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
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Online publication date: 2009-10-19
Reumatologia 2009;47(4):212-222
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.
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.
Sieper J. Developments in the scientific and clinical undestanding of the spondyloarthritides. Arthritis Res Ther 2009; 11: 208. .
Schett G. Osteoimmunology in rheumatic diseases. Arthritis Res Ther 2009; 11: 210. .
Toussirot E, Dumoulin G, Nguyen N, et al. Changes in bone cell enzymatic activities in ankylosing spondylitis and relationship with the inflammatory proces. Arthritis Rheum 2006; 54: S466. .
Lories R, Luyten F, de Vlam K. Progress in spondylarthritis. Mechanism of new bone formation in spondyloarthritis. Arthritis Res Ther 2009; 11: 221. .
Johnson ML, Kamel MA. The Wnt signaling pathway and bone metabolism. Curr Opin Rheumatol 2007; 19: 376-382. .
Lories R, Luyten F. Bone morphogenic proteins in destructive and remodelling arthritis. Arthritis Res Ther 2007; 9: 207. .
Loddenkemper K, Burmester GR. What is the rank of RANKL in spondylarthritis? Arthritis Rheum 2008; 58: 641-644. .
Toussirot E, Wendling D. Antiinflammatory treatment with bisphosphonates in ankylosing spondylitis. Curr Opin Rheumatol 2007; 19: 340-345. .
Osterman T, Kippo K, Laurén L, et al. Effect of clodronate on established collagen-induced arthritis in rats. Inflamm Res 1995; 44: 258-263. .
Herrak P, Görtz B, Hayer S, et al. Zoledronic acid protects against local and systemic bone loss in tumor necrosis factor-mediated arthritis. Arthritis Rheum 2004; 50: 2327-2337. .
Sims NA, Green JR, Glatt M, et al. Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen-induced arthritis. Arthritis Rheum 2004; 50: 2338-2346. .
Pan B, Farrugia AN, To LB, et al. The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-αlpha converting enzyme (TACE). J Bone Miner Res 2004; 19: 147-154. .
Pennanen N, Lapinjoki S, Urtti A, Mönkkönen J. Effect of liposomal and free bisphosphonates on the IL-1 beta, IL-6 and TNF alpha secretion from RAW 264 cells in vitro. Pharm Res 1995; 12: 916-922. .
Yamamoto K, Yoshino S, Shue G, Nagashima M. Inhibitory effect of bone resorption and inflammation with etidronate therapy in patients with rheumatoid arthritis for 3 years and in vitro assay in arthritis models. Rheumatol Int 2006; 26: 627-632. .
Francois RJ, Neure L, Sieper J, Braun J. Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases. Ann Rheum Dis 2006; 65: 713-720. .
Braun J, Baraliakos X, Zelder C. Clinical and histopathological findings in patients with ankylosing spondylitis before and after surgical treatment for axis correction and erection of the spine. Arthritis Rheum 2006; 54: S466. .
Bollow M, Enzweiler C, Taupitz M, et al. Use of contrast enhanced magnetic resonance imaging to detect spinal inflammation in patients with spondyloarthritides. Clin Exp Rheumatol 2002; 20: S167-S174. .
Cairns AP, Wright SA, Taggart AJ, et al. An open study of pulse pamidronate treatment in severe ankylosing spondylitis, and its effect on biochemical markers of bone turnover. Ann Rheum Dis 2005; 64: 338-339. .
Grover R, Shankar S, Aneja R, et al. Treatment of ankylosing spondylitis with pamidronate: an open label study. Ann Rheum Dis 2006; 65: 688-689. .
Haibel H, Brandt J, Rudwaleit M, et al. Treatment of active ankylosing spondylitis with pamidronate. Rheumatology (Oxford) 2003; 42: 1018-1020. .
Maksymowych WP, Jhangri GS, Leclercq S, et al. An open study of pamidronate in the treatment of refractory ankylosing spondylitis. J Rheumatol 1998; 25: 714-717. .
Maksymowych WP, Lambert R, Jhangri GS, et al. Clinical and radiological amelioration of refractory peripheral spondyloarthritis by pulse intravenous pamidronate therapy. J Rheumatol 2001; 28: 144-155. .
Toussirot E, Le Huédé G, Lohse A, et al. Transient efficacy of pulse pamidronate treatment in active spondylarthropathies: an open study of 35 cases. Clin Exp Rheumatol 2006; 24: 348. .
Maksymowych WP, Jhangri GS, Fitzgerald AA, et al. A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug-refractory ankylosing spondylitis. Arthritis Rheum 2002; 46: 766-773. .
Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol 2007; 81: 584-592. .
Meunier PJ, Confavreux E, Tupinon I, et al. Prevention of early postmenopausal bone loss with cyclical etidronate therapy (a double-blind, placebo-controlled study and 1-year follow-up). J Clin Endocrinol Metab 1997; 82: 2784-2791. .
Hesegava J, Nagashima M, Yamamoto M, et al. Bone resorption and inflammatory inhibition efficacy of intermittent cyclical etidronate therapy in rheumatoid arthritis. J Rheumatol 2003; 30: 474-479. .
Schett G. Joint remodelling in inflammatory disease. Ann Rheum Dis 2007; 66 (Suppl 3): iii42-iii44. .
van der Heijde D, Landewé R, Baraliakos X, et al.; Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy Study Group. Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 2008; 58: 3063-3070. .
van der Heijde D, Landewé R, Einstein S, et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 2008; 58: 1324-1331. .
Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007; 13: 156-163. .
Maksymowych WP, Chiowchanwisawakit P, Clare T, et al. Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis. Arthritis Rheum 2009; 60: 93-102. .
Kim HR, Kim HY, Lee SH. Elevated serum levels of soluble receptor activator of nuclear factors-kB ligand (sRANKL) and reduced bone mineral density in patients with ankylosing spondylitis (AS). Rheumatology 2006; 45: 1197-1200. .
Vandooren B, Cantaert T, Noordenbos T, et al. The abundant synovial expression of the RANK/RANKL/Osteoprotegerin system in peripheral spondylarthritis is partially disconnected from inflammation. Arthritis Rheum 2008; 58: 718-729.
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