OBJECTIVE

Increased parathyroid activity associated with chronic kidney disease is often managed with calcitriol, which can elevate serum calcium (Ca) by increasing bone resorption and intestinal absorption, whereas paricalcitol promotes less bone resorption. This study compared intestinal Ca absorption in hemodialysis patients treated with calcitriol versus paricalcitol (dose ratio 1:3).

METHODS

Patients (n = 22) aged>> or =20 years, on maintenance hemodialysis for>> or =2 months with intact parathyroid hormone (iPTH) levels of >200 pg/ml were enrolled in a single-center, double-blind, active-controlled, randomized, crossover trial. Mean fractional intestinal Ca absorption (+/-SE) was measured by the single-tracer method ((42)Ca) and evaluated with an analysis of variance crossover model.

RESULTS

Mean fractional intestinal Ca absorption was significantly lower after paricalcitol (0.135 +/- 0.006) versus calcitriol treatment (0.158 +/- 0.006, p = 0.022), a 0.023 difference in absolute Ca absorption fraction. Overall Ca absorption was low in the study population, indicating that regulation of Ca absorption may be dysfunctional. There were no significant differences in serum PTH, Ca, phosphorus (P), or Ca x P.

CONCLUSIONS

Overall, paricalcitol-treated patients absorbed approximately 14% less Ca compared with calcitriol-treated patients with similar effects on PTH. In hemodialysis patients, paricalcitol may provide a benefit by lowering the Ca available for removal by dialysis and/or for deposit in bone or soft tissues.

Recent studies have indicated that parathyroid hormone-related protein (PTHrP) may have important actions in lactation, affecting the mammary gland, and also calcium metabolism in the newborn and the mother. However, there are as yet no longitudinal studies to support the notion of an endocrine role of this peptide during nursing. We studied a group of 12 nursing mothers, mean age 32 years, after they had been nursing for an average of 7 weeks (B) and also 4 months after stopping nursing (A). It was assumed that changes occurring between A and B correspond to the effect of lactation. Blood was assayed for prolactin (PRL), PTHrP (two-site immunoradiometric assay with sheep antibody against PTHrP(1-40), and goat antibody against PTHrP(60-72), detection limit 0.3 pmol/l), intact PTH (iPTH), ionized calcium (Ca2+), 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), alkaline phosphatase (alkP), as well as for creatinine (Cr), protein, phosphorus (P), and total calcium (Ca). Fasting 2-h urine samples were analyzed for Ca excretion (CaE) and renal phosphate threshold (TmP/GFR). PRL was significantly higher during lactation than after weaning (39 +/- 10 vs. 13 +/- 9 micrograms/l; p = 0.018) and so was PTHrP (2.8 +/- 0.35 vs. 0.52 +/- 0.04 pmol/l; p = 0.002), values during lactation being above the normal limit (1.3 pmol/l) in all 12 mothers. There was a significant correlation between PRL and PTHrP during lactation (r = 0.8, p = 0.002). Whole blood Ca2+ did not significantly change from A (1.20 +/- 0.02 mmol/l) to B (1.22 +/- 0.02, mmol/l), whereas total Ca corrected for protein (2.18 +/- 0.02 mmol/l) or uncorrected (2.18 +/- 0.02 mmol/l) significantly rose during lactation (2.31 +/- 0.02 mmol/l, p = 0.003 and 2.37 +/- 0.03 mmol/l, p = 0.002, respectively). Conversely, iPTH decreased during lactation (3.47 +/- 0.38 vs. 2.11 +/- 0.35 pmol/l, A vs. B, p = 0.02). Serum-levels of 25(OH)D3 and 1,25(OH)2D3 did not significantly change from A to B (23 +/- 2.3 vs. 24 +/- 1.9 ng/ml and 29.5 +/- 6.0 vs. 21.9 +/- 1.8 pg/ml, respectively). Both TmP/GFR and P were higher during lactation than after weaning (1.15 +/- 0.03 vs. 0.86 +/- 0.05 mmol/l GF, p = 0.003 and 1.25 +/- 0.03 vs. 0.96 +/- 0.05 mmol/l, p = 0.002, respectively) as was alkP (74.0 +/- 7.1 vs. 52.6 +/- 6.9 U/l, p = 0.003). CaE did not differ between A and B (0.015 +/- 0.003 vs. 0.017 +/- 0.003 mmol/l GF, A vs. B, NS). We conclude that lactation is accompanied by an increase in serum PRL. This is associated with a release of PTHrP into the maternal blood circulation. A rise in total plasma Ca ensues, probably in part by increased bone turnover as suggested by the elevation of alkP. PTH secretion falls, with a subsequent rise of TmP/GFR and plasma P despite high plasma levels of PTHrP.

Both blunted osteocytic production of the Wnt inhibitor sclerostin (Scl) and increased T-cell production of the Wnt ligand Wnt10b contribute to the bone anabolic activity of intermittent parathyroid hormone (iPTH) treatment. However, the relative contribution of these mechanisms is unknown. In this study, we modeled the repressive effects of iPTH on Scl production in mice by treatment with a neutralizing anti-Scl antibody (Scl-Ab) to determine the contribution of T-cell-produced Wnt10b to the Scl-independent modalities of action of iPTH. We report that combined treatment with Scl-Ab and iPTH was more potent than either iPTH or Scl-Ab alone in increasing stromal cell production of OPG, osteoblastogenesis, osteoblast life span, bone turnover, bone mineral density, and trabecular bone volume and structure in mice with T cells capable of producing Wnt10b. In T-cell-null mice and mice lacking T-cell production of Wnt10b, combined treatment increased bone turnover significantly more than iPTH or Scl-Ab alone. However, in these mice, combined treatment with Scl-Ab and iPTH was equally effective as Scl-Ab alone in increasing the osteoblastic pool, bone volume, density, and structure. These findings demonstrate that the Scl-independent activity of iPTH on osteoblasts and bone mass is mediated by T-cell-produced Wnt10b. The data provide a proof of concept of a more potent therapeutic effect of combined treatment with iPTH and Scl-Ab than either alone.

OBJECTIVE

To assess the impact of the administration of ergocalciferol on serum parathyroid hormone levels at different stages of chronic kidney disease (CKD).

METHODS

A continuous series of 85 patients with stages 3-5 CKD but excluding patients on dialysis referred to the Kaiser Kidney Program were followed. Baseline serum intact parathyroid hormone (iPTH) and serum 25(OH)D levels were measured. All patients were administered ergocalciferol in doses ranging from 800 iu/day to 100,000 iu/week. We obtained serum levels of iPTH and 25(OH)D for a post-treatment endpoint after a median treatment period of 90 days.

RESULTS

Pre- and post-treatment serum iPTH levels displayed a mean difference of 2.8 pmol/L (95% CI 1.3-4.4, P < 0.001). Patients with stage 4 CKD had a mean difference of 3.6 pmol/L (95% CI 1.7-5.5, P < 0.001) between pre- and post-iPTH levels. Serum iPTH levels decreased among CKD stages 3 and 5, but were not statistically significant. All CKD groups analysed in the present study had significant increases in serum 25(OH)D levels. None of the study population required cessation of vitamin D therapy and no adverse outcomes were reported.

CONCLUSIONS

Ergocalciferol supplementation appears a safe and effective treatment for CKD populations which may raise levels of serum 25(OH)D levels and decrease iPTH levels.

BACKGROUND

Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5. Although phosphate binders are often used in patients on peritoneal dialysis (PD), no large randomized controlled studies evaluating their use solely in this population have previously been reported.

METHODS

In this multicentre, open-label study, adult patients on PD with serum phosphorus >5.5 mg/dl were randomized (2:1) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate. Doses were titrated to achieve serum phosphorus of 3.0-5.5 mg/dl. Changes in serum phosphorus, calcium, intact parathyroid hormone (iPTH), lipids and plasma biomarkers were assessed.

RESULTS

A total of 253 patients were screened, 143 of whom were randomized (sevelamer hydrochloride, n = 97; calcium acetate, n = 46). Treatment groups were well balanced with regard to baseline demographics. Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate (P < 0.001). Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group (P = 0.001) but not in the sevelamer hydrochloride group. Sevelamer hydrochloride was also associated with decreases in total cholesterol, low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase (all P < 0.001 versus baseline). Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients. Hypercalcaemia was experienced by more calcium acetate-treated patients (18 versus 2%; P = 0.001).

CONCLUSIONS

In summary, sevelamer hydrochloride provides a reduction in serum phosphorus compared to that obtained with calcium-based binders in PD patients. The effects of sevelamer hydrochloride appear similar in both PD and haemodialysis populations.

OBJECTIVE

This study was designed to investigate the effects of omega-3 fatty acids on depression and chronic inflammation in hemodialysis patients.

METHODS

Fifty-four maintenance hemodialysis patients were randomized to ingest two omega-3 (each containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid) or placebo capsules, three times daily for 4 months.

METHODS

Beck Depression Inventory (BDI) score and serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and at the end of the study.

RESULTS

Omega-3 supplement lowered BDI score significantly after 4 months of intervention. Among pro- and anti-inflammatory mediators, only serum ferritin level and IL-10 to IL-6 ratio showed significant changes in favor of omega-3 supplement during the study. In linear regression model adjusted for baseline values, omega-3 treatment was a significant predictor of reduced serum CRP, ferritin, and iPTH levels, and increased IL-10 to IL-6 ratio. No significant association was found between the anti-inflammatory and anti-depressant effects of omega-3 supplement.

CONCLUSIONS

Supplemental use of omega-3 fatty acids decreases depressive symptoms in hemodialysis patients apart from their anti-inflammatory effects.

Acute and chronic parathyroid insufficiency syndromes are the most common complication after total thyroidectomy. Permanent hypoparathyroidism imposes an important medical burden on patient lifestyle due to the need for lifetime medication, regular visits and significant long-term costs. Its true prevalence has been underestimated due to lack of clear definitions, inadequate follow-up and conflicts of interest when reporting individual patient series. The aim of this review is to propose precise definitions for the different syndromes associated to parathyroid failure based on the follow-up and management of patients developing hypocalcemia (<8 mg/dL at 24 hours) after first-time total thyroidectomy for cancer or goiter at our unit. Short and long-term post-thyroidectomy parathyroid failure presents as three different metabolic syndromes: (I) postoperative hypocalcemia is defined as a s-Ca <8 mg/dL (<2 mmol/L) within 24 hours after surgery requiring calcium/vit D replacement therapy at the time of hospital discharge; (II) protracted hypoparathyroidism as a subnormal iPTH concentration (<13 pg/mL) and/or need for calcium/vit D replacement at 4-6 weeks; and (III) permanent hypoparathyroidism as a subnormal iPTH concentration (<13 pg/mL) and/or need for calcium/vit D replacement 1 year after total thyroidectomy. Each of these syndromes has its own pattern of recovery and should be approached with different therapeutic strategies.

OBJECTIVE

Osteoporosis is frequently found in patients with cholestatic liver disease (primary biliary cirrhosis/primary sclerosing cholangitis) and chronic viral hepatitis. There is limited information about the long-term effect of liver transplantation (OLT) on bone metabolism. The aim of this study was to investigate the effect of liver transplantation on bone metabolism in patients with cholestatic and viral liver diseases.

METHODS

We randomly recruited 193 patients with chronic viral hepatitis or cholestatic liver diseases. Bone density (Z-score) and markers of bone metabolism (intact parathyroid hormone [iPTH], PTH 70-84, osteocalcin, procollagen, telopeptide, and vitamin D) were determined before and at time points (< and>> 24 months) post-OLT.

RESULTS

Before OLT, bone density (Z-score) was decreased in patients with cholestatic (-1) and viral (-0.4) liver diseases. In both groups bone density continued to decrease in the periods up to and more than 24 months after OLT. In the cholestatic group, bone density decreased significantly compared to pre-OLT (p < 0.05) and to the viral hepatitis group (p < 0,001). Markers of bone metabolism showed that after OLT, bone metabolism was enhanced and shifted versus bone resorption. Immunosuppressive drug therapy (glucocorticoids, cyclosporin, FK 506) directly correlated with increased bone metabolism post-OLT.

CONCLUSIONS

Bone loss is a long-term problem after OLT, particularly in patients with cholestatic liver diseases. Drug therapy is a main factor of bone loss. Pre- and post-OLT therapy to reduce bone loss is recommended.

Bone loss is a known complication of severe burn injury. It is, in part, due to increased endogenous glucocorticoids that contribute to the reduction in bone formation and osteoblast differentiation, hypercalciuria secondary to hypoparathyroidism, and vitamin D deficiency. In this study we attempted to prevent post-burn bone loss by acute intravenous administration of the bisphosphonate pamidronate. We enrolled 43 children, with burns of>> 40% total body surface area, in a randomized, double-blind, placebo-controlled study, administering the study drug within 10 days of burn injury and again 1 week later. Dual energy X-ray absorptiometry was performed prior to drug therapy, at hospital discharge and at 6 months post-burn. Urine specimens were obtained at baseline and discharge for determination of calcium and free deoxypyridinoline. Blood was obtained along with the urine specimens for measurement of intact parathyroid hormone (iPTH) and ionized calcium (Ca) levels. Following doxycycline labeling, intra-operative iliac crest bone biopsies were obtained, and bone histomorphometry was determined. At time of discharge there were no differences in total body bone mineral content (BMC), but lumbar spine BMC was significantly higher in the pamidronate group (P < 0.005). By 6 months post-burn the differences in lumbar spine BMC persisted, but, now, total body BMC was significantly higher in the pamidronate group (P < 0.05). Bone histomorphometry and levels of urine Ca and free deoxypyridinoline failed to show significant increases in bone formation or decreases in bone resorption. Pamidronate did not exacerbate the hypocalcemia in burn patients. In summary, acute intravenous pamidronate administration following burns may help to preserve bone mass, perhaps by inhibiting the glucocorticoid-induced apoptosis of osteoblasts and osteocytes.

OBJECTIVE

Intraoperative quick intact parathyroid hormone (iPTH) assay (IOPTH) has become a valuable adjunct in parathyroid surgery reliably predicting cure from hyperparathyroid state. Similarly to parathyroid surgery, the accuracy of the assay in predicting postoperative calcemia after thyroid surgery is related to blood sample timing and the criteria applied with no guidelines widely accepted, so far. This study compares different IOPTH criteria in predicting hypoparathyroidism-related hypocalcemia after thyroid surgery.

METHODS

The study included 200 consecutive patients undergoing total thyroidectomy. Three blood samples for IOPTH were taken in each patient: preoperatively--baseline (BL), at the end of surgery--skin closure (SC), and at 4 h postoperatively (4H). Serum calcium was routinely monitored at 4, 12, 24, 48, and 72 h postoperatively. The incidence and severity of hypocalcemia and related symptoms were matched to IOPTH results. The following criteria were tested: A, greater than 50% drop from BL at SC; B, greater than 70% drop from BL at SC; C, greater than 50% drop from BL at 4H; D, greater than 70% drop from BL at 4H; E, serum iPTH less than 15 pg/ml at SC; F, serum iPTH less than 10 pg/ml at SC; G, serum iPTH less than 15 pg/ml at 4H; H, serum iPTH less than 10 pg/ml at 4H. The accuracy of the tested criteria was calculated in predicting serum calcium level less than 2.0 mmol/l at any point after thyroidectomy.

RESULTS

Tested criteria had the following value in predicting serum calcium level less than 2.0 mmol/l after thyroidectomy (sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy, respectively): A (60, 89, 38, 95, and 86%), B (80, 93, 57, 98, and 92%), C (70, 90, 44, 96, and 88%), D (85, 95, 65, 98, and 94%), E (80, 91, 50, 98, and 90%), F (90, 95, 69, 99, and 95%), G (90, 95, 70, 99, and 95%), H (95, 99, 90, 99, and 98%).

CONCLUSIONS

The criterion of iPTH serum level less than 10 pg/ml at 4 h postoperatively has the highest accuracy in predicting serum calcium level below 2.0 mmol/l after total thyroidectomy when compared with the other criteria.

Assessments of serum 25-hydroxyvitamin D levels in 1,683 Japanese from a population-based cohort revealed prevalences of vitamin D insufficiency and deficiency were 81.3 and 1.2%, respectively. Vitamin D deficiency was significantly associated with female sex, examined month, current smoking, lack of regular walking, higher intact parathyroid hormone (iPTH), and poor daily vitamin D intake.

BACKGROUND

To clarify the characteristics of subjects with vitamin D insufficiency and deficiency among men and women in the general Japanese population.

METHODS

We initiated research on osteoarthritis/osteoporosis against disability (ROAD), a large-scale population-based cohort study, in 2005-2007. Blood examination was performed to measure serum 25-hydroxyvitamin D (25D) and iPTH levels and biochemical markers of bone turnover in 1,683 participants (595 men, 1,088 women). Participants completed an interviewer-administered questionnaire, measurements of bone mineral density, and x-ray examination. Vitamin D deficiency and insufficiency were defined by serum 25D levels <10 and ≥10 but <30 ng/mL, respectively.

RESULTS

The prevalence of vitamin D insufficiency and deficiency was 81.3 and 1.2%, respectively. Multinominal logistic regression analyses using potentially confounding variables revealed vitamin D insufficiency was significantly associated with age (+1 year, relative risk ratio, 0.98; 95% confidence interval, 0.96-0.99), gender (women vs. men, 2.28; 1.59-3.30), residing areas (coastal area vs. mountainous area, 0.58; 0.41-0.81), examined month (October, November, December vs. January, 0.51; 0.34-0.76), and serum levels of iPTH (+1 pg/mL, 1.02; 1.01-1.03). Vitamin D deficiency was significantly characterised by female sex (20.5; 3.1-136.7), examined month (0.28; 0.09-0.95), current smoking habit (6.39; 1.78-23.0), lack of regular outside walking (3.96; 1.34-11.7), higher iPTH (1.02; 1.01-1.03) and poor daily vitamin D intake (+10 μg/day, 0.48; 0.24-0.93).

CONCLUSIONS

A high prevalence of vitamin D insufficiency and a low prevalence of vitamin D deficiency were found in Japanese men and women, and the characteristics of vitamin D status were clarified.

The concentration or threshold of 25-hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the 2-phase regression approach used, 2 distinct clusters for a single 25(OH)D threshold have been reported: 16-20 ng/mL (40-50 nmol/L) and 30-32 ng/mL (75-80 nmol/L). To rationalize the apparently disparate published results, we compared thresholds from several regression models including a 3-phase one to estimate simultaneously 2 thresholds before and after adjusting for possible confounding for age, BMI, glomerular filtration rate, dietary calcium, and season (April-September vs. October-March) within a single data set, i.e. data from the Tufts University Sites Testing Osteoporosis Prevention/Intervention Treatment study, consisting of 181 men and 206 women (total n = 387) ages 65-87 y. Plasma 25(OH)D and serum iPTH concentrations were (mean +/- SD) 22.1 +/- 7.44 ng/mL (55.25 +/- 18.6 nmol/L) and 36.6 +/- 16.03 pg/mL (3.88 +/- 1.7 pmol/L), respectively. The 3-phase model identified 2 thresholds of 12 ng/mL (30 nmol/L) and 28 ng/mL (70 nmol/L); similar results were found from the 2-phase models evaluated, i.e. 13-20 and 27-30 ng/mL (32.5-50 and 67.5-75 nmol/L) and with previous results. Adjusting for confounding did not change the results substantially. Accordingly, the 3-phase model appears to be superior to the 2-phase approach, because it simultaneously estimates the 2 threshold clusters found from the 2-phase approaches along with estimating confidence limits. If replicated, it may be of both clinical and public health importance.

Intermittent parathyroid hormone (iPTH) is the only FDA-approved therapy for bone loss due to conditions such as osteoporosis that increases bone formation by osteoblasts; all other therapies approved for osteoporosis block bone resorption by osteoclasts. The anabolic effects of iPTH are likely due to a combination of multiple mechanisms, including induction of immediate-early genes, increased expression and/or activity of essential osteoblast transcription factors, and downregulation of anti-osteogenic proteins, such as sclerostin. In contrast, continuous administration of PTH induces bone loss primarily due to up-regulation of RANKL expression and inhibition of osteoprotegerin expression.

The use of the intraoperative parathyroid hormone assay (QPTH) to guide a limited parathyroidectomy in patients with sporadic primary hyperparathyroidism (SPHPT) is well established. The advantage of having this assay performed in the operating room is immediate feedback for (1) confirming the complete excision of all hyperfunctioning parathyroid(s); (2) differential jugular venous sampling for localization; and (3) diagnosing suspected tissue without histopathology. For these reasons, the reliability of the hormone measurement and a short assay turnaround time are essential for surgical guidance. We report our experience using a new "point-of-care" assay for intact parathyroid hormone (iPTH). A new two-site chemiluminescent immunometric assay was used. The antibodies are inside a microtiter well, where the iPTH is measured by a strip luminometer after incubation for 5 minutes. Sixteen frozen samples were measured simultaneously using the traditional iPTH assay and this new assay for comparison. Fifty-one patients with SPHPT underwent parathyroidectomy guided by this new assay. The criteria used to predict postoperative normocalcemia was a drop in the hormone level of < or = 50% from the highest preincision or preexcision levels at 10 minutes after excision of all hypersecreting gland(s). The correlation between the traditional and new assays was 0.98. The assay predicted the postoperative calcium levels in all patients except one (false negative-delayed drop). The assay turnaround time was 8 minutes. This new point-of-care assay is reliable for predicting postoperative calcium levels when used with the described criteria. It has advantages over the traditional assay in that it is faster and easier to perform.

BACKGROUND

Technetium-99m-sestamibi scanning and the intraoperative intact parathyroid hormone (iPTH) assay have permitted development of focused parathyroid techniques for treatment of primary hyperparathyroidism. The purpose of this study was to assess if any pre- and intraoperative factors (degree of sestamibi uptake and iPTH levels) were associated with postoperative results (resected gland weight and parathyroid nuclear morphology).

METHODS

We performed a retrospective analysis of 101 consecutive patients who underwent preoperative sestamibi scintigraphy and a targeted parathyroid exploration for primary hyperparathyroidism. Sestamibi uptake was graded visually on a 4-point scale of 0 (no uptake or false-negative result) to 3 (high uptake) and compared with respect to iPTH levels, gland morphology, and specimen weight. A Kruskal-Wallis test and a Pearson test were used for the statistical analysis.

RESULTS

Degree of sestamibi uptake was associated with gland weight (median weight of 250 mg, 340 mg, 655 mg, 1,400 mg for grades 0, 1, 2, and 3, respectively, p < 0.001). The uptake of sestamibi was also associated with preoperative PTH levels (median PTH levels of 113, 151, 129, and 170 pg/mL for grades 0, 1, 2, and 3, respectively, p = 0.02), but not with the other parameters. The weight of resected gland(s) was associated with preoperative PTH levels (p = 0.02), and with some of the morphologic nuclear data (mean surface area (p = 0.02), maximum diameter (p = 0.01), and perimeter of the nuclei (p = 0.01).

CONCLUSIONS

These data suggest that false-negative sestamibi scanning (visual score of 0) might result when hypersecreting parathyroid glands are small. Preoperative PTH level might be useful to estimate the amount of hypersecreting tissue to be resected.

BACKGROUND

Commonly used assays for intact parathyroid hormone (iPTH) detect not only the biologically active 84-amino acid hormone [PTH1-84], but cross-react with an N-terminal-truncated fragment. Because iPTH assays often fail to predict success of parathyroidectomy in patients with renal hyperparathyroidism (rHPT), we compared results of a 3rd-generation PTH1-84 assay (Bio-iPTH; Nichols Institute Diagnostics) with two 2nd-generation iPTH assays (from Nichols and Roche Diagnostics) by evaluating the PTH clearance kinetics during surgical treatment.

METHODS

We collected blood samples in short time intervals from 35 consecutive surgical patients with rHPT. Three patients had to be excluded from further calculations; the remainder were grouped according to kidney function and postoperative outcome. All samples were analyzed with the 3 automated PTH assays, which have different specificities.

RESULTS

Twenty minutes after removal of the last gland, the PTH1-84 values decreased to within the reference intervals in all patients with total and subtotal resection; however, iPTH concentrations normalized in only one half of these patients. In patients with poor renal function, the half-life of PTH1-84 was shorter than the half-lives obtained with the iPTH assays.

CONCLUSIONS

The accuracy of PTH monitoring during surgery for rHPT depends on renal function and assay specificity. All assays tested showed similar effectiveness in detecting missed glands, but the assay for PTH1-84 gave more reliable results than the iPTH assays, which overestimated the concentration of PTH and hampered the intrasurgical diagnosis of resection sufficiency.

Phosphatonin fibroblast growth factor-23 (FGF-23) is involved in phosphate (P) excretion and vitamin D metabolism. Recently, FGF-23 has been suggested to be responsible for the hypophosphatemia and inappropriately low calcitriol levels observed after renal transplantation. We performed a prospective study to investigate FGF-23 levels in patients with end-stage renal disease before and after renal transplantation and their probable association with markers of bone and mineral metabolism. Intact FGF-23 levels were determined before and at 3, 6, and 12 months posttransplantation in 18 renal transplant recipients. Intact parathyroid hormone (iPTH), calcium (Ca), P, 25(OH)VitD, and 1,25(OH)(2)VitD levels were measured at the same time periods. Renal threshold phosphate concentration (TmPO(4)/GFR) was also calculated at 3, 6, and 12 months posttransplantation. The results showed that FGF-23 levels decreased by 89% 3 months posttransplantation (346 +/- 146 versus 37 +/- 9 pg/mL, P < .01) and remained stable throughout the study period. iPTH and P levels also decreased significantly after renal transplantation, while Ca and 1,25(OH)(2)VitD increased. Pretransplantation FGF-23 was significantly correlated with P levels at 3 months posttransplantation (P < .005). In conclusion, FGF-23 levels decrease dramatically after successful renal transplantation. Pre-transplantation FGF-23 correlate with P levels 3 months posttransplantation.

BACKGROUND

We aimed to investigate different treatment drugs for the prevention of post-transplant bone loss.

METHODS

Sixty adult male recent renal transplant recipients were enrolled into the study. Patients were randomized into 4 groups: group I received daily alfacalcidol 0.5 microg PO; group II received oral alendronate 5 mg/day; group III received intranasal salmon calcitonin 200 IU every other day; and group IV was considered a control group. Every patient was supplemented with daily 500 mg oral calcium carbonate. Parameters of bone metabolism were measured before and at 12 months after starting treatment. Bone mineral density (BMD) was measured by (DEXA) at lumber spine, femoral neck, and forearm before and after treatment period.

RESULTS

BMD was increased at lumber spine by 2.1%, 0.8%, 1.7%, by 1.8%, 0.6%, 1.6% at femoral neck, and by 3.2%, 1.9%, 2.6% at forearm in groups I, II, and III, respectively, while it decreased by 3.2%, 3.8%, and 1.8% at the same sites, respectively, in control group (P= <0.05). iPTH level decreased significantly in group I, while the decrease was insignificant in other groups (P= 0.003). All other parameters were not statistically significant between treatment groups. Apart from transient hypocalcaemia in 3 patients in group II, and 2 patients in group III, no other significant adverse effects were noted.

CONCLUSIONS

This study proves that early bone loss that occurs during the first 12 months after renal transplantation could be prevented by alfacalcidol, calcitonin, or alendronate. Among the treatment groups, alfacalcidol significantly improved the hyperparathyroidism. All treatment drugs are safe and tolerable.

OBJECTIVE

The aims of the study were to quantify the prevalence of asymptomatic coeliac disease (CD) in a cohort of osteoporotic females, and to investigate the features of bone loss.

METHODS

We studied 255 women (mean age 66.6 +/- 8.5 SD) with primary osteoporosis (WHO diagnostic criteria). After the first CD screening with the measure of serum IgG antigliadin antibodies (IgG-AGA), 53 women showed a positive test: antibodies to tissue transglutaminase (TG-ab) were subsequently determined to confirm the diagnosis of CD. Bone metabolism was evaluated by: serum and urinary calcium, serum and urinary phosphate, serum alkaline phosphatase, urinary crosslaps, serum 25(OH)D and serum parathyroid hormone.

RESULTS

High levels of IgG-AGA and TG-ab were observed in 24 patients with a prevalence of serological disease of 9.4%. These women were characterized, in comparison with the other patients, by a statistically significant reduction in serum 25(OH)D (17.8 +/- 7.2 vs. 55.1 +/- 20.3 nmol L(-1), P < 0.01) together with a significant increase of iPTH (65.1 +/- 29.7 vs. 35.1 +/- 20.0 pg mL(-1); P < 0.01). Patients with high TG-ab levels showed also slightly raised values of urinary crosslaps (288 +/- 88 vs. 270 +/- 90 microm mol(-1) Cr). In IgG-AG positive patients a statistically significant inverse correlation was found between 25(OH)D serum levels and log-transformed TG-ab values (r: -0.95, P < 0.001). Intestinal biopsies were obtained in 10 TG-ab positive women and verified CD in six patients.

CONCLUSIONS

These data support the hypothesis that patients with undiagnosed celiac disease develop high remodelling processes related to calcium malabsorption, secondary hyperparathyroidism and unavailability of vitamin D with a consequent more marked bone loss.

Reports of decreased serum 25-hydroxyvitamin D (25-OHD) and altered bone metabolism associated with antiepileptic drug (AED) treatment are inconsistent and predominantly restricted to adults. In this cross-sectional observational study, the aim was to evaluate the influence of AED treatment on vitamin D status and markers of bone turnover in children with epilepsy. In 38 children taking AEDs and 44 healthy control subjects, blood samples were collected to determine the levels of serum 25-OHD, intact parathyroid hormone (iPTH), calcium (Ca), phosphate (P), bone alkaline phosphatase (BAP), osteocalcin (OC) and C terminal telopeptide of type I collagen (ICTP). More than 75% of the patients were vitamin D deficient (serum 25-OHD<20 ng/mL) and 21% of the patients had an insufficient vitamin D status (serum 25-OHD=20-30 ng/mL). In the patients, the serum levels of OC (p = 0.002) and BAP (p < 0.001) were significantly increased, but ICTP (p = 0.002) concentrations were significantly decreased compared with the control group. When patients where divided into two groups according to their medication (mono- or polytherapy), significantly lower 25-OHD (p = 0.038) and ICTP (p = 0.005) levels and elevated BAP (p = 0.023) concentrations were found in patients under polytherapy. An association between 25-OHD and the measured bone markers could not be determined. Our results indicate that the prevalence of vitamin D deficiency in epilepsy patients under AED treatment is high, especially under polytherapy, and alteration markers of bone formation and resorption suggests an accelerated skeletal turnover. The routine monitoring of serum 25-OHD and vitamin D supplementation on an individual basis should be considered.

With improved long-term survival following liver transplantation (LT), issues relating to the assessment of the liver allograft in long-term survivors are becoming increasingly relevant. Histological abnormalities are commonly present in late post-transplant biopsies, including protocol biopsies from patients who appear to be well with good graft function. Recurrent disease is the commonest recognised cause of abnormal graft histology, but may be modified by the effects of immunosuppression or interactions with other graft complications, resulting in complex or atypical changes. Other abnormalities seen in late post-transplant biopsies include rejection (which often has different appearances to those seen in the post-transplant period), de novo disease, "idiopathic" post-transplant hepatitis (IPTH) and nodular regenerative hyperplasia. In many cases graft dysfunction has more than one cause and liver biopsy may help to identify the predominant cause of graft damage. Problems exist with the terminology used to describe less well understood patterns of graft injury, but there is emerging evidence to suggest that late rejection, de novo autoimmune hepatitis and IPTH may all be part of an overlapping spectrum of immune-mediated injury occurring in the late post-transplant liver allograft. Careful clinico-pathological correlation is very important and the wording of the biopsy report should take into account therapeutic implications, particularly whether changes in immunosuppression may be indicated. This article will provide an overview of the main histological changes occurring in long-term survivors post-LT, focusing on areas where the assessment of late post-transplant biopsies is most relevant clinically.

The influence of calcitropic hormones on functional mobility has been studied in vitamin D (calcidiol) deficient elderly or elderly with a history of falls, however, data in community-dwelling independent vitamin D replete elderly are missing. We therefore assessed in an observational survey the association of calcidiol (25(OH)D3) and calcitriol (D-hormone / 1,25(OH)2D3) status as well as of daily calcium intake on functional mobility in older subjects We evaluated 192 women and 188 men, aged superior 70 years and living independently. Average Timed-up and go test (TUG-test) in seconds was taken as measure of functional mobility. Calcidiol and D-hormone serum concentrations and daily calcium intake were studied in multivariate controlled linear regression models with TUG-test performance as the dependent variable and/or as dichotomous variables (deficient vs. non-deficient, above vs. below the median, respectively). Subjects with low D-hormone serum concentrations took significantly more time to perform the TUG-test (low = 7.70s +/- 2.52 SD ; high = 6.70s +/- 1.29 SD; p = 0.004). In the linear multivariate controlled regression model increased D-hormone serum concentrations predicted better TUG-test performance (estimate -0.0007, p = 0.044). Participants with a calcium intake of>> or =512 mg/day were significantly faster to perform the TUG-test than participants with a daily calcium intake of <512 mg/day (estimate:-0.43, p = 0.007). Other significant predictors of better TUG-test performance in both models were: male gender, less comorbid conditions, younger age, lower BMI, iPTH serum levels and creatinine clearance. Calcidiol serum levels were not associated with TUG-test performance. Higher D-hormone status and a calcium intake of>> or =512 mg/day in community-dwelling independent older persons are significant determinants of better functional mobility. Therefore, to ensure optimal functional mobility, the care of older persons should address correction of D-hormone deficiency and increasing daily calcium intake.

This study was conducted to determine the frequency of vitamin D deficiency and its correlation with different factors. Three hundred and thirteen healthy children and adolescents (192 females and 121 males aged 8-18 years, mean +/- SD, 12.7 +/- 2.3 years) were enrolled, and measurements of serum 25-hydroxyvitamin D [25(OH)D] (using EIA) and intact parathyroid hormone (iPTH) (using immunoradiometric assay (IRMA)) were conducted. The grades of vitamin D status were defined according to blood level of 25(OH)D as follows: severely deficient < 12.5; deficient,>> or = 12.5 and < 25; insufficient,>> or = 25 and < 50; normal>> or = 50 and < 250 nmol/L. Severe deficiency was detected in 25% of subjects (males 8%; females 92%), deficiency in 27% (males 34%; females 66%) and insufficiency in 26% (males 58%; females 42%). The mean 25(OH)D level in males was significantly greater than that in females (p < 0.001), and this level was significantly higher in prepubertal compared to pubertal subjects (p < 0.001). 25(OH)D had a negative correlation with iPTH (p < 0.001). The curve of iPTH began to rise when 25(OH)D reached 75 nmol/L. The level of 25(OH)D had a negative correlation with BMI-SDS and height-SDS in females (p-value, 0.01 and 0.039, respectively). The subjects did not have any signs or symptoms of rickets. Frequency of vitamin D deficiency did not have any significant seasonal variation. Furthermore, vitamin D deficiency was not found to be related to the type or location of the subjects' homes. In this study, subclinical vitamin D deficiency was significantly more prevalent in females, particularly those undergoing puberty. Children who were obese and taller than average, had lower levels of 25(OH)D, and level of 25(OH)D should be maintained>> 75 nmol/L in order to prevent PTH rising.

BACKGROUND

There is a high drug treatment burden on patients receiving long-term dialysis therapy. Abnormalities of calcium and phosphate metabolism are associated with increased mortality, and attempts to correct these disturbances may improve survival.

METHODS

We prospectively evaluated the targets of the currently used Kidney Disease: Improving Global Outcomes (KDIGO) guidelines in 8377 prevalent patients receiving intermittent haemodialysis therapy in France from July 2007 to December 2009.

RESULTS

Adjusted Cox analyses showed that only one among six targets was predictive of mortality, i.e. a serum intact parathyroid hormone (iPTH) <130 pg/mL. A continuous risk analysis using fractional polynomials showed a 10% increase in hazard ratio (HR) for mortality for a serum phosphate <0.71 (2.2) and >1.98 (6.14) mmol/L (mg/dL), a non-corrected serum calcium <1.59 (6.37) and >2.41 (9.66) mmol/L (mg/dL) and a serum iPTH <100 and >1090 pg/mL.

CONCLUSIONS

The findings of our observational study confirm the existence of a grey zone, in which precise biochemical targets are difficult to define, with the exception of avoiding extreme values. Given the absence of intervention trials proving the clinical usefulness of phosphorus control, and pending the results of large clinical trials on the effect of optimal PTH and calcium control on hard outcomes, the present findings may help to refine future recommendations for the treatment of chronic haemodialysis patients.