THU0271 Increase in bone mineral density and decrease in WNT3A, OPG, CTX-I and osteocalcin in patients with ankylosing spondylitis treated with alendronate
Authors: H. Forsblad-d’Elia, M. Nurkkala, K. Zetterberg, E. Klingberg, H. Carlsten
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondylitis (AS) is associated with an increased prevalence of osteoporosis. The risk of vertebral fractures is elevated and these fractures can be complicated by neurological injuries. In addition, AS is characterised by an enhanced pathological new bone formation resulting in syndesmophyte formation in the spine. The knowledge of pharmacological treatment of osteoporosis in AS is limited. <h3>Objectives</h3> To investigate the effects of treatment with alendronate, 70 mg once weekly, and a daily dose of 500-1000 mg calcium and 400-800 IE vitamin D<sub>3</sub>on BMD and on biomarkers of bone metabolism in AS patients with osteoporosis, in a 2-year non-controlled prospective trial. <h3>Methods</h3> AS patients fulfilling the modified New York criteria of AS with BMD less than -2.5 SD, T-score in lumbar spine and/or hip alternatively BMD less than -2.0 SD in addition to at least one fragility fracture were included. The patients were investigated by dual energy X-ray absorptiometry (DXA) at base-line and annually thereafter. Blood-samples were obtained at baseline, after 1, 3, 6, 12, 18 and 24 months of treatment in the morning after an overnight fast. The samples were stored in -20° until the time of analysis. Serum levels of the biomarkers Wingless proteins (Wnt3a), Dickkopf-1 (Dkk-1), sclerostin, soluble receptor activator of nuclear factors-κB ligand (sRANKL), osteoprotegerin (OPG), degradation products of C-terminal telopeptides of Type-l collagen (CTX-I) and osteocalcin were measured with sandwich enzyme-linked immunosorbent assays (ELISA). Wilcoxon Signed Rank Test was applied for comparison with baseline values. <h3>Results</h3> Sixteen patients (50% women) with a mean age of 56.1±12.8 years, disease duration 18.7±11.4 years, median BASDAI score 4.2 range (1.3-8.1) and BASMI 4.4 (1.0-6.6) were included. Five patients dropped out during the 2 years. No severe adverse events occurred. BMD increased by 9.9±5.7% (p=0.003) in lumbar spine, 3.0±3.3% (p=0.016) in total hip and by 4.2±13.5% (NS) in distal radius. During the 2-year trial serum levels of Wnt3a decreased from median 3.88 range (2.93-6.21) ng/ml to 1.74 (1.08-2.84) ng/ml (p&lt;0.001), OPG decreased from 4.07 (2.08-7.78) pmol/l to 3.06 (1.35-4.54) (p&lt;0.001), CTX-I decreased from 0.50 (0.16-1.34) ng/ml to 0.18 (0.07-0.41) ng/ml (p&lt;0.001) and osteocalcin decreased from 20.11 (11.55-59.78) ng/ml to 7.94 (5.63-14.13) ng/ml (p&lt;0.001). The other biomarkers did not change significantly during the 2-year follow-up. <h3>Conclusions</h3> We show, for the first time, a prompt and sustained decrease of the biomarkers Wnt3a, OPG, CTX-I and osteocalcin in osteoporotic AS patients treated with alendronate during 2 years. The results indicate a down regulatory effect on both osteclastic and osteblastic activity. The treatment also resulted in a significant and large increase in BMD in lumbar spine and total hip. <h3>Disclosure of Interest</h3> None Declared