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Ymittos Athens, Greece

Makras P.,251 Hellenic Air Force | Anastasilakis A.D.,424 Military Hospital | Polyzos S.A.,Aristotle University of Thessaloniki | Bisbinas I.,424 Military Hospital | And 2 more authors.
Calcified Tissue International | Year: 2011

The acute-phase response (APR) is frequently observed in patients treated with intravenous (iv) zoledronate (ZOL). We investigated whether a short course of rosuvastatin (ROSU) could attenuate the ZOL-induced APR through blocking the mevalonate pathway at a proximal level. Twenty-eight osteoporotic postmenopausal women with no prior bisphosphonate use (mean age 65.3 ± 1.9 years) were subjected to ZOL iv infusion. Patients were randomly assigned into either a ROSU+ group (n = 12), which received ROSU 10 mg/day starting 5 days before the infusion of ZOL for a total period of 11 days, or a ROSU- group (n = 16), which did not receive ROSU. The visual analog pain scale (VAS) for musculoskeletal symptoms and body temperature was used to define clinically APR. In addition, white blood cell (WBC) count, leukocytic subpopulations, and C-reactive protein (CRP) were obtained before and 48 h following the infusion. Seven (58.3%) patients in the ROSU+ group and 13 (81.3%) in the ROSU- group experienced APR (P = not significant). No difference was found in fever and VAS measurements. CRP and granulocytes increased significantly in both groups; WBC count increased, while lymphocytes and eosinophils decreased significantly only in the ROSU- group. In a post hoc analysis of only patients with an APR, all laboratory parameters exhibited a similar significant change solely within the ROSU- group. In conclusion, our data suggest that a short course of ROS at this dose cannot prevent the ZOL-induced APR among osteoporotic women. Milder changes in acute-phase laboratory parameters in ROSU+ patients suggest that studies with higher doses may be warranted. © 2011 Springer Science+Business Media, LLC. Source


Polyzos S.A.,Harvard University | Makras P.,251 Hellenic Air Force | Efstathiadou Z.,Hippokration General Hospital of Thessaloniki | Anastasilakis A.D.,424 General Military Hospital
Expert Opinion on Investigational Drugs | Year: 2015

Introduction: Intermittent parathyroid hormone (PTH) administration, acting through multiple signaling pathways, exerts an osteoanabolic effect on the skeleton that surpasses the effect of other antiosteoporotic agents. However, its efficacy is limited by the coupling effect and relatively common adverse events. Thus, the development of more sophisticated PTH receptor analogs seems imperative. Areas covered: In this review, the authors summarize the role of PTH signaling pathway in bone remodeling. The authors also summarize investigational analogs targeting this pathway, which may be potential treatments for osteoporosis. Expert opinion: β-arrestins are multifunctional cytoplasmic molecules that are decisive for regulating intracellular PTH signaling. Recently, in preclinical studies, arrestin analogs have achieved the anabolic bone effect of PTH without an accompanying increase in bone resorption. However, it is not yet known whether these analogs have adverse effects and there are no clinical data for their efficacy to date. On the other hand, several molecules derived either from PTH and PTH-related protein (PTHrP) molecules have been developed. Alternative routes of PTH 1-34 delivery (oral, transdermal), the PTH analog ostabolin and the N-terminal PTHrP analogs PTHrP 1-36 and abaloparatide, have recently been or are currently being tested in clinical trials and are more likely to become available for use in the near future. © 2015 Informa UK, Ltd. Source


Tsagari A.,KAT General Hospital | Toulis K.A.,424 General Army Hospital | Makras P.,251 Hellenic Air Force | Skagias K.,Doctors Hospital | And 2 more authors.
Hormone and Metabolic Research | Year: 2012

The primary aim of the study was to explore the potential relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and Mini Nutritional Assessment (MNA) score, a surrogate for protein energy undernutrition, in elderly (65 years old) subjects with and without a hip fracture. A secondary aim of the study was to provide estimates of the MNA discriminatory performance in the detection of subjects with low levels of 25(OH)D (<20ng/ml). The study population consisted of 101 patients with a hip fracture, recruited from a single urban Hospital in Athens, Greece, and 85 community dwelling subjects with no history of hip fracture. Serum 25(OH)D was measured, nutritional status was determined by the MNA questionnaire in all subjects, and linear correlation between variables was investigated. Receiver operator characteristic (ROC) curve analysis was performed and discriminatory performance was further assessed by calculating positive and negative likelihood ratios (LR). MNA scores were significantly correlated with 25(OH)D levels (rho=0.685, p<0.001) and this finding was robust in both groups and unaffected by gender. ROC curve analysis demonstrated an area under the curve (AUC) of 0.860 [standard error (SE): 0.026, 95% confidence interval (CI): 0.810-0.910], which provided a significantly better estimation of 25(OH)D status than simple guess (p<0.001). The lowest cutoff value in MNA score, providing a sensitivity over 90% was 25.25, which was associated with a sensitivity of 90.9% and a specificity of 53.6%. The same analysis revealed acceptable results only within hip fracture patients. MNA score might be a satisfactory surrogate marker for 25(OH)D levels with which it is linearly correlated. However, it appears that its discriminatory performance, as a diagnostic tool for 25(OH)D insufficiency, is rather suboptimal. © Georg Thieme Verlag KG Stuttgart - New York. Source


Anastasilakis A.D.,424 General Military Hospital | Polyzos S.A.,Aristotle University of Thessaloniki | Makras P.,251 Hellenic Air Force | Gkiomisi A.,424 General Military Hospital | And 3 more authors.
Osteoporosis International | Year: 2013

Activin-A is expressed in bone and seems to regulate osteoclastogenesis. In this study, serum activin-A was increased in postmenopausal women with low bone mass and was positively correlated to age and negatively to lumbar spinal bone mineral density (BMD). Serum activin-A levels did not change 3 months after zoledronic acid infusion. Introduction: The aims of the study were to evaluate prospectively the circulating activin-A levels in postmenopausal women with low bone mass and explore possible correlations with clinical and laboratory data, as well as the 3-month effect of zoledronic acid infusion. Methods: Postmenopausal women with low bone mass assigned to receive zoledronic acid infusion (Patients, n = 47) and age-matched, postmenopausal women with normal bone mass (Controls, n = 27) were recruited on an outpatient basis. Main outcome measurement was serum activin-A levels. Results: Serum activin-A was higher in patients at baseline compared to controls (p < 0.001) and activin-A in the serum of patients and controls was positively correlated with age (Spearman's coefficient of correlation [rs] = 0.325; p = 0.005) and negatively with lumbar spinal (LS) BMD (rs = -0.425; p < 0.001). In multiple linear regression analysis, only age (B = 8.93; 95 % CI = 4.39-13.46; p < 0.001) was associated with serum activin-A levels at baseline, independent from group (patients or controls), previous anti-osteoporotic treatment, LS BMD and follicle-stimulating hormone. Circulating activin-A levels were not affected 3 months after zoledronic acid infusion. Conclusions: Serum activin-A is increased in postmenopausal women with low bone mass compared with postmenopausal women with normal bone mass and is positively correlated to age and negatively to LS BMD. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation. Source


Anastasilakis A.D.,424 General Military Hospital | Polyzos S.A.,Aristotle University of Thessaloniki | Makras P.,251 Hellenic Air Force | Gkiomisi A.,424 General Military Hospital | And 3 more authors.
Osteoporosis International | Year: 2014

Summary: In vitro data suggest that myokine irisin may affect bone metabolism by promoting osteoblast differentiation while inhibiting osteoclast differentiation. In this study, circulating irisin levels were associated with previous osteoporotic fractures but not with bone mass and were not affected by denosumab or teriparatide treatment for 3 months. Introduction: This study aimed to evaluate predictors of circulating irisin in postmenopausal women with low bone mass and to assess a potential effect of denosumab or teriparatide treatment for 3 months. Methods: Serum samples for irisin measurement were obtained from (a) postmenopausal women with low bone mass (lumbar spinal [LS] or femoral neck [FN] bone mineral density [BMD] T-score â‰. 2.0) and their age-matched controls at baseline and 3 months after denosumab (Dmab) injection (Dmab group, n∈=∈50; Dmab control group, n∈=∈25) and (b) women with more severe disease (LS or FN BMD T-score â‰.;-2.8) and their age-matched controls at the above-mentioned time points after teriparatide (TPTD) initiation (TPTD group, n∈=∈25; TPTD control group, n∈=∈25). Results: At baseline, irisin levels were inversely correlated with age (partial coefficient (r p )∈=∈-0.24; p∈=∈0.009), parathyroid hormone (PTH) (r p ∈=∈-0.30; p∈=∈0.001), and creatinine (r p ∈=∈-0.23; p∈=∈0.016) in univariate analysis, and were lower in women with (n∈=∈26; 41.6∈±∈2.7 ng/dL) than without previous osteoporotic fracture(s) (n∈=∈99; 51.0∈±∈1.6 ng/dL; p∈=∈0.007). In multiple linear regression, previous osteoporotic fracture(s) and PTH were independently negatively associated with irisin [p∈=∈0.04, CI -16.1 to -0.4 and p∈=∈0.002, CI -0.3 to -0.07, respectively], but only the association with PTH remained after controlling for creatinine levels. Serum irisin levels were not different between women with or without low bone mass and were not affected by either Dmab or TPTD treatment for 3 months. Conclusions: Circulating irisin levels were associated with previous osteoporotic fracture(s); whether this association is independent or is due to confounding by lower muscle mass, potentially reflected by lower creatinine levels, remains to be fully clarified. © 2014 International Osteoporosis Foundation and National Osteoporosis Foundation. Source

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