Biochemical markers of bone turnover in patients with spinal metastases after resistance training under radiotherapy--a randomized trial.

BACKGROUND: To compare the effects of resistance training versus passive physical therapy on bone turnover markers (BTM) in the metastatic bone during radiation therapy (RT) in patients with spinal bone metastases. Secondly, to evaluate an association of BTM to local response, skeletal-related events (SRE), and number of metastases. METHODS: In this randomized trial, 60 patients were allocated from September 2011 to March 2013 into one of the two arms: resistance training (Arm A) or passive physical therapy (Arm B) with thirty patients in each arm during RT. Biochemical markers such as pyridinoline (PYD), desoxy-pyridinoline (DPD), bone alkaline phosphatase (BAP), total amino-terminal propeptide of type I collagen (PINP), beta-isomer of carboxy-terminal telopeptide of type I collagen (CTX-I), and cross-linked N-telopeptide of type I collagen (NTX) were analyzed at baseline, and three months after RT. RESULTS: Mean change values of PYD and CTX-I were significantly lower at 3 months after RT (p = 0.035 and p = 0.043) in Arm A. Importantly, all markers decreased in both arms, except of PYD and CTX-I in arm B, although significance was not reached for some biomarkers. In arm A, the local response was significantly higher (p = 0.003) and PINP could be identified as a predictor for survivors (OR 0.968, 95%CI 0.938-0.999, p = 0.043). BAP (OR 0.974, 95%CI 0.950-0.998, p = 0.034) and PINP (OR 1.025, 95%CI 1.001-1.049, p = 0.044) were related with an avoidance of SRE. CONCLUSIONS: In this group of patients with spinal bone metastases, we were able to show that patients with guided resistance training of the paravertebral muscles can influence BTM. PYD and CTX-I decreased significantly in arm A. PINP can be considered as a complementary tool for prediction of local response, and PINP as well as BAP for avoidance of SRE. TRIAL REGISTRATION: Clinical trial identifier NCT 01409720. August 2, 2011.

Automated Competitive Protein-Binding Assay for Total 25-OH Vitamin D, Multicenter Evaluation and Practical Performance.

BACKGROUND: The Roche Elecsys Vitamin D Total competitive protein-binding assay uses recombinant vitamin D binding protein for measuring 25-hydroxyvitamin D (25-OHD), which is different from commonly used antibody assays. METHODS: The assay, standardized against LC-MS/MS, was tested at four sites. Evaluation included precision; between-laboratory variability; functional sensitivity; correlation to LC-MS/MS, HPLC, and immunoassays; as well as robustness, traceability, and EQAS performance. RESULTS: Precision testing showed within-run coefficient of variations (CVs) of ≤ 7%, within-laboratory CVs of <9.5%, between-laboratory precision CVs of ≤ 10.1%, and a functional sensitivity below 9.8 nmol/l (at CV 12.9%). The assay showed equivalent 25-OHD levels for matched serum and plasma samples, good reagent lot-to-lot consistency in pooled sera over time, and good agreement with HPLC (relative bias -8.8%). Comparison with LC-MS/MS methods yielded relative biases of -15.4, -13.5, -10.2, and 3.2%. Comparison against immunoassays showed a relative bias of 14.5% (DiaSorin Liaison) and -58.2% (IDS-iSYS). The overall mean results in 2 years DEQAS was 102% of the ALTM. In a certified reference patient panel, the average bias was < 4% for the sum of 25-OHD2 and 25-OHD3. CONCLUSION: The Elecsys Vitamin D Total assay demonstrated good overall performance and is, according to present standards, very suitable for automated measurement of 25-OHD.

Clinical evaluation of commercial automated SARS-CoV-2 immunoassays.

OBJECTIVE: Numerous immunoassays for detecting antibodies directed against SARS-CoV-2 have been rapidly developed and released. Validations of these have been performed with a limited number of samples. The lack of standardisation might lead to significantly different results. This study compared ten automated assays from six vendors in terms of sensitivity, specificity and reproducibility. METHODS: This study compared ten fully automated immunoassays from the following vendors: Diasorin, Epitope Diagnostics, Euroimmun, Roche, YHLO, and Snibe. The retrospective part of the study included patients with a laboratory-confirmed COVID-19 infection, and controls comprised patients with a suspected infection, in whom the disease was excluded. Furthermore, biobanked sera were taken as negative controls (n = 97). The retrospective part involved four groups: (1) laboratory-confirmed COVID-19 infection (n = 183); (1B) suspected COVID-19 infection (n = 167) without a qRT-PCR result but positive serological results from at least two different assays, and suspected COVID-19 infection due to a positive serological result from the Roche assay (n = 295); (2) biobanked sera obtained from patients before the emergence of SARS-CoV-2 (n = 97) as negative controls; and (2A) probably COVID-19-negative sera with negative serological results from at least two different assays (n = 152). RESULTS: Overall diagnostic sensitivities were: Euroimmun (IgA) 87%; Epitope Diagnostics (IgG) 83%; YHLO (IgG) 77%; Roche (IgM/IgG) 77%; Euroimmun (IgG) 75%; Diasorin (IgG) 53%; Epitope Diagnostics (IgM) 52%; Snibe (IgG) 47%; YHLO (IgM) 35%; and Snibe (IgM) 26%. Diagnostic specificities were: YHLO (IgG) 100%; Roche, 100%; Snibe (IgM/IgG) 100%; Diasorin (IgG) 97%; Euroimmun (IgG) 94%; YHLO (IgM) 94%; Euroimmun (IgA) 83%. CONCLUSION: Assays from different vendors substantially varied in terms of their performance. These findings might facilitate selection of appropriate serological assays.

Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves' disease (GD): an international multicentre trial.

BACKGROUND: 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. OBJECTIVE: To evaluate this assay system in clinical routine based on an international multicentre trial and to compare the results with other established TRAb assays. PATIENTS AND MEASUREMENTS: 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. RESULTS: 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. CONCLUSION: 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.

First automated assay for thyrotropin receptor autoantibodies.

BACKGROUND: 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. METHODS: Development of a fast and fully automated TRAb assay on the Elecsys/cobas e electrochemiluminescence immunoassay platform. RESULTS: 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. CONCLUSIONS: Availability of a fast and automatic TRAb assay offers an attractive alternative to the manual TRAb assays for the differential diagnosis of hyperthyroidism.

Preoperative shock wave therapy reduces ischemic necrosis in an epigastric skin flap model.

Extracorporeal shock wave therapy (ESWT) has recently been demonstrated to improve skin flap survival. In all these studies EWST was applied immediately after the surgical intervention. Thus, the purpose of this study was to determine the preoperative effect of ESWT as a noninvasive technique to precondition flap tissue in a rat epigastric skin flap model. EWST and control groups each contained 10 animals. ESWT was applied 7 days before the surgical intervention, whereas the control group received no treatment. Follow-up evaluation was performed on postoperative day 5. The mean area of flap necrosis, expressed as a percentage of the total flap area, was calculated. A significant reduction of the average flap necrosis area was observed in the ESWT group (27.2% +/- 9.6%) compared with the control group (46.1% +/- 7.9% (P < 0.05). In summary, this study indicates that preoperative ESWT may enhance skin flap survival in a rodent model.

Accuracy and clinical implications of seven 25-hydroxyvitamin D methods compared with liquid chromatography-tandem mass spectrometry as a reference.

BACKGROUND: The most reliable assessment of vitamin D status is measurement of plasma 25-hydroxyvitamin D (25[OH]D) concentration. High variability in 25(OH)D measurements due to utilized test and assay technologies and the lack of standardization against reference materials and reference method often confounds proper assessment of vitamin D status. METHODS: We evaluated the accuracy of six routinely available methodologies: high-performance liquid chromatography (HPLC), the IDS-radioimmunoassay (IDS-RIA) and enzyme immunoassay (IDS-EIA), the Nichols Advantage automated protein-binding assay (Advantage), two versions of the DiaSorin automated immunoassay (Liaison 1 and Liaison 2)--and one prototype automated immunoassay (Elecsys) for assessment of the 25(OH)D(3) status in a cohort of 300 randomly selected patients' samples compared with the reference method liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Passing-Bablok regression analysis demonstrated a slope for each method compared with LC-MS/MS that varied from 0.62 (IDS-EIA) to 1.0 (HPLC). The Advantage and the Liaison 1 showed significant deviation from linearity with highly variable individual results vs. the LC-MS/MS. Difference plots revealed a considerable persistent proportional bias for the IDS-RIA and IDS-EIA. All evaluated methods except HPLC demonstrated a more or less considerable deviation of individual 25(OH)D(3) values compared with LC-MS/MS defined target concentrations. CONCLUSIONS: Standardization of methods for the quantification of 25(OH)D on a human-based sample panel by means of LCMS/MS would help to reduce the inter-method variability with respect to accuracy existing in 25(OH)D measurement considerably. However, there will still remain differences in the accuracy of methods utilizing sample purification before final quantification or immunological reaction when compared with those methods without separate sample purification.

Partial Body UV Exposure in Chronic Kidney Disease and Extrarenal Vitamin D Metabolism.

BACKGROUND/AIM: Exposure of the skin to sunshine is the major natural source of vitamin D. In order to imitate this natural production of vitamin D for patients with chronic kidney disease, hemodialysis patients were exposed three times a week to radiation of the front part of both legs to normalize the vitamin D status. PATIENTS AND METHODS: Partial body UVB irradiation was performed during the routine dialysis session. Twenty-two patients took part, with a mean age of 61.7 (range=35-81) years. RESULTS: Serum levels of 25(OH)D3 and 1,25(OH)2D3 increased into the mid normal range. Intact parathyroid hormone decreased by 25% and osteocalcin by 45%. 24-Hour blood-pressure monitoring demonstrated decreases in systolic and diastolic blood pressure. CONCLUSION: Partial body exposure to UVB radiation normalized not only the serum level of 25(OH)D3, but also that of 1,25(OH)2D3, which resulted in a significant decrease in parathyroid hormone, osteocalcin levels, and also in blood pressure. Sunshine imitating UVB exposure utilizes the capacity of the skin to convert extrarenally vitamin D3 to 25(OH)D3 and 1,25(OH)2D3.

Multicenter evaluation of a rapid electrochemiluminescent adrenocorticotropic hormone (ACTH) immunoassay.

BACKGROUND: Measuring plasma adrenocorticotropic hormone (ACTH) is a key step in the differential diagnosis of hypothalamic-pituitary-adrenal disorders. METHODS: The recently developed electrochemiluminescence Elecsys ACTH immunoassay (Roche Diagnostics, Mannheim, Germany) was evaluated at six clinical laboratories on the Modular E170 and/or the Elecsys 2010 (Roche Diagnostics) immunoanalysers. RESULTS: The within-run and between-run imprecision was

Roche Elecsys Prolactin II assay: reactivity with macroprolactin compared with eight commercial assays for prolactin and determination of monomeric prolactin by precipitation with polyethylene glycol.

Hyperprolactinaemia due to macroprolactin (MPRL) can lead to misdiagnosis and inappropriate treatment. We studied the new Roche Elecsys Prolactin assay (PRL II) which has been developed to reduce reactivity with MPRL. We investigated the performance of the PRL II assay at six laboratory sites to determine precision and establish reference intervals for total immunoreactive PRL and for monomeric PRL determined by precipitation with polyethylene glycol (PEG). We compared the reactivities with macroprolactin of the PRL II, the PRL I and seven other PRL assays. The PRL II assay reacted less strongly than the PRL I assay and similarly to the ADVIA Centaur assay with macroprolactin. PEG precipitation can be used with the PRL II assay to estimate the concentration of monomeric PRL.

Roche Elecsys Prolactin II assay: reactivity with macroprolactin compared with eight commercial assays for prolactin and determination of monomeric prolactin by precipitation with polyethylene glycol.

Hyperprolactinaemia due to macroprolactin (MPRL) can lead to misdiagnosis and inappropriate treatment. We studied the new Roche Elecsys Prolactin assay (PRL II) which has been developed to reduce reactivity with MPRL. We investigated the performance of the PRL II assay at six laboratory sites to determine precision and establish reference intervals for total immunoreactive PRL and for monomeric PRL determined by precipitation with polyethylene glycol (PEG). We compared the reactivities with macroprolactin of the PRL II, the PRL I and seven other PRL assays. The PRL II assay reacted less strongly than the PRL I assay and similarly to the ADVIA Centaur assay with macroprolactin. PEG precipitation can be used with the PRL II assay to estimate the concentration of monomeric PRL.

Urinary iodine: comparison of a simple method for its determination in microplates with measurement by inductively-coupled plasma mass spectrometry.

The aim of our study was to develop and validate an inexpensive, rapid, easy to use quantitative method to determine urinary iodine without major procurement costs for equipment. The rationale behind introducing this method is the increasing demand for urinary iodine assessments. Our study included 103 patients (76 female, 27 male), age (arithmetic mean) 52 ± 17.3 years. Urinary iodine was determined in microplates by a modification of the Sandell-Kolthoff reaction. The results were compared with inductively-coupled plasma mass spectrometry (ICP-MS) for iodine, considered as reference method. Geometric mean of urinary iodine determined by the Sandell-Kolthoff reaction method was 62.69 µg/l (95% confidence interval 53.16-73.92) whereas by the ICP-MS method it was 65.53 µg/l (95% confidence interval 54.77-78.41). Passing-Bablok regression equations for both methods gave y = 3.374 + 0.873x (y: Sandell-Kolthoff method, x: ICP-MS). Spearman´s correlation coefficient was 0.981, indicating a very high degree of agreement between the two methods. Bland-Altman plots showed no significant systematic difference between the two methods. The modified Sandell-Kolthoff method using microtiter plate technique presented here is a simple, inexpensive semi-automated method to determine urinary iodine with very little toxic waste. Comparison with the ICP-MS-technique yielded a good agreement between the two methods.

Vitamin D Status in Chronic Kidney Disease - UVB Irradiation Is Superior to Oral Supplementation.

BACKGROUND: In chronic kidney disease (CKD) a deficiency of 1,25-dihydroxyvitamin D is common. The aim of this review was to compare vitamin D status after oral supplementation of vitamin D3 to that of serial suberythemal irradiation in end-stage kidney disease (ESKD) patients. PATIENTS AND METHODS: Ninety-five patients, with a mean age of 62 (range=35-82) years, were treated with a mean dose of 35,000 (20,000-60,000) IU vitamin D3 per week for a period of 18 months. Fourteen patients, with a mean age of 51 (range=41-57) years, were whole-body UVB irradiated for over 6 months. From 3 hemodialysis patients skin biopsies were performed. RESULTS: With oral supplementation 25(OH)D3 increased by 60%. With UV irradiation 25(OH)D3 increased by 400%. Gene expression analysis demonstrated an improvement in the vitamin D receptor (VDR) by 0.65 fold, in 1-alpha-hydroxylase (CYP27B1) by 1.0 fold, and in 25-hydroxylase (CYP2R) by 1.2 fold. CONCLUSION: Serial suberythemal UVB irradiation of patients with CKD on dialysis is capable to improve serum 25(OH)D3 and 1,25(OH)2D3 by enhancing the skin's ability to activate vitamin D.

Evaluation of serum beta-carboxy-terminal cross-linking telopeptide of type I collagen as marker of bone resorption in chronic hemodialysis patients.

BACKGROUND: The carboxy-terminal cross-linking telopeptide of type I collagen (beta-CrossLaps, beta-CTX) is released into the circulation during degradation of type I collagen and serves as a marker of bone resorption. beta-CTX is known to undergo a diurnal rhythm in normal individuals and to accumulate in chronic renal failure. beta-CTX has a potential role in noninvasive diagnosis of renal bone disease. METHODS: Serum beta-CTX was compared to parathyroid hormone (PTH) and other biochemical bone markers in 90 unselected hemodialysis patients. RESULTS: Mean beta-CTX was elevated above the normal range (1.72 +/- 0.93 microg/l); there were large individual variations. Serum beta-CTX was significantly correlated with various PTH assays (r >0.56) and with tartrate-resistant acid phosphatase 5b (TRACP 5b, r = 0.629), bone-specific alkaline phosphatase (r = 0.404) and osteocalcin (r = 0.534, all correlations p < 0.001). The correlation between beta-CTX and PTH was significantly higher than the correlation between TRACP 5b and PTH. Several factors which could confound interpretation of serum beta-CTX were assessed in further studies: (i) There was no recognizable influence of the time of blood sampling (morning dialysis shift versus afternoon dialysis shift) on serum beta-CTX. (ii) Serum beta-CTX was not significantly related to residual diuresis of patients. CONCLUSIONS: We found a high association between beta-CTX and other established markers of bone and calcium metabolism demonstrating the potential utility of beta-CTX as marker of bone resorption in renal bone disease. However, further studies employing bone histology are still warranted to exactly define the influence of glomerular retention on serum beta-CTX in end-stage renal disease.

Markers of bone resorption--measurement in serum, plasma or urine?

OBJECTIVE: We compared an established urine marker (total deoxypyridinoline (DPD), related to creatinine (cr)) with a plasma marker (CTX) to evaluate whether the methods are equally suited to detect increased bone resorption in women after the menopause and to see whether both markers show normal bone resorption in postmenopausal women on hormone replacement therapy (HRT). METHODS: DPD in first morning void urines was measured by an automated HPLC system. CTX ("beta-CrossLaps") was measured on the automated electrochemiluminescence analyzer E170 (Roche Diagnostics, Germany). For CTX, EDTA plasma and serum samples taken from fasting patients in the morning between 08.00 and 08.30 were analyzed. 49 women were premenopausal, 43 women were postmenopausal without HRT, and 13 women were postmenopausal on HRT (mostly on oral medication) for more than six months. RESULTS AND DISCUSSION: Inter-assay coefficients of variation (CVs) at three different concentrations were 6.0%, 6.7% and 7.2% for the assay of DPD and 2.58%, 1.83% and 1.99% for CTX, respectively. CTX was more stable in EDTA plasma than in serum. 21/43 (49%) of postmenopausal women without HRT showed increased DPD/cr ratios and 19/43 (44%) showed elevated CTX concentrations. Regarding postmenopausal women on HRT, DPD/cr ratios were elevated in 3/13 women, whereas plasma CTX showed levels within the premenopausal range in all 13 women. It is discussed that in some cases a lower muscle mass as a result of increasing age or as a result of oral HRT might increase the urinary DPD/cr ratio by lowered excretion of cr. This effect would raise the number of cases with an elevated DPD/cr ratio after the menopause out of proportion. CONCLUSION: CTX is determined with very high precision on the E170. CTX, if measured in EDTA plasma samples from fasting patients in the morning, seems to indicate bone resorption in women on HRT correctly as normal. The DPD/cr ratio in urine of women on HRT is increased in some cases above normal, presumably by lowered excretion of cr. According to our results, plasma (or serum) markers of bone resorption seem to be preferable over cr-related urine markers.

Multicenter evaluation of a new immunoassay for intact PTH measurement on the Elecsys System 2010 and 1010.

BACKGROUND AND OBJECTIVE: The determination of parathyroid hormone (PTH) is of great clinical relevance in the assessment of calcium metabolic disorders. Although PTH was one of the first hormones measured by immunoassays, there are still many difficulties in its determination due to the low concentration of the hormone in blood and due to the heterogeneity of PTH resulting from different circulating hormone fragments. The aim of our multicenter-study was to evaluate the technical performance and the clinical validity of a new immunoassay for intact PTH measurement on the Elecsys Systems 2010 and 1010. METHODS AND RESULTS: The multicenter evaluation was performed in 11 clinical laboratories. The Elecsys PTH assay is a one step sandwich electrochemiluminescence immunoassay based upon the streptavidin-biotin technology. Two monoclonal antibodies are used in the assay providing detection of intact PTH. The imprecision study yielded within-run and between-days coefficients of variation of 3.1% - 6.6% and 3.4% - 15.6%, respectively using a three level control (PreciControl Bone, Roche Diagnostics) and human pool sera at two different concentrations (HS-low: 20 - 60 pg/ml, HS-high > 65 pg/ml). The analytical sensitivity calculated as the mean value plus 2 standard deviations of a within-run imprecision was below 2.70 pg/ml using zero calibrator matrix. Dilution linearity was observed up to 4890 pg/ml using zero calibrator matrix or human pool sera. Recoveries ranged between 85% - 115%. Serum, EDTA- and heparin plasma were evaluated for PTH measurement. Due to a better analyte stability (48h at 21 degrees C; 3d at 4 degrees C) EDTA plasma was recommended for PTH measurement. Results of the Elec sys PTH immunoassay correlated well (r = 0.926 - 0.994) with three different immunoradiometric assays (N-tact PTH SP, DiaSorin; Nichols Allegro Intact PTH, Nichols Institute Diagnostics; ELSA-PTH, CISBio International) and two different immunochemiluminometric assays (PTH-Intact-Immulite, DPC Biermann; Nichols Advantage Intact PTH, Nichols Institute Diagnostics) in technical and clinical method comparisons. The Passing/Bablok regression analysis yielded slopes of 0.692 - 1.729 and intercepts of -13.982 - +15.763 pg/ml. Deviations from slope 1.0 and intercept 0.0 were not unexpected due to differences in immunoassay standardization and probably due to the presence of different PTH fragments and a variable affinity of the used antibodies to these PTH fragments. Highly similar PTH concentration pattern of the Elecsys immunoassay and the Quick-Intraoperative Intact PTH immunoassay (Nichols Institute Diagnostics) obtained from specimens taken intraoperatively support the applicability of the Elecsys immunoassay to monitor the success of parathyroid resection. A reference range of 12.3 - 56.0 pg/ml calculated from PTH values of 43 apparently healthy individuals confirms reference limits published in the literature. The partition of collectives according to age showed, that individuals > 50 years have slightly higher PTH concentrations, independently of gender. This shift could be due to age itself or to an increased prevalence of individuals without obvious calcium metabolic disorders in this collective. CONCLUSION: The Elecsys PTH assay is a useful and reliable tool for determination of intact PTH. Our data support the intended use of the assay in clinical applications related to disorders of calcium metabolism.

Do depressed patients without activation of the hypothalamus-pituitary-adrenal (HPA) system have metabolic disturbances?

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 1mg 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.

Nonoxidized, biologically active parathyroid hormone determines mortality in hemodialysis patients.

BACKGROUND: It was shown that nonoxidized PTH (n-oxPTH) is bioactive, whereas the oxidation of PTH results in a 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 (χ², 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.

Impact of oral ibandronate 150 mg once monthly on bone structure and density in post-menopausal osteoporosis or osteopenia derived from in vivo µCT.

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.