Heinz Jürgen Roth

Medizinisches Versorgungszentrum Dr. Stein + Kollegen, Mönchengladbach, North Rhine-Westphalia, Germany

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Publications (34)110.65 Total impact

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    ABSTRACT: The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.
    Journal of Bone and Mineral Metabolism 06/2015; DOI:10.1007/s00774-015-0681-3 · 2.11 Impact Factor
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    ABSTRACT: OBJECTIVE: Although emerging evidence indicates an association between vitamin D and serum lipids, the data are still inconsistent. The purpose of the present study was to investigate whether 25-hydroxycholecalciferol (25-hydroxyvitamin D3; 25(OH)D3) or intact parathyroid hormone (iPTH) was independently related to serum lipids in elderly women and men. DESIGN: Cross-sectional study. Fasting serum levels of 25(OH)D3, iPTH, TAG, total cholesterol (TC), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) were assessed. Body composition was measured by bioelectrical impedance analysis. Lifestyle factors, such as nutrient intake, time spent outdoors, physical activity, smoking, supplement intake and medication, were assessed by questionnaires. Multiple regression analyses were performed to examine associations of 25(OH)D3 and iPTH with serum lipids. SETTING: Giessen, Germany. SUBJECTS: One hundred and ninety-three well-functioning German elderly aged 66-96 years. RESULTS: After adjusting for age, body fat, physical activity, smoking, alcohol intake, lipid-modifying drugs and either iPTH or 25(OH)D3, 25(OH)D3 was a predictor of TAG (standardised coefficient beta (β)=-0·180), HDL-C (β=0·197), LDL-C:HDL-C (β=-0·298) and TC:HDL-C (β=-0·302) in women, whereas iPTH was a predictor of HDL-C (β=-0·297) in men. In sub-analysis, associations between 25(OH)D3 and TC (β=-0·252), HDL-C (β=0·230), LDL-C (β=-0·324), LDL-C:HDL-C (β=-0·412) and TC:HDL-C (β=-0·380) were found in women with 25(OH)D3 concentrations above or equal the median vitamin D status (62·3 nmol/l), but not in women with lower 25(OH)D3 concentrations. CONCLUSIONS: In the elderly, associations of 25(OH)D3 and iPTH with serum lipids may differ by sex and may require a vitamin D status above 62 nmol/l.
    Public Health Nutrition 10/2014; 18(09):1-8. DOI:10.1017/S1368980014002286 · 2.48 Impact Factor
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    ABSTRACT: Objective Although homocysteine has been proposed as a cardiovascular risk factor, interventional trials lowering homocysteine have not consistently demonstrated clinical benefit. Recent evidence proposed the homocysteine metabolite S-adenosylhomocysteine (SAH) rather than homocysteine itself as the real culprit in cardiovascular disease. Of note, SAH is predominantly excreted by the kidneys, and cannot be lowered by vitamin supplementation. Due to its cumbersome measurement, data from large studies on the association between SAH, kidney function and cardiovascular disease are not available. Methods We recruited 420 apparently healthy subjects into our I Like HOMe FU study. Among all study participants, we assessed parameters of C1 metabolism (homocysteine, SAH and S-adenosylmethionine), renal function (estimated glomerular filtration rate [eGFR]) and subclinical atherosclerosis (common carotid intima-media-thickness [IMT]). eGFR was estimated by the CKD-EPIcreat-cys equation. Results Traditional cardiovascular risk factors and subclinical atherosclerosis were associated with SAH, but not with homocysteine (IMT vs SAH: r = 0.129; p = 0.010; IMT vs homocysteine: r = 0.009; p = 0.853). Moreover, renal function was more closely correlated with SAH than with homocysteine (eGFR vs SAH: r = −0.335; p < 0.001; eGFR vs homocysteine: r = −0.250; p < 0.001). The association between eGFR and SAH remained significant after adjustment for traditional cardiovascular risk factors. Conclusion In summary, cardiovascular risk factors, subclinical atherosclerosis and eGFR are more strongly associated with SAH than with homocysteine in apparently healthy subjects. Thus, SAH might represent a more promising target to prevent cardiovascular disease than homocysteine.
    Atherosclerosis 05/2014; 234(1):17–22. DOI:10.1016/j.atherosclerosis.2014.02.002 · 3.97 Impact Factor
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    ABSTRACT: CKD-mineral and bone disorders (CKD-MBD) measures contribute to cardiovascular morbidity in patients with CKD. Among these, fibroblast growth factor (FGF)-23 and its coreceptor Klotho may exert direct effects on vascular and myocardial tissues. Klotho exists in a membrane-bound and a soluble form (sKlotho). Recent experimental evidence suggests sKlotho has vasculoprotective functions. Traditional and novel CKD-MBD variables were measured among 444 patients with CKD stages 2-4 recruited between September 2008 and November 2012 into the ongoing CARE FOR HOMe study. Across tertiles of baseline sKlotho and FGF-23, the incidence of two distinct combined end points was analyzed: (1) the first occurrence of an atherosclerotic event or death from any cause and (2) the time until hospital admission for decompensated heart failure or death from any cause. Patients were followed for 2.6 (interquartile range, 1.4-3.6) years. sKlotho tertiles predicted neither atherosclerotic events/death (fully adjusted Cox regression analysis: hazard ratio [HR] for third versus first sKlotho tertile, 0.75 [95% confidence interval (95% CI), 0.43-1.30]; P=0.30) nor the occurrence of decompensated heart failure/death (HR for third versus first sKlotho tertile, 0.81 [95% CI, 0.39-1.66]; P=0.56). In contrast, patients in the highest FGF-23 tertile had higher risk for both end points in univariate analysis. Adjustment for kidney function attenuated the association between FGF-23 and atherosclerotic events/death (HR for third versus first FGF-23 tertile, 1.23 [95% CI, 0.58-2.61]; P=0.59), whereas the association between FGF-23 and decompensated heart failure/death remained significant after adjustment for confounders (HR for third versus first FGF-23 tertile, 4.51 [95% CI, 1.33-15.21]; P=0.02). In this prospective observational study of limited sample size, sKlotho was not significantly related to cardiovascular outcomes. FGF-23 was significantly associated with future decompensated heart failure but not incident atherosclerotic events.
    Clinical Journal of the American Society of Nephrology 03/2014; 9(6). DOI:10.2215/CJN.07870713 · 5.25 Impact Factor
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    ABSTRACT: Context: Relations between fibroblast growth factor-23 (FGF-23), soluble-alpha klotho (s-α klotho), and kidney function in chronic kidney disease (CKD) are still unclear. Especially the role of s-α klotho requires further study. Objective: To analyze the relation of s-α klotho to estimated glomerular filtration rate (eGFR), FGF-23 and other parameters of calcium-phosphate metabolism, and to investigate the response of s-α klotho to cholecalciferol. Design and setting: Eight-week RCT (Vitamin D and Chronic Renal Insuffiency). Patients: Twenty-four CKD patients stage 1-5. Interventions: 40000 IU cholecalciferol or placebo weekly. Main outcome measure: S-α klotho determined by ELISA with anti-human klotho antibodies 67G3 and 91F1. Results: For all patients, s-α klotho concentrations did not differ between CKD stages. When patients were subdivided based on FGF-23 concentrations a positive association of s-α klotho with eGFR became apparent in patients with lower than median FGF-23 concentrations but not in those above median value. Patients with s-α klotho below 204 pg/ml showed higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase (b-ALP) compared to patients with higher s-α klotho. Treatment with cholecalciferol significantly increased 1,25-diOHD. The increase of FGF-23 had only borderline significance. There was no significant effect of high-dose cholecalciferol administration for 8 weeks on plasma s-α klotho. Conclusions: CKD patients with s-α klotho below 204 pg/ml had higher age, lower phosphate clearance, and lower b-ALP. An association of s-α klotho with eGFR was observed only in presence of close to normal, but not high, FGF-23 concentrations. Cholecalciferol treatment did not change s-α klotho concentrations.
    The Journal of Clinical Endocrinology and Metabolism 02/2014; 99(5):jc20134171. DOI:10.1210/jc.2013-4171 · 6.31 Impact Factor
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    ABSTRACT: This study compared features of the metabolic syndrome between healthy controls and depressed patients without activation of the hypothalamus–pituitary–adrenal (HPA) system. After exclusion of non-suppressors to 1 mg dexamethasone, we included 20 depressed inpatients and 34 healthy controls in the analyses. We assessed HPA system activity (diurnal saliva cortisol profile, cortisol excretion), normetanephrine excretion as well as fasting glucose, lipid profile and blood pressure. With regard to body composition, we measured waist circumference as well as visceral fat and adrenal volume by magnetic resonance (MR) imaging. Five depressed patients (25%) and five healthy controls (15%) fulfilled the criteria of the metabolic syndrome according NCEP-ATP-III. Depression was significantly related with fasting glucose and negatively associated with mean blood pressure (BP) and, by trend, with low HDL-cholesterol. We conclude that depressed patients may have modest metabolic disturbances even in the complete absence of activation of stress-responsive systems. Hence some metabolic disturbances in depressed patients may not be explicable by HPA activation. Additional factors are required to mediate the link between affective and metabolic disorders.
    Psychoneuroendocrinology 01/2014; 39(1):104–110. DOI:10.1016/j.psyneuen.2013.09.030 · 5.59 Impact Factor
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    ABSTRACT: Background:It was shown that nonoxidized PTH (n-oxPTH) is bioactive, whereas oxidized PTH at methionine residues results in loss of biological activity.Methods:In this study we analyzed the association of n-oxPTH on mortality in hemodialysis patients using a recently developed assay system.Results:Hemodialysis patients (224 men, 116 women) had a median age of 66 years. One hundred seventy patients (50%) died during the follow-up period of 5 years. Median n-oxPTH levels were higher in survivors (7.2 ng/L) compared with deceased patients (5.0 ng/L; P = .002). Survival analysis showed an increased survival in the highest n-oxPTH tertile compared with the lowest n-oxPTH tertile (χ(2), 14.3; P = .0008). Median survival was 1702 days in the highest n-oxPTH tertile, whereas it was only 453 days in the lowest n-oxPTH tertile. Multivariable-adjusted Cox regression showed that higher age increased odds for death, whereas higher n-oxPTH reduced the odds for death. Another model analyzing a subgroup of patients with intact PTH (iPTH) concentrations at baseline above the upper normal range of the iPTH assay (70 ng/L) revealed that mortality in this subgroup was associated with oxidized PTH but not with n-oxPTH levels.Conclusions:The predictive power of n-oxPTH and iPTH on the mortality of hemodialysis patients differs substantially. Measurements of n-oxPTH may reflect the hormone status more precisely. The iPTH-associated mortality is most likely describing oxidative stress-related mortality.
    The Journal of Clinical Endocrinology and Metabolism 10/2013; 98(12). DOI:10.1210/jc.2013-2139 · 6.31 Impact Factor
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    ABSTRACT: Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970(s) and 80(s). However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies. © 2013 S. Karger AG, Basel.
    Kidney and Blood Pressure Research 07/2013; 37(4-5):240-251. DOI:10.1159/000350149 · 1.82 Impact Factor
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    ABSTRACT: Background Imatinib is a highly effective drug in up-front treatment of chronic myeloid leukemia (CML). In children impaired longitudinal growth has been reported as side effect exerted by this drug under prolonged therapy. We therefore prospectively evaluated alterations of bone biochemical markers in pediatric patients with CML under ongoing imatinib exposure. Material/Methods Bone metabolic markers (calcium, phosphate, magnesium, parathyroid hormone, vitamin D, procollagen type l N propeptide [PINP], and C-terminal cross-linking telopeptide of collagen [CTX-I], osteocalcin [OC]; pyridinoline [PYD], and desoxypyridinoline [DPD]) were determined in 17 patients with CML aged 4–17 years under imatinib treatment in three-month intervals over a 2.5 year period. Results Hyperparathyroidism developed in 8/17 patients and low 25-hydroxyvitamin-D3 levels were found in 15/17 patients. Increased OC levels were detected in 58% of all specimen showing a linear significant decline of −0.30 μg OC per l per week (p=0.04). Serum PINP was lowered in 25% and serum CTX-I was above the normal range in 57% of the specimen originating exclusively from prepupertal patients. Urine PYD and Urine DPD levels were above the normal range in 10% and 9%, respectively, of all specimen collected and a statistically significant linear decline of −0.16 nmol DPD/mg creatinine/week was calculated (p=0.01). Conclusions Bone remodeling may be dysregulated by imatinib. Data suggest that impaired bone formation exceeds that of decreased bone resorption. Regular evaluation of the skeletal actions during long-term imatinib treatment in childhood CML is warranted.
    Medical science monitor: international medical journal of experimental and clinical research 12/2012; 18(12):CR721-728. DOI:10.12659/MSM.883599 · 1.22 Impact Factor
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    ABSTRACT: A decreased expression of the fibroblast growth factor (FGF)-23 coreceptor Klotho was postulated as an early alteration in chronic kidney disease mineral and bone disorder, resulting in a compensatory increase in plasma FGF-23 levels. Klotho exists in both membrane-bound and secreted (sKlotho) forms, the latter of which may exert vasculoprotective effects. Here we analyzed plasma sKlotho levels in a large cohort of 312 patients with stage 2-4 chronic kidney disease, and assessed plasma levels of FGF-23, sKlotho, parathyroid hormone, and urinary fractional phosphate excretion. Patients were prospectively followed for an average of 2.2 years for the occurrence of death or initiation of renal replacement therapy. The levels of sKlotho were significantly associated with age, but not with the glomerular filtration rate or other parameters of calcium-phosphate metabolism. Moreover, while patients with high FGF-23 levels faced worst outcome even after adjustment for confounders, we found no prognostic impact of sKlotho. Thus, plasma levels of sKlotho were not related to kidney function and did not predict adverse outcome in patients with chronic kidney disease. Future studies are needed to understand how tissue expression, urinary excretion, and plasma levels of Klotho diverge in progressive chronic kidney disease.Kidney International advance online publication, 15 August 2012; doi:10.1038/ki.2012.288.
    Kidney International 08/2012; 83(1). DOI:10.1038/ki.2012.288 · 8.52 Impact Factor
  • Journal of clinical psychopharmacology 08/2012; 32(4):574-6. DOI:10.1097/JCP.0b013e31825ddf1b · 3.76 Impact Factor
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    ABSTRACT: Oxidation of PTH at methionine residues results in loss of biological activity. PTH may be oxidized in patients with renal disease. The aim of this study was to develop an assay considering oxidation of PTH. Oxidized hPTH was analyzed by high resolution nano-liquid chromatography coupled to ESI-FTT tandem mass spectrometry (nanoLC-ESI-FT-MS/MS) directly and after proteolytic cleavage. The oxidized hPTH(1-84) sample shows TIC-peaks at 18-20 min and several mass peaks due to mass shifts caused by oxidations. No significant signal for oxidized hPTH(1-84) species after removal of oxidized PTH molecules by a specific column with monoclonal antibodies (MAB) raised against the oxidized hPTH was detectable. By using this column in samples from 18 patients on dialysis we could demonstrate that measured PTH concentrations were substantially lower when considering oxidized forms of PTH. The relationship between PTH concentrations determined directly and those concentrations measured after removal of the oxidized PTH forms varies substantially. In some patients only 7% of traditionally measured PTH was free of oxidation, whereas in other patients 34% of the traditionally measured PTH was real intact PTH. In conclusion, a huge but not constant proportion of PTH molecules are oxidized in patients requiring dialysis. Since oxidized PTH is biologically inactive, the currently used methods to detect PTH in daily clinical practice may not adequately reflect PTH-related bone and cardiovascular abnormalities in patients on dialysis.
    PLoS ONE 07/2012; 7(7):e40242. DOI:10.1371/journal.pone.0040242 · 3.23 Impact Factor
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    ABSTRACT: Background Emerging evidence indicates that there is an association between vitamin D and obesity. The aim of this study was to investigate whether the level of serum 25-hydroxyvitamin D3 [25(OH)D3] in the elderly is influenced by parameters of anthropometry and body composition independent of potential confounding lifestyle factors and the level of serum intact parathyroid hormone (iPTH). Methods Cross-sectional data of 131 independently living participants (90 women, 41 men; aged 66–96 years) of the longitudinal study on nutrition and health status in senior citizens of Giessen, Germany were analysed. Concentrations of 25(OH)D3 and iPTH were ascertained by an electrochemiluminescence immunoassay. Body composition was measured by a bioelectrical impedance analysis. We performed univariate and multiple regression analyses to examine the influence of body composition on 25(OH)D3 with adjustments for age, iPTH and lifestyle factors. Results In univariate regression analyses, 25(OH)D3 was associated with body mass index (BMI), hip circumference and total body fat (TBF) in women, but not in men. Using multiple regression analyses, TBF was shown to be a negative predictor of 25(OH)D3 levels in women even after controlling for age, lifestyle and iPTH (ß = −0.247; P = 0.016), whereas the associations between BMI, hip circumference and 25(OH)D3 lost statistical significance after adjusting for iPTH. In men, 25(OH)D3 was not affected by anthropometric or body composition variables. Conclusions The results indicate that 25(OH)D3 levels are affected by TBF, especially in elderly women, independent of lifestyle factors and iPTH.
    Nutrition & Metabolism 05/2012; 9(1):42. DOI:10.1186/1743-7075-9-42 · 3.36 Impact Factor
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    ABSTRACT: Although several studies indicate a link between vitamin D status and blood pressure (BP), the results are inconsistent. The purpose of this study is to investigate whether in predominantly non-obese elderly people without vitamin D deficiency or very high intact parathyroid hormone (iPTH) levels serum 25-hydroxyvitamin D3 [25(OH)D3] and iPTH are independently associated with BP. Cross-sectional data of 132 non-institutionalised subjects (90 women and 42 men, aged 66- 96 years) from Giessen, Germany, were analysed. Serum 25(OH)D3 and iPTH were measured by an electrochemiluminescence immunoassay and BP was determined with a sphygmomanometer. We performed univariate and multiple regression analyses to examine the influence of 25(OH)D3 and iPTH on BP with adjustments for age, body composition and lifestyle factors. While iPTH had no impact on BP, 25(OH)D3 was negatively associated with systolic BP in men, but not in women. After splitting the cohort into antihypertensive medication users and non-users, 25(OH)D3 was a significant predictor for systolic and diastolic BP only in men not receiving antihypertensive medicine, even after multiple adjustment. Adjustment for 25(OH)D3 resulted in an inverse association of iPTH with diastolic BP also only in men without intake of antihypertensive medicine. In elderly men without vitamin D deficiency and not taking antihypertensive medicine, 25(OH)D3 may be a negative determinant of BP, independent of iPTH, body composition and lifestyle factors. Furthermore, iPTH may be an independent negative determinant of diastolic BP in men not taking antihypertensive medicine.
    Nutrition & Metabolism 03/2012; 9(1):20. DOI:10.1186/1743-7075-9-20 · 3.36 Impact Factor
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    ABSTRACT: The goal was to analyze the link between blood levels of calcidiol and all-cause, cardiac and infectious diseases, and mortality due to cancer in hemodialysis patients. This study retrospectively evaluated a representative sub-cohort (n=6,518) of German hemodialysis patients from the incidence cohorts 1997-2006. Most (58.8%) were found to be vitamin D deficient (25(OH)D<20 ng/ml), with 41.2% being severely deficient (25(OH)D<12.5 ng/ml). All-cause mortality risk more than doubled in patients with severe deficiency (adjusted odds ratio (aOR)=2.67; 95% confidence interval (CI)=2.30-3.10; p<0.0001). Comparable data were obtained for mortality from cardiac disease (aOR=1.57; 95% CI=1.30-1.88; p<0.0001), infectious disease (aOR=1.48; 95% CI=1.15-1.90; p=0.0026), and cancer (aOR=1.51; 95% CI=1.09-2.08; p=0.0121), respectively. These data highlight the need to ensure primarily adequate 25(OH)D levels in dialysis patients for an advantage of survival.
    Anticancer research 01/2012; 32(1):391-5. · 1.87 Impact Factor
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    ABSTRACT: The effect of ibandronate 150 mg/once monthly in the treatment of post-menopausal osteopenia and osteoporosis on bone micro-structure at the distal tibia and radius has not been considered to date. Seventy post-menopausal women with osteoporosis or osteopenia were recruited. All subjects received calcium and vitamin D supplementation and were randomized to either a group which took 150 mg ibandronate oral monthly or a placebo group over a 12-month period. μCT measures of the distal tibia and radius were conducted every three months, with DXA lumbar spine and hip measurements conducted only pre and post and serum markers of bone formation and resorption measured every 6 months. After 12-months no significant impact of ibandronate on the primary outcome measures bone-volume to tissue-volume and trabecular separation at the distal tibia (p≥0.15) was found. Further multiple regression analyses of the primary end-points indicated a significant effect favoring the ibandronate intervention (p=0.045). Analysis of secondary end-points showed greater increases in distal tibia cortical thickness, cortical density and total density (p≤0.043) with ibandronate and no significant effects at the distal radius, but greater increases of hip DXA-BMD and lumbar spine DXA-BMD (p≤0.017). Ibandronate use resulted in a marked reduction in bone turnover (p<0.001). While ibandronate resulted in greater mineralization of bone, this effect differed from one body region to another. There was some impact of ibandronate on bone structure (cortical thickness) at the distal tibia, but not on bone-volume to tissue-volume or trabecular separation.
    Bone 10/2011; 50(1):317-24. DOI:10.1016/j.bone.2011.10.027 · 4.46 Impact Factor
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    ABSTRACT: A new electrochemiluminescence testosterone immunoassay (Elecsys® Testo II) was evaluated. Within-run precision, total precision, and method comparisons to the former immunoassay and LC-MS/MS were investigated. Reference intervals were established for adults and children. Imprecision ranged from 0.9% to 8.5%. Method comparisons revealed slopes from 0.68 to 1.32 and coefficients of correlation from 0.893 to 0.991. Improved agreement with LC-MS/MS was demonstrated, especially for female patients. The assay may be a suitable alternative for laboratories with no access to MS techniques.
    Clinical biochemistry 10/2010; 44(2-3):264-7. DOI:10.1016/j.clinbiochem.2010.09.024 · 2.28 Impact Factor
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    ABSTRACT: Most recently, a new rapid and fully automated electrochemiluminescence immunoassay for the determination of TSH receptor autoantibodies (TRAb) based on the ability of TRAb to inhibit the binding of a human thyroid-stimulating monoclonal antibody (M22) has been established. To evaluate this assay system in clinical routine based on an international multicentre trial and to compare the results with other established TRAb assays. Totally 508 Graves' disease (GD), 142 autoimmune thyroiditis, 107 subacute thyroiditis, 109 nonautoimmune nodular goitre, 23 thyroid cancer patients and 446 normal controls were retrospectively evaluated. ROC plot analysis revealed an area under curve of 0.99 (95% CI: 0.99-1.0) indicating a high assay sensitivity and specificity. The highest sensitivity (99%) and specificity (99%) was seen at a cut-off level of 1.75 IU/l. Here, the calculated positive predictive value was 95%, whereas the negative predictive value was 100%. Applying the ROC plot-derived cut-off of 1.75 IU/l we found a sensitivity for TRAb positivity within the group of newly diagnosed GD patients of 97% which is in accordance to the sum of different nonautomated porcine TSH receptor-based assays with a sensitivity of 94% indicating an excellent analytical performance of the new assay format. Detailed comparison of the automated and the sum of manual assays revealed a near identical specificity. Our results demonstrate that this new assay system has a high sensitivity for detecting GD and specificity for discriminating from other thyroid diseases. This assay may represent the future technology for rapid fully automated TRAb detection.
    Clinical Endocrinology 10/2009; 71(4):566-73. DOI:10.1111/j.1365-2265.2008.03512.x · 3.35 Impact Factor
  • Dieter Gassner · Werner Stock · Ruth Golla · Heinz-Jürgen Roth
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    ABSTRACT: Hyperthyroidism in Graves' disease (GD) is often associated with the production of autoantibodies (TRAb) to the thyrotropin receptor (TSHR). Current manual second generation TRAb assays demonstrate high clinical sensitivity, but are labor-intensive and time consuming. Until recently, technical difficulties prevented the availability of an automatic TRAb assay. Development of a fast and fully automated TRAb assay on the Elecsys/cobas e electrochemiluminescence immunoassay platform. A labeled thyroid-stimulating human monoclonal TSHR autoantibody (M22) was used in an automated M22-binding inhibition assay. TRAb are detected by their ability to competitively inhibit M22-binding to solubilized porcine TSHR (pTSHR). High clinical sensitivity could be maintained by assembling multiple TSHR binding sites within a soluble oligomeric immunocomplex for improved TRAb binding. Requirement of sufficient on board stability of the delicate TSHR structure in solution for several days was met by pre-complexation of the pTSHR with a capture antibody to its C-terminus in combination with the use of structure-stabilizing chemical chaperones. Total imprecision coefficient of variation (CV) at 1.71 (approximate cut-off) was found to be 11.4%. TRAb results were available within 30 min. Availability of a fast and automatic TRAb assay offers an attractive alternative to the manual TRAb assays for the differential diagnosis of hyperthyroidism.
    Clinical Chemistry and Laboratory Medicine 08/2009; 47(9):1091-5. DOI:10.1515/CCLM.2009.245 · 2.96 Impact Factor
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    Bone 05/2009; 44. DOI:10.1016/j.bone.2009.01.019 · 4.46 Impact Factor

Publication Stats

542 Citations
110.65 Total Impact Points


  • 2012–2014
    • Medizinisches Versorgungszentrum Dr. Stein + Kollegen
      Mönchengladbach, North Rhine-Westphalia, Germany
  • 2004–2014
    • Labor Dr. Gärtner und Kollegen
      Ravensburg, Baden-Württemberg, Germany
  • 2009
    • Roche
      • Roche Tissue Diagnostics
      Basel, BS, Switzerland
  • 2003
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany