McClung M.R.,Oregon Osteoporosis Center |
Zanchetta J.R.,Institute Investigaciones Metabolicas |
Hoiseth A.,Curato Rontgeninstitutt |
Kendler D.L.,Clinical Research Center |
And 12 more authors.
Journal of Clinical Densitometry | Year: 2013
FREEDOM was a phase 3 trial in 7808 women aged 60-90. yr with postmenopausal osteoporosis. Subjects received placebo or 60 mg denosumab subcutaneously every 6. mo for 3. yr in addition to daily calcium and vitamin D. Denosumab significantly decreased bone turnover; increased dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD); and significantly reduced new vertebral, nonvertebral, and hip fractures. In a subset of women (N= 209), lumbar spine, total hip, and femoral neck volumetric BMD (vBMD) were assessed by quantitative computed tomography at baseline and months 12, 24, and 36. Significant improvement from placebo and baseline was observed in aBMD and vBMD in the denosumab-treated subjects at all sites and time points measured. The vBMD difference from placebo reached 21.8%, 7.8%, and 5.9%, respectively, for the lumbar spine, total hip, and femoral neck at 36. mo (all p≤ 0.0001). Compared with placebo and baseline, significant increases were also observed in bone mineral content (BMC) at the total hip (p< 0.0001) largely related to significant BMC improvement in the cortical compartment (p< 0.0001). These results supplement the data from DXA on the positive effect of denosumab on BMD in both the cortical and trabecular compartments. © 2013 The International Society for Clinical Densitometry.
Genant H.K.,University of California at San Francisco |
Genant H.K.,Synarc Inc. |
Libanati C.,Amgen Inc. |
Engelke K.,Friedrich - Alexander - University, Erlangen - Nuremberg |
And 11 more authors.
Bone | Year: 2013
In the FREEDOM study, denosumab treatment (60. mg every 6. months) decreased bone resorption, increased bone mineral density (BMD), and reduced new vertebral, nonvertebral, and hip fractures over 36. months in postmenopausal women with osteoporosis. In a subset of these women, hip quantitative computed tomography (QCT) was performed at baseline and months 12, 24, and 36. These scans were analyzed using Medical Image Analysis Framework (MIAF) software, which allowed assessment of total hip integral, trabecular, subcortical, and cortical compartments; the cortical compartment was further divided into 2 areas of interest (outer and inner cortex). This substudy reports changes in BMD and bone mineral content (BMC) from baseline and compared placebo with denosumab over 36. months of treatment (placebo N=26; denosumab N=36). Denosumab treatment resulted in significant improvements in total hip integral volumetric BMD (vBMD) and BMC from baseline at each time point. At month 36, the mean percentage increase from baseline in total hip integral vBMD and BMC was 6.4% and 4.8%, respectively (both p. <. 0.0001). These gains were accounted for by significant increases in vBMD and BMC in the trabecular, subcortical, and cortical compartments. In the placebo group, total hip integral vBMD and BMC decreased at month 36 from baseline by 1.5% and 2.6%, respectively (both p. <. 0.05). The differences between denosumab and placebo were also significant at months 12, 24, and 36 for integral, trabecular, subcortical, and cortical vBMD and BMC (all p. <. 0.05 to <. 0.0001). While the largest percentage differences occurred in trabecular vBMD and BMC, the largest absolute differences occurred in cortical vBMD and BMC. In summary, denosumab significantly improved both vBMD and BMC from baseline and placebo, assessed by QCT MIAF, in the integral, trabecular, subcortical, and cortical hip compartments, all of which are relevant to bone strength. © 2013.
Szydlarska D.,Central Clinical Hospital MSWiA |
Szydlarska D.,Medical University of Warsaw |
Grzesiuk W.,Medical University of Warsaw |
Trybuch A.,Institute of Cardiology |
And 3 more authors.
Endokrynologia Polska | Year: 2012
Introduction: The aim of this study was to find a correlation between insulin-like factor 3 (INSL3) and androgens: androstenedione (A), free testosterone (fT), and total testosterone (T), in two groups of polycystic ovary syndrome (PCOS) women: those with a body mass index (BMI) lower than 25 kg/m2 and those with a BMI higher than 25 kg/m2. The association between INSL3 and other serum parameters: luteinising hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and glucose and insulin were also investigated. Material and methods: The study group comprised 37 PCOS women aged 27 ± 4 years. The control group consisted of 34 healthy, premenopausal women (aged 24.2 ± 1.2) with regular menses and no signs of hyperandrogenism. There were 27 PCOS women of normal weight (BMI < 25 kg/m2), and ten overweight individuals (BMI ≥ 25-30 kg/m 2). Correlations between level of INSL3 and LH, FSH, T, fT, A, DHEA-S, SHBG, metabolic tests, height, weight, and WHR (waist-to-hip ratio) were also investigated. Results: PCOS women showed non-significantly higher levels of INSL3 compared to the healthy controls (64.6 ± 27.7 and 62.7 ± 20.0 ng/mL, respectively). However, we identified very strong correlations between INSL3 and androstenedione (r = 0.48, p = 0.0115), and free (r = 0.44, p = 0.0108) and total testosterone (r = 0.46, p = 0.0057) in the PCOS subgroup with a BMI of < 25 kg/m2. There was no statistically significant correlation between INSL3 and LH in any subject of the PCOS group, nor between INSL3 and FSH, DHEA-S, glucose, basal insulin concentration or HOMA-IR. Conclusions: We found a positive correlation between INSL3 and androgens in PCOS women, especially those with a BMI of < 25 kg/m2. This may play a key role in PCOS pathophysiology.
Olszewska M.,Medical University of Warsaw |
Warszawik O.,Central Clinical Hospital MSWiA |
Rakowska A.,Central Clinical Hospital MSWiA |
Slowinska M.,Central Clinical Hospital MSWiA |
And 2 more authors.
Endokrynologia Polska | Year: 2010
Hair loss may accompany several endocrine disorders, including hypopituitarism, hypothyreosis, hyperthyreosis, hypoparathyroidism, diabetes mellitus, growth hormone deficiency, hyperprolactinaemia, polycystic ovary syndrome, SAHA syndrome, congenital adrenal hyperplasia, Cushing syndrome, or virilising tumours. Most patients with endocrine disorders present with diffuse non-scarring alopecia, such as anagen effluvium, telogen effluvium or androgenetic alopecia. Focal non-scarring alopecia, such as alopecia areata coexisting with autoimmune thyroiditis, is less frequent and scarring alopecia is a rare finding in patients with endocrine abnormalities. In some cases an endocrine disorder may be suspected based on dermatological findings during hair loss evaluation. Classic methods of hair evaluation include hair weighing, pull test, wash test, the trichogram, and histopathological examination. Newly developed non-invasive diagnostic techniques include the phototrichogram, trichoscan, trichoscopy, and reflectance confocal microscopy.
Franek E.,Central Clinical Hospital MSWiA |
Franek E.,Polish Academy of Sciences |
Januszkiewicz-Caulier J.,Central Clinical Hospital MSWiA |
Blach A.,Central Clinical Hospital MSWiA |
And 5 more authors.
Kardiologia Polska | Year: 2012
Background: Periodontal disease is an inflammatory process which results in increased cardiovascular risk in patients with type 2 diabetes mellitus (DM2). It is not clear, however, whether periodontal inflammation may be associated with increased markers of atherosclerosis in these patients. Aim: This cross-sectional study aimed to answer the question of whether periodontal disease in DM2 is associated with increased markers and risk factors of atherosclerosis. Methods: One hundred and twenty one patients were included in the study. Sixteen were classified as periodontally healthy (BGI-H), 87 as having gingivitis (BGI-G), and 18 as having periodontitis with moderate bleeding (BGI-P2), according to the new Offenbacher classification. In all patients, intima-media thickness (IMT), pulse wave velocity (PWV), lipids, and C-reactive protein (CRP) were assessed. Results: Patients with periodontitis and gingivitis had a higher IMT value compared to the BGI-H group (0.804 ± 0.112 and 0.772 ± 0.127 vs 0.691 ± 0.151 mm, p < 0.01 and p < 0.05, respectively, odds ratio 5.25 for having IMT ≥ 0.8 mm, 95% CI 1.1; 25). Patients from the BGI-P2 group also had higher blood pressure (BP) compared to the BGI-G and BGI-H groups, and higher CRP compared to the BGI-G group (4.6 ± 2.3 vs 3.8 ± 4.8 mg/L, p < 0.01). Lipid parameters and PWV were comparable in all the groups. Conclusions: Periodontal inflammation in patients with DM2 seems to be associated with increased IMT and BP, but not with greater arterial stiffness. These results support the hypothesis that periodontal disease may be associated with a vascular pathology. Copyright © Polskie Towarzystwo Kardiologiczne.
Horst-Sikorska W.,Poznan University of Medical Sciences |
Dytfeld J.,Poznan University of Medical Sciences |
Wawrzyniak A.,Poznan University of Medical Sciences |
Marcinkowska M.,Poznan University of Medical Sciences |
And 6 more authors.
Molecular Biology Reports | Year: 2013
The goal of the study was to investigate the possibility of an association between polymorphisms and single alleles of BsmI, ApaI, TaqI of the vitamin D receptor (VDR) gene with bone mineral density (BMD) and prevalence of vertebral/non-vertebral fractures in a group of postmenopausal Polish women with osteoporosis. The study group comprised of 501 postmenopausal females with osteoporosis (mean age 66.4±8.9), who were diagnosed on the basis of either the WHO criteria or self-reported history of low-energy fractures. The three polymorphisms were determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism). BMD at the lumbar spine and femoral neck was assessed by dual energy X-ray absorptiometry (DXA). 285 fractures were reported in the whole group (168 vertebral and 117 non-vertebral). Incidence of non-vertebral fractures was significantly higher in the carriers of single alleles a of ApaI, b of BsmI and T of TaqI VDR gene polymorphisms (p=0.021, 0.032, 0.020, respectively). No significant associations between allelic variants of the studied polymorphisms and BMD or fracture incidence were found. (1).The presence of single alleles a,b and T of ApaI, BsmI, TaqI VDR gene polymorphisms respectively, might serve as an indicator of non-vertebral fractures. (2). Lack of association between the VDR gene polymorphisms and BMD suggests that VDR contributes to low-energy fractures also through other ways. © 2012 The Author(s).
Ambroszkiewicz J.,Institute of Mother and Child |
Klemarczyk W.,Institute of Mother and Child |
Gajewska J.,Institute of Mother and Child |
Chelchowska M.,Institute of Mother and Child |
And 2 more authors.
Pediatric Endocrinology, Diabetes and Metabolism | Year: 2010
Introduction: Vegetarian diets can be healthy when they are well balanced and if a variety of foods is consumed. However, elimination of animal products from the diet (vegan diets) decreases the intake of some essential nutrients and may influence the bone metabolism. This is especially important in childhood and adolescence, when growth and bone turnover are most intensive. The aim of the study was to assess the effect of vegan diet on bone density (BMD) density and serum concentrations of bone metabolism markers. Material and methods: We examined a family on vegan diet which consisted of parents and two children. Dietary constituents were analysed using a nutritional program. Total and regional BMD were measured by dual-energy X-ray absorptiometry. Concentrations of calcium and phosphate in serum obtained from fasting patients were determined by colorimetric methods, 25-hydroxyvitamin D by the chemiluminescence method and bone turnover markers by specific enzyme immunoassays. Results: In studied vegans, the dietary intake of phosphate was adequate while calcium and vitamin D were below the recommended range. Concentrations of calcium, phosphate and bone turnover markers in the serum of all subjects were within the physiological range, but 25-hydroxyvitamin D level was low. Age-matched Z-score total BMD was between -0.6 and 0.3 in adults, however in children it was lower (-0.9 and -1.0). Z-score BMD lumbar spine (L2-L4) was between -0.9 to -1.9 in parents and -1.5 to -1.7 in children. Conclusions: Our results suggest that an inadequate dietary intake of calcium and vitamin D may impair the bone turnover rate and cause a decrease in bone mineral density in vegans. The parameters of bone density and bone metabolism should be monitored in vegans, especially children, in order to prevent bone abnormalities.
Kowalska I.,Medical University of Bialystok |
Borawski J.,Medical University of Bialystok |
Nikolajuk A.,Medical University of Bialystok |
Budlewski T.,Medical University of Bialystok |
And 4 more authors.
Endocrine | Year: 2011
Subclinical hypothyroidism is associated with an increased risk of atherosclerosis. The aim of this study was to investigate the concentration of plasma soluble intercellular adhesion molecule-1 and adiponectin in relation to insulin sensitivity in patients with subclinical hypothyroidism and to estimate if L-thyroxine treatment had an influence on these parameters. 13 women with subclinical hypothyroidism and 14 euthyroid controls were included in the study. A physical examination was conducted, hyperinsulinemic euglycemic clamp and plasma soluble intercellular adhesion molecule-1, adiponectin and lipids profiles were measured at baseline in both groups and in the group with subclinical hypothyroidism the above procedures were performed after L-thyroxine therapy (mean time of treatment 5.0 months) in stable euthyroid state. Insulin sensitivity and adiponectin were not different at baseline in the two studied groups. Plasma soluble intercellular adhesion molecule-1 concentration was significantly higher in the patients with subclinical hypothyroidism (P = 0.011). The comparison of lipids profiles revealed that only LDL-cholesterol concentration was higher (P = 0.011) in the group with subclinical hypothyroidism. After therapy, we observed an improvement of insulin sensitivity (P = 0.012) and a decrease of plasma glucose (P = 0.019) and soluble intercellular adhesion molecule-1 (P = 0.01), whereas adiponectin concentration remained unchanged. We concluded that L-thyroxine treatment in patients with subclinical hypothyroidism might exert a beneficial effect by reducing cardiovascular risk factors. © Springer Science+Business Media, LLC 2011.
Franek E.,Central Clinical Hospital MSWiA |
Franek E.,Polish Academy of Sciences
Endokrynologia Polska | Year: 2011
Denosumab is the international name of a human, monoclonal antibody approved for the treatment of osteoporosis. This antibody is associated with RANK ligand (RANKL), inactivating it. In consequence, the formation and survival of osteoclasts are suppressed, leading to their apoptosis. All this results in lower bone resorption, while bone mineral density (BMD) increases. Denosumab also reduces the risk of vertebral and non-vertebral fractures. This agent is similarly effective in various stages of renal function impairment; it does not impair fracture healing processes nor contribute to atherosclerosis progression in patients with high cardiovascular risks. Following an analysis of adverse effects, performed in the FREEDOM study (in which it was demonstrated that the incidence of the majority of adverse effects observed in the course of denosumab use was similar to that in the placebo group), its safety for patients can definitely be confirmed.
Adamczak M.,Medical University of Silesia, Katowice |
Blach A.,Medical University of Silesia, Katowice |
Kolonko A.,Medical University of Silesia, Katowice |
Szotowska M.,Medical University of Silesia, Katowice |
And 4 more authors.
Clinical Transplantation | Year: 2011
Background: Low plasma adiponectin concentration is associated with more frequent occurrence of left ventricular hypertrophy (LVH) and more exaggerated intima-media thickness of common carotid artery (IMT). IMT is an early surrogate marker of atherosclerosis. This study aimed to assess the relationship between plasma adiponectin concentration and left ventricular mass index (LVMI) and IMT in kidney transplant patients (KTP). Methods: In 88 adult KTP, plasma adiponectin concentration, LVMI, and IMT were estimated. LVH was defined as LVMI >110 or >125g/m 2 for females and males, respectively. Data presented are means and 95% CI. Results: Plasma adiponectin concentration was similar in KTP with (n=42) or without LVH (n=46) (13.5 [11.4-15.6] vs. 13.1 [11.6-14.6] μg/mL, respectively), as well as in KTP subgroups divided according to the IMT value tertiles (p=0.42) (11.7 [10.0-13.3], 14.2 [11.7-16.6], and 14.0 [11.7-16.4] μg/mL in the lowest, middle, and highest tertiles, respectively). Plasma glucose concentrations were similar in KTPs with LVH or without LVH. No significant correlation was found between plasma adiponectin concentration and both LVMI (R=-0.02; p=0.87) and IMT (R=0.09; p=0.38), respectively. Conclusion: Results of this cross-sectional study do not confirm the roles of low adiponectin and high glucose in the pathogenesis of LVH and atherosclerosis in KTP. © 2010 John Wiley & Sons A/S.