Gluer C.-C.,Universitatsklinikum Schleswig Holstein |
Marin F.,Lilly Research Center |
Ringe J.D.,Klinikum Leverkusen |
Hawkins F.,Hospital 12 Of Octubre |
And 18 more authors.
Journal of Bone and Mineral Research | Year: 2013
Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T-score ≤ -1.5 standard deviations. Subjects received 20 μg/d teriparatide (n = 45) or 35 mg/week risedronate (n = 47) for 18 months. Primary objective was to compare lumbar spine (L1-L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high-resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p = 0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 < p < 0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p = 0.056). In conclusion, in this 18-month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE-derived strength than risedronate. Copyright © 2013 American Society for Bone and Mineral Research.
Farahmand P.,University of Cologne |
Marin F.,Lilly Research Center |
Hawkins F.,Hospital 12 Of Octubre |
Moricke R.,Institute For Praventive Medizin And Klinische Forschung |
And 17 more authors.
Osteoporosis International | Year: 2013
Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal- propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients. © 2013 The Author(s).
Ma Y.L.,Lilly Research Laboratories |
Marin F.,Lilly Research Center |
Stepan J.,Charles University |
Ish-Shalom S.,Bone and Mineral Metabolism Unit |
And 10 more authors.
Bone | Year: 2011
The periosteum contains osteogenic cells that regulate the outer shape of bone and contribute to determine its cortical thickness, size and position. We assessed the effects of subcutaneous injections of teriparatide (TPTD, 20μg/day) or oral strontium ranelate (SrR, 2g/day) in postmenopausal women with osteoporosis on new bone formation activity at the periosteal and endosteal bone surfaces using dynamic histomorphometric measurements. Evaluable tetracycline-labeled transiliac crest bone biopsies were analyzed from 27 patients in the TPTD group, and 22 in the SrR group after six months of treatment. Measurements were conducted on the thicker and thinner cortices separately, and comparisons between the thicker, thinner and combined cortices were carried out. At the combined periosteal cortex, the mineralization surface as a percent of bone surface (MS/BS%) was greater for TPTD (mean±SE: 8.08±1.22%) than SrR (3.22±1.05%) (p<0.005). The difference in mineral apposition rate (MAR) between TPTD (0.35±0.06μm/day) and SrR (0.14±0.06μm/day) was also significant (p<0.05), while that of bone formation rate per bone surface (BFR/BS) between TPTD (0.014plusmn;0.004 mm 3/mm 2/year) and SrR (0.004plusmn;0.003 mm 3/mm 2/year) was not (p=0.057). Statistically significant differences between the two treatments were also observed for MS/BS%, BFR/BS, MAR and the double-labeled perimeter in the periosteum of the thicker, but not thinner, iliac crest cortices. The comparison between the thicker and thinner cortices of both periosteal and endosteal surfaces showed statistically significant differences for MAR and the double-labeled perimeter for TPTD treated women. There were no statistically significant differences in any bone formation dynamic measurements between the two cortices in the SrR group.In conclusion, most of the bone formation and mineralization variables were significantly higher for TPTD- than SrR-treated women at both the periosteal and endosteal combined cortices. The response to TPTD for dynamic bone formation measurements in the periosteal surface was greater for the thicker than thinner cortex, but this difference was not significant in SrR treated patients. This may reflect a greater ability of TPTD to enhance responsiveness of bone to the mechanical loading environment. These effects on bone formation may underlie the improvement in bone quality in patients with osteoporosis treated with TPTD. © 2011 Elsevier Inc.
Vlachaki E.,Hippokration Hospital |
Kalogeridis A.,Aristotelion University |
Neokleous N.,General Hospital |
Perifanis V.,Hippokration Hospital |
And 3 more authors.
Molecular Biology Reports | Year: 2012
The report of Janus Kinase 2 (JAK2) mutations in myeloid malignancies with high frequency in myeloproliferative neoplasms has been well known since 2005. By monitoring allele burden, it is found that the expression of JAK2V617F mutation is increasing significantly from essential thrombocytosis to polycythemia vera. Furthermore, JAK2 abnormalities are reported in the majority of unexplained thrombotic episodes. Thalassemic syndromes are characterized by ineffective erythropoiesis and thrombocytosis, mainly due to splenectomy. The high incidence of thromboembolic events has led to the identification of a prothrombotic state in these patients. The contribution of JAK2 mutations to the hypercoagulable state of thalassemic patients is still unknown. Furthermore, the potential role of Janus Kinase mutations in hepcidin expression and consequently in ineffective erythropoiesis is still under investigation. This study was scheduled to determine whether the presence of JAK2V617F mutation in thalassemic patients is associated with thrombocytosis. We studied 20 patients DNA with beta-thalassemia for JAK2V617F mutation by using RG-PCR method. None of the patients were positive for this particular mutation. More studies are needed to prove the role of JAK2 in ineffective erythropoiesis, iron metabolism and thrombocytosis and to determine if using JAK2 inhibitors in thalassemic patients can be a potential therapeutic option. © Springer Science+Business Media B.V. 2011.
Lagopoulos V.,Hippokratio Hospital |
Gigi E.,Aristotelion University
Hippokratia | Year: 2011
Anaphylactic reactions in the peri-operative period are often serious and potentially life-threatening conditions, involving multiple organ systems in which the clinical manifestations are the consequence of the release of preformed mediators from mast cells and basophils. Anaphylaxis is an immune mediated type I allergic reaction following the massive release of mediators from mast cells and basophils as a response to an allergen. Anaphylactoid reactions are defined as those reactions that produce the same clinical picture with anaphylaxis but are not IgE mediated, occur through a direct nonimmune-mediated release of mediators from mast cells and/or basophils or result from direct complement activation. The occurrence of these reactions during anesthesia, although quite rare, remains a major concern for the anesthesiologists. Thus, the need for systematic screening before surgery and the awareness and expert advice to anaesthesiologists seems to be very critical.
Fytanidis D.K.,Democritus University of Thrace |
Soulis J.V.,Democritus University of Thrace |
Papaioannou V.C.,Democritus University of Thrace |
Giannoglou G.D.,Aristotelion University
Proceedings of the IEEE/EMBS Region 8 International Conference on Information Technology Applications in Biomedicine, ITAB | Year: 2010
Although genetic factors seem to be important, basic mechanisms related to arterial wall cell malfunction, which leads to atherosclerosis formation, depend on the blood flow properties. The present study correlates the factors simulating pulsatile blood flow in the human arteries (aortic arch) using patient-specific geometry. Using numerical techniques we examine the relation between time-Averaged Wall Shear Stress (A WSS) and Oscillatory Shear Index (OSI). The velocity vector oscillates and at the same time alters its direction in places with low A WSS values. Low A WSS and high OSI values do not always collocate. Regional differences between A WSS magnitude and OSI may answer the question as to where atherosclerotic lesions predominately develop and progress at specific aortic regions. This analysis gives information for deeper understanding of the atherosclerosis mechanisms. © 2010 IEEE.