Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab

Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab

70 Abstracts with autoimmune rheumatic diseases. A descriptive study in male and female patients over 18 years with diagnosis of RA, SLE, spondyloar...

56KB Sizes 0 Downloads 0 Views

70

Abstracts

with autoimmune rheumatic diseases. A descriptive study in male and female patients over 18 years with diagnosis of RA, SLE, spondyloarthropathy, vasculitis, Sjogren's syndrome, overlap syndrome, undifferentiated connective tissue disease was carried out and a comparison with a control population was performed. Exclusion criteria: supplemented with vitamin D, pregnancy, presence of another autoimmune disease, intestinal malabsorption, chronic liver or kidney disease or cancer. Results (mean ± SE): 75 patients with autoimmune rheumatic disease were included and were classified into 3 groups: SLE and other collagen diseases (n = 23), spondyloarthropathies (n = 7) and RA (n = 45). As a control group, 45 patients matched by age and body mass index without rheumatic diseases were included. There were no significant differences in age, BMI, serum calcium and serum phosphate. A significant difference in the levels of total alkaline phosphatase (IU/l) was observed (Kruskal–Wallis test, p b 0.0001) being higher in RA group vs control and RA vs SLE (Dunn's postest). While the four groups showed vitamin D insufficiency (control: 26.35 ± 1.92 ng/ml, SLE and other collagen diseases: 19.73 ± 1.19 ng/ml, spondyloarthropathies: 15.54 ± 1.84 ng/ml, and RA: 19.53 ± 0.86 ng/ml) significant differences between groups were observed (Kruskal–Wallis test, p b 0.0001). RA patients and patients with spondyloarthropathy showed lower levels of 25(OH)D than the control group (Dunn's postest). Conclusion: All patients with rheumatic diseases studied showed vitamin D insufficiency and lower levels were found in patients with RA and spondyloarthropathies compared to controls.

doi:10.1016/j.bone.2015.12.042

Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab A. Sánchez, L.R. Brun, H. Salerni, P. Costanzo, L. Maffei, V. Premrou, M.A. Sarli, P. Rey, M.S. Larroudé, M.L. Brance, A.M. Galich, E. Vega, M.B. Zanchetta, V. Farías, M.S. Moggia, M.M. Pavlove, S. Karlsbrum Grupo Argentino de Estudio de la Osteoporosis, Argentina E-mail address: [email protected] (L.R. Brun) Previous studies have demonstrated that both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis. In addition, the effect of both drugs on bone mineral density (BMD) has been separately studied in Argentinean patients. After one year of treatment, a significant BMD increase was observed with both drugs; however, the percentage of change was different: SrR (n = 441) + 3.73% at the lumbar spine (LS), +2.00% at the femoral neck (FN) and + 1.54% in total hip (TH); Dmab (n = 285) LS + 5.95%, FN +4.60%, and TH +3.91%. Therefore, the aim of this study was to compare the densitometric response in postmenopausal osteoporotic women treated with SrR or Dmab. We only included patients previously treated with bisphosphonates (SrR: n = 350, and Dmab: n = 180). Patients were considered responders if the percentage change in BMD was N 3%, and non-responders if they had lesser BMD gains after one year. Results: SrR = LS: 51.24% responders and 48.76% non-responders; FN: 37.86% responders and 62.14% nonresponders; TH: 28.71% responders and 71.29% non-responders. Dmab = LS: 66.94% responders and 33.06% non-responders; FN: 71.43% responders and 28.57% nonresponders; TH: 51.72% responders and 48.28% non-responders. The chi2 analysis between Dmab and SrR showed significantly higher percentage of responders in patients treated with Dmab in all regions evaluated (LS: p = 0.0030; FN: p b 0.0001; TH: p = 0.0002). Conclusion: In patients with postmenopausal osteoporosis previously treated with bisphosphonates, Dmab produced significantly greater densitometric gains, and the percentage of responders was higher among Dmab users.

doi:10.1016/j.bone.2015.12.043

Bone tissue regeneration implanting matrix obtained by recombinant DNA techniques D.J. Colettaa,b, A. Ibañez Fonsecaa,c, L.R. Missanaa,d,e, G.E. Bumaguinb, E.J. Vitellib, F. Garbinob, F. Zabalzab, C. Amavetb, M. Aimoneb, M.V. Jammald,e, M. Alonsoc, J.C. Rodríguez-Cabelloc, S. Feldmanb a Ex-aequo, Faculty of Medical Cs. Rosario Nac. Univ., Argentina b LABOATEM, Faculty of Medical Cs. Rosario Nac. Univ., Argentina c BIOFORGE Research Group, Valladolid Univ. CIBER-BBN, Valladolid, Spain d PROIMI-CONICET Tucumán, Argentina e Faculty of Odontology, Tucumán Univ. Tucumán, Argentina E-mail address: [email protected] (S. Feldman) The aim of bone regeneration using tissue engineering is to promote de novo bone regeneration by response from biodegradable matrix. Our object was to analyze

the ability from an elastin-like recombinant (ELRs) matrix implanted in femoral injure in rabbits, it would promote bone tissue regeneration. ELRs were obtained using recombinant DNA strategies by Escherichia coli (strain BL21 (DE3, NOVAGEN)) transformed with an expression vector derived from pET-25(+) plasmid, which contains ELRs coding genes. Plasmids were genetically designed in order to achieve bioactivity adding the following sequences: (a) RGD for cellular adhesion, (b) BMP-2 (Bone morphogenetic protein-2), and (c) an elastase recognition dominium. In addition to this, changing some amino acids allowed us to obtain a hydrogel soluble at − 4 °C but that transforms to a gel at room temperature. We have previously developed a medial distal femoral defect (6 mm diameter) in New Zealand female rabbits. Seven rabbits with femoral defects received 100 μl of ELRs, that immediately jellified into the injury. The experimental animals showed immediate recovery without observed clinical alterations in contrast to controls (temperature, general conditions, feeding habits, mobility of the injured foot). All these aspects were controlled up to 3 month after implant, when animals were euthanized. The exact implant area was suited by X-ray. Tomographic analysis (Toshiba Alexion equipment, with 16 detectors, algorithm of bone reconstruction, 3D) showed cortical defect repair at the medial cortical from distal metaphysis-epiphysis area. One case show one mm diameter defect. The others demonstrate full repair. Samples were decalcified by modified Morse Solution and processed in histological routine manners. Serial sections (5u) were stained by H&E and studied by optical microscopy. The results showed a thick new bone formed in “mosaic pattern”, with many vascular canals surrounding remains of implanted matrix. The degraded matrix shows granular mineralized areas covered by osteoblast-like cells. In the surrounding zone some trabeculae were lined by two or more osteoblasts lines. Osteocytes were arresting. These are original results by in vivo bone tissue formation from a biodegradable matrix obtained using DNA recombinant technique and probably potentiated by the in situ effect of BMP-2.

doi:10.1016/j.bone.2015.12.044

Ursodeoxycholic acid blocks the inhibition of calcium uptake produced by sodium deoxycholate in mature enterocytes A.M. Marchionatti, V.A. Rodriguez, M.A. Rivoira, A.V. Perez, N.G. Tolosa de Talamoni Laboratorio “Dr. Fernando Cañas”, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Argentina E-mail address: [email protected] (A.M. Marchionatti) The intestinal Ca2 + absorption is inhibited by sodium deoxycholate (NaDOC) and is increased by ursodeoxycholic acid (UDCA). In this work, we studied the effect of both bile acids (BA) on the Ca2 + uptake in enterocytes and the possible mechanisms involved. Adult male Wistar rats were used: 1) controls, 2) treated with NaDOC (10 mM), 3) treated with UDCA (60 mg/100 g b.w.) and 4) treated with NaDOC + UDCA, via luminal for 30 min. Enterocytes were obtained with different degree of maturation and Ca2 + uptake was performed by using 45Ca2 +. Gene expression of FAS and FASL was quantified by real time PCR. The protein expression of FAS, FASL, procaspase-8, caspase-8 and inducible nitric oxide synthase (iNOS) was analyzed by Western blot. Results were evaluated by one-way analysis of variance (ANOVA) and the Bonferroni's test. Ca2 + uptake was lower in mature enterocytes treated with NaDOC and higher in enterocytes treated with UDCA in comparison with the controls. In immature enterocytes Ca2 + uptake remained unchanged with the different treatments. The protein expression of FAS, FASL and caspase-8 increased with NaDOC, while procaspase-8 decreased with this treatment, and the gene expression of FAS and FASL was not altered. NaDOC treatment apparently caused nitrosative stress because there was increase in iNOS protein expression and in the NO content. In conclusion, NaDOC inhibits the intestinal Ca2 + absorption because it decreases Ca2 + uptake by mature enterocytes due, at least in part, to the stimulation of the apoptotic extrinsic pathway and the nitrosative stress. On the contrary, UDCA blocks apoptosis in mature enterocytes and prevents the adverse effects of NaDOC, aborting the inhibition of intestinal cation absorption.

doi:10.1016/j.bone.2015.12.045

Effects of phytoestrogens on proliferation and migration of normal and tumoral cells. Signaling pathways involved V. Lezcano, S. Morelli Instituto de Investigaciones Biológicas y Biomédicas del Sur (INBIOSUR), Dpto. Biología, Bioquímica y Farmacia — Universidad Nacional del Sur, Bahía Blanca, Pcia. de Buenos Aires, Argentina E-mail address: [email protected] (V. Lezcano)