in comparison to cytokine production straight before the first run of etidronate.
Conclusions:
1. Etidronate has anti-resorptive and anti-inflammatory properties in men with AS.
2. There was no correlation between CRP and bone markers, sRANKL, OPG and sRANKL/OPG ratio which may suggest a lack of relationship between inflammation and bone remodeling in AS.
3. Etidronate treatment does not influence the number of proinflammatory monocytes CD14+CD16+ in peripheral blood and increases the PHA-stimulated cytokine production by peripheral blood mononuclear cells, with prevalent immunosuppressive IL-10 synthesis.