Parathyroid Hormone-Related Changes of Bone Structure.

Parathyroid hormone (PTH) increases the release of serum calcium through osteoclasts, which leads to bone resorption. Primary, PTH stimulates osteoblasts leading to increase RANKL (receptor activator for nuclear factor kappa-B ligand) expression and thus differentiation of osteoclasts. In kidneys, PTH increases calcium and decrease phosphate reabsorption. In kidneys, PTH stimulates 1alpha-hydroxylase to synthesize active vitamin D. Primary hyperparathyroidism (PHPT) is characterized by skeletal or renal complications. Nowadays, the classical form of PHPT is less seen and asymptomatic or subclinical (oligo symptomatic) forms are more frequent. Previously, it was thought that cortical bone is preferably affected by PHPT and that predispose bones to fracture at sites with a higher amount of cortical bone. However, an increased risk of vertebral fractures has been found by most of the studies showing that also trabecular bone is affected. Bone Mass measurement (BMD) at all skeletal sites is advised, but another specific tool for fracture assessment is needed. Trabecular bone score (TBS), an indirect measure of trabecular bone, maybe a useful method to estimate fracture risk. TBS is associated with vertebral fractures in PHPT regardless of BMD, age, BMI and gender. Furthermore, there is an association between TBS and high resolution peripheral quantitative computed tomography (HR-pQCT) parameters in the trabecular and cortical compartment. However, studies considering the effect of PHPT treatment on TBS are more conflicting. Secondary hyperparathyroidism caused by vitamin D deficiency was associated with impaired bone microarchitecture in all age categories, as measured by TBS and Hr-pQCT with further improvement after treatment with vitamin D.

Fibroblast Growth Factor 23 and Klotho Are Associated With Trabecular Bone Score but Not Bone Mineral Density in the Early Stages of Chronic Kidney Disease: Results of the Cross-Sectional Study.

This study evaluates bone mineral density (BMD) and trabecular bone score (TBS) in relationship with new markers of chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23), and klotho. The patients in this cross-sectional study were divided as follows: group A -patients in stages G1-3; group B -patients in stages G4 - 5 according to KDIGO. Plasma levels of soluble klotho and FGF23 were determined by ELISA. Bone mineral density (BMD) and trabecular bone score (TBS) were measured. 74 patients with CKD (mean age 68.8 years) were included in the study. Higher levels of FGF23 were observed in group B (N=15) compared to group A (N=59; p=0.001) were observed. FGF23 was higher in group A compared to group B. Significant difference in TBS within the first 3 stages of CKD was observed (mean TBS in G1=1.375 vs. G2=1.340 vs. G3a=1.24; p<0.05) and negative correlation of FGF23 and TBS (R=-0.33; p=0.05) and positive correlation between klotho and TBS (R=0.419; p=0.04) was observed. This study confirmed that FGF23 and klotho are associated with TBS, but TBS reflects a decrease in kidney function only in the first 3 stages of CKD. Thus, FGF23 and klotho together with TBS are promising markers of early trabecular bone impairment in CKD.

Prediction of Vertebral Fractures by Trabecular Bone Score in Patients With Ankylosing Spondylitis.

Ankylosing spondylarthritis (AS) is associated falsely increased lumbar spine bone mineral density (BMD). New tool for discrimination of subjects at fracture risk is needed. Vertebral fracture (VF) prediction of routine methods for osteoporosis assessment, BMD and trabecular bone score (TBS), in patients with AS. Cross-sectional study of all AS patients regularly followed at the rheumatology outpatient clinics of two centers. All subjects undergone BMD measurement at lumbar spine (LS), total hip (TH) and femoral neck (FN) using Hologic® Horizon device. TBS at L1-4 in all subjects by TBS InSight® software were assessed. Vertebral fracture assessment (VFA) was performed using the lateral spine imaging IVA™ and graded using Genant semi-quantitative approach. 119 AS subjects (90 males/29 females), mean age 47.6 years were included in the study. In 20 patients 34 VFs were detected, from whom 7 patients had multiple fractures. Subjects with VF were older and had lower FN BMD, TBS in comparison to non-VF subjects. No differences in LS BMD, FN BMD or BASDAI between groups were observed. Among patients with VF only 3 had T-score less than -2.5 but 7 has TBS less than 1.23 which means highly degraded microarchitecture. AS patients with VF have lower TBS and FN BMD in comparison to non-VF subjects. In addition, TBS was able to detect 20 % more VFs than BMD. Therefore, TBS seems promising in VF discrimination among patients with AS.

The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up.

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

Treatment With Cholecalciferol Leads to Increase Of Selected Semen Parameters in Young Infertile Males: Results of a 6-month Interventional Study.

High incidence of infertility along with low vitamin D levels was detected in otherwise healthy young men. The aim is to observe the effect of vitamin D supplementation on semen parameters as assessed by semen analysis in infertile men. In total, 45 men (mean age 36.6 years) in consecutive order were included, of whom 34 finished the study. Subjects were supplemented by vitamin D (cholecalciferol) 2500 IU/day. Vitamin D levels were assessed by HPLC. Semen analysis was performed strictly following 2010 WHO guidelines. Study periods were baseline and month 6. During follow-up, 20 %, 7.4 %, 22 % and 0.7 % increase in serum vitamin D levels, progressive sperm motility, sperm concentration and sperm morphology, respectively, were observed (all p<0.05). At follow-up end, 9 patients (26 %) reached normal sperm parameters of whom 2 fertilized their partner. There was no correlation between vitamin D and semen parameters observed. This study proves that vitamin D supplementation is possibly a modulator of sperm parameters in vitamin D deficient, otherwise healthy men. Although a direct relationship between vitamin D and sperm parameters was not observed obtaining adequate vitamin D levels could likely play a role in the male factor of infertility.

3D Echocardiography - A Useful Method for Cardiovascular Risk Assessment in End-Stage Renal Disease Patients.

Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI). We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD.

Parathyroid Hormone-Related Changes of Bone Structure.

Parathyroid hormone (PTH) increases the release of serum calcium through osteoclasts, which leads to bone resorption. Primary, PTH stimulates osteoblasts leading to increase RANKL (receptor activator for nuclear factor kappa-B ligand) expression and thus differentiation of osteoclasts. In kidneys, PTH increases calcium and decrease phosphate reabsorption. In kidneys, PTH stimulates 1alpha-hydroxylase to synthesize active vitamin D. Primary hyperparathyroidism (PHPT) is characterized by skeletal or renal complications. Nowadays, the classical form of PHPT is less seen and asymptomatic or subclinical (oligo symptomatic) forms are more frequent. Previously, it was thought that cortical bone is preferably affected by PHPT and that predispose bones to fracture at sites with a higher amount of cortical bone. However, an increased risk of vertebral fractures has been found by most of the studies showing that also trabecular bone is affected. Bone Mass measurement (BMD) at all skeletal sites is advised, but another specific tool for fracture assessment is needed. Trabecular bone score (TBS), an indirect measure of trabecular bone, maybe a useful method to estimate fracture risk. TBS is associated with vertebral fractures in PHPT regardless of BMD, age, BMI and gender. Furthermore, there is an association between TBS and high resolution peripheral quantitative computed tomography (HR-pQCT) parameters in the trabecular and cortical compartment. However, studies considering the effect of PHPT treatment on TBS are more conflicting. Secondary hyperparathyroidism caused by vitamin D deficiency was associated with impaired bone microarchitecture in all age categories, as measured by TBS and Hr-pQCT with further improvement after treatment with vitamin D.

Fibroblast Growth Factor 23 and Klotho Are Associated With Trabecular Bone Score but Not Bone Mineral Density in the Early Stages of Chronic Kidney Disease: Results of the Cross-Sectional Study.

This study evaluates bone mineral density (BMD) and trabecular bone score (TBS) in relationship with new markers of chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23), and klotho. The patients in this cross-sectional study were divided as follows: group A -patients in stages G1-3; group B -patients in stages G4 - 5 according to KDIGO. Plasma levels of soluble klotho and FGF23 were determined by ELISA. Bone mineral density (BMD) and trabecular bone score (TBS) were measured. 74 patients with CKD (mean age 68.8 years) were included in the study. Higher levels of FGF23 were observed in group B (N=15) compared to group A (N=59; p=0.001) were observed. FGF23 was higher in group A compared to group B. Significant difference in TBS within the first 3 stages of CKD was observed (mean TBS in G1=1.375 vs. G2=1.340 vs. G3a=1.24; p<0.05) and negative correlation of FGF23 and TBS (R=-0.33; p=0.05) and positive correlation between klotho and TBS (R=0.419; p=0.04) was observed. This study confirmed that FGF23 and klotho are associated with TBS, but TBS reflects a decrease in kidney function only in the first 3 stages of CKD. Thus, FGF23 and klotho together with TBS are promising markers of early trabecular bone impairment in CKD.

Prediction of Vertebral Fractures by Trabecular Bone Score in Patients With Ankylosing Spondylitis.

Ankylosing spondylarthritis (AS) is associated falsely increased lumbar spine bone mineral density (BMD). New tool for discrimination of subjects at fracture risk is needed. Vertebral fracture (VF) prediction of routine methods for osteoporosis assessment, BMD and trabecular bone score (TBS), in patients with AS. Cross-sectional study of all AS patients regularly followed at the rheumatology outpatient clinics of two centers. All subjects undergone BMD measurement at lumbar spine (LS), total hip (TH) and femoral neck (FN) using Hologic® Horizon device. TBS at L1-4 in all subjects by TBS InSight® software were assessed. Vertebral fracture assessment (VFA) was performed using the lateral spine imaging IVA™ and graded using Genant semi-quantitative approach. 119 AS subjects (90 males/29 females), mean age 47.6 years were included in the study. In 20 patients 34 VFs were detected, from whom 7 patients had multiple fractures. Subjects with VF were older and had lower FN BMD, TBS in comparison to non-VF subjects. No differences in LS BMD, FN BMD or BASDAI between groups were observed. Among patients with VF only 3 had T-score less than -2.5 but 7 has TBS less than 1.23 which means highly degraded microarchitecture. AS patients with VF have lower TBS and FN BMD in comparison to non-VF subjects. In addition, TBS was able to detect 20 % more VFs than BMD. Therefore, TBS seems promising in VF discrimination among patients with AS.

The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up.

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

3D Echocardiography - A Useful Method for Cardiovascular Risk Assessment in End-Stage Renal Disease Patients.

Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI). We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD.

Treatment With Cholecalciferol Leads to Increase Of Selected Semen Parameters in Young Infertile Males: Results of a 6-month Interventional Study.

High incidence of infertility along with low vitamin D levels was detected in otherwise healthy young men. The aim is to observe the effect of vitamin D supplementation on semen parameters as assessed by semen analysis in infertile men. In total, 45 men (mean age 36.6 years) in consecutive order were included, of whom 34 finished the study. Subjects were supplemented by vitamin D (cholecalciferol) 2500 IU/day. Vitamin D levels were assessed by HPLC. Semen analysis was performed strictly following 2010 WHO guidelines. Study periods were baseline and month 6. During follow-up, 20 %, 7.4 %, 22 % and 0.7 % increase in serum vitamin D levels, progressive sperm motility, sperm concentration and sperm morphology, respectively, were observed (all p<0.05). At follow-up end, 9 patients (26 %) reached normal sperm parameters of whom 2 fertilized their partner. There was no correlation between vitamin D and semen parameters observed. This study proves that vitamin D supplementation is possibly a modulator of sperm parameters in vitamin D deficient, otherwise healthy men. Although a direct relationship between vitamin D and sperm parameters was not observed obtaining adequate vitamin D levels could likely play a role in the male factor of infertility.

Effect of antidiabetic treatment on bone.

Patients with diabetes mellitus are at an increased risk of bone fractures. Several groups of effective antidiabetic drugs are available, which are very often given in combination. The effects of these medications on bone metabolism and fracture risk must not be neglected. Commonly used antidiabetic drugs might have a positive, neutral or negative impact on skeletal health. Increased risk of fracture has been identified with use of thiazolidinediones, most definitively in women. Also treatment with sulfonylureas can have adverse effects on bone. One consequence of these findings has been greater attention to fracture outcomes in trails of new diabetes medication (incretins and SGLT-2 inhibitors). The effect of insulin on bone is discussed and the risk of fractures in patients using insulin seems to be unrelated to insulin as itself. The aim of the review is to summarize effects of antidiabetic treatment on bone - bone mineral density, fractures and bone turnover markers. The authors also try to recommend a strategy how to treat patients with diabetes mellitus regarding the risk of osteoporotic fractures. In this review the problem of how to treat osteoporosis in patient with diabetes is also discussed.

Pathophysiology of growth hormone secretion disorders and their impact on bone microstructure as measured by trabecular bone score.

This article is focused on endocrine-mediated osteoporosis caused by growth hormone (GH) disorders; adult GH deficiency and acromegaly. GH and insulin like growth factor-1 (IGF-1) stimulate linear bone growth through complex hormonal interactions and activates epiphyseal prechondrocytes. GH, via receptor activator of nuclear factor-kappaB (RANK), its ligand (RANK-L), and the osteoprotegerin system, stimulates production of osteoprotegerin and its accumulation in bone matrix. Malfunction of this mechanism, could lead to specific bone impairment. However, the primary problem of bone disease in GH secretion disorders is the primary prevention of osteoporotic fractures, so it is important to determine bone quality that better reflects the patient's actual predisposition to fracture. A method estimating bone quality from lumbar spine dual X-ray absorptiometry (DXA) scans is trabecular bone score (TBS). TBS in addition to bone mineral density (BMD) is a promising predictor of the osteoporotic fracture risk in women with postmenopausal osteopenia. In acromegaly TBS better defines risk of fracture because BMD is normal or even increased. TBS helps to monitor the effect of growth hormone therapy. Despite these findings, TBS should not be used alone, but a comprehensive consideration of all fracture risk factors, BMD and bone turnover markers is necessary.

Good long-term glycemic compensation is associated with better trabecular bone score in postmenopausal women with type 2 diabetes.

Osteoporosis is an increasingly widespread disease, as well as diabetes mellitus. It is now accepted that osteoporotic fractures are a serious co-morbidity and complication of diabetes. Despite of good bone mineral density in Type 2 Diabetes (T2DM) patients is the fracture risk elevated. It is due to reduced bone quality. To determine the effect of glycemic compensation on bone density and trabecular bone score (TBS) in T2DM. We analyzed a cohort of 105 postmenopausal women with T2DM. For all patients, central bone density (spinal and lumbar spine) was tested by DXA methodology, glycemic control parameters were assessed, and anthropometric parameters were measured. Bone quality was analyzed using TBS software. The results were statistically processed. Good glycemic compensation with glycated hemoglobin (A1c) value <7.0 % DCCT did not lead to BMD changes in patients with T2DM. However, patients with HbA1c <7 % DCCT had significantly better TBS (1.254±0.148 vs. 1.166±0.094, p=0.01). There was a negative correlation between TBS and glycated hemoglobin (r= -0,112, p<0.05) with glycemic fasting (r= -0.117, p<0.05). The optimal effect on TBS is achieved when all three markers of glycemic compensation (glycated hemoglobin, fasting plasma glucose and postprandial glycemia) are in optimal range. By using ROC curves glycated hemoglobin has the most significant effect on TBS. Optimal glycemic compensation, evaluated by glycated hemoglobin, does not lead to changes in BMD but has a beneficial effect on TBS in T2DM. Good glycemic control is required also for reduction of the risk of osteoporosis and osteoporotic fractures.

Impact of smoking cigarette on the mRNA expression of cytokines in mucosa of inflammatory bowel disease.

It is well known that smoking is the risk factor in the development and clinical course of Crohn s disease (CD), but on the other hand, smoking is a protective factor against ulcerative colitis (UC). The pathways that are influenced by smoking in CD and UC are poorly understood. The aim of our study was to analyse the influence of smoking on the mRNA expression of cytokines in mucosa in patients with CD and UC. We performed a cross-sectional study. The cohort consisted of 86 IBD patients (48 CD patients and 38 UC patients) and took place at the IBD Centre at the University Hospital Bratislava-Ruzinov. We took the demographic and clinical data of each patient, including information about their smoking habits. We performed a colonoscopy on each patient and took biopsies from both inflamed and non-inflamed sigma (CD, UC) and terminal ileum (CD). mRNA was extracted from mucosal biopsy samples for each cytokine and was normalized to a housekeeping gene (GAPDH). Finally, we compared the mRNA expression of target cytokines in the mucosa of smokers and non-smokers in IBD patients. Smokers with Crohn s disease have a significantly higher mRNA expression of pro-inflammatory cytokine TNF ? (p=0.003) in inflamed mucosa in sigma compared with non-smokers. In smokers with ulcerative colitis, we observed significantly higher mRNA expression of anti-inflammatory cytokine IL 10 (p=0.022) in non-inflamed mucosa of sigma. Similarly, smokers with UC have a significantly decreased mRNA expression of cytokine TLR 2 (p=0.024) and CCR1 (p=0.049) in non-inflamed mucosa of sigma. Based on our results, smoking has a positive influence on cessation and the clinical course of UC due to the stimulation of anti-inflammatory cytokine IL 10 in mucosa. On the other hand, smokers with CD have a higher expression of pro-inflammatory cytokine TNF ?, which could be associated with a worsening of the disease and response to therapy.

Influence of vitamin D on the expression of mRNA of cytokines in the mucosa of inflammatory bowel disease patients.

The aim of this study was to analyze the influence of 25(OH)VD serum concentration on the expression of mRNA cytokines (IL-6, IL-8, IL-12, IL-17, IL-23, TNFα, CCR1, CCR2, CCR5, CCR9, CCL5, TLR2, TLR4, TLR5, CD207 ,CD206, FoxP3) in mucosa of IBD patients. The cohort consisted of 86 IBD patients (48 CD and 38 UC) followed at the IBD center of University Hospital Bratislava-Ruzinov. We performed colonoscopy in each patient and took biopsies from mucosa of sigma and terminal ileum. Serum concentration of 25(OH)VD was assessed at the time of colonoscopy. mRNA was extracted from mucosal biopsy samples for each cytokine. Then we analyzed the correlation between VD and the expression of mRNA of cytokines from biopsies samples.  In CD we observed a significant positive correlation of serum concentration 25(OH)VD and the expression mRNA level of IL-6. There was also trend towards significant positive correlation of the expression mRNA of TNFα, IL-10, IL-23, TLR 2 in inflamed mucosa of terminal ileum as well as the expression mRNA of CCR5 and CCR1 in non-inflamed mucosa from terminal ileum. We also found a trend towards positive correlation between 25(OH)VD and the expression mRNA of IL-23, TLR4, CD 207, CCR1, CCR5 and CD 206 in non-inflamed mucosa of sigma in UC.VD significantly correlated with the levels of expression of several inflammatory cytokines including TNFα in colonic mucosa of patients with IBD (Tab. 4, Fig. 3, Ref. 31).

Mixed gonadal dysgenesis: whole life follow-up of a rare case.

There are two forms of gonadal dysgenesis - mixed and pure. In the mixed form, some differentiated gonads as well as some either ovarian or testicular rudiments are present. This form results in a number of phenotypes with a possibility of malignant transformation. In the pure form occurring in female gender, also some rudimental gonads are bilaterally present. In the case of simultaneous presence of Y chromosome, also some malignant transformation may appear (Siklar et al. 2007). Chromosomal aberrations are present in 2-7 % adult pairs with fertility disorders and in 0.6 % of newborns. However, only few cases with similar chromosomal aberrations were described so far (Roubin et al. 1977; Alexander et al. 1978; Teyssier et al. 1982; Caglayan et al. 2009). Mixed gonadal dysgenesis presents as a unilateral testis, usually intraabdominal, also with a streak gonad on contralateral side, and persistent mullerian structures. 45X/45XY karyotype is the most frequent in such cases with predominance of 45X cells in both peripheral lymphocytes and gonads. We present a rare case of a left undescended testis, normally descended right testis, with penoscrotal hypospadias, who had a normal karyotype and whose histopathological findings were endometrial tissue and fallopian tube in left testicular biopsy. Gonadal dysgenesis should always be kept in mind because of a possibility of undescended testis and proximal hypospadias. If karyotype reveals a 46XY gonadal dysgenesis, these patients need the careful follow-up to screen for gonadoblastoma in remaining normal testis. Subjecting the patients to prophylactic orchidectomy with hormone replacement can be an additional option in such patients.

[Obesity and a risk of carcinoma]. / Obezita a riziko karcinómov.

At present, obesity and tumour diseases represent an important healthcare issue that has its socioeconomic and social dimensions. It has been known from literature for some time that certain types of tumours are more common in obese people than in people with normal body weight. About 3.2% of newly diagnosed cancers in men and 8.8% in women are associated with high body mass index (BMI). However, many studies suggest a more significant correlation between a waist-to-hip ratio (WHR) and a risk of cancer than a BMI. This is in line with the current orientation of knowledge not only to the quantity but mainly to the distribution of adipose tissue within a body with focus on metabolically active adipose tissue. Similarly, pathogenesis of cancers in obese patients is determined by a range of important mechanisms and metabolites such as insulin, insulin-like growth factors (IGFs), insulin resistance, inflammatory cytokines, adiponectin, leptin and many others. Despite this, many interconnections remain unknown. However, based on the results of many clinical and epidemiological studies we may argue that obesity is considered a risk factor of a number of tumour diseases such as prostate tumours, breast cancers in postmenopausal women, endometrial tumours, kidney or gastrointestinal tumours (stomach, oesophagus, colon).

The level of TSH appeared favourable in maintaining bone mineral density in postmenopausal women.

OBJECTIVE: Since the positive role of thyrotropin (TSH) in bone remodeling has been recently emphasized, this cross-section study is aimed to evaluate the association of bone status with the level of TSH and free thyroxine (FT4) in the cohort of postmenopausal women after long-term treatment of thyroid disorders and age matched controls. METHODS: Urinary calcium (dUCa) and serum level of TSH, FT4 and of bone turnover markers (BTMs) such as alkaline phosphatase (ALP), osteocalcin (OC), cross linked N-telopeptide of type 1 collagen (NTx) as well as lumbar spine L 1-4 (BMD-L) and femoral hip (BMD-F) mineral density were determined in 113 postmenopausal women consisting of 42 patients with Graves disease treated by carbimazole, 32 patients with thyroid cancer treated with L-thyroxine and 39 age matched women without any thyroid and osteological disorders. For statistical evaluation t-test, Pearson's correlation coefficient and linear multiple regression were used. RESULTS: To compare the association of TSH versus FT4 with BMD and BTMs the pooled cohort of all 113 women was divided in two groups in terms of TSH level: 1. 34 women with low TSH (>or=0.50 mU/l); 2. 79 women with normal TSH (0.51-4.3 mU/l). In spite of significantly higher FT4 level, the Group 2 with normal TSH level had significantly higher BMD-L and BMD-F (p<0.001) and, in contrast, significantly lower urinary dUCa, ALP, OC (all at p<0.001) and NTx (p<0.01) as compared to the Group 1 with low TSH level. Linear multiple regression showed highly significant influence of TSH on BMD-L and BMD-F0 (p<0.001) independent of age, FT4 and body mass index, while that of FT4 was not significant. The strength of linear interrelation between all variables used was finally tested by Pearson's correlation coefficient (Table 3) which was highly positive for TSH with BMD-F and BMD-L, but highly negative for TSH with serum NTx, OC, ALP) and urinary calcium (dUCa). In contrast, no significant correlation was found between the level of FT4 and BMD. CONCLUSIONS: Irrespectively of FT4 level, postmenopausal women with normal TSH level showed a favorable bone status as compared to these with low level of TSH which is consistent with the view that TSH itself possibly participates in playing a favorable role in influencing the bone mineral density in adult women.