Intermittent parathyroid hormone (iPTH) treatment expands hemopoietic stem and progenitor cells (HSPCs), but the involved mechanisms and the affected HSPC populations are mostly unknown. Here we show that T cells are required for iPTH to expand short-term HSPCs (ST-HSPCs) and improve blood cell engraftment and host survival after BM transplantation. Silencing of PTH/PTH-related protein receptor (PPR) in T cells abrogates the effects of iPTH, thus demonstrating a requirement for direct PPR signaling in T cells. Mechanistically, iPTH expands ST-HSPCs by activating Wnt signaling in HSPCs and stromal cells (SCs) through T-cell production of the Wnt ligand Wnt10b. Attesting to the relevance of Wnt10b, iPTH fails to expand ST-HSPCs in mice with Wnt10b(-/-) T cells. Moreover, iPTH fails to promote engraftment and survival after BM transplantation in Wnt10b null mice. In summary, direct PPR signaling in T cells and the resulting production of Wnt10b play a pivotal role in the mechanism by which iPTH expands ST-HSPCs. The data suggest that T cells may provide pharmacologic targets for HSPC expansion.

We sought to determine if the high phosphorus, moderately low calcium intake typical of U.S. teenagers and young adults alters parathyroid function as it does in experimental animals. Because those animals ultimately developed osteopenia, it has been suggested that low dietary calcium to phosphorus ratios may reduce peak bone mass and increase susceptibility to osteoporotic fracture later in life. However, it is not known whether PTH secretion or action increases in response to commonly consumed phosphorus-rich, calcium-poor foods. We studied the 24-h mineral and hormonal responses of eight men and eight women, aged 18-25 yr, after 8 days of ingesting a control diet that had calcium (820 mg) and phosphorus (930 mg) contents near the recommended daily intakes, and a test diet with calcium and phosphorus contents (1660 mg phosphorus, 420 mg calcium) typical of current intakes. Both diets were made from common grocery store foods. The 24-h mean serum immunoreactive PTH levels increased in men (11%; P less than 0.006) and women (22%; P less than 0.003) during the test diet. In both sexes, the test diet significantly increased serum phosphorus, plasma 1,25-dihydroxyvitamin D, and urinary hydroxyproline and cAMP excretion; in women only it decreased serum ionized and total calcium levels. Thus, short term ingestion of a diet typifying current levels of calcium and phosphorus intake resulted in elevated serum iPTH levels and indexes of PTH action in young adults.

High prevalences of vitamin D deficiency have been reported in non-Western immigrants moving to Western countries, including Norway, but there is limited information on vitamin D status in infants born to immigrant mothers. We aimed to describe the vitamin D status and potentially correlated factors among infants aged 6 weeks and their mothers with Pakistani, Turkish or Somali background attending child health clinics in Norway. Eighty-six healthy infants and their mothers with immigrant background were recruited at the routine 6-week check-up at nine centres between 2004 and 2006. Venous or capillary blood was collected at the clinics from the mother and infant, and serum separated for analysis of 25-hydroxyvitamin D (s-25(OH)D) and intact parathyroid hormone (s-iPTH). The mean maternal s-25(OH)D was 25.8 nmol/l, with 57 % below 25 nmol/l and 15 % below 12.5 nmol/l. Of the mothers, 26 % had s-iPTH)5.7 pmol/l. For infants, mean s-25(OH)D was 41.7 nmol/l, with 47 % below 25 nmol/l and 34 % below 12.5 nmol/l. s-25(OH)D was considerably lower in the thirty-one exclusively breast-fed infants (mean 11.1 nmol/l; P < 0.0001). Use of vitamin D supplements and education showed a positive association with maternal s-25(OH)D. There was no significant association between mother's and child's s-25(OH)D, and no significant ethnic or seasonal variation in s-25(OH)D for mothers or infants. In conclusion, there is widespread vitamin D deficiency in immigrant mothers and their infants living in Norway. Exclusively breast-fed infants who did not receive vitamin D supplements had particularly severe vitamin D deficiency.

Unilateral and minimally invasive parathyroidectomies with endoscopic and video-assisted technique have been introduced. Most of these procedures utilize preoperative localization and intraoperative monitoring of parathyroid hormone. There are only a few reports on these procedures. The objective of this study was to evaluate video-assisted parathyroidectomy (MIVAP) for surgery in patients with primary hyperparathyroidism (pHPT). From February 1997 to June 1999 a series of 123 consecutive patients with pHPT at four surgical centers were evaluated. The patients' ages ranged from 18 to 77 years (median 50 years). Preoperatively, sestamibi scintigraphy and ultrasonography for localization were performed for all patients. Selection criteria for a MIVAP procedure excluded patients with negative localization, suspicion of multiglandular disease (MGD) or thyroid malignancy, a large thyroid mass, and prior surgery or irradiation to the neck. MIVAP was performed with a 1.5 cm suprasternal incision; the operation was then done through this incision with a 30 degree 5 mm endoscope and microsurgical instruments with brief CO2 insufflation for adenoma identification. We then proceeded with an open technique through the small incision under video-assistance. Intraoperative monitoring of intact parathyroid hormone (iPTH) assays was used in all patients. Among the 123 patients in whom MIVAP was attempted, the procedure was accomplished in 109 (89%). Conversion to conventional cervicotomy was required in 14 (11%) patients because of failed localization, failure of the iPTH level to fall appropriately, or technical problems. There was no persistent or recurrent HPT during the 3 to 12-month follow-up. Oral calcium replacement for symptomatic hypocalcemia postoperatively was given in 7 (6%) cases. A unilateral transient laryngeal nerve palsy, resolving within 6 months postoperatively, occurred in two (2%) patients. The median hospital stay was 1.5 days (range 0.5-5.0 days). This study showed the feasibility of MIVAP as an alternative surgical treatment for pHPT in a selected group of patients. Further studies are necessary to evaluate the efficacy and rationale of MIVAP compared to other techniques for parathyroidectomy in pHPT patients.

OBJECTIVE

To determine the sensitivity and positive predictive value (PPV) of subtraction scintigraphy (SS) vs. ultrasonography (US) of the neck combined with rapid intact parathyroid hormone (iPTH) assay in US-guided fine-needle parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach.

METHODS

The results of SS for localization of parathyroid adenoma were determined in 121 patients with primary hyperparathyroidism (pHPT) and compared with findings at surgery and with the results of US alone (in patients without nodular goitre) and US in combination with the iPTH assay in US-guided fine-needle aspirates (FNAs) of suspicious parathyroid lesions (in patients with concomitant nodular goitre).

METHODS

All 121 patients had biochemically documented pHPT; all were referred for first-time surgery.

METHODS

SS was performed with 99mTc-sestamibi and 99mTc-pertechnetate. High-resolution US of the neck was performed by a single endocrine surgeon and combined with US-guided FNAs of suspicious parathyroid lesions in all patients with nodular goitre (n = 43).

RESULTS

The sensitivity and PPV of SS were significantly higher in patients without vs. with goitre (89.3% and 95.7%vs. 74.3% and 76.5%, respectively; P < 0.001). The sensitivity and PPV of US were significantly higher in patients without vs. with goitre (96% and 97.3%vs. 67.7% and 71.9%, respectively; P < 0.001). The iPTH assay of US-guided FNAs of suspicious parathyroid lesions in patients with nodular goitre significantly improved both the sensitivity and PPV of US imaging (90.7% and 100%, respectively), allowing for an accurate choice of surgical approach in 118 (97.5%) of 121 patients. SS was more accurate than US alone in detection of ectopic parathyroid adenomas. However, US alone was characterized by a higher sensitivity in detection of small parathyroid adenomas (< 500 mg) at typical sites (P < 0.01).

CONCLUSIONS

Both the sensitivity and PPV of SS and US alone are comparable, with significantly less accurate results obtained in patients with goitre. In cases of equivocal results of US and/or in patients with concomitant goitre, an iPTH assay in US-guided FNAs of suspicious parathyroid lesions may be used to establish the nature of the mass, distinguish between parathyroid and nonparathyroid tissue (goitre, lymph nodes) and improve the accuracy of US parathyroid imaging, allowing for successful directing of surgical approach in a majority of patients.

OBJECTIVE

Regarding interactions between pro-inflammatory cytokines and bone metabolism in rheumatoid arthritis (RA), we investigated the relationship between the serum levels of interleukin (IL)-1beta, IL-6, soluble interleukin-2 receptor (sIL-2r), C-reactive protein (CRP), the vitamin D metabolites 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], intact parathyroid hormone (iPTH) as well as serum and urinary parameters of bone turnover in 74 post-menopausal women with RA.

RESULTS

SIL-2r correlated negatively with 1,25(OH)2D3 (P < 0.01), whereas IL-6 showed a positive correlation with urinary excretion of deoxypyridinoline collagen cross-links (P < 0.01). 1,25(OH)2D3 (P < 0.01) and iPTH (P < 0.01) were negatively related to CRP, whereas the urinary excretion of pyridinoline (P < 0.01) and deoxypyridinoline (P < 0.01)-collagen cross-links showed a positive correlation with CRP. 1,25(OH)2D3 (P < 0.01) and iPTH (P < 0.05) were positively related to bone alkaline phosphatase as a marker of osteoblast function.

CONCLUSIONS

Our data indicate that IL-6 is a critical determinant of increased bone resorption in post-menopausal RA women with high disease activity and that serum levels of 1,25(OH)2D3 are inversely related to T-cell activation.

Dichloromethylene diphosphonate (Cl2MDP) is a diphosphonate which markedly inhibits bone resorption. We have tested Cl2MDP in Paget's disease, a disorder characterized by increased bone remodeling. Sixty-three patients with progressive Paget's disease were treated for 6 months with Cl2MDP at daily oral doses of 400, 800, 1600, or 2400 mg. Thirty-nine patients received calcium and vitamin D supplements during treatment. patients in all treatment groups had significant reduction in serum alkaline phosphatase, urinary hydroxyproline, skeletal uptake of 99mtechnetium-diphosphonate scintiscans, and resorption parameters on iliac crest biopsy samples as assessed by quantitative histomorphometry. Treatment was well tolerated and did not induce a skeletal mineralization defect. The reduction in alkaline phosphatase and urinary hydroxyproline persisted 1 yr after withdrawal of treatment. The biochemical remission was sustained in half of the patients 2 yr after the end of treatment and was accompanied by a marked reduction of bone pain. a daily dose of 800 mg is recommended as the best of control of clinical and biochemical symptoms. The transient increase in iPTH levels observed in patients treated with Cl2MDP alone did not occur when calcium and vitamin D were added. We conclude that Cl2MDP is effective in the treatment of Paget's disease of bone and provides a prolonged response. Dietary supplementation with calcium and vitamin D is desirable to prevent secondary hyperparathyroidism.

The authors evaluated the prevalence, magnitude, and contributing factors for osteopenia in insulin-dependent diabetes mellitus (IDDM). We measured bone mineral density (BMD) in the lumbar spine and femoral region in 90 patients aged 18-54 years with IDDM using dual-energy x-ray absorptiometry. The blood-glucose control, insulin dosage, duration of disease, and presence of chronic complications of diabetes were evaluated. Serum ionized calcium, magnesium, phosphorus, alkaline phosphatase (ALP), 25-hydroxycholecalciferol, immunoreactive parathyroid hormone (iPTH), and urinary calcium, phosphorus, and hydroxyproline were also analyzed. Thirty-one patients (34%) were classified as having a reduced BMD (less than 2 SD below the mean). The comparison between normal and low BMD patients showed that the osteopenics had a tendency to be younger (median, 28 years versus 32 years), showed a higher mean plasma glucose (15.5 +/- 5.0 mmol/L versus 12.9 +/- 3.8 mmol/L; p = 0.018), longer duration of disease (11.2 +/- 2.1 years versus 5.0 +/- 1.3 years; p = 0.004), and needed a higher insulin dosage (56 +/- 17 U/day versus 43 +/- 16 U/day; p < 0.001). There was a positive correlation between mean glucose levels, duration of disease, insulin dosage, and bone-mass decrease. A higher incidence of chronic complications, mainly retinopathy (58% versus 25%) and neuropathy (52% versus 22%) was found in the low BMD group. There was no alteration of serum calcium, phosphorus, iPTH, 25-hydroxycholecalciferol, and urinary calcium and phosphorus. The ALP levels were significantly higher in the osteopenic group, and magnesium and hydroxyproline levels were lower in the whole diabetic group, but these measurements did not correlate with BMD reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol (C) treatment strategies for secondary hyperparathyroidism remain controversial regarding efficacy and safety. In children, intermittent C administration has been suspected of impairing body growth. In a prospective, randomized multicenter study, we compared the effect of daily versus twice weekly C on plasma intact parathyroid hormone (iPTH) levels and growth in 24 prepubertal children with chronic renal insufficiency (mean creatinine clearance 20+/-9 ml/min per 1.73 m(2)). After a 3-week washout period, the patients were randomly assigned to 10 ng/kg per day or 35 ng/kg twice a week oral C. The C dose was kept constant for 2 months and could then be adapted to maintain an iPTH target range of 140-280 pg/ml. Median (range) baseline iPTH levels were 567 (114-1209) pg/ml in the daily and 332 (93-614) pg/ml in the intermittent treatment group ( P=NS). After 12 months, iPTH had decreased to 255 (85-710) and 179 (51-443) pg/ml ( P<0.01). The average weekly dose of C was 76+/-34 and 62+/-34 ng/kg ( P=NS). Five episodes of calcium phosphate product>/=70 occurred in the daily group and four in the intermittent group. The change in height standard deviation score during the study period was not affected by either treatment modality (-0.18+/-0.34 vs. -0.05+/-0.52, P=NS). Daily and intermittent C do not differentially affect growth rate and are equally effective in controlling secondary hyperparathyroidism in children with chronic renal failure.

BACKGROUND

Paricalcitol is a vitamin D analog approved for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure. This study was designed to evaluate the long-term efficacy and safety of paricalcitol. Additional analysis evaluated the effects of paricalcitol in hypocalcemic and hyperphosphatemic subpopulations.

METHODS

One hundred sixty-four end-stage renal disease (ESRD) patiesnts on hemodialysis were treated in an open-label, multicenter study lasting up to 13 months in duration. After a baseline or washout period, an initial starting dose of 0.04-0.393 microg/kg was given 2-3 times per week. This dose was adjusted at the discretion of the investigator according to the patient's intact parathyroid hormone level (iPTH), calcium level, and calcium-phosphorus (Ca x P) product. The therapy was intended to reproduce expected clinical use of paricalcitol. Patients represented a wide cross-section of the ESRD population, and were not excluded from the study based on age or underlying disease.

RESULTS

The mean paricalcitol dose level throughout the study was 0.10 microg/kg. The mean iPTH levels (baseline mean 628.3 +/- 27.65 pg/ml) decreased rapidly during the first 4 months of therapy, and reached the designated target range (100-300 pg/ml) by month 5 (mean 295.3 +/- 25.69 pg/ml). A maximum mean decrease in iPTH level of 409 +/- 35.01 pg/ml was seen at month 13. Throughout the course of the study, the mean normalized calcium level was maintained well within the normal range (9.44-9.94 mg/dl). The mean phosphorus level was maintained in an acceptable range throughout the study (5.92-6.53 mg/dl). Mean Ca x P product was maintained between 52 and 65. Mean alkaline phosphatase levels decreased significantly from baseline with a maximum mean decrease of 62 +/- 17.3 U/l observed at month 9. In 34 initially hypocalcemic patients (mean of 7.7 mg/dl) iPTH levels decreased from baseline, on average, by 443 +/- 81.86 pg/ml while mean calcium levels rose by 1.2 +/- 0.23 mg/dl to reach the normal range. In 35 initially hyperphosphatemic patients (mean of 8.0 mg/dl) iPTH levels decreased, on average, by 515 +/- 103.31 pg/ml with an associated mean decrease in phosphorus of 0.57 +/- 0.52 mg/dl. Adverse events that were considered by the investigator to have a possible. probable, or definite relationship to study drug occurred in 26% of patients. Other than expected temporary effects of hypercalcemia and hyperphosphatemia. the only possible trends for causally-related adverse events were for nausea/vomiting and metallic taste.

CONCLUSIONS

This long-term study of paricalcitol demonstrates that it rapidly and effectively suppresses iPTH levels in a wide spectrum of ESRD patients and caused no unexpected adverse events.

BACKGROUND

Rapamycin is an effective immunosuppressant widely used to maintain the renal allograft in pediatric patients. Linear growth may be adversely affected in young children since rapamycin has potent anti-proliferative and anti-angiogenic properties.

METHODS

Weanling three week old rats were given rapamycin at 2.5 mg/kg daily by gavage for 2 or 4 weeks and compared to a Control group given equivalent amount of saline. Morphometric measurements and biochemical determinations for serum calcium, phosphate, iPTH, urea nitrogen, creatinine and insulin-growth factor I (IGF-I) were obtained. Histomorphometric analysis of the growth plate cartilage, in-situ hybridization experiments and immunohistochemical studies for various proteins were performed to evaluate for chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption.

RESULTS

At the end of the 2 weeks, body and tibia length measurements were shorter after rapamycin therapy associated with an enlargement of the hypertrophic zone in the growth plate cartilage. There was a decrease in chondrocyte proliferation assessed by histone-4 and mammalian target of rapamycin (mTOR) expression. A reduction in parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) and an increase in Indian hedgehog (Ihh) expression may explain in part, the increase number of hypertrophic chondrocytes. The number of TRAP positive multinucleated chondro/osteoclasts declined in the chondro-osseous junction with a decrease in the receptor activator of nuclear factor kappa beta ligand (RANKL) and vascular endothelial growth factor (VEGF) expression. Although body and tibial length remained short after 4 weeks of rapamycin, changes in the expression of chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption which were significant after 2 weeks of rapamycin improved at the end of 4 weeks.

CONCLUSIONS

When given to young rats, 2 weeks of rapamycin significantly decreased endochondral bone growth. No catch-up growth was demonstrated at the end of 4 weeks, although markers of chondrocyte proliferation and differentiation improved. Clinical studies need to be done to evaluate these changes in growing children.

Hypocalcemia during magnesium (Mg) depletion has been well described, but the precise mechanism(s) responsible for its occurrence is not yet fully understood. The hypocalcemia has been ascribed to decreased parathyroid hormone (PTH) secretion as well as skeletal resistance to PTH. Whereas the former is well established, controversy exists as to whether or not Mg depletion results in skeletal resistance to PTH. These studies examine the skeletal response to PTH in normal dogs and dogs fed a Mg-free diet for 4-6 mo. Isolated tibia from normal (serum Mg 1.83+/-0.1 mg/100 ml) and experimental dogs (serum Mg 1.34+/-0.15 mg/100 ml) were perfused with Krebs-Henseleit buffer during a constant infusion of 3 ng/ml of synthetic bovine PTH 1-34 (syn b-PTH 1-34). The arteriovenous (A-V) difference for immunoreactive PTH (iPTH) across seven normal bones was 37.5+/-3%. In contrast, the A-V difference for iPTH was markedly depressed to 10.1+/-1% across seven bones from Mg-depleted dogs. These findings correlated well with a biological effect (cyclic AMP [cAMP] production) of syn b-PTH 1-34 on bone. In control bones, cAMP production rose from a basal level of 5.8+/-0.2 to 17.5+/-0.7 pmol/min after syn b-PTH 1-34 infusion. In experimental bones, basal cAMP production was significantly lower than in controls, 4.5+/-0.1 pmol/min, and increased to only 7.1+/-0.4 pmol/min after syn b-PTH 1-34 infusion. Even when PTH concentrations were increased to 20 ng/ml, cAMP production by experimental bones was lower than in control bones perfused with 3 ng/ml. Histological examination of bones from Mg-deficient dogs showed a picture compatible with skeletal inactivity. These studies demonstrate decreased uptake of iPTH and diminished cAMP production by bone, which indicates skeletal resistance to PTH in chronic Mg deficiency.

BACKGROUND

Variability among assays used to measure intact parathyroid hormone (iPTH) is of particular concern because of the routine use of iPTH assay results to guide management of osteodystrophy and calcium metabolism in patients with end-stage renal disease (ESRD). The aim of this study was to determine the extent to which results from commercially available iPTH assays diverge from results obtained with the Nichols Allegro(R) Intact PTH immunoradiometric assay (IRMA), which was used as evidence in the development of the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines.

METHODS

We divided EDTA plasma from 46 dialysis patients with ESRD and measured iPTH values with the following commercially available iPTH assays: Nichols' Allegro iPTH IRMA, Nichols Advantage iPTH immunochemiluminescent assay (ICMA), Scantibodies' Total Intact PTH IRMA, DiaSorin's N-tact iPTH IRMA, DPC's Coat-A-Count iPTH IRMA, Roche's Elecsys iPTH ICMA, and DSL's Active iPTH IRMA.

RESULTS

Method comparison showed considerable interassay differences in the measurement of iPTH in ESRD patients. IPTH values assessed by other methods ranged, on average, from 60% to 152% of the Nichols Allegro IRMA values. Of the 6 iPTH assays tested, only the Scantibodies Total Intact PT IRMA (P = 0.7554) and the Roche Elecsys iPTH ICMA (P = 0.1327) resulted in iPTH values not statistically different from those obtained with the Nichols Allegro iPTH IRMA.

CONCLUSIONS

Noncomparability among iPTH assays remains a distinct problem for the management of ESRD patients. These results should be taken into consideration when determining the course of medical treatment based on measured iPTH concentrations.

BACKGROUND

Different factors may predict loss of appendicular muscle mass (LossAMM) and loss of muscle strength (LossMS). We investigated the relationship between LossAMM or LossMS and baseline anthropometric measures, lifestyle habits, hormones, lipid profiles, and inflammatory markers in 49 healthy postmenopausal women (54.1 +/- 4.3 years) in a 24-36-month prospective study.

METHODS

We measured parameters of lifestyle habits, anthropometry, lipid profiles, and blood levels of testosterone, estrone, estradiol, cortisol, dihydroepiandrostenedione, luteinizing hormone, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, thyroxine, leptin, adiponectin, C-reactive protein (CRP), and interleukin-6 and interleukin-2 receptors. Percentage of loss per year of isometric knee extensor strength defined LossMS, and percentage of loss of AMM per year (dual x-ray absorptiometry) defined LossAMM.

RESULTS

The means (standard deviation) for LossMS and LossAMM were 1.17%/y (2.03) and 0.60%/y (0.74) and did not correlate (r = -0.001; p =.99). LossMS correlated negatively with level of physical activity (r = -0.28), femoral BMD (r = -0.30), alcohol consumption (r = -0.30), and luteinizing hormone (r = -0.32) and positively with estrone (r = 0.29) and iPTH (r = 0.32) (each at p <.05). LossAMM correlated negatively with AMM (r = -0.41; p <.01). Stepwise regression analyses showed that LossMS was significantly predicted by baseline physical activity (beta = -0.39) with an explanation of variation of the model (R(2)) of 6%, body mass index (BMI) (-0.40; 3%), high-density lipoprotein cholesterol (-0.29; 3%), estrone (0.32; 6%), iPTH (0.27; 7%), and interleukin-2 receptor (0.32; 5%). LossAMM was predicted by baseline height (0.56; 47%), body mass index (1.04; 83%), AMM (-0.92; 76%), thyroxine (-0.33; 8%), estrone (-0.61; 30%), and dihydroepiandrostenedione (0.44; 28%).

CONCLUSIONS

LossMS and LossAMM in young postmenopausal women were not correlated with one another, and were determined by different factors.

Magnesium has been shown to increase bone mineral density when used in the treatment of osteoporosis, yet its mechanism of action is obscure. In this study, the effects of daily oral magnesium supplementation on biochemical markers of bone turnover were investigated. Twenty postmenopausal women have been divided into two groups. Ten patients were given magnesium citrate (1,830 mg/day) orally for 30 days. Ten postmenopausal women of matching age, menopause duration, and BMI were recruited as the control group and followed without any medication. Fasting blood and first-void urine samples were collected on days 0, 1, 5, 10, 20, and 30, respectively. Total magnesium, calcium, phosphorus, iPTH and osteocalcin were determined in blood samples. Deoxypyridinoline levels adjusted for creatinine were measured in urine samples. Thirty consecutive days of oral magnesium supplementation caused significantly decrease in serum iPTH levels in the Mg-supplemented group (p < 0.05). Serum osteocalcin levels were significantly increased (p < 0.001) and urinary deoxypyridinoline levels were decreased (p < 0.001) in the Mg-supplemented group. This study has demonstrated that oral magnesium supplementation in postmenopausal osteoporotic women suppresses bone turnover.

BACKGROUND

Evidence derived from healthy subjects suggests that African Americans have higher serum parathyroid hormone (PTH) levels and decreased bone responsiveness to PTH than Caucasians. African American patients with end-stage renal disease (ESRD) also have higher serum PTH than Caucasians. Studies that correlate intact PTH (iPTH) levels with bone turnover in ESRD patients were performed in a predominantly Caucasian population.

METHODS

In this study, serum iPTH and bone histomorphometric data were analyzed for racial differences in 76 ESRD patients (Caucasian = 48, African Americans = 28). Bone turnover was determined by histomorphometric measurement of activation frequency in all patients.

RESULTS

Age, duration of dialysis, and calcium and phosphorus levels were similar between the two groups. iPTH levels (pg/mL; mean +/- SE) were significantly higher in the African American group (534 +/- 79 vs. 270 +/- 46, P < 0.01). Also, alkaline phosphatase levels (IU/L) were significantly higher in the African American group (162 +/- 31 vs. 144 +/- 43, P < 0.01). Correlations between PTH levels and activation frequency were r = 0.60, P < 0.01 in Caucasians and r = 0.22, P = NS in African Americans. The mean PTH level in African American patients with histologic findings of low bone turnover was 460 +/- 115 vs. 168 +/- 41 in Caucasian patients with similar bone turnover (P < 0.01). In patients with low bone turnover, African Americans had significantly higher osteoid volume and thickness, number of osteoblasts and osteoclasts, erosion surface, peritrabecular fibrosis, and single-label surface than Caucasians. However, erosion depth, bone formation rate per osteoblast and mineralization apposition rate were similar between the two groups.

CONCLUSIONS

There is no correlation between iPTH and bone turnover in African Americans with ESRD. A substantial number of African American patients with low bone turnover have very high serum PTH levels. Bone histomorphometric results reveal differences in remodeling dynamics and responses to PTH between African American and Caucasian patients. Further studies utilizing newer PTH measurement assays are needed to better delineate the correlation between PTH and bone turnover in the various racial groups.

BACKGROUND

Over 8% of adults in the United States are estimated to have moderate (stages 3 and 4) chronic kidney disease (CKD), which is increasingly recognized as one of the independent predictors for cardiovascular (CV) disease and related mortality. Secondary hyperparathyroidism with elevated serum intact parathyroid hormone (iPTH) is associated with increased CV mortality in end-stage renal disease and this relationship is unclear in moderate CKD.

METHODS

Medical records of 196 patients at Harry S. Truman Memorial Veterans Hospital with stages 3 and 4 CKD (glomerular filtration rate, GFR 16-59 ml/min/1.73 m(2)) who had iPTH levels determined from 4/2006 to 9/2007 were reviewed. CV event was defined as occurrence of any of the following during follow-up: myocardial infarction, stroke, coronary/carotid/peripheral artery revascularization, and death due to CV reasons.

RESULTS

During median follow-up of 27.2 months, 48 patients had CV events, while 148 patients did not. iPTH was elevated (156.43 ± 107.49) for patients who had CV events compared with those without (109.12 ± 86.54, P = 0.003). Among the covariates studied in the multivariate analysis including history of vascular disease, 25-OH Vit D, corrected calcium, phosphorus levels, calcium-phosphorus product, and GFR, iPTH level was found to have a positive association with CV events during follow-up period (odds ratio = 1.3 for 50 pg/ml change in iPTH, 95% CI: 1.03-1.55, P = 0.02)). Cardiovascular disease history was the only other significant variable with estimated odds ratio of 5.9 (P = 0.002).

CONCLUSIONS

iPTH level in patients with stages 3 and 4 CKD is associated with increased incidence of cardiovascular events independent of calcium-phosphorous level.

OBJECTIVE

To study the relationship of intraoperative intact parathyroid hormone levels (iPTH) with parathyroid adenoma weight and volume in patients with primary hyperparathyroidism.

METHODS

Retrospective evaluation of consecutive patients undergoing minimally invasive parathyroidectomy with iPTH measurement. Data collected include preoperative serum calcium, ionized calcium, and serum parathyroid hormone (PTH) levels, iPTH levels at baseline, 5 minutes, and 10 minutes, and parathyroid adenoma weight. Adenoma volume was calculated using an equation for the volume of a spheroid object.

RESULTS

Thirty patients underwent minimally invasive parathyroidectomy with iPTH measurement for a single parathyroid adenoma between March 2004 and January 2006. There were 8 men and 22 women, with a mean age of 59.3 (range 26-92) years. A significant correlation between preoperative serum calcium and ionized calcium levels and parathyroid adenoma weight was identified (P = .0008 and P = .03, respectively). A significant correlation was also shown between baseline iPTH measurements and parathyroid adenoma volume (P = .03). There was no correlation between baseline iPTH levels and parathyroid adenoma weight. There was a significant correlation between parathyroid adenoma weight and percentage decrease of iPTH levels at 10 minutes compared to baseline (P = .04).

CONCLUSIONS

Preoperative serum calcium and baseline iPTH levels may be useful in predicting parathyroid adenoma weight and volume, respectively. Adenoma weight may relate to the percentage decrease of iPTH levels at the 10-minute postparathyroidectomy interval.

Not all children with X-linked hypophosphatemia (XLH) have demonstrated improved linear growth with calcitriol [1,25-(OH)2D3] and inorganic phosphate (Pi) therapy. To assess which factors are associated with a favorable growth response during this treatment, we retrospectively compared demographics and biochemical parameters of bone metabolism to the linear growth patterns of 20 children with XLH who were prepubertal and had not required osteotomy. A total of 15 patients had family histories consistent with XLH; 5 appeared to be sporadic cases. During 3 years of therapy, the growth velocities of 12 patients had been at or above the mean for age (good growers) and those of 8 patients had been below the mean (poor growers). Data from the two groups were contrasted. We found no difference between the good growers and poor growers before or after the 3 year period of therapy in mean age, dietary calcium, calcitriol dose or compliance, or Pi dose or compliance. Both groups increased their mean fasting serum Pi levels with treatment. The TmP/GFR (mean +/- SEM) of the good growers improved with therapy (1.9 +/- 0.2 to 2.6 +/- 0.2 mg/dl, p = 0.01), and their posttreatment value was higher compared to that of the poor growers (2.6 +/- 0.1 versus 2.2 +/- 0.1 mg/dl, p = 0.02). However, their enhanced TmP/GFR was not associated with a reduction in serum iPTH levels (before, 693 +/- 50; after, 688 +/- 76 pg/ml; p = 0.9). The Z test for binomial proportions showed that the group that grew well contained a disproportionate number of girls (10 of 12, p = 0.04). Our findings suggest that calcitriol may exert a direct effect on the renal tubule to improve Pi reclamation in XLH. The observation that heterozygous girls appear to respond better than hemizygous boys to calcitriol and Pi therapy provides evidence for a gene dosage effect in the expression of this X-linked dominant disorder.

Total and ionic calcium, magnesium, phosphorus, albumin, and immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) were measured in serum or plasma from 30 women throughout pregnancy (beginning before 12 weeks' gestation) and the puerperium. Total calcium levels declined during gestation, paralleling a progressive fall in albumin concentration, whereas ionic calcium values declined only very slightly. Although iPTH levels in early pregnancy were lower than postpartum values (suggesting that iPTH may decline initially following conception), the major portion of gestation was characterized by progressively increasing concentrations which at term averaged 53% above early pregnancy levels and 33% above puerperal values. Thus, the principal adjustment during pregnancy is "physiologic hyperparathyroidism" which acts to preserve maternal homeostasis by maintaining the concentration of calcium ions in extracellular fluid in the presence of expanding fluid volume, increased renal function, and placental transfer. iCT levels were not affected consistently by pregnancy and exhibited highly variable patterns; half of the subjects demonstrated an increase during the first and second trimesters and then a decline in the third trimester and the remaining half was equally divided between those with no change and those with progressively falling levels.

OBJECTIVE

To determine vitamin D and bone status in adolescent girls, pre-menopausal women and men of Pakistani origin, to single out determinants of vitamin D status and to determine the association between vitamin D status, bone metabolism and bone status.

METHODS

Cross-sectional study, Copenhagen (55 degrees N), January-November. Serum 25-hydroxyvitamin D (S-25OHD), serum intact parathyroid hormone (S-iPTH), bone turnover markers and whole body and lumbar spine bone mineral density were measured. Sun, smoking and clothing habits, age, body mass index (BMI), and vitamin D and calcium from food and from supplements were recorded. Thirty-seven girls (median age, range: 12.2 years, 10.1-14.7), 115 women (36.2 years, 18.1-52.7) and 95 men (38.3 years, 17.9-63.5) of Pakistani origin (immigrants or descendants with Pakistani parents) took part in the study.

RESULTS

Median concentration of S-25OHD was 10.9, 12.0 and 20.7 nmol/l for girls, women and men, respectively. Forty-seven per cent of the girls, 37% of the women and 24% of the men had elevated S-iPTH, and there was a negative relationship between S-iPTH and S-25OHD. Use of vitamin D-containing supplements had a positive association with S-25OHD for men (P=0.04) and women (P=0.0008). Twenty-one per cent of the women and 34% of the men had osteopenia. Neither S-25OHD nor S-iPTH was associated with lumbar spine or whole body bone mineral content.

CONCLUSIONS

Severely low vitamin D status and elevated S-iPTH is common among Pakistani immigrants in Denmark. The low vitamin D status is not associated with bone markers or bone mass among relatively young Pakistanis.

BACKGROUND

Chronic kidney disease (CKD) patients affected by mineral bone disorders (MBD) have higher rates of all-cause and cardiovascular-related mortality. Approximately, one-third of dialysis patients have low serum parathyroid hormone (PTH) levels (≤ 150 pg/mL). However, the reason why these patients have higher mortality compared to patients with normal PTH levels has not yet been fully elucidated.

METHODS

The FARO study was performed on 2453 Italian patients followed prospectively from 28 dialysis centres over a 2-year period. Data were collected every 6 months and end points included time-to-death cumulative probability in patients with serum intact PTH (iPTH) ≤ 150 pg/mL and the effect of vitamin D receptor activation (VDRA) therapy. Kaplan-Meier curves and proportional hazards regression models stratified by PTH levels (i.e. ≤ 150 and >150 pg/mL) were used to determine cumulative probability of time-to-death and adjusted hazard ratios (HRs) for demographic, clinical and CKD-MBD treatment characteristics.

RESULTS

The cumulative probability of death was higher (P < 0.01) for patients with serum iPTH levels ≤ 150 pg/mL [25.1%, 95% confidence interval (CI): 22.1-28.5 at 18 months] versus those with serum iPTH levels within the normal range (18.0%, 95% CI: 16.1-20.1). In a model with time-dependent covariates restricted to time periods when patients had iPTH levels ≤ 150 pg/mL, lower mortality was observed in patients treated with VDRA [i.e. HR = 0.62, 95% CI: 0.42-0.92 for oral or intravenous (IV) calcitriol; HR = 0.18, 95% CI: 0.04-0.8 for IV paricalcitol] versus those not receiving any VDRA (P < 0.01) independently of other variables. Patients who received IV paricalcitol, compared with either oral or IV calcitriol, showed reduced mortality, but this was not statistically significant (HR = 0.3, 95% CI: 0.07-1.31, P = 0.11).

CONCLUSIONS

Results from this observational study suggest that VDRA therapy was associated with improved survival in dialysis patients, even with low serum iPTH levels.

BACKGROUND

Reference intervals are indispensable in evaluating laboratory test results; however, appropriately partitioned pediatric reference values are not readily available. The Canadian Laboratory Initiative for Pediatric Reference Intervals (CALIPER) program is aimed at establishing the influence of age, sex, ethnicity, and body mass index on biochemical markers and developing a comprehensive database of pediatric reference intervals using an a posteriori approach.

METHODS

A total of 1482 samples were collected from ethnically diverse healthy children ages 2 days to 18 years and analyzed on the Abbott ARCHITECT i2000. Following the CLSI C28-A3 guidelines, age- and sex-specific partitioning was determined for each analyte. Nonparametric and robust methods were used to establish the 2.5th and 97.5th percentiles for the reference intervals as well as the 90% CIs.

RESULTS

New pediatric reference intervals were generated for 14 biomarkers, including α-fetoprotein, cobalamin (vitamin B12), folate, homocysteine, ferritin, cortisol, troponin I, 25(OH)-vitamin D [25(OH)D], intact parathyroid hormone (iPTH), thyroid-stimulating hormone, total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine. The influence of ethnicity on reference values was also examined, and statistically significant differences were found between ethnic groups for FT4, TT3, TT4, cobalamin, ferritin, iPTH, and 25(OH)D.

CONCLUSIONS

This study establishes comprehensive pediatric reference intervals for several common endocrine and immunochemical biomarkers obtained in a large cohort of healthy children. The new database will be of global benefit, ensuring appropriate interpretation of pediatric disease biomarkers, but will need further validation for specific immunoassay platforms and in local populations as recommended by the CLSI.

BACKGROUND

Vitamin D deficiency is common worldwide. No homogenous reference values have yet been established and no studies of values have been conducted in Spain involving a large number of participants.

OBJECTIVE

To study the population concentrations of vitamin D in a representative sample of the Spanish population.

METHODS

The study involved two cohorts from Spain, the Asturias study and the Pizarra study, which are two prospective, population-based studies involving 2260 participants. In 1262 subjects (age: 20-83 years) we studied 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), calcium, phosphorus and creatinine.

RESULTS

The median population values of 25-hydroxyvitamin D and iPTH were 22.46 ng/ml and 42.29 pg/ml, respectively. The values of 25-hydroxyvitamin D were significantly higher in summer and correlated with age (β = -0.05 ± 0.01, P < 0.0001), creatinine (β = 6.42 ± 1.17, P < 0.0001) and iPTH (-0.07 ± 0.01, P < 0.0001), but not with calcium, phosphorus or sex. The increase in iPTH with age was seen whatever the values of 25-hydroxyvitamin D, and was greater in the older persons. The concentration of iPTH rose continuously with effect from 25-hydroxyvitamin D values below ≈30 ng/ml. Values above ≈35 ng/ml were associated with a significantly lower concentration of iPTH.

CONCLUSIONS

One-third (33.9%) of the Spanish population may be at risk for Vitamin D deficiency. The 25-hydroxyvitamin D values above 30 ng/ml can safely discard 'hyper PTH'. The increase in iPTH concentration is greater in older persons for similar values of 25-hydroxyvitamin D.