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Biomedical subjects

S Kudlacek

Publications and source records attributed to S Kudlacek.

At least 19 recordsLinked to original sources
PubMed2006

Receptor activator of nuclear factor kappaB ligand and osteoprotegerin in men with thyroid cancer.

BACKGROUND: Suppressive thyroid hormone therapy is generally a lifelong treatment for patients with differentiated thyroid cancer (DTC). However, long-standing thyrotropin (TSH) suppression is a risk factor for osteoporosis. Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) are central regulators of bone turnover. The aim was to analyze the effects of a suppressive thyroid hormone therapy in males with DTC on the OPG/RANKL system and on bone metabolism. PATIENTS AND METHODS: The OPG and soluble RANKL (sRANKL) were determined in 40 men (mean age, 53.2 years) with DTC on suppressive thyroid hormone therapy (TSH; 0.053 +/- 0.037 mU L(-1), duration 5.7 +/- 4.4 years) and 120 healthy controls matched for age. The markers of bone metabolism were C-terminal telopeptide of type I collagen in serum (sCTx) and osteocalcin (OC). RESULTS: The control group had OPG values (mean +/- SD) of 1.9 +/- 1.0 pmol L(-1) and sRANKL values of 0.40 +/- 0.62 pmol L(-1). In patients with DTC, results for OPG were 3.03 +/- 1.04 pmol L(-1) (P < 0.05) and for sRANKL were 0.13 +/- 0.16 pmol L(-1) (P < 0.05). The control group presented values for sCTx of 2669 +/- 1132 pmol L(-1) and for OC of 17.89 +/- 6.5 ng mL(-1). Patients with DTC on suppressive thyroid hormone therapy had increased sCTx values of 3810 +/- 2020 pmol L(-1) (P = 0.03) but comparable OC values of 19.21 +/- 7.67 ng mL(-1) (NS). CONCLUSIONS: Suppressive thyroid hormone therapy in men with DTC increased bone degradation and induced significant changes in the OPG/RANKL system. These changes include, besides the risk of osteoporosis, possible negative effects on the vascular function and an increased risk of cardiovascular disease.

Adult↗
PubMed2005

Serum levels of cathepsin K decrease with age in both women and men.

Bone turnover increases with age. In a previous study, we reported on bone metabolism in young and elderly women and men. The aim of the present investigation was to evaluate potential age- and gender-related changes in cathepsin K, a cysteine protease that plays an important role in the degradation of the organic matrix of bone. Twenty-five healthy premenopausal women, 24 young healthy men, 26 elderly women, and 25 elderly men participated in the study. Elderly women and men had significantly lower cathepsin K levels than younger ones. In both men and women, serum levels of cathepsin K were negatively correlated with age. In men there was a statistically significant negative correlation between serum levels of cathepsin K and osteoprotegerin, which inhibits osteoclast differentiation and activation. No association was found between serum levels of cathepsin K and bone-specific alkaline phosphatase, osteocalcin, or 25-hydroxy vitamin D. Thus, the age-related increase in OPG, which markedly inhibits the expression of cathepsin K, may also reduce serum levels of cathepsin K. Despite the age-related increase in bone resorption, this study shows lower cathepsin K values in elderly women and men than in younger subjects. It might be speculated that a different enzyme could compensate for the decline in cathepsin K during old age.

Adult↗
PubMed2005

Molecularly-defined lactose malabsorption, milk consumption and anthropometric differences in adult males.

BACKGROUND: Lactose malabsorption (LM) may be associated with reduced skeletal calcium content. Diagnosis to date has been based on indirect methods, with a high false-negative rate. Identification of the LCT polymorphism led to development of a PCR-based test. AIM: To evaluate the PCR-based test compared to a combination the hydrogen breath test and the lactose tolerance test, and investigate anthropometrical differences, changes in bone mineral density and oral calcium intake according to LCT polymorphism and milk-drinking habits. METHODS: All participants (n = 278) underwent clinical examination, with measurement of height, weight and bone density (DXA), and were genotyped for LCT polymorphism (LCT CC or LCT TT: CC is associated with LM). A subgroup (n = 51) had a hydrogen breath test and a lactose tolerance test, in addition to genotyping. RESULTS: Detection of LM by LCT polymorphism was highly significant (p = 0.001). The correlation between LCT genotype and self-reported milk-intolerance or dislike of milk with was slight, but the correlation with functional tests was highly significant. Non-milk-drinkers were lighter (-5 kg) and significantly shorter (-4 cm) than milk-drinkers (p = 0.07 and 0.04, respectively). Total calcium consumption was lower among non-milk-drinkers by about 18% (p = 0.03). DISCUSSION: Genotyping is an economic, quick and convenient method for diagnosing lactose malabsorption, with results comparable to existing tests. Sufficient calcium consumption may be relevant to body growth, as milk-drinkers were taller. Negative calcium bone balance may be prevented when provision is made for adequate calcium intake.

Adult↗
PubMed2004

Bone metabolism in patients more than five years after bone marrow transplantation.

We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG)--antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P=0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.

Adult↗
PubMed2003

Serum levels of osteoprotegerin increase with age in a healthy adult population.

Regulation of the balance of osteoblastic and osteoclastic activity is critical for the understanding of normal cell biology and forms the basis of metabolic bone diseases. Our study reports about influences of age and gender on serum levels of osteoprotegerin (OPG) and its association to other clinical parameters of bone metabolism in a precisely determined cohort of 1134 healthy subjects at 17 Austrian outpatient bone clinics, aged between 19 and 96 years (females n = 687, 50 +/- 21 years, 19-94, and males n = 447, 52 +/- 13.5 years, 24-96). Mean OPG serum levels for all participants were 50.83 +/- 51.47 pg/ml (n = 1134; median 36, 2-584) and we observed a sharp increase in females after 60 years and in males after 70 years of age. OPG serum levels increased significantly by age, 2.1 pg/ml in females and 1.9 pg/ml in males for every year (P < 0.0001). Correlation of OPG serum levels and several bone parameters of bone metabolism showed that OPG negatively correlated with serum iPTH (r = -0.14; P < 0.001) and with serum estradiol in females (r = -0.16, P < 0.0001). Bone mineral density measured by DXA method at the spine and at the hip did not correlate with OPG serum levels, except a borderline negative correlation at the trochanteric region (r = -0.1, P < 0.05) in females only. Our results show a significant increase of osteoprotegerin with age in healthy females and males but fluctuations do not predict bone mineral density under in vivo conditions.

Adult↗
PubMed2003

Assessment of vitamin D and calcium status in healthy adult Austrians.

BACKGROUND: Because there is reason to assume that also in Austria calcium and vitamin D malnutrition is wide-spread, we initiated a comprehensive study on calcium and vitamin D status in relation to bone health in a large group of the normal adult population. SUBJECTS AND METHODS: We assessed dietary calcium and vitamin D intake, serum concentrations of Ca2+, phosphate, alkaline phosphatase, 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), follicle-stimulating hormone (FSH), sex hormones and bone mineral density (BMD) by double-energy X-ray absorptiometry at five different skeletal sites in 648 females and 400 males (age 21-76 years). RESULTS: Mean daily intake of vitamin D (101 IU, range 0.2-320) and calcium (569 mg, range 40-2170) was significantly less than the respective recommended dietary allowances. Two hundred and seventy-one (26%) individuals had hypovitaminosis D with serum 25(OH)D < 12 ng mL(-1), while serum Ca2+ was less than normal in 82 (7.8%) subjects. Multiple regression analysis revealed significant correlations between mean calcium intake and BMD in the femoral region in the men (r = 0.13, P < 0.05) though not in the women. No consistent data could be obtained for associations between BMD and vitamin D status, except for 25(OH)D and BMD at the spine in the men (r = 0.10, P < 0.05). 25(OH)D correlated negatively (P < 0.05) with age in the women (r = -0.11) and with PTH in the women (r = -0.11) and men (r = -0.16). Inversely, a significant (P < 0.001) age-related increase in PTH was observed in both sexes (men, r = 0.19; women, r = 0.14). CONCLUSIONS: Prevalence of hypovitaminosis D in adult Austrians is an imminent risk for development of secondary hyperparathyroidism with advancing age, and requires timely correction of nutritional deficits.

Absorptiometry, Photon↗
PubMed2003

Normative data of bone mineral density in an unselected adult Austrian population.

BACKGROUND: There is increasing evidence that correct interpretation of bone mineral density (BMD) measurements by dual energy X-ray absorptiometry (DEXA) requires a population-specific reference range. We therefore collected data on age-related BMD in a random sample of the normal adult Austrian population to establish an appropriate normative database. METHODS: We measured BMD by DEXA at five different skeletal sites in 1089 subjects, i.e. 654 females and 435 males, aged between 21-76 years, who had been recruited by 17 centres across Austria. RESULTS: Age-related bone loss was observed until age 65 years with significant changes at the lumbar spine (r = -0.23), total hip (r = -0.07), trochanter (r = -0.10), femoral neck (r = -0.30) and Ward's triangle (r = -0.40) in the women but only at the femoral neck (r = -0.23) and at Ward's triangle (r = -0.40) in the men. When we calculated T scores from the BMD data of the young normal adult study population and used the T score set points according to the WHO classification of osteopenia and osteoporosis, we found that, depending on the skeletal site measured, 7.6-27.4% of the women and 16-41% of the men in our study group had low bone mass, whereas 0.6-2.7% of the female and 0.2-1.0% of the male study population were osteoporotic. However, osteoporosis was indicated in 4-9-fold more females and 5-15-fold more males when we based our estimates on the normative data provided by the manufacturers of the DEXA systems. CONCLUSION: Our data underscore the importance of using a population-specific reference range for DEXA measurements to avoid overdiagnosis of osteoporosis.

Absorptiometry, Photon↗
PubMed2001

Bone turnover markers and sex hormones in men with idiopathic osteoporosis.

BACKGROUND: In contrast to osteoporosis in postmenopausal women, osteoporosis in men has received much less attention. PATIENTS AND METHODS: We determined various biochemical parameters of bone metabolism and sex hormones in 31 men with idiopathic osteoporosis and 35 age matched control subjects. RESULTS: In the men with osteoporosis, a significantly increased urinary excretion of deoxypyridinoline (5.3 +/- 0.2 vs. 4.6 +/- 0.2 nmol mmol-1 creatinine; P = 0.033) in addition to increased serum levels of the c-terminal telopeptide of type I collagen (2677 +/- 230 vs. 2058 +/- 153 pmol; P = 0.037) were found. While parameters of bone formation were not significantly different in the patients and controls, serum bone sialoprotein levels were significantly decreased in the patients (3.7 +/- 0.8 vs. 12.4 +/- 4.0 ng mL-1; P = 0.021). Moreover, in men with idiopathic osteoporosis, lower levels of estradiol (91.3 +/- 5.8 vs. 114.6 +/- 7.8 pmol L-1; P = 0.044), higher levels of sex hormone binding globulin (31.5 +/- 3.1 vs. 24.2 +/- 1.4 nmol L-1; P = 0.034) and a decreased free androgen index (42.6 +/- 5.2 vs. 56.4 +/- 5.9; P = 0.016) were seen. Serum estradiol levels correlated negatively with several parameters of bone resorption. CONCLUSIONS: In men with idiopathic osteoporosis, bone resorption is increased and exceeds bone formation. The excessive bone resorption seen in idiopathic male osteoporosis may be due to decreased estradiol levels and low levels of bioavailable testosterone.

Adult↗
PubMed2001

[Osteoporosis in the man].

Osteoporosis in men is a severe condition probably more frequent than generally expected. The life-time risk of a low trauma fracture in a 60 year old man is 25%; moreover, approximately one third of hip fractures occurs in men. In contrast to postmenopausal osteoporosis, osteoporosis in men is frequently a secondary condition. In approximately 50% of cases, male osteoporosis is associated with an underlying disease or condition such as hypogonadism or long-term glucocorticoid treatment. Data from our group indicate that low serum estradiol levels and elevated sex hormone binding globulin levels may play a role in the pathogenesis of idiopathic male osteoporosis. Potential treatment modalities of osteoporosis in men include calcium and vitamin D supplementation, testosterone, fluoride, bisphophonates, calcitonin and parathyroid hormone. Currently, the data available favor the use of an aminobisphosphonate for the treatment of (idiopathic or glucocorticoid induced) osteoporosis.

Aged↗
PubMed2000

Gender differences in fracture risk and bone mineral density.

We have investigated gender-related differences of bone mineral density and fracture threshold in 136 males (age, 60.7+/-9.3 years) and 337 females (age, 59.7+/-7.8 years) without evidence of secondary osteoporosis. Women and men were examined for total amount of spine fractures and bone mineral density by quantitative computed tomography (QCT) of three non-fractured vertebral bodies L1-L5. Females with lumbar fractures (n=96) when compared with non-fracture women (n=241) were older and had lower bone density at their vertebral sites. Males with vertebral fractures (n=52) were older and had a significantly reduced bone mineral density of the spine when compared with healthy males (n=84). When we compared gender-related vertebral fracture rates, we observed a significantly higher prevalence of vertebral fractures in the male population. After matching males and females for age and bone mineral density to exclude an influence of either variable, we compared the prevalence of vertebral fracture risk in both sexes with logistic regression analysis. Data of estimated fracture risk, differed very significantly for sex and bone density at the vertebral site, indicating that men present fracture at a higher bone density level compared with females; in 10% of study population fractures occurred at a QCT level of 105 mg/cm(3) in women and 120 mg/cm(3) in men. The estimated odds ratio for sex of 3.1 (95% CI) means a three-fold increased risk for vertebral fractures compared to males at a given density level. These results underline that a decreased bone mineral density leads to the occurrence of spine fractures in females and males as well.

Aged↗
PubMed2000

Surface markers and transendothelial migration of dendritic cells from elderly subjects.

Age-related changes of immune functions have been extensively investigated in both humans and animal models; nevertheless, the literature on potential alterations of dendritic cells, potent antigen presenting cells responsible for initiating immune responses, with aging is very scarce. We studied the immuno-phenotype of peripheral blood dendritic cells of elderly and young subjects by three-color flow cytometry. In addition, the capacity of transendothelial migration, an important step in inflammatory reactions, of peripheral blood dendritic cells of elderly subjects was investigated in an in vitro model. The expression of HLA-DR in the peripheral blood dendritic cells of the elderly subjects was significantly decreased when compared to the young control subjects. The expression of various other surface markers was similar in the young and elderly subjects. The ability of transendothelial migration of dendritic cells was found to be unimpaired in the elderly subjects. Both in the young and elderly subjects a significantly higher expression of CD29, CD86, HLA-DR, and HLA-DQ in the dendritic cells that had migrated through the endothelium in comparison to nonadherent, nonmigrating cells was found. In the migrating dendritic cells of the elderly subjects a significantly increased expression of CD11c was observed, whereas the expression of CD54 was significantly enhanced in the migrating dendritic cells of the young subjects only. In conclusion, our results demonstrate intact functions and a normal immunophenotype of dendritic cells derived from elderly subjects. Dendritic cells thus seem to be functional and therefore are not responsible for the well-known decline of T cell functions with aging.

Aged↗
PubMed2000

Immunology and aging.

Aging is accompanied by numerous functional and phenotypic changes in T cells, B cells and monocytes/macrophages; moreover, increases in autoimmunity, infections and occurrence of cancer have been reported in aged people. Healthy elderly persons, defined according to the criteria of the SENIEUR protocol, show various alterations in immunocompetent cells. Recent data have shown that the distribution of the subsets of peripheral blood, T-cell subtypes, is influenced by age. With increasing age, CD45RA(+) naive cells are replaced by CD45RA(-) memory CD4(+) T cells. In the CD8(+) T-cell subset, we found an increased proportion of cells co-expressing CD57. In monocytes also, some alterations of the immunophenotype, for example the expression of the adhesion molecule CD54, were observed. A relative deficit of transendothelial migration with aging was found in T cells, whereas this function was not impaired in monocytes. The immunophenotype and the function of dendritic cells do no t appear to be affected by aging. Due to their capacity to present antigens to T cells and to induce T-cell proliferation, dendritic cells may provide a useful tool for immunotherapy. In conclusion, investigations of immune functions in aging people reveal that there is an alteration of the immunophenotype of T cells and monocytes. Several functions of T-cell accompanying mechanisms, for example cytokine production and cell migration, are also affected by aging. In contrast, dendritic cells do not seem to be influenced by the aging process.

Journal Article↗
PubMed2000

Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate bone mineral density and biochemical parameters of bone metabolism in ambulatory premenopausal female patients with systemic lupus erythematosus (SLE). METHODS: 30 women who fulfilled the ARA criteria for the classification of SLE were studied. Lumbar and femoral bone mineral density was determined by dual energy x ray absorptiometry. Various laboratory parameters including serum calcium, serum phosphorus, alkaline phosphatase, bone specific isoform of alkaline phophatase, propeptide of type 1 procollagen, deoxypyridinoline excretion, telopeptide of type 1 collagen, serum creatinine, osteocalcin, parathyroid hormone, 25-OH vitamin D, testosterone, progesterone, estradiol, follicle stimulating hormone and luteinotropic hormone were measured. RESULTS: According to the WHO criteria 39% of all patients with SLE studied had normal bone mineral density, 46% had osteopenia and 15% had osteoporosis at the lumbar spine; at the femoral neck 38.5% had normal bone mineral density, 38.5% had osteopenia and 23% suffered from osteoporosis. Significantly lower osteocalcin levels were found in SLE patients. All other bone resorption and formation markers measured were not statistically different, but higher serum albumin corrected calcium and lower phosphorus values were found in the SLE group. Of all sex hormones tested lower testosterone and higher follicle stimulating hormone concentrations were seen in patients with SLE. CONCLUSION: A high incidence was found of osteopenia and osteoporosis in premenopausal patients with SLE. Bone diminution in SLE seems to be attributable, at least in part, to decreased bone formation in SLE patients.

Adolescent↗
PubMed1999

[Prevention and prophylaxis of osteoporosis: options and limitations].

Osteoporosis is considered a systemic disease involving decreased bone mineral content and increased fracture risk. Therefore, for young people, adults and also the elderly, any measures have to taken which could prevent fractures. In this respect, clinically, femoral neck fractures are most important, however, in vertebral fractures a rise in morbidity and mortality can also be demonstrated. Radius fractures occurring in advanced age lead to increasing care being required and loss of independence. From today's point of view, it is tried to divide preventive measurements into primary and secondary steps, depending on whether healthy subjects or patients suffering from chronic diseases are affected. To evaluate the fracture risk, apart from anamnesis, bone density measurement and, in recent times, biomarker are suitable for the assessment of bone turnover. As primary prevention, basic lifestyle measures are recommended, in case of a concomitant relevant basic disease secondary prophylaxis is instituted to contain bone mineral loss. The following survey is to show the importance of prevention and of prophylaxis in osteoporosis both for healthy people and for patients with various accompanying diseases, and to list present possible preventive measures.

Adult↗
PubMed1998

[Lumbar bone density. Risk factor for vertebral fractures in women].

BACKGROUND AND OBJECTIVE: The direct connections between a reduction in bone density and an increase in the incidence of fractures with increasing age is well known. When interpreting bone density measurements the attending physician is confronted with an overlap of false-positive and false-negative parameters, as is also the case with biochemical data. Aim of this study was to determine, in addition to bone density, a fracture threshold, i.e. a value for bone density with maximal sensitivity and specificity, in a representative cohort of women. PATIENTS AND METHODS: 534 healthy women (mean age 60.9 +/- 8.07, range 40-83 years), seen in an out-patient osteological clinic between 1993 and 1996 were included. After full biochemical investigation to exclude a metabolic bone disease, bone density (LBD) of the lumbar vertebrae 1-5 and the number of vertebral body fractures were documented, together with age and menopausal status. LBD was measured by quantitative computed tomography (qCT), results being analysed with the Wilcoxon 2-sample test and logistic regression and assessed by receiver operating characteristics (ROC) analysis. RESULTS: None of the women with a qCT value over 111 mg/cc had evidence of vertebral fractures. Those with values under 60 mg/cc had at least one vertebral fracture (defined as at least 15% reduction in vertebral body height). There was a highly significant negative correlation between age and LBD (r = -0.56; P < 0.0001), as well as between LBD and the number of fractured vertebrae (r = -0.58, P < 0.0001). But there was no longer any correlation between age and number of vertebral body fractures once allowance was made for LBD (r = 0.001, not significant). The least overlap of false-positive and false-negative values was at an LBD with qCT values of 102 mg/cc. CONCLUSIONS: LBD is the determining variable for fracture risk independent of age. Despite an overlap of false-positive and false-negative LBD values, the probability of fractures can be predicted from bone mineral content.

Adult↗
PubMed1996

The effect of age on the transendothelial migration of human T lymphocytes.

Since the migration of immunologically active cells into perivascular tissue is an important step in acute and chronic inflammation, the authors studied the possible influence of age on the transendothelial migration of T cells in an in vitro model. After incubation on collagen gels coated with human endothelial cells, three populations of T cells of elderly and young subjects were harvested: non-adherent (NAD), bound (BND) and migrated (MIG) cells. The percentages of the BND and MIG fractions were similar in the young and elderly groups. Phenotypic analysis showed that in the starting population of the elderly subjects T-cell subpopulations that have an increased capacity of transendothelial migration (e.g., CD4+ memory cells, CD8+/CD57+ cells) were enriched: nevertheless ageing was not associated with an increase in the transendothelial migration of T cells.

Adult↗