BACKGROUND

Patients receiving dialysis therapy for end-stage kidney failure have a high cardiovascular mortality that can only be partially explained by traditional risk factors.

METHODS

This study was a post hoc analysis of a prospectively gathered data set from a randomized trial comparing outcomes in new haemodialysis patients treated with sevelamer or calcium-containing phosphate binders. Patients were followed from the time of enrollment until death or censor on 31 December 2005. Median follow-up was 3.6 years. Demographics, cardiovascular risk factors, laboratory data, medication use and severity of vascular calcification were available at baseline and over the first 18 months of dialysis.

RESULTS

Baseline predictors of mortality included age, creatinine, heart rate, iPTH, C-reactive protein (CRP), coronary and aortic calcium scores and the presence of aortic valve calcification. Over the first 18 months, averages of diastolic blood pressure, BUN, creatinine, albumin, phosphorus, iPTH and CRP were all significantly different between survivors and non-survivors. A stepwise multivariable adjusted Cox regression model demonstrated that low BUN and albumin and high CRP along with the use of calcium-containing phosphate binders (rather than sevelamer) were the strongest predictors of mortality in patients new to haemodialysis.

CONCLUSIONS

These findings suggest that non-traditional risk factors, such as inflammation and malnutrition measured during the first 18 months of dialysis, are important determinates of survival in new dialysis patients. In addition, the unique risk factor for dialysis patients, the use of calcium-containing phosphate binders, was associated with a higher mortality rate in patients new to dialysis.

BACKGROUND

The importance of 25-hydroxyvitamin D (25-OHD) serum levels in hemodialysis chronic renal failure has not been so far histologically evaluated. Information still lacking relate to the effect of 25-OHD deficiency on serum parathyroid hormone (PTH) levels and on bone and its relationship with calcitriol levels.

METHODS

This retrospective study has been performed on a cohort of 104 patients on hemodialysis from more than 12 months, subjected to transiliac bone biopsy for histologic, histomorphometric, and histodynamic evaluation. The patients, 61 males and 43 females, mean age 52.9 +/- 11.7 years, hemodialysis length 97.4 +/- 61.4 months, were treated with standard hemodialysis and did not receive any vitamin D supplementation. Treatment with calcitriol was not underway at the time of the biopsy. Transiliac bone biopsies were performed after double tetracycline labels. In addition, serum intact PTH (iPTH), alkaline phosphatase, and 25-OHD were measured. Calcitriol serum levels was also measured in a subset of patients (N= 53). The patients were divided according to serum 25-OHD levels in three groups: (1) 0 to 15 (15 patients), (2) 15 to 30 (38 patients), and (3) >30 ng/mL (51 patients).

RESULTS

There was no significant difference in average age, hemodialysis age, serum PTH [490 +/- 494, 670 +/- 627, and 489 +/- 436 pg/mL, respectively (mean +/- SD)], alkaline phosphatase, and calcitriol between the three groups. The parameters double-labeled surface, trabecular mineralizing surface, and bone formation rate were significantly lower in group 1 than in the other groups (P < 0.03, < 0.03, and < 0.02, respectively). Osteoblast surface and adjusted apposition rate were borderline significantly lower in group 1 (P < 0.06 and < 0.10). There was no statistical difference in the biochemical and bone parameters between groups 2 and 3. A positive significant correlation was found between several bone static and dynamic parameters and 25-OHD levels in the range 0 to 30 ng/mL, showing a vitamin D dependence of bone turnover at these serum levels. However, actual evidence of an effect on bone of 25-OHD deficiency was found at serum levels below 20 ng/mL. With increasing 25-OHD levels beyond 40 ng/mL, a downslope of parameters of bone turnover was also observed.

CONCLUSIONS

Since PTH serum levels are equally elevated in low and high 25-OHD patients, while calcitriol levels are constantly low, an effect of 25-OHD deficiency (group 1) on bone, consisting of a mineralization and bone formation defect, can be hypothesized. The effect of vitamin D deficiency or bone turnover is found below 20 ng/mL. The optimal level of 25-OHD appears to be in the order of 20 to 40 ng/mL. Levels of the D metabolite higher than 40 ng/mL are accompanied by a reduction of bone turnover.

BACKGROUND

Adynamic bone disease (ABD) is caused by a relative or absolute parathyroid hormone (PTH) deficiency. Teriparatide (PTH1-34) is an osteoanabolic agent in clinical use. Here, it was hypothesized that treatment with teriparatide improves bone mineral density (BMD) of ABD patients.

METHODS

Seven hemodialysis patients with ABD and a median iPTH level of 22 pg/ml were evaluated in this open-label, prospective, 6-month observational pilot-study. All patients received 20 μg teriparatide/day subcutaneously. Serologic bone markers, BMD and coronary artery calcification (CAC) were measured at baseline and after 6 months.

RESULTS

Teriparatide therapy led to a significant increase in lumbar spine (0.885 ± 0.08 vs. 0.914 ± 0.09 g/cm(2), p < 0.02), but not femoral neck (0.666 ± 0.170 vs. 0.710 ± 0.189 g/cm(2), p = 0.18) BMD. Compared to pretreatment values, calculated monthly changes in BMD improved significantly in both the lumbar spine and femoral neck (p < 0.02). Changes in serologic markers of bone turnover and CAC scores were not statistically significant.

CONCLUSIONS

Teriparatide therapy might improve low BMD in hemodialysis patients with ABD. Further clinical studies are needed to establish teriparatide as a therapeutic option for dialysis patients with ABD.

BACKGROUND

The incidence of fractures is substantially increased in patients with chronic kidney disease (CKD) compared to the general population. The factors associated with increased bone fracture in this population are not well understood. Vitamin D deficiency has been associated with decreased bone mass and higher incidence of fractures in the general population. In this study, we aimed to assess the association between fracture and vitamin D status and other factors potentially associated with fracture in patients on maintenance hemodialysis.

METHODS

One hundred and forty-four patients were assessed and interviewed about previous low-trauma fractures. Evidence of fracture was obtained from medical records and also through patient interviews. Routine laboratory results were collected from medical records. Serum intact PTH (iPTH) and 25(OH) vitamin D(3) were measured. All patients underwent bone densitometry of the lumbar spine, femoral neck and distal radius. Bone quality was also assessed with quantitative bone ultrasound (QUS). Descriptive statistics, logistic regression models were used to analyze factors associated with fractures.

RESULTS

One hundred and thirty patients were included in the final analysis. Patients with fractures (n = 21) had lower 25(OH) vitamin D(3) levels (15.8 nmol/l (interquartile range, IQR: 27) vs. 30.0 nmol/l (IQR: 28.5), P = 0.029), were more likely females, had longer duration of end-stage kidney disease, and lower bone mineral density (BMD) at the distal radius. QUS parameters were not associated with fractures. Multivariate analyses revealed that serum 25(OH) vitamin D(3) concentration, BMD at the radius, iPTH less than 100 pg/ml and history of fractures were independent predictors of new bone fracture after the initiation of dialysis therapy.

CONCLUSIONS

Increased bone fragility in dialysis patients is associated with vitamin D deficiency and relative hypoparathyroidism in addition to reduced BMD at the radius. Further studies are needed to determine whether patients with vitamin D deficiency benefit from vitamin D supplementation to reduce fracture risk.

Calcium is an essential nutrient required in substantial amounts, but many diets are deficient in calcium making supplementation necessary or desirable. The objective of this study was to compare the oral bioavailability of calcium from calcium formate, a new experimental dietary calcium supplement, to that of calcium citrate and calcium carbonate. In a four-way crossover study, either a placebo or 1200 mg of calcium as calcium carbonate, calcium citrate, or calcium formate were administered orally to 14 healthy adult female volunteers who had fasted overnight. After calcium carbonate, the maximum rise in serum calcium ( approximately 4%) and the fall in serum intact parathyroid hormone 1-84 (iPTH) (approximately 20-40%) did not differ significantly from placebo. After calcium citrate, the changes were modestly but significantly (p < 0.05) greater, but only at 135 to 270 min after ingestion. In contrast, within 60 min after calcium formate serum calcium rose by approximately 15% and serum iPTH fell by 70%. The mean increment in area under the plasma concentration-time curve (0-270 min) for serum calcium after calcium formate (378 mg . min/dl) was double that for calcium citrate (178 mg . min/dl; p < 0.01), whereas the latter was only modestly greater than either placebo (107; p < 0.05) or calcium carbonate (91; p < 0.05). In this study, calcium formate was clearly superior to both calcium carbonate and calcium citrate in ability to deliver calcium to the bloodstream after oral administration. Calcium formate may offer significant advantages as a dietary calcium supplement.

BACKGROUND

The role of sclerostin as a key regulator of bone formation remains unknown after Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (SG).

OBJECTIVE

The study objectives were evaluation of sclerostin and Dickkopf-1 (DKK-1) serum levels after surgery and correlations with bone turnover markers (P1NP, CTX), parathyroid hormone (iPTH) and areal bone mineral density (BMD), changes at total body, lumbar spine and total hip.

METHODS

This was a prospective observational single-center two-arm study in premenopausal women with acute adipositas over 24 months.

METHODS

Participants were 52 premenopausal women (40 ± 8 years, BMI 43.4) after RYGB and 38 premenopausal women (41 ± 7 years, BMI 45.7) after SG.

METHODS

Prior to surgery and 1, 3, 6, 9, 12, 18, and 24 months after surgery sclerostin, DKK-1, CTX, P1NP levels and BMD were measured.

RESULTS

Sclerostin, CTX and (to a lesser extent) P1NP increased after surgery and remained elevated during the entire study period (P < 0.001). DKK-1 declined during months 3-9 (P < 0.005) and then remained unchanged, serum phosphate continuously increased (P < 0.001), iPTH remained within the upper normal limit. Sclerostin increases were significantly positively correlated with CTX and P1NP increases and negatively correlated with BMD loss. BMD independently declined regardless of RYGB and SG. Elevations of sclerostin, CTX, P1NP, and phosphate, but not DKK-1 and iPTH, were significant discriminating factors for BMD loss (AUC 0.920).

CONCLUSIONS

Rapid and sustained increases of sclerostin, CTX, and to a lesser extent, P1NP cause an increase in bone metabolism and result in BMD loss at all skeletal sites.

BACKGROUND

Vitamin D and calcium metabolism are involved in vascular smooth muscle cell proliferation, endothelial function and blood pressure (BP) regulation. Their physiopathology has been a matter of intensive clinical investigation with variable and sometimes contradictory results. Vitamin D insufficiency is highly prevalent in the general population, particularly among the elderly. We evaluated the association between serum 25(OH)-D levels and arterial BP in this population.

METHODS

An epidemiological cross-sectional study was designed to analyse the prevalence of hypovitaminosis D ('D'AVIS' study) in our reference area. The study was performed on a representative random sample of the population over 64 years of age obtained from five primary health care areas. A medical record, arterial BP and biological analysis: serum 25(OH)-D, iPTH, creatinine, urea, calcium, albumin were obtained.

RESULTS

A total of 237 subjects (53% women), aged between 64 and 93 (mean 71.7 +/- 5.3), were evaluated. The mean serum 25(OH)-D levels were 17.21 +/- 7.57 ng/ml (interval 5-54; 86% had <25 ng/ml). The mean BP was 138.8 +/- 14/80 +/- 7.4 mmHg, and 46% were on antihypertensive treatment. A significant negative association was observed between serum 25(OH)-D levels and systolic (r = -0.153, P = 0.018) and diastolic BP (r = -0.152, P = 0.019). This association persisted after controlling for possible confounders in the multivariate analyses.

CONCLUSIONS

Low serum 25(OH)-D levels were inversely and independently associated with BP. Supplemental measures to prevent hypovitaminosis D in this population would be important, not only to protect the skeletal system but also for the possible beneficial effects on the cardiovascular system and the BP regulation.

OBJECTIVE

Data on the prevalence of hypovitaminosis D in Indians living in the western part of the country are limited. The authors aimed to study the vitamin D status and dietary intake of calcium and phytates in healthy adult volunteers from a city in the western part of India.

METHODS

This cross-sectional study was conducted at a tertiary care centre in western India. A total of 1137 young (age: 25-35 years), healthy volunteers of both sexes were included in the study. All subjects were assessed for sun exposure, dietary intake of energy, protein, fat, calcium and phytates. Biochemical investigations included calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH), total proteins, albumin and creatinine in serum and spot urinary calcium to creatinine ratio.

RESULTS

The serum 25(OH)D concentration for the whole study population was low (17.4±9.1 ng/ml), and that for men and women were 18.9±8.9 ng/ml and 15.8±9.1 ng/ml, respectively. Seventy per cent of the study population had hypovitaminosis D (25(OH)D <20 ng/ml) with a slightly higher prevalence in women (76%). Mean dietary calcium intake of the study population was 322.92±135.17 mg/day and was very low when compared with the recommended dietary allowance (400 mg/day for adults of both sexes) issued by the Indian Council of Medical Research. Dietary phytate was much higher than calcium intake with a dietary phytate to calcium ratio of 2.25±0.76. Serum iPTH had significant negative correlation with 25(OH)D (r=-0.23, p<0.001).

CONCLUSIONS

Hypovitaminosis D, low dietary calcium and high phytate consumption are highly prevalent among young healthy adults in the western part of India.

Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its therapeutic potential in bone disorders has remained unexplored. We show that raising S1P levels in adult mice through conditionally deleting or pharmacologically inhibiting S1P lyase, the sole enzyme responsible for irreversibly degrading S1P, markedly increased bone formation, mass and strength and substantially decreased white adipose tissue. S1P signaling through S1P2 potently stimulated osteoblastogenesis at the expense of adipogenesis by inversely regulating osterix and PPAR-γ, and it simultaneously inhibited osteoclastogenesis by inducing osteoprotegerin through newly discovered p38-GSK3β-β-catenin and WNT5A-LRP5 pathways. Accordingly, S1P2-deficient mice were osteopenic and obese. In ovariectomy-induced osteopenia, S1P lyase inhibition was as effective as intermittent parathyroid hormone (iPTH) treatment in increasing bone mass and was superior to iPTH in enhancing bone strength. Furthermore, lyase inhibition in mice successfully corrected severe genetic osteoporosis caused by osteoprotegerin deficiency. Human data from 4,091 participants of the SHIP-Trend population-based study revealed a positive association between serum levels of S1P and bone formation markers, but not resorption markers. Furthermore, serum S1P levels were positively associated with serum calcium , negatively with PTH , and curvilinearly with body mass index. Bone stiffness, as determined through quantitative ultrasound, was inversely related to levels of both S1P and the bone formation marker PINP, suggesting that S1P stimulates osteoanabolic activity to counteract decreasing bone quality. S1P-based drugs should be considered as a promising therapeutic avenue for the treatment of osteoporotic diseases.

To determine the relationships among bone mass, bone growth and serum glucose control in young, insulin-dependent diabetics, we performed photon absorptiometry and radiogrammetry on a clinically well-characterized group of 78 diabetics (mean age 15.2 yr, mean duration of diabetes 6.7 yr). Total and ionized calcium (TCa, ICa), magnesium (Mg), immunoreactive parathyroid hormone (iPTH) and phosphorus (P) were measured in fasting serum. Bone age was calculated from hand x-rays; and bone measurements, heights, and weights were standardized against normal groups of corresponding age, sex, and race. Mean deviation of bone mass measurement score was 1.24 SD below the normal mean (p less than .001); mean cortical area score was .22 SD and percent cortical area .25 SD below the normal means (both p less than .05). Radical width and metacarpal width for the diabetics were not less than normal. Mean percentiles for height and weight were 52.3 and 57.1 respectively, the latter significantly elevated (p less than .02). Bone mass and cortical area were inversely related to duration of disease (r = -.228, p less than .05; r = -.216, p less than .05). They were not correlated with serum parameters of mineral metabolism or of glucose control. Bone age was not significantly different from chronological age in those who had not achieved maturity (14.4 versus 14.5 yr). Mean age of menarche was 12.9 yr. When compared to normals the diabetic sample had diminished serum ICa (p less than .001), and Mg (p less than .001), though P and iPTH were not significantly different. We have demonstrated: (1) bone mass in this sample of juvenile diabetics is depressed, without evidence of impaired overall growth or delayed maturation, (2) this reduced bone mass probably results from a failure to gain the normal component of endosteal bone expected at this age, (3) this abnormality in bone growth progresses with disease but does not appear to vary with serum glucose control, and (4) in this population of diabetics there is a minimal but significant reduction in serum total and ionized calcium and serum magnesium without compensatory elevation of parathyroid hormone. The relationship of this metabolic abnormality of impaired bone growth in unknown.

BACKGROUND

Vitamin D insufficiency poses a problem in many parts of the world, the elderly being an especially vulnerable group. This insufficiency results from an inadequate amount of sunshine and a low dietary intake of vitamin D. Typically, insufficiency is accompanied with high intact parathyroid hormone, (S-iPTH) concentrations.

OBJECTIVE

We studied how serum 25-hydroxy vitamin D (S-25-OHD) concentrations respond to different doses of vitamin D3 supplementation. Secondly to determine the smallest efficient dose to maintain serum 25-OHD concentration above the insufficiency level. We also studied which dose would be efficient in decreasing S-iPTH concentration in these subjects.

METHODS

Forty-nine 65- to 85-year-old women participated. The women were randomly assigned into one of four groups receiving 0 (placebo), 5, 10 or 20 microg of vitamin D3 daily for 12 weeks. Fasting morning blood was drawn at the beginning of the study, and thereafter every second week. Calciotropic variables were assessed from serum and urine samples.

RESULTS

The S-25-OHD concentration increased significantly (p < 0.001) in all supplemented groups [5 microg: by 10.9 (8.5) nmol/L, 10 microg: by 14.4 (6.9) nmol/L, 20 microg: by 23.7 (11.9) nmol/L], whereas it decreased in the placebo group by 8.3 (13.2) nmol/L. Equilibrium in S-25-OHD concentration was reached in all groups after 6 weeks of supplementation at 57.7 (8.9) nmol/L, 59.9 (8.9) nmol/L and 70.9 (8.9) nmol/L in the groups with increasing vitamin D supplementation. The dose-response to supplementation decreased with increasing vitamin D status at baseline, r = -0.513, p = 0.002. S-iPTH tended to decrease in those with highest dose response to supplementation.

CONCLUSIONS

A clear dose response was noted in S-25-OHD to different doses of vitamin D3. The recommended dietary intake of 15 microg is adequate to maintain the S-25-OHD concentration around 40-55 nmol/L during winter, but if the optimal S-25-OHD is higher than that even higher vitamin D intakes are needed. Interestingly, subjects with lower vitamin D status at baseline responded more efficiently to supplementation than those with more adequate status.

OBJECTIVE

Low vitamin D status is associated with secondary hyperparathyroidism and increased bone turnover in the general population and can aggravate the hyperparathyroidism of chronic kidney disease (CKD) patients. It is also correlated to low bone mineral density (BMD), but this correlation is less clear in CKD patients. Aims of our study were to investigate these associations in CKD stages 3 and 4 patients, and to identify significant predictors of BMD in this population.

METHODS

Serum 25-hydroxyvitamin D (25OHD) levels, BMD at the femur and radius, and bone mineral metabolism parameters were measured in 89 CKD stages 3 and 4 patients. Vitamin D status was defined according to the NKF/KDOQI guidelines.

RESULTS

Mean 25OHD levels were 53.8+/-32.1 nmol/L and correlated to the severity of proteinuria. Thirty-five patients (39%) had vitamin D insufficiency, 29 (33%) had vitamin D deficiency and five (6%) had severe deficiency. Of the 89 patients, two had osteoporosis and 31 had osteopenia either at femur or radius. Independent predictors for the total femur BMD were the intact parathyroid hormone (iPTH) levels and the body mass index (BMI). For the total radius BMD, independent predictor was only the BMI. Serum 25OHD levels were not directly associated with BMD, but they were independent predictors of iPTH.

CONCLUSIONS

Vitamin D insufficiency and deficiency are very common in CKD stages 3 and 4 population and may indirectly affect, via effects on iPTH, the BMD of these patients.

BACKGROUND

Scopinaro biliopancreatic diversion (BPD) is associated with malabsorption of calcium and vitamin D, which manifests as a secondary hyperparathyroidism (SHP) and may lead to osteopenia.

METHODS

96 morbidly obese patients were studied (age 19-60 years, 23 men and 73 women, with mean initial BMI 53) following intervention by Scopinaro BPD. The change in iPTH levels, urine DPD, Pyrilinks-D of DPC and serum CTx were studied at 0, 3, 6, 12, 18 and 24 months after surgery. Postoperatively, they were given supplements of calcium and vitamin D3. The control group consisted of 67 non-obese women and 10 men.

RESULTS

The iPTH levels gradually increased after BPD, with a substantial difference compared to presurgery levels at month 6. In spite of the calcium and vitamin D supplements, 77% of the patients with presurgery SHP did maintain high levels of iPTH after 2 years. The percentage of SHP among the patients with normal pre-surgery iPTH was 58%. The basal figures of DPD/cre were significantly higher than in the control group, 9.06 (4.6-13.5) nM/mMcre vs 3.9 (2.8-5.6) in men and 6.75 (5.4-7.9) vs 7.67 (3.3-11.6) in women, but not CTx, 0.24 (0.02-0.89) vs 0.22 (0.07-0.55). After the operation, there was a noticeable increase which persisted at 2 years. There was a lack of correlation between the levels of iPTH and the bone resorption markers, i.e. the first ones decreased from month 6 in men and from month 12 in women, while the levels of iPTH continued to increase.

CONCLUSIONS

In obese patients, we found no correlation between iPTH levels and BMI. Supplements of calcium and vitamin D did not prevent the appearance of SHP following BPD. The patients with high pre-surgery iPTH levels have a higher risk of malabsorption of calcium and vitamin D. Following malabsorptive bariatric surgery, there is an increase in bone resorption, which results in DPD and CTx increase. Those markers do not correlate with iPTH, and this may suggest that there is a phenomenon of bone reshaping parallel to the loss of weight.

Vitamin D is a particularly concerning nutrient for children with homozygous SS sickle cell disease (SCD-SS) due to their increased skin melanin concentrations, reduced levels of physical activity, and poor vitamin D intake. The goal of this study was to compare the vitamin D status of children with SCD-SS to healthy African-American children living in the same geographic area. Growth, dietary intake, serum 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone (iPTH) concentrations were measured in 61 African-American subjects with SCD-SS and 89 healthy African-American control subjects age 5 to 18 years from the Philadelphia, PA, region (latitude 39.95 degrees N). Median serum 25(OH)D concentrations were 15 ng/mL (95% confidence interval [CI]: 13, 17) in subjects with SCD-SS and 21 ng/mL (95% CI: 18, 22) in healthy control subjects (P<0.0002). Vitamin D deficiency [25(OH)D<11 mg/mL] was found in 33% of subjects with SCD-SS and 9% of healthy control subjects (P<0.001); 25% of subjects with SCD-SS and 17% of healthy control subjects had elevated iPTH [(>59 rhog/mL), P<0.05]. Ninety-three percent of subjects with SCD-SS and 90% of healthy subjects had vitamin D insufficiency [25(OH)D<30 mg/mL]. The risk of vitamin D deficiency among subjects with SCD-SS was 5.3 (95% CI: 2.5, 8.2) times greater than control subjects, adjusted for season and age. Poor vitamin D status was prevalent in children with SCD-SS and healthy African-American children living in the same geographic area. However, children with SCD-SS were at greater risk for vitamin D deficiency than healthy African-American children.

BACKGROUND

Morbidly obese patients have been reported to present with vitamin D insufficiency and secondary hyperparathyroidism. Scattered data are available regarding the effects of bariatric surgery on vitamin D status. We studied calcium metabolism and vitamin D status before and after bariatric surgery.

METHODS

In this prospective study, 64 patients (M5/F59) fulfilled the inclusion criteria (i.e. 2 calcidiol serum determinations in the winter season) among 457 morbidly obese individuals who underwent Roux-en-Y gastric bypass (RYGBP) a mean of 36 months previously. Laboratory data (serum calcium, phosphorus, creatinine, alkaline phosphatase, albumin, calcidiol, albumin and iPTH) were determined before and after RYGBP. Pre- and postoperative calcidiol levels were categorized as being normal (>50 nmol/L), insufficient (25-50 nmol/L), and deficient (<25 nmol/L). Pre- and postoperative mild secondary hyperparathyroidism was defined as iPTH >7.3 pmol/L with simultaneous normal values for creatinine, calcium and phosphorus.

RESULTS

RYGBP produced a significant weight loss coupled with a simultaneous increase in calcidiol (+28%, P<0.0005) and decrements in total alkaline phosphatase (-53%, P<0.0005) and iPTH (-74%, P=0.001). Corrected serum calcium, phosphorus, and creatinine levels were indistinguishable before and after RYGBP. Additionally, 37.5% of the patients maintained their calcidiol category, while 42.2 % improved it and 20.3% lost one category.

CONCLUSIONS

RYGBP does not completely correct pre-existing vitamin D deficient states with secondary hyperparathyroidism. Low calcidiol bioavailability and or insufficient sunlight exposure do probably persist after bariatric surgery. While randomized controlled studies are warranted, it seems advisable to support vitamin D supplementation as well as increasing sunlight exposure in the morbidly obese population.

The immunoreactive parathyroid hormone (iPTH) in the plasma of hyperparathyroid man consists largely of carboxyl (COOH)-terminal fragments of the hormone. Although these fragments have been thought to arise principally or solely from peripheral metabolism of intact human PTH {hPTH(1-84)} secreted from the parathyroid gland, there is disagreement about the source of iPTH fragments in vivo. To reexamine this question, we fractionated peripheral and thyroid or parathyroid venous effluent sera from four patients with primary hyperparathyroidism using a high-resolution gel filtration system (Bio-Gel P-150 columns run by reverse flow). The column effluents were analyzed using two PTH radioimmunoassays, one directed toward the amino(NH(2))-terminal region of the molecule, the other toward the COOH-terminal region. In all four thyroid or parathyroid venous effluent sera studied, iPTH was 9-180 times higher than in peripheral serum from the same patient; after fractionation, hPTH(1-84) accounted for only a portion of the total iPTH (35-55% with the assay directed toward the COOH-terminal region of hPTH, >90% with the NH(2)-terminal directed assay.) The remaining iPTH eluted from Bio-Gel P-150 after hPTH(1-84) as NH(2)-or COOH-terminal hPTH fragments. These results suggest that parathyroid tumors secrete large quantities of hPTH fragments. Based on estimates of their molar concentrations in serum, tumor-secreted COOH-terminal hPTH fragments could account for most of these peptides in peripheral serum if their survival times were, as estimated by several other workers, 5-10 times that of hPTH(1-84). We conclude that, in contrast to published information, secretory products of hyperfunctioning parathyroid tissue are probably a major source of serum PTH immunoheterogeneity.

The immunoreactive forms of parathyroid hormone (iPTH) in the plasma of six patients with primary, adenomatous hyperparathyroidism and six patients with ectopic hyperparathyroidism due to non-parathyroid cancer were compared by using gel filtration on columns of Bio-Gel P-150 and radioimmunoassay of iPTH in eluted fractions after concentration. We found much less (p<0.001) small (mol wt<9,500) COOH-terminal fragments of iPTH in plasma samples from ectopic hyperparathyroid patients (0.52+/-0.13 ng eq/ml) than in samples from primary hyperparathyroid patients (3.70+/-1.15 ng eq/ml). The quantity of iPTH eluting with or before native bovine PTH [1-84] was the same in both syndromes (ectopic hyperparathyroidism, 0.82+/-0.22 ng eq/ml; primary hyperparathyroidism, 0.73+/-0.09 ng eq/ml), and these values correlated positively with plasma calcium concentration (ectopic hyperparathyroidism, r=0.908; primary hyperparathyroidism, r=0.919). In both syndromes, plasma samples had an iPTH component that eluted well before PTH [1-84] (mol wt 9,500), but this component was present in much larger quantities in three patients with ectopic hyperparathyroidism. We conclude that (a) the decreased quantity of biologically inactive COOH-terminal fragments of iPTH circulating in ectopic hyperparathyroidism accounts for the previously reported relatively lower total serum iPTH values in this syndrome as compared with primary hyperparathyroidism (Riggs et al. 1971. J. Clin. Invest. 50: 2079); (b) there appears to be sufficient iPTH with presumed biologic activity to account for the hypercalcemia in both syndromes; (c) a large PTH component, not previously recognized in plasma, is present in both ectopic and primary hyperparathyroidism and may exist as the predominant immunoreactive form of the hormone in some patients with ectopic hyperparathyroidism.

BACKGROUND

Successful parathyroidectomy depends on recognition and excision of all hyperfunctioning parathyroid glands. Because histologic definition is limited, multiglandular disease (MGD) is usually determined grossly by means of estimation of gland size and the experience of the surgeon, resulting in frequency varying from 8% to 33%. Normalization of elevated intraoperative intact parathyroid hormone (iPTH) levels after excision of all hyperfunctioning glands is necessary for postoperative normocalcemia and indicates normal secretion of remaining parathyroids. Abnormal hormone secretion measured during operation has been used to define the extent of excision and the incidence of MGD.

METHODS

One hundred ten consecutive parathyroidectomy patients with no previous neck surgery or history of multiple endocrine neoplasia had intraoperative iPTH assays performed before and after excision of any suspected abnormal parathyroid gland(s). A drop in iPTH level after gland excision predicted postoperative normal calcium levels.

RESULTS

All patients except one had normalization of serum calcium levels (average follow-up, 15 months). One hundred five patients had only one hyperfunctioning gland removed, and all have remained normocalcemic. Five (5%) patients had more than one gland involved: four had two or more hyperfunctioning parathyroids and one patient, who had a large parathyroid cyst removed, remained hypercalcemic.

CONCLUSIONS

By using a biochemical assay, instead of estimated size, to predict which parathyroid glands are hypersecreting, the incidence of MGD in primary hyperparathyroidism was found to be 5%.

BACKGROUND

Conventional hemodialysis (HD) is associated with profound disturbances in calcium and phosphate metabolism and abnormal parathyroid hormone (PTH) levels. Effects of more frequent HD on calcium and phosphate balance have not been fully elucidated.

METHODS

The London Daily/Nocturnal Hemodialysis Study examined effects of quotidian HD, either daily HD (n = 11) or nocturnal HD (n = 12), on calcium and phosphate metabolism, bone alkaline phosphatase levels, and intact PTH (iPTH) levels.

RESULTS

Daily HD patients showed a slight decrease in predialysis serum phosphate levels, no changes in phosphate-binder requirements or serum calcium levels, and slight increases in serum bone alkaline phosphatase and iPTH levels. Nocturnal HD patients showed a trend for decreased predialysis phosphate levels, with significantly lower values than daily HD and matched control patients on conventional HD therapy at several times. Phosphate-binder use by nocturnal HD patients was significantly reduced. Both quotidian HD groups showed decreases in calcium x phosphate product, with significantly lower values for nocturnal HD patients (38.11 mg(2)/dL(2)) compared with daily HD and control patients (53.99 and 52.51 mg(2)/dL(2), respectively) at 18 months. Bone alkaline phosphatase levels increased slightly and attained statistical significance compared with baseline values for both quotidian HD groups. A trend for increases in serum iPTH levels, coupled with increasing levels of bone alkaline phosphatase in nocturnal HD patients, led to the decision to increase the dialysate calcium concentration from 5.0 to 7.0 mg/dL. This 1-time adjustment resulted in a reversal of the trend and a return to baseline values.

CONCLUSIONS

This study shows the superior control of serum phosphate levels in nocturnal HD patients compared with daily HD or conventional HD patients and the benefits of dialysate with a greater calcium concentration in slow nocturnal HD.

BACKGROUND

Percutaneous ethanol injection therapy (PEIT) is used for advanced secondary hyperparathyroidism. We investigated the efficacy, remission period and risk of relapse to determine the effect of the number of hyperplastic glands and other factors on the therapeutic effect of PEIT.

METHODS

We studied 321 patients divided into two groups: effective [serum corrected calcium (cCa) level < or =10.5 mg/dl and serum intact parathyroid hormone (iPTH) level < or =250 pg/ml], and ineffective (failed to achieve the target levels). Advanced hyperplasia was defined as an estimated volume>> or =0.5 cm(3) on ultrasonography.

RESULTS

PEIT was effective in 201 patients (62.6%), in whom serum iPTH levels dropped from 603+/-292 to 183+/-62 pg/ml (ng/l) and serum cCa levels from 10.7+/-0.8 to 10.1+/-0.5 mg/dl. Univariate analysis identified age, the number of hyperplastic glands and iPTH level as factors related to the efficacy of PEIT. The odds ratio for success vs failure by multivariate analysis was 0.55 times for the number of hyperplastic glands>> or =0.5 cm(3) >> or =2 vs 0,1) and 0.29 times for iPTH >> or =500 vs <500 pg/ml). Using the Kaplan-Meier method, the number of hyperplastic glands>> or =0.5 cm(3) >> or =2 vs 0,1) was a factor affecting the remission period, with a remission significantly longer seen in the group with one hyperplastic gland (P=0.0025).

CONCLUSIONS

Superior results in efficacy rate, remission period and risk of relapse are obtained when PEIT is restricted to patients with one hyperplastic gland>> or =0.5 cm(3).

BACKGROUND

Alfacalcidol is efficient for treating secondary hyperparathyroidism in patients on maintenance haemodialysis (HD). Little is known about the direct impact of high-dose alfacalcidol on anaemia in end-stage renal failure. We therefore carried out a prospective study over 18 months to examine the direct effect of high-dose alfacalcidol on erythropoiesis in erythropoietin (rHuEpo)-dependent anaemic patients on HD for more than 6 months with moderate hyperparathyroidism.

METHODS

Twelve patients received oral alfacalcidol at a dosage of 6-7 micrograms per week and calcium carbonate during the first 12 months, calcium carbonate without alfacalcidol during the next 3 months, and again alfacalcidol and calcium carbonate during the last 3 months. Criteria for selection were haemoglobin < 10 g/dl, iPTH>> 250 pg/ml, transferrin saturation (TS)>> 25%, S-ferritin>> 300 micrograms/l, and S-aluminium < 40 micrograms/l.

RESULTS

Haemoglobin (Hb) and reticulocyte counts increased during the first phase, decreased and returned to a baseline prior to starting vitamin D treatment in the second phase, and again increased when alfacalcidol was reintroduced, whereas iPTH decreased during the first 3 months of the first phase and then remained stable, as did S-calcium, which increased during the first 3 months and then remained constant. S-phosphate increased during the first and third phases, and decreased during the second phase. Two patients during the first phase and one patient during the third phase presented hypercalcaemia; requiring a temporary discontinuation of alfacalcidol.

CONCLUSIONS

High-dose alfacalcidol is efficient in anaemic patients with moderate hyperparathyroidism on maintenance HD and has a direct effect on erythropoietic cells regardless of serum calcium and iPTH levels.

OBJECTIVE

An increasing amount of evidence suggests that 25-hydroxy vitamin D3 (25(OH)D3) may contribute to the bone health of patients with chronic kidney disease (CKD). The underlying vitamin D status of these patients, however, has often been neglected. In a cross-sectional study we assessed the association between vitamin D status and parathyroid function, bone turnover, bone mass and structure in patients on maintenance hemodialysis.

METHODS

69 patients on maintenance hemodialysis were assessed by bone densitometry (DEXA) and quantitative bone ultrasound (QUS). Serum 25-hydroxy vitamin D3 levels, serum markers of bone turnover and clinical data were tabulated.

RESULTS

A high prevalence of potentially significant vitamin D3 deficiency was found in this patient group: 59% of the patients had a 25(OH)D3 level below 20 nmol/l. There was a significant negative correlation between serum 25(OH)D3 levels and serum intact parathyroid hormone (iPTH) (r = -0.231, p < 0.05), and this association remained significant after controlling for potential covariables. Furthermore, we show here that serum 25(OH)D3 concentration is positively correlated with bone mineral density (BMD) measured at the radius (r = 0.424, p < 0.01). Finally, we show for the first time that 25(OH)D3 levels are significantly and independently correlated with broadband ultrasound attenuation (beta = 0.262, p < 0.05) measured with calcaneal quantitative bone ultrasound (QUS) in patients with chronic renal failure.

CONCLUSIONS

Vitamin D3 deficiency may contribute to the impaired bone health of patients on maintenance dialysis.

OBJECTIVE

Primary hyperparathyroidism is a common endocrine disorder which is diagnosed biochemically and for which therapy is surgical. A prerequisite for minimally invasive surgery, which minimizes morbidity and cost, is accurate localization of the involved gland(s). The aim of this study was to evaluate the usefulness of (18)F-fluorocholine PET/CT for preoperative localization of hyperfunctioning parathyroid tissue.

METHODS

(18)F-Fluorocholine PET/CT and conventional parathyroid scintigraphic imaging consisting of (99m)Tc-sestaMIBI SPECT/CT, (99m)Tc-sestaMIBI dual-phase imaging and (99m)Tc-sestaMIBI/pertechnetate subtraction imaging were performed in 24 patients. The diagnostic performance of the imaging methods was compared against histology as the gold standard and postoperative serum Ca(2+) and iPTH values.

RESULTS

The sensitivity and specificity of (18)F-fluorocholine PET/CT were 92% and 100%, respectively, in contrast to 49% and 100%, 46% and 100%, and 44% and 100% for (99m)Tc-sestaMIBI SPECT/CT, (99m)Tc-sestaMIBI/pertechnetate subtraction imaging and (99m)Tc-sestaMIBI dual-phase imaging, respectively. Combined conventional scintigraphic imaging had a sensitivity and specificity of 64% and 100%, respectively. The performance of (18)F-fluorocholine PET/CT was superior particularly in patients with multiple lesions or hyperplasia.

CONCLUSIONS

(18)F-Fluorocholine PET/CT appears to be a promising, effective imaging method for localization of hyperfunctioning parathyroid tissue.

The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.