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PTH
Kinds of PTH Terms modified by PTH Selected AbstractsVacuolar H+ -ATPase expression is increased in acid-secreting intercalated cells in kidneys of rats with hypercalcaemia-induced alkalosisACTA PHYSIOLOGICA, Issue 4 2007W. Wang Abstract Aims:, Hypercalcaemia is known to be associated with systemic metabolic alkalosis, although the underlying mechanism is uncertain. Therefore, we aimed to examine whether hypercalcaemia was associated with changes in the expression of acid,base transporters in the kidney. Methods:, Rats were infused with human parathyroid hormone (PTH, 15 ,g kg,1 day,1), or vehicle for 48 h using osmotic minipumps. Results:, The rats treated with PTH developed hypercalcaemia and exhibited metabolic alkalosis (arterial HCO: 31.1 ± 0.8 vs. 28.1 ± 0.8 mmol L,1 in controls, P < 0.05, n = 6), whereas the urine pH of 6.85 ± 0.1 was significantly decreased compared with the pH of 7.38 ± 0.1 in controls (P < 0.05, n = 12). The observed alkalosis was associated with a significantly increased expression of the B1-subunit of the H+ -ATPase in kidney inner medulla (IM, 233 ± 45% of the control level). In contrast, electroneutral Na+ -HCO cotransporter NBCn1 and Cl,/HCO anion exchanger AE2 expression was markedly reduced in the inner stripe of the outer medulla (to 26 ± 9% and 65 ± 6%, respectively). These findings were verified by immunohistochemistry. Conclusions:, (1) hypercalcaemia-induced metabolic alkalosis was associated with increased urinary excretion of H+; (2) the increased H+ -ATPase expression in IM may partly explain the enhanced urinary acidification, which is speculated to prevent stone formation because of hypercalciuria and (3) the decreased expression of outer medullary AE2 suggests a compensatory reduction of the transepithelial bicarbonate transport. [source] Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidismDIABETIC MEDICINE, Issue 10 2009F. Tassone Abstract Aims, An increased frequency of both impaired glucose tolerance and Type 2 diabetes mellitus (DM) has been reported in primary hyperparathyroidism (pHPT), thus we sought to investigate insulin sensitivity and insulin secretion in a large series of pHPT patients. Subjects and methods, One hundred and twenty-two consecutive pHPT patients without known DM were investigated [age (mean ± sd) 59.3 ± 13.6 years, body mass index (BMI) 25.7 ± 4.2 kg/m2; serum calcium 2.8 ± 0.25 mmol/l; PTH 203.2 ± 145.4 ng/l]. Sixty-one control subjects were matched, according to the degree of glucose tolerance, in a 2 : 1 patient:control ratio. Fasting- and oral glucose tolerance test-derived estimates of insulin sensitivity and secretion were determined by means of the quantitative insulin sensitivity check index (QUICKI) and the insulin sensitivity index (ISI) composite. Results, Both the QUICKI and ISI composite were lower in pHPT patients than control subjects (P < 0.03 and P < 0.05, respectively) after adjusting for age, systolic blood pressure and BMI. Conversely, all insulin secretion estimates were significantly increased in pHPT patients than in control subjects (P < 0.04 and P < 0.03, respectively) and after adjusting for age, systolic blood pressure and BMI. Log serum calcium levels were negatively associated with the QUICKI and log ISI composite (R = ,0.30, P = 0.001; R = ,0.23, P = 0.020, respectively) in pHPT patients. Serum calcium levels significantly and independently contributed to impaired insulin sensitivity in multivariate analysis (QUICKI as dependent variable: , = ,0.31, P = 0.004, R2 = 0.15; log ISI composite as dependent variable: , = ,0.29, P = 0.005, R2 = 0.16). Conclusions, Our study confirms a reduction in both basal and stimulated insulin sensitivity in primary hyperparathyroidism, in spite of increased insulin secretion. Moreover, our data show for the first time a significant relationship between hypercalcaemia and insulin sensitivity in this condition. [source] Cytopathologist-performed ultrasound-guided fine-needle aspiration of parathyroid lesions,DIAGNOSTIC CYTOPATHOLOGY, Issue 5 2010David Lieu M.D., M.B.A. Abstract The gold standard to determine the cause of primary hyperparathyroidism (PHPT) is bilateral neck exploration. As most cases are caused by parathyroid adenoma, there is a movement toward preoperative localization of the abnormal gland by ultrasound and/or Tc99 -sestamibi scan and minimally invasive parathyroidectomy. Nonpalpable thyroid nodules are common and cannot be differentiated from parathyroid lesions by imaging alone. This study examines cytopathologist-performed ultrasound-guided fine-needle aspiration (UG-FNA) in diagnosis of parathyroid lesions. Between January 1, 2007 and December 31, 2008, seven patients with PHPT or other parathyroid lesions with one or more sonographically-visible thyroid masses underwent cytopathologist-performed UG-FNA with immediate cytological evaluation (ICE). One mass was palpable and nine were nonpalpable. Three parathyroid adenomas, two benign colloid nodules, one papillary carcinoma, three parathyroid cysts, and one thyroid cyst were diagnosed. The nodules in three patients with parathyroid adenomas were identified as follicular lesion/neoplasm on ICE. Additional UG-FNA passes were made to obtain tissue for immunohistochemistry stains, which confirmed parathyroid origin. Two of these patients had a separate benign colloid nodule and one had a thyroid cyst diagnosed by UG-FNA. The PHPT patient with papillary carcinoma on UG-FNA had the malignancy confirmed at surgery and a sonographically occult parathyroid adenoma. The three patients with thyroid cysts identified by radiology were suspected of being parathyroid cysts on the basis of real-time sonographic features at the biopsy table. The clear cyst fluid obtained by UG-FNA had markedly elevated PTH. Cytopathologist-performed UG-FNA can distinguish between parathyroid and thyroid nodules in patients with suspected parathyroid lesions. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] Ordered Mesoporous Carbon Functionalized with Polythionine for Electrocatalytic ApplicationELECTROANALYSIS, Issue 7 2009Bin Qi Abstract A polythionine (PTH) functionalized ordered mesoporous carbon (OMC) material (PTH/OMC) was presented. The electrochemistry kinetic characteristics of this material are investigated and compared with pure OMC. The results showed that compared with OMC, PTH/OMC possesses a much higher electron transfer rate. For the application of this material, an electrocatalytic based NADH biosensor was constructed on glassy carbon electrode (GCE). Instead of 0.592,V on bare GCE and 0.206,V on OMC/GCE, the amperometric detection of NADH could be effectively performed on the present biosensor with operation potential be set at 0.0,V. In addition, the sensor showed good reproducibility and stability. [source] Electrochemical Immunoassay for Carbohydrate Antigen-125 Based on Polythionine and Gold Hollow Microspheres Modified Glassy Carbon ElectrodesELECTROANALYSIS, Issue 17 2007Xiao-Hong Fu Abstract A new electrochemical immunosensor for the detection of carbohydrate antigen-125 (CA125), a carcinoma antigen, was developed by immobilization CA125 antibody (anti-CA125) on gold hollow microspheres and porous polythionine (PTH) modified glassy carbon electrodes (GCE). The gold hollow microspheres provided a biocompatible microenvironment for proteins, and greatly amplified the coverage of anti-CA125 molecules on the electrode surface. The performance and factors influencing the immunosensor were investigated in detail. The detection is based on the current change before and after the antigen-antibody interaction. Under optimal conditions, the amperometric changes were proportional to CA125 concentration ranging from 4.5 to 36.5,U/mL with a detection limit of 1.3,U/mL (at 3,). The CA125 immunosensor exhibited good precision, high sensitivity, acceptable stability, accuracy and reproducibility. The as-prepared immunosensors were used to analyze CA125 in human serum specimens. Analytical results suggest that the developed immunoassay has a promising alternative approach for detecting CA125 in the clinical diagnosis. [source] Vitamin D Levels and Bone Turnover in Epilepsy Patients Taking Carbamazepine or OxcarbazepineEPILEPSIA, Issue 3 2006Scott Mintzer Summary:,Purpose: Evidence suggests that enzyme-inducing antiepileptic drugs (AEDs) may decrease serum 25-hydroxyvitamin D (25-OHD) levels and increase bone turnover. We sought to determine whether these are affected by treatment with carbamazepine (CBZ) or oxcarbazepine (OXC). Methods: We measured serum levels of 25-OHD, parathyroid hormone (PTH), osteocalcin (OCLN), bone alkaline phosphatase (BAP), and urinary N-telopeptides of type I collagen cross-links (NTX) in normal controls (n = 24) and in epilepsy patients taking CBZ (n = 21) or OXC (n = 24) in monotherapy. CBZ patients were subsequently switched overnight to OXC monotherapy, and after 6 weeks, the tests were repeated. Results: 25-OHD levels were lower in each drug-treated group (OXC, 19.4 ± 2.3 pg/ml; CBZ, 20.4 ± 2.4) than in the controls (27.5 ± 2.8) (ANOVA, p = 0.052). This difference was significant for the OXC group (p < 0.05). PTH, BAP, and NTX did not differ significantly among groups. OCLN levels were somewhat elevated in the OXC group (2.79 ± 0.47 ng/ml) and more clearly and significantly elevated in the CBZ group (3.63 ± 0.36) compared with controls (2.38 ± 0.41) (p = 0.053). Because the data were very similar between OXC and CBZ groups, they were combined to increase statistical power. The combined drug-treatment group had significantly higher BAP (p = 0.02) and lower 25-OHD (p = 0.015) than did controls. The latter remained significant even after accounting for the confounding effects of age on 25-OHD levels (p < 0.05). No significant differences were found after CBZ patients were switched to OXC. Conclusions: Epilepsy patients taking OXC or CBZ have significantly lower 25-OHD than do normal controls, with a pattern of changes in other bone biomarkers suggestive of secondary hyperparathyroidism. It may be prudent for patients taking CBZ or OXC to be prescribed 25-OHD replacement. [source] Validation and clinical utility of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone in the horseEQUINE VETERINARY JOURNAL, Issue 3 2003J. C. ESTEPA Summary Reasons for performing study: Parathyroid hormone (PTH) plays a critical role in the regulation of mineral metabolism in mammals. Until recently, the standard method for PTH measurement has been the 2nd generation intact-PTH (I-PTH) assay. Current evidence indicates that the I-PTH assay binds to the PTH molecule and to an inactive N-terminally truncated PTH fragment that tends to accumulate in the blood of uraemic patients. Therefore, a new 3rd generation PTH assay that detects only the whole PTH molecule (W-PTH; cyclase-activating PTH [CAP]) has been developed. Objectives: To validate this more specific W-PTH assay for measurement of equine PTH and evaluate its clinical utility. Methods: W-PTH and I-PTH were measured in plasma samples from normal horses (adults and foals) and horses with nutritional secondary hyperparathyroidism (N2HPT) and with chronic renal failure (CRF). Replicate measurements and dilutional paralellism were used for assay validation. Changes in blood ionized calcium were induced by EDTA and CaCl2 administration. Results: Performance of the W-PTH assay (accuracy, sensitivity, specificity and ability to detect changes in PTH in response to changes in calcium) was similar to that of the I-PTH assay. Surprisingly, the relative W-PTH concentration in normal horses and foals was higher than the relative I-PTH concentration. W-PTH values remained higher than I-PTH during acute hypo- and hypercalcaemia. An increase in both W-PTH and I-PTH concentrations was found in horses with N2HPT. In horses with CRF, W-PTH and I-PTH values were very low and no increase in I-PTH was observed. Conclusions: The W-PTH assay can be used for measurement of equine PTH. Potential relevance: The use of W-PTH assay is likely to improve the diagnosis of mineral metabolism in horses. [source] Parathyroid hormone stimulates the endothelial expression of vascular endothelial growth factorEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2008G. Rashid ABSTRACT Background, We showed previously that parathyroid hormone (PTH) may stimulate the endothelial expression of pro-atherosclerotic and pro-inflammatory markers. Considering the impact of PTH on vasculature, we decided to evaluate its effect on mRNA and intra-cellular protein expressions of endothelial vascular endothelial growth factor (VEGF) taking into account that VEGF may play a role in the pathogenesis of endothelial dysfunctions. Materials and methods, Human umbilical vein cords endothelial cells (HUVEC) were stimulated for 24 h with 10,12,10,10 mol L,1 PTH. The VEGF-165 mRNA expression (critical in stimulating endothelial cell proliferation) was evaluated by RT/PCR and the intra-cellular VEGF protein expression by flow cytometry. The pathways by which PTH may have an effect on VEGF expression were also evaluated. Results, PTH (10,10 mol L,1) significantly increased VEGF-165 mRNA expression (P < 0·05). The addition of 50 nmol L,1 protein kinase C (PKC) and 10 µmol L,1 protein kinase A (PKA) inhibitors significantly reduced the VEGF-165 mRNA expression (P = 0·01). We also examined whether nitric oxide (NO) may be involved in the PTH-induced stimulation of VEGF-165 expression. Pre-treatment of the cells with 200 µmol L-nitro arginine methyl ester (L-NAME, NO synthase inhibitor) was found to inhibit VEGF-165 mRNA expression (P = 0·006). VEGF protein could not be detected in the medium of HUVEC but it was present in the cell cytoplasm. PTH had no significant effect on cytoplasmatic VEGF protein expression. Conclusion, The stimulatory effect of PTH on endothelial VEGF-165 mRNA expression is partly through PKC and PKA pathways and is also NO dependent. [source] The role of calcimimetics in the treatment of hyperparathyroidismEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2007R. P. Wüthrich Abstract Calcimimetics reduce serum levels of parathyroid hormone (PTH) and calcium, with a leftward shift in the set-point for calcium-regulated PTH secretion. The aim of this publication is to review the data available for calcimimetics in primary, secondary and tertiary hyperparathyroidism (HPT). Parathyroidectomy (PTX) is currently the only curative treatment for primary HPT, and recommended for patients with moderate-to-severe disease, as defined by a 2002 National Institute's of Health summary statement. In general, patients with primary HPT not meeting these surgical criteria, as well as those with contraindication or refusal for surgery, are monitored for signs and symptoms of primary HPT. There are currently no non-surgical therapies approved for use in primary HPT, although bisphosphonates are used in some patients, in an effort to control serum calcium levels. Calcimimetics decrease PTH and calcium levels and are a potential alternative for patients contraindicated for PTX, or who have failed previous PTX and have recurrent primary HPT. Secondary HPT develops early in chronic kidney disease and is present virtually in all patients with end-stage renal disease (ESRD). Secondary HPT is a progressive disease and is associated with several systemic complications, including renal osteodystrophy, soft tissue and vascular calcifications, and adverse cardiovascular outcomes. In ESRD patients, calcimimetics were shown to simultaneously reduce PTH, calcium, phosphate and calcium × phosphate product. In addition, observational analyses of use of calcimimetics in the ESRD population have shown a reduction of important clinical outcomes. In renal allograft recipients with tertiary HPT and hypercalcaemia, calcimimetics are a promising treatment option to control the parameters of calcium phosphate metabolism and may be a valid alternative to PTX. Based on its unique mechanism of action, the calcimimetic cinacalcet may play a role in the medical treatment of primary and tertiary forms of HPT, in addition to the registered indication for the treatment of secondary HPT. [source] Human parathyroid cell proliferation in response to calcium, NPS R-467, calcitriol and phosphateEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2001M-C. Roussanne It remains uncertain how calcium, phosphate and calcitriol regulate parathyroid cell growth. The present study was aimed at examining possible direct effects of these modulators and of the calcimimetic NPS R-467 on parathyroid cell growth in vitro. Cell proliferation was determined by [3H]thymidine incorporation and cell cycle antigen Ki 67 expression in a parathyroid cell culture model derived from uraemic patients. The effect of NPS R-467 on parathyroid hormone (PTH) secretion and intracellular [Ca2+]i response was also examined. Increasing the [Ca2+] in the medium from 0·5 to 1·7 mM increased DNA synthesis (P < 0·005) and the number of Ki 67-positive cells (P < 0·005). However, NPS R-467 (0·01,1 µM) inhibited 3[H]thymidine incorporation by 35% in the presence of 0·5 mM [Ca2+]e. Exposure of cells to Ca2+ or NPS R-467 led to a rapid increase of intracellular Ca2+, although the pattern of increase differed. Addition of calcitriol (10,10,10,7 M) to the culture medium suppressed [3H]thymidine incorporation dose-dependently. Finally, high levels of phosphate (3·5 mM) in the medium led to a significant (P < 0·05) increase in [3H]thymidine incorporation. The observed stimulatory effect of Ca2+ in the medium in vitro appears to be at variance with the inhibitory effect of calcimimetic NPS R-467 in vitro. In an attempt to solve these apparent discrepancies, and based on the notion of a reduced calcium-sensing receptor (CaR) expression in parathyroid tissues of uraemic patients, we hypothesize that Ca2+ may regulate parathyroid cell proliferation via two different pathways, with predominant growth inhibition in cases of high CaR expression or activation, but prevailing stimulation of proliferation in cases of low CaR expression. [source] Effect of parathyroid hormone-related protein on fibroblast proliferation and collagen metabolism in human skinEXPERIMENTAL DERMATOLOGY, Issue 4 2002Emanuela Maioli Abstract: The parathyroid hormone-related protein (PTHrp), structurally similar to the parathyroid hormone (PTH) in its NH2 -terminal part, was first identified as a tumour-derived peptide responsible for a paraneoplastic syndrome known as humoral hypercalcemia of malignancy. The PTHrp gene is expressed not only in cancer but also in normal tissues during adult and/or fetal life, where it plays predominantly paracrine and/or autocrine roles. In the skin PTHrp produced by keratinocytes acts on fibroblasts by complex cooperative circuits involving cytokines and growth factors. In this report, we studied the direct effects of synthetic PTHrp 1,40 on proliferation and collagen synthesis and matrix metalloproteinase-2 (MMP-2) activity in cultures of fibroblasts isolated from normal human skin. Fibroblasts exposure to varying doses of PTHrp for 48 h, significantly and dose-dependently inhibited proliferation evaluated by [3H]-thymidine incorporation into DNA. A dose-dependent stimulation of cAMP released into the medium was concomitantly observed. In contrast, PTHrp had no effect on collagen synthesis evaluated either by [3H]-proline incorporation or by radioimmunoassay (RIA) of the carboxyterminal fragment of type I procollagen (PICP). MMP-2 activity, evaluated by quantitative zymographic analysis, was significantly increased by PTHrp treatment at doses of 160 and 320 nM. These findings indicate that PTHrp may play a role in normal dermal physiology by controlling both fibroblast proliferation and extracellular matrix degradation. [source] Prediction of hypocalcemia after using 1- to 6-hour postoperative parathyroid hormone and calcium levels: An analysis of pooled individual patient data from 3 observational studiesHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2010Jeffrey Saad Jumaily BS Abstract Background. Parathyroid hormone (PTH) levels up to 6 hours postthyroidectomy have been shown to have excellent predictive power in determining hypocalcemia. In this study, we investigate the usefulness of combining calcium and PTH to increase the predictive power. Methods. Individual patient data were obtained from 3 studies (152 patients) that fulfilled our criteria (using PTH assay within hours postthyroidectomy to predict symptomatic hypocalcemia). Results. Changes in combined PTH and calcium threshold levels checked 1 to 6 hours after thyroidectomy were excellent in predicting postoperative hypocalcemia. A decrease in PTH of 60%, coupled with a simultaneous decrease in calcium of 10%, 5 to 6 hours postoperatively resulted in a sensitivity and specificity of 100%. However, combined PTH and calcium threshold changes were not significantly better than using PTH threshold changes alone. Conclusions. Threshold changes in serum calcium and PTH, checked hours after surgery, can be used together to accurately predict whether a patient will become hypocalcemic after thyroidectomy. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] Comparison of perioperative management and outcome of parathyroidectomy between older and younger patientsHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2008Gideon Bachar MD Abstract Background. The aim of this study was to compare the clinical status, surgical course, and outcomes of patients with primary hyperparathyroidism (PHPT), over the age of 70, with younger patients. Methods. Between 1996 and 2006, 951 patients underwent parathyroidectomies for PHPT, of whom 190 were over the age of 70. Patient data were collected from chart reviews and a computerized database. Results. Fewer older patients were asymptomatic at presentation. No between-group differences in serum calcium were seen; however, parathyroid hormone (PTH) levels were higher in the older group. Hospitalization time was longer for the elderly. Duration of surgery, surgical success rates, and postoperative complications were similar between the 2 groups. Conclusion. Surgical treatment of PHPT has both physiological benefits and helps to preserve quality of life. Our findings suggest that there is no practical difference in perioperative management and surgical outcomes for older patients. Surgeons should consider parathyroidectomy in PHPT patients regardless of age. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] Clinical and operative management of persistent hyperparathyroidism after renal transplantation: A single-center experienceHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2007Hanna Gilat MD Abstract Background. Persistent (tertiary) hyperparathyroidism (TH) after renal transplantation may cause considerable morbidity and necessitate parathyroidectomy. This study investigated the characteristics of this patient subgroup. Methods. The medical data and pathology specimens of 20 kidney transplant recipients who underwent parathyroidectomy for TH in 2001 to 2004 were reviewed. Results. Treatment consisted of subtotal resection of 3.5 glands in 13 patients, resection of 3 to 3.5 glands under intraoperative parathyroid hormone monitoring (iPTH) in 5 patients, and selective resection in 2 patients with markedly asymmetric gland enlargement. Eighteen patients had hyperplasia,diffuse in 10, nodular in 4, or both in 2; 2 patients had 1 large nodule in every gland. Six patients had postoperative complications. Follow-up of 2 years revealed recurrent hypercalcemia in 1 patient and a high level of PTH (>60 pg/mL) in 12. Conclusion. Subtotal resection for TH may be insufficient. The use of iPTH monitoring is recommended. Renal transplant recipients have distinctive characteristics and require special perioperative attention. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] Assessment of parathyroid autotransplantation for preservation of parathyroid function after total thyroidectomyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2003Magdy I. El-Sharaky MD Abstract Background. Hypoparathyroidism with permanent hypocalcemia is a well-recognized complication after thyroid surgery. Aim. This study was conducted to assess the role of immediate parathyroid autotransplantation in the preservation of parathyroid function after total thyroidectomy. Patients and Methods. Twenty-eight patients had autotransplantation of parathyroid glands resected or devascularized during total thyroidectomy. Data were collected prospectively regarding demographics, indication for surgery, operative procedure, pathologic diagnosis, number of glands transplanted, and subsequent course. Thyroid nodules were evaluated by ultrasonography, radionuclide scanning, and/or fine-needle aspiration cytology. All patients had serum ionized calcium, phosphorus, and intact parathyroid hormone (PTH) levels measured preoperatively and monitored regularly postoperatively for a period of 14 weeks and again at 6 months after operation. Patients were categorized into three groups according to the number of glands transplanted: one (group 1, n = 6), two (group 2, n = 14), or three glands (group 3, n = 8). In three other volunteers, one parathyroid gland was transplanted in the brachioradialis and subjected to electron microscopy 1, 2, and 4 weeks after transplantation. Results. Total thyroidectomy was performed for malignant disease in 16 patients (57.1%) and for benign disease in 12 (42.9%) patients. All patients reverted to asymptomatic normocalcemia without the need for any medications within 4 to 14 weeks. Normal levels of serum markers were regained slower when one gland was transplanted compared with two or three glands (P < .01). Electron microscopic examination showed evidence of ischemic degeneration in the transplanted tissues 1 week postoperatively. Regeneration started by the second week and coincided with normalization of PTH levels. Optimum resting and nearly normal status of parathyroid tissue was achieved by the fourth week. Conclusions. This study showed that active PTH production coincides with regeneration of parathyroid cells and that autotransplantation of at least two resected or devascularized glands during total thyroidectomy nearly eliminates permanent postoperative hypoparathyroidism, thus improving the safety of total thyroidectomy performed for malignant or benign disease. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 799,807, 2003 [source] Comparison between different dialysate calcium concentrations in nocturnal hemodialysisHEMODIALYSIS INTERNATIONAL, Issue 2 2007Nigel D. TOUSSAINT Abstract Benefits of dialysate with greater calcium (Ca) concentration are reported in nocturnal hemodialysis (NHD) to prevent Ca depletion and subsequent hyperparathyroidism. Studies with patients dialyzing against 1.25 mmol/L Ca baths demonstrate increases in alkaline phosphatase (ALP) and parathyroid hormone (PTH) and increasing dialysate Ca subsequently corrects this problem. However, whether 1.5 or 1.75 mmol/L dialysate Ca is most appropriate for NHD is yet to be determined, and differences in the effect on mineral metabolism of daily vs. alternate daily NHD have also not been well defined. We retrospectively analyzed mineral metabolism in 48 patients, from 2 institutions (30 at Monash and 18 at Geelong), undergoing home NHD (8 hr/night, 3.5,6 nights/week) for a minimum of 6 months. Thirty-seven patients were dialyzed against 1.5 mmol/L Ca bath and 11 patients against 1.75 mmol/L. We divided patients into 4 groups, based on dialysate Ca and also on the hours per week of dialysis, <40 (1.5 mmol/L, n=29 and 1.75 mmol/L, n=8) or ,40 (n=4 and 7). We compared predialysis and postdialysis serum markers, time-averaged over a 6-month period, and the administration of calcitriol and Ca-based phosphate binders between 1.5 and 1.75 mmol/L Ca dialysate groups. Baseline characteristics between all groups were similar, with a slightly longer, but nonsignificant, duration of NHD in both 1.75 mmol/L dialysate groups compared with 1.5 mmol/L. The mean predialysis Ca, phosphate, and Ca × P were similar between the 1.5 and 1.75 mmol/L groups, regardless of NHD hr/week. Postdialysis Ca was significantly greater, with 1.75 vs. 1.5 mmol/L in those dialyzing <40 hr/week (2.64±0.19 vs. 2.50±0.12 mmol/L, p=0.046), but postdialysis Ca × P were similar (2.25±0.44 vs. 2.16±0.29 mmol2/L2, p=0.60). Parathyroid hormone was also lower with 1.75 vs. 1.5 mmol/L baths in the <40 hr/week groups (31.99±26.99 vs. 14.47±16.36 pmol/L, p=0.03), although this difference was not seen in those undertaking NHD ,40 hr/week. Hemoglobin, ALP, and albumin were all similar between groups. There was also no difference in vitamin D requirement when using 1.75 mmol/L compared with the 1.5 mmol/L dialysate. Multivariate analysis to determine independent predictors of postdialysis serum Ca showed a statistically significant positive association with predialysis Ca, dialysate Ca, and total NHD hr/week. An elevated dialysate Ca concentration is required in NHD to prevent osteopenia but differences in serum markers of mineral metabolism between 1.5 and 1.75 mmol/L Ca dialysate in NHD in our study were few. This was similar for patients undertaking NHD <40 or ,40hr/week, although differences in the frequency of NHD may also be as important as dialysate Ca with regard to serum Ca levels. With concerns that prolonged higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca dialysate bath is still unknown and further studies addressing bone metabolism with larger NHD numbers are required. [source] Pulse Pressure Determinants in Chronic Hemodialysis PatientsHEMODIALYSIS INTERNATIONAL, Issue 1 2003V Kovacic Introduction: Hypertension contributes to the cardiovascular morbidity in patients undergoing chronic hemodialysis therapy (PCHD). Pulse pressure (PP) was recognized as a correlate of mortality in PCHD. In order to demonstrate determinants of predialysis and postdialysis PP values in a group of PCHD, we conducted this study. Subjects and methods: Study subjects were 23 PCHD. Study time was 15 months. One hundred thirty six single hemodialysis (HD) treatments were processed. PP was computed as systolic-diastolic blood pressure (mmHg). Statistical methods used were Student's t test for independent data, multivariate analysis of variance, Pearson's correlation, and forward stepwise multiple regression analysis. Results: Postdialysis and predialysis PPs differed significantly (65.51 ± 19.00 vs. 60.55 ± 19.35, p = 0.002). We did not find gender differences in PP before and after HD. PP before HD was in negative correlation with phosphorus concentration (r = , 0.244, p = 0.002), parathyroid hormone (PTH)(r = , 0.177, p = 0.020), hemoglobin (r = , 0.301, p < 0.001), single HD duration (r = , 0.162, p = 0.030), ultrafiltration rate per HD (r = , 0.290, p = 0.001), years on the chronic hemodialysis treatment (r = , 0.261, p = 0.001) and ultrafiltration volume/dry body mass ratio (UF/W)(r = , 0.222, p = 0.005) and in positive concentration with weekly erythropoietin (r = 0.391, p < 001) and age (r = 0.285, p < 0.001). PP after HD was in significant negative correlation with phosphorus concentration (r = , 0.205, p = 0.009), PTH (r = , 0.187, p = 0.015), hemoglobin (r = , 0.238, p = 0.005), ultrafiltration per HD (r = , 0.370, p < 0.001), dry body mass index (r = , 0.225, p = 0.003), years of the chronic hemodialysis treatment (r = 0.330, p < 0.001), UF/W (r = , 0.340, p < 0.001) and in positive concentration with weekly erythropoietin (r = 0.361, p < 0.001) and age (r = 0.227, p = 0.004). Multiple regression analyses unveiled the strongest and negative correlations between PP after HD and UF/W ratio (, = , 0.41, p < 0.001). The strongest, but positive correlation was found between PP before HD and erythropoietin per week (, = 0.51, p < 0.001). Conclusion: Determinants of the pre/post PP values are similar. Ultrafiltration is a strong predictor of postdialysis PP value. [source] Osteoprotegerin and bone turnover markers in heavily pretreated HIV-infected patientsHIV MEDICINE, Issue 3 2005E Seminari Objectives To characterize osteoprotegerin (OPG) levels, bone remodelling and bone mineral density (BMD) in heavily pretreated HIV-infected patients on antiretroviral therapy, and to evaluate the clinical factors associated with bone density decline. Methods Heavily pretreated (>5 years) HIV-positive patients were enrolled in this cross-sectional, observational study, which was based on a total body bone densitometry examination and a comprehensive evaluation of bone and mineral parameters. Results Sixty-eight patients (55 male and 13 female) with a median age of 41 years (range 25,60 years) were included in the study. Their antiretroviral treatment lasted for 82 months. On the basis of the World Health Organization criteria, nine patients (13.2%) were osteoporotic [T-score<,2.5 standard deviation (SD)] and 19 patients (27.9%) were osteopenic (T-score between,1 and,2.5). The principal outcomes associated with the presence of a low BMD were high OPG and lysylpyridinoline/creatinine ratio (Dpd) values. Most of the patients (39 of 48; 81.25%) showed vitamin D insufficiency [Vitamin D (25(OH)D)<18 ng/mL] with secondary hyperparathyroidism (13 of 50 patients: 26%), which proved to be correlated to osteocalcin (BGP) levels [parathyroid hormone (PTH) vs. BGP: r=0.34; P<0.01]. There was an inverse correlation between T-scores and serum osteocalcin and alkaline phosphatase (AP) levels, on one hand, and Dpd, on the other. High AP and Dpd values were associated with relative risks of 4.1 [95% confidence interval (CI)=1.01,17.6] and 7.2 (95% CI=1.67,31.03), respectively, of a pathological T-score. Multivariate analysis revealed that the factors associated with the presence of osteopenia or osteoporosis were older age and lower body mass index. Conclusions About 40% of our heavily pretreated subjects with advanced HIV infection had a low BMD, and 56% (24 of 44 patients) showed a high bone turnover rate with marked osteoclast activation. High OPG levels may protect against bone resorption. [source] Serum levels of vitamin D, PTH and calcium and breast cancer risk,a prospective nested case,control studyINTERNATIONAL JOURNAL OF CANCER, Issue 9 2010Martin Almquist Abstract Previous studies indicate that calcium and its regulating hormones, i.e., parathyroid hormone (PTH) and vitamin D, might affect breast cancer risk. Evidence also suggests that this relationship could be influenced by menopausal status and BMI. We examined breast cancer risk related to prediagnostic serum levels of vitamin D (25OHD2 and 25OHD3), PTH and calcium using a nested case,control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analyzed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels of 25OHD3, PTH and calcium. There was a weak, nonsignificant inverse association between breast cancer risk and 25OHD3, and the OR for the 2nd, 3rd and 4th quartiles, as compared to the first, were 0.84 (0.60,1.15), 0.84 (0.60,1.17) and 0.93 (0.66,1.33). Serum calcium was positively associated with breast cancer in premenopausal women (OR for the 4th quartile = 3.10:1.33,7.22 and p for quartile trend = 0.04), and in women with BMI > 25 (OR for the 4th quartile = 1.94:1.12,3.37 and p for trend < 0.01). There was no association between baseline serum PTH and breast cancer risk. [source] Gingival health status in renal transplant recipients: relationship between systemic inflammation and atherosclerosisINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2007G. Genctoy Summary Cardiovascular disease (CVD) is the leading cause of mortality in renal transplant recipients (RTR). Systemic and periodontal inflammation has been suggested to have a possible role in the development of atherosclerosis. In the present study, we aimed to investigate the relationship between gingival health status, inflammation and atherosclerosis in RTRs. Eighty-three RTR (50 male, 33 female) were enrolled in the study. Routine biochemical analyses, serum lipoproteins, C-reactive protein, fibrinogen, homocystein, parathyroid hormone (PTH) and cyclosporin A (CsA) trough levels were studied. All patients had 24-h ambulatory blood pressure monitoring and B-mode ultrasound of the common carotid arteries. Gingival status was evaluated by the Löe and Silness gingival index (GI). Mean GI value was 2.3 ± 0.5. Fifty patients (60.3%) had GI value , 2.1 (severe gingivitis; group A). Thirty-three patients (39.7%) had GI value < 2.1 (no or moderate gingivitis; group B). Age, carotid intima-media thickness (CIMT) and mean time on dialysis before transplantation were significantly higher in group A than in B. Systemic inflammation markers were not different between group A and group B. Mean CIMT was positively correlated with GI (r = 0.425; p = 0.001) and negatively correlated with high-density lipoprotein cholesterol (r = ,0.256; p = 0.023). After the correction for confounding variables, mean CIMT was still significantly correlated with GI (r = 0.376, p = 0.02). In RTR, gingival inflammation seems to be associated with CIMT in the absence of systemic inflammation. Thus, gingivitis may, in part, play a role in the development of systemic atherosclerosis without causing any aggravation in systemic inflammatory response. [source] Calcium supplement necessary to correct hypocalcemia after total parathyroidectomy for renal osteodystrophyINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2000Masayuki Nakagawa Abstract Background: Prediction of the extent of calcium supplement will facilitate safe and efficient management of hypocalcemia in the early postoperative stage of total parathyroidectomy with autotransplantation (PTXa) in patients with renal osteodystrophy. Methods: The correlation between the extent of calcium deficiency, estimated by the amount of calcium supplement over 48 h after PTXa and using various parameters such as carboxy terminal parathyroid hormone (c-PTH), intact PTH (i-PTH), alkaline phosphatase (ALP), serum calcium, serum phosphorus, duration of hemodialysis, total weight of resected parathyroid glands and degree of subperiosteal resorption of the middle phalanx was examined in 49 patients who underwent PTX with subcutaneous autotransplantation. Bone mineral density (BMD) was also determined before, 3 months and 1 year after PTXa with dual energy X-ray absorptiometry (DEXA) in 13 patients. Results: There was a positive correlation between pre-operative i-PTH level (r = 0.56, P < 0.0005) or ALP level (r = 0.50, P < 0.0005) and the amount of calcium supplement over 48 h after PTXa in these patients. Furthermore, the degree of subperiosteal resorption, determined by Jensen's classification, was significantly correlated with the amount of calcium supplement after PTX (P < 0.05). Bone mineral density 3 months after (P < 0.0005) and 1 year after PTXa (P < 0.001) significantly increased compared with BMD before PTXa in all patients examined. Conclusion: These findings suggest that the pre-operative determination of i-PTH, ALP levels and degree of subperiosteal resorption allow the management of hypocalcemia safely and efficiently in renal osteodystrophy patients after PTXa. [source] Heterogeneity in Serum 25-Hydroxy-Vitamin D Response to Cholecalciferol in Elderly Women with Secondary Hyperparathyroidism and Vitamin D DeficiencyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2010Andrea Giusti MD OBJECTIVES: To compare the effects on parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D) of two dosing regimens of cholecalciferol in women with secondary hyperparathyroidism (sHPTH) and hypovitaminosis D and to investigate variables affecting 25(OH)D response to cholecalciferol. DESIGN: Randomized-controlled trial with 6-month follow-up. SETTING: Two osteoporosis centers in northern Italy. PARTICIPANTS: Sixty community-dwelling women aged 65 and older with sHPTH and hypovitaminosis D, creatinine clearance greater than 65 mL/min and without diseases or drugs known to influence bone and vitamin D metabolism. INTERVENTION: Cholecalciferol 300,000 IU every 3 months, once at baseline and once at 3 months (intermittent D3 group) or cholecalciferol 1,000 IU/day (daily D3 group). MEASUREMENTS: Serum PTH, 25(OH)D, calcium, bone-specific alkaline phosphatase, ,-C-terminal telopeptide of type I collagen, phosphate, 24-hour urinary calcium excretion. RESULTS: The two groups had similar baseline characteristics. All participants had vitamin D deficiency [25(OH)D<20 ng/mL)], and 36 subjects (60%) had severe deficiency (<10 ng/mL), with no difference between the groups (severe deficiency: intermittent D3 group, n=18; daily D3 group, n=18). After 3 and 6 months, both groups had a significant increase in 25(OH)D and a reduction in PTH. Mean absolute increase±standard deviation of 25(OH)D at 6 months was higher in the intermittent D3 group (22.7±11.8 ng/mL) than in the daily D3 group (13.7±6.7 ng/mL, P<.001), with a higher proportion of participants in the intermittent D3 group reaching desirable serum concentration of 25(OH)D , 30 ng/mL (55% in the intermittent D3 group vs 20% in the daily D3 group, P<.001). Mean percentage decrease of PTH in the two groups was comparable, and at 6 months, a similar proportion of participants reached normal PTH values. 25(OH)D response to cholecalciferol showed a wide variability. In a logistic regression analysis, body mass index and type of treatment appeared to be significantly associated with normalization of 25(OH)D values. CONCLUSION: Cholecalciferol 300,000 IU every 3 months was more effective than 1,000 IU daily in correcting vitamin D deficiency, although the two groups achieved similar effects on PTH at 6 months. Only 55% of the higher-dose intermittent group reached desirable concentrations of 25(OH)D, suggesting that yet-higher doses will be required for adequate vitamin D repletion. [source] Low Serum Vitamin D Does Not Predict New Disability or Loss of Muscle Strength in Older WomenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2002René Verreault MD OBJECTIVES: To determine whether serum levels of 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) predict accelerated decline in muscular strength or onset of new disability in mobility and upper extremity functioning over a 3-year follow-up. DESIGN: A community-based prospective cohort study. PARTICIPANTS: Six hundred twenty-eight moderately to severely disabled women aged 65 and older living in the community. MEASUREMENTS: Subjects were divided into three groups of baseline 25(OH)D serum levels (deficiency: <25 nmol/L; low normal: 25,52 nmol/L; high normal: ,53 nmol/L) and into tertiles of PTH levels. Objective performance measures (hip flexor, knee extensor, and grip strengths; walking speed; and time for repeated chair stands) and disability in activities involving mobility and upper extremity function were assessed at baseline and every 6 months for 3 years. Decline in performance measures and onset of new disability were compared between 25(OH)D and PTH groups using random effects models and proportional hazards models, respectively, while adjusting for age, race, education, body mass index, baseline performance, and chronic conditions. RESULTS: The annual rate of decline over 3 years in muscular strength, walking speed, and time to perform repeated chair stands was similar across 25(OH)D groups. We observed a nonsignificantly faster decline in proximal muscle strength and walking speed with increasing PTH levels. There was no association for either measure between serum levels and the risk of incident disability in activities relating to mobility and upper extremity function. CONCLUSION: This study does not support the hypothesis that vitamin D deficiency is associated with loss in muscular strength and decline in mobility and upper extremity functioning over time in older women who were moderately to severely disabled at baseline. [source] Parathyroid hormone (PTH),induced bone gain is blunted in SOST overexpressing and deficient miceJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2010Ina Kramer Abstract Intermittent parathyroid hormone (PTH) treatment is a potent bone anabolic principle that suppresses expression of the bone formation inhibitor Sost. We addressed the relevance of Sost suppression for PTH-induced bone anabolism in vivo using mice with altered Sost gene dosage. Six-month-old Sost overexpressing and 2-month-old Sost deficient male mice and their wild-type littermates were subjected to daily injections of 100,µg/kg PTH(1,34) or vehicle for a 2-month period. A follow-up study was performed in Sost deficient mice using 40 and 80,µg/kg PTH(1,34). Animals were sacrificed 4 hours after the final PTH administration and Sost expression in long bone diaphyses was determined by qPCR. Bone changes were analyzed in vivo in the distal femur metaphysis by pQCT and ex vivo in the tibia and lumbar spine by DXA. Detailed ex vivo analyses of the femur were performed by pQCT, µCT, and histomorphometry. Overexpression of Sost resulted in osteopenia and Sost deletion in high bone mass. As shown before, PTH suppressed Sost in wild-type mice. PTH treatment induced substantial increases in bone mineral density, content, and cortical thickness and in aging wild-type mice also led to cancellous bone gain owing to amplified bone formation rates. PTH-induced bone gain was blunted at all doses and skeletal sites in Sost overexpressing and deficient mice owing to attenuated bone formation rates, whereas bone resorption was not different from that in PTH-treated wild-type controls. These data suggest that suppression of the bone formation inhibitor Sost by intermittent PTH treatment contributes to PTH bone anabolism. © 2010 American Society for Bone and Mineral Research [source] Overexpression of secreted frizzled-related protein 1 inhibits bone formation and attenuates parathyroid hormone bone anabolic effectsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2010Wei Yao Abstract Secreted frizzled-related protein 1 (sFRP1) is an antagonist of Wnt signaling, an important pathway in maintaining bone homeostasis. In this study we evaluated the skeletal phenotype of mice overexpressing sFRP1 (sFRP1 Tg) and the interaction of parathyroid hormone (PTH) treatment and sFRP1 (over)expression. Bone mass and microarchitecture were measured by micro-computed tomography (µCT). Osteoblastic and osteoclastic cell maturation and function were assessed in primary bone marrow cell cultures. Bone turnover was assessed by biochemical markers and dynamic bone histomorphometry. Real-time PCR was used to monitor the expression of several genes that regulate osteoblast maturation and function in whole bone. We found that trabecular bone mass measurements in distal femurs and lumbar vertebral bodies were 22% and 51% lower in female and 9% and 33% lower in male sFRP1 Tg mice, respectively, compared with wild-type (WT) controls at 3 months of age. Genes associated with osteoblast maturation and function, serum bone formation markers, and surface based bone formation were significantly decreased in sFRP1 Tg mice of both sexes. Bone resorption was similar between sFRP1 Tg and WT females and was higher in sFRP1 Tg male mice. Treatment with hPTH(1-34) (40,µg/kg/d) for 2 weeks increased trabecular bone volume in WT mice (females: +30% to 50%; males: +35% to 150%) compared with sFRP1 Tg mice (females: +5%; males: +18% to 54%). Percentage increases in bone formation also were lower in PTH-treated sFRP1 Tg mice compared with PTH-treated WT mice. In conclusion, overexpression of sFRP1 inhibited bone formation as well as attenuated PTH anabolic action on bone. The gender differences in the bone phenotype of the sFRP1 Tg animal warrants further investigation. © 2010 American Society for Bone and Mineral Research [source] Bone mineralization defects and vitamin D deficiency: Histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675,patientsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2010Matthias Priemel Abstract Parathyroid hormone (PTH) is only one measurable index of skeletal health, and we reasoned that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25-Hydroxyvitamin D [25(OH)D] level. A cohort from the northern European population with its known high prevalence of vitamin D deficiency therefore would be ideal to answer the latter question. We examined 675 iliac crest biopsies from male and female individuals, excluding all patients who showed any signs of secondary bone diseases at autopsy. Structural histomorphometric parameters, including osteoid indices, were quantified using the Osteomeasure System according to ASBMR standards, and serum 25(OH)D levels were measured for all patients. Statistical analysis was performed by Student's t test. The histologic results demonstrate an unexpected high prevalence of mineralization defects, that is, a pathologic increase in osteoid. Indeed, 36.15% of the analyzed patients presented with an osteoid surface per bone surface (OS/BS) of more than 20%. Based on the most conservative threshold that defines osteomalacia at the histomorphometric level with a pathologic increase in osteoid volume per bone volume (OV/BV) greater than 2% manifest mineralization defects were present in 25.63% of the patients. The latter were found independent of bone volume per trabecular volume (BV/TV) throughout all ages and affected both sexes equally. While we could not establish a minimum 25(OH)D level that was inevitably associated with mineralization defects, we did not find pathologic accumulation of osteoid in any patient with circulating 25(OH)D above 75,nmol/L. Our data demonstrate that pathologic mineralization defects of bone occur in patients with a serum 25(OH)D below 75,nmol/L and strongly argue that in conjunction with a sufficient calcium intake, the dose of vitamin D supplementation should ensure that circulating levels of 25(OH)D reach this minimum threshold (75,nmol/L or 30,ng/mL) to maintain skeletal health. © 2010 American Society for Bone and Mineral Research [source] Wintertime Vitamin D Supplementation Inhibits Seasonal Variation of Calcitropic Hormones and Maintains Bone Turnover in Healthy Men,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2009Heli T Viljakainen Abstract Vitamin D is suggested to have a role in the coupling of bone resorption and formation. Compared with women, men are believed to have more stable bone remodeling, and thus, are considered less susceptible to the seasonal variation of calcitropic hormones. We examined whether seasonal variation exists in calcitropic hormones, bone remodeling markers, and BMD in healthy men. Furthermore, we determined which vitamin D intake is required to prevent this variation. Subjects (N = 48) were healthy white men 21,49 yr of age from the Helsinki area with a mean habitual dietary intake of vitamin D of 6.6 ± 5.1 (SD) ,g/d. This was a 6-mo double-blinded vitamin D intervention study, in which subjects were allocated to three groups of 20 ,g (800 IU), 10 ,g (400 IU), or placebo. Fasting blood samplings were collected six times for analyses of serum (S-)25(OH)D, iPTH, bone-specific alkaline phosphatase (BALP), and TRACP. Radial volumetric BMD (vBMD) was measured at the beginning and end of the study with pQCT. Wintertime variation was noted in S-25(OH)D, S-PTH, and S-TRACP (p < 0.001, p = 0.012, and p < 0.05, respectively) but not in S-BALP or vBMD in the placebo group. Supplementation inhibited the winter elevation of PTH (p = 0.035), decreased the S-BALP concentration (p < 0.05), but benefited cortical BMD (p = 0.09) only slightly. Healthy men are exposed to wintertime decrease in vitamin D status that impacts PTH concentration. Vitamin D supplementation improved vitamin D status and inhibited the winter elevation of PTH and also decreased BALP concentration. The ratio of TRACP to BALP shows the coupling of bone remodeling in a robust way. A stable ratio was observed among those retaining a stable PTH throughout the study. A daily intake of vitamin D in the range of 17.5,20 ,g (700,800 IU) seems to be required to prevent winter seasonal increases in PTH and maintain stable bone turnover in young, healthy white men. [source] Theoretical Implications of the Biomechanical Fracture ThresholdJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008Tony M Keaveny Abstract Because of the dichotomous nature of a bone fracture, when ,, the ratio of the applied impact force to the bone strength, is greater than a critical value,the biomechanical fracture threshold,fracture should occur. We sought to elucidate the conceptual implications of this biomechanical fracture threshold with application to hip fracture. We used data from the PaTH study, a 2-yr clinical trial in postmenopausal women treated with alendronate, PTH, or their combination. Outcomes included the force applied to the hip in a sideways fall as estimated from subject height and weight; femoral strength as determined by QCT-based finite element analysis; the load-to-strength ratio ,; and total hip areal BMD from DXA. Results indicated that those with "very low" femoral strength (<2000 N) invariably had load-to-strength ratio , values well above the theoretical biomechanical fracture threshold (, = 1), but those with "moderately low" femoral strength (2000,4000 N) displayed , values both above and below the theoretical biomechanical fracture threshold. This finding implies that the risk of a hip fracture can be high in those with only moderately low BMD because femoral strength can be low relative to fall impact forces. The observed weak correlation between areal BMD and the load-to-strength ratio , (r2 = 0.14) suggests that consideration of the biomechanical fracture threshold may improve fracture risk assessment, particularly for those in the osteopenic range. Regarding treatment effects, only those subjects having load-to-strength ratio , values within a relatively narrow "transition zone" of ±20% of the assumed biomechanical fracture threshold at baseline were predicted to change fracture status during the trial. In theory, outcomes of fracture trials may be dominated by the responses of those within the "transition zone" at baseline, and treatment benefits in terms of fracture efficacy may depend the patient's baseline status with respect to the biomechanical fracture threshold. We conclude that consideration of the theoretical implications of the biomechanical fracture threshold may lead to new insights and advances in the assessment and treatment of osteoporosis. [source] Effects of PTH and Alendronate on Type I Collagen Isomerization in Postmenopausal Women With Osteoporosis: The PaTH Study,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2008Patrick Garnero Abstract Fracture efficacy of PTH and alendronate (ALN) is only partly explained by changes in BMD, and bone collagen properties have been suggested to play a role. We analyzed the effects of PTH(1,84) and ALN on urinary ,,/,, CTX ratio, a marker of type I collagen isomerization and maturation in postmenopausal women with osteoporosis. In the first year of the previously published PaTH study, postmenopausal women with osteoporosis were assigned to PTH(1,84) (100 ,g/d; n = 119), ALN (10 mg/d; n = 60), or PTH and ALN together (n = 59). We analyzed patients on ALN alone (n = 60) and a similar number of patients assigned to PTH alone (n = 63). During the second year, women on PTH in the first year were reallocated to placebo (n = 31) or ALN (n = 32) and women with ALN continued on ALN. During the first year, there was no significant change in ,,/,, CTX ratio with PTH or ALN. At 24 mo, there was a marked increase of the ,,/,, CTX ratio in women who had received PTH during the first year, followed by a second year of placebo (median: +45.5, p < 0.001) or ALN (+55.2%, p < 0.001). Conversely, the ,,/,, CTX ratio only slightly increased (+16%, p < 0.05) after 2 yr of continued ALN. In conclusion, treatment with PTH(1,84) for 1 yr followed by 1 yr of placebo or ALN may be associated with decreased type I collagen isomerization. The influence of these biochemical changes of type I collagen on bone fracture resistance remains to be studied. [source] Exogenous PTH and Endogenous 1,25-Dihydroxyvitamin D Are Complementary in Inducing an Anabolic Effect on Bone,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2008Rana Samadfam Abstract PTH and 1,25(OH)2D each exert dual anabolic and catabolic skeletal effects. We assessed the potential interaction of PTH and 1,25(OH)2D in promoting skeletal anabolism by comparing the capacity of exogenous, intermittently injected PTH(1-34) to produce bone accrual in mice homozygous for the 1,(OH)ase-null allele [1,(OH)ase,/, mice] and in wildtype mice. In initial studies, 3-mo-old wildtype mice were either injected once daily (40 ,g/kg) or infused continuously (120 ,g/kg/d) with PTH(1,34) for up to 1 mo. Infused PTH reduced BMD, increased the bone resorption marker TRACP-5b, and raised serum calcium but did not increase serum 1,25(OH)2D. Injected PTH increased serum 1,25(OH)2D and BMD, raised the bone formation marker osteocalcin more than did infused PTH, and did not produce sustained hypercalcemia as did PTH infusion. In subsequent studies, 3-mo-old 1,(OH)ase,/, mice, raised on a rescue diet, and wildtype littermates were injected with PTH(1,34) (40 ,g/kg) either once daily or three times daily for 1 mo. In 1,(OH)ase,/, mice, baseline bone volume (BV/TV) and bone formation (BFR/BS) were lower than in wildtype mice. PTH administered intermittently increased BV/TV and BFR/BS in a dose-dependent manner, but the increases were always less than in wildtype mice. These studies show that exogenous PTH administered continuously resorbs bone without raising endogenous 1,25(OH)2D. Intermittently administered PTH can increase bone accrual in the absence of 1,25(OH)2D, but 1,25(OH)2D complements this PTH action. An increase in endogenous 1,25(OH)2D may therefore facilitate an optimal skeletal anabolic response to PTH and may be relevant to the development of improved therapeutics for enhancing skeletal anabolism. [source] | |||||||||||||||||||||||||||||||||||||