Secondary hyperparathyroidism (SHPT) is one of the major complications of chronic kidney disease (CKD) and is associated with elevated serum intact parathyroid hormone (iPTH). Calcitriol, a non-selective vitamin D receptor agonist (VDRA) that suppresses iPTH is used for SHPT treatment, but its use is frequently complicated by hypercalcemia. Paricalcitol, a selective VDRA, demonstrated efficacy in iPTH suppression compared to maxacalcitol in a Phase 2 study (M11-609) in Japanese subjects. The current larger Phase 3 study (M11-517), evaluated the efficacy of intravenous paricalcitol injection compared to intravenous maxacalcitol injection with respect to iPTH and calcium control using a non-inferiority primary endpoint. In this double-blind, double-dummy, parallel-group study, eligible Japanese CKD subjects with SHPT on hemodialysis were randomized 1:1 to receive intravenous paricalcitol or intravenous maxacalcitol injections for 12 weeks. Dynamic allocation of subjects on the basis of screening iPTH levels was used to ensure equal distribution of subjects with iPTH <500 pg/mL and ≥500 pg/mL into the two treatment groups. 255 subjects were randomized to receive paricalcitol (N = 127) or maxacalcitol (N = 128). Primary efficacy analysis indicated that 27.7% in the paricalcitol group vs. 30.5% in the maxacalcitol group (95% CI -14.34% to 8.79%, P = 0.353) achieved target iPTH in the last 3 weeks without hypercalcemia during treatment, failing to achieve the non-inferiority margin of -5% that was set based upon agreement with the PMDA. Both intravenous paricalcitol and maxacalcitol were effective in reducing iPTH and provided similar safety profiles; however, non-inferiority for paricalcitol vs. maxacalcitol was not demonstrated.

Bone density and related biochemical parameters were investigated in institutionalised children and adults with severe handicaps, who were classified according to the degree of limited mobility (group 1, bed-ridden; group 2, capable of crawling; group 3, capable of walking) and according to whether or not they were receiving anticonvulsants. As determined by microdensitometric analysis of radiograms of the second metacarpal bone, bone width (D), bone pattern area (sigma GS) and bone salt density (sigma GS/D) were decreased in the patients, the decreases being most prominent in group 1, followed by groups 2 and 3, in that order. Significant decreases of sigma GS and sigma GS/D, but not of D, were found in patients on anticonvulsant treatment in comparison to patients without therapy. Serum alkaline phosphatase (Al-p) and parathyroid hormone (iPTH) as well as urinary calcium and cyclic adenosine-3',5'-monophosphate (cAMP) excretion were significantly increased in group 1. In comparison to patients without therapy, anticonvulsant-treated children showed significantly decreased levels of serum calcium (Ca), ionised Ca (Ca2+), 25-hydroxy vitamin D3 and urinary phosphate (PO4) excretion, and elevated levels of Al-p, iPTH and calcitonin (iCT). It is suggested that limited physical activity results in a mild hyperparathyroid state, which is aggravated in patients on anticonvulsant treatment.

Osteopenia and osteoporosis are currently receiving particular attention as late effects of therapy in survivors of childhood acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate abnormalities in bone mass and mineral homeostasis in children with ALL after induction therapy (during consolidation treatment). Lumbar spine (L2-L4) bone mineral density (BMD, g/cm(2)) was measured by dual energy X-ray absorptiometry in 20 children with ALL, a median of 25.9 months postdiagnosis and results were expressed as z-scores relative to healthy Caucasian children (controls). Serum levels of intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, phosphate, and magnesium were also analyzed. In addition, the body mass indexes (kg/cm(2)) of patients and controls were calculated. Results were compared with those of 40 healthy controls. Among the 20 children with ALL (12 boys and 8 girls), 12 presented z-scores < 1 SD (normal) and 8 were osteopenic (z-score between 1 and 2.5 SD). In addition, children with ALL had reduced lumbar BMDs (z-score -0.817) in comparison to healthy controls (z-score -0.353) (p = .04). Moreover, alkaline phosphatase and intact parathyroid hormone values were significantly increased compared to controls values. The data demonstrate that bone metabolism in children with ALL during consolidation therapy is disturbed, resulting in a reduced BMD and z-score with respect to healthy controls. Since a reduced BMD predisposes to osteopenia and osteoporosis, specific attention and therapeutic interventions should be considered.

BACKGROUND

Data on the risk factors and clinical course of hungry bone syndrome are lacking in dialysis and renal transplant patients who undergo parathyroidectomy. In this study, we aimed to assess the risks and clinical course of hungry bone syndrome and calcium repletion after parathyroidectomy in dialysis and renal transplant patients.

METHODS

We performed a retrospective review of parathyroidectomies performed at The Nebraska Medical Center.

RESULTS

We identified 41 patients, ie, 30 (73%) dialysis and eleven (27%) renal transplant patients. Dialysis patients had a significantly higher pre-surgery intact parathyroid hormone (iPTH, P<0.001) and a larger iPTH drop after surgery (P<0.001) than transplant recipients. Post-surgery hypocalcemia in dialysis patients was severe and required aggressive and prolonged calcium replacement (11 g) versus a very mild hypocalcemia requiring only brief and minimal replacement (0.5 g) in transplant recipients (P<0.001). Hypophosphatemia was not detected in the dialysis group. Phosphorus did not increase immediately after surgery in transplant recipients. The hospital stay was significantly longer in dialysis patients (8.2 days) compared with transplant recipients (3.2 days, P<0.001).

CONCLUSIONS

The clinical course of hungry bone syndrome is more severe in dialysis patients than in renal transplant recipients. Young age, elevated alkaline phosphatase, elevated pre-surgery iPTH, and a large decrease in post-surgical iPTH are risk factors for severe hungry bone syndrome in dialysis patients.

BACKGROUND

Active Vitamin D analogues are used clinically for prevention and treatment of secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. Nutritional vitamin D supplementation is used for additional local parathyroid (PTH) suppression, with lower incidence of hypercalcemia and hyperphosphatemia. This study evaluates the possible beneficial effects of combined vitamin D treatment (paricalcitol and cholecalciferol).

METHODS

Sixty HD patients with serum parathyroid hormone (iPTH) >300 pg/mL were enrolled. All patients administered 2 mcg/day of paricalcitol and were randomly allocated into control group (placebo) or study group (cholecalciferol) for 16 weeks. Serum 25(OH)D₃, iPTH and human cathelicidin (hCAP-18) were measured at baseline and during follow-up.

RESULTS

iPTH levels decreased in the study group appropriately and were more significantly decreased at 16 weeks. Study group had significantly increased 25(OH)D₃ levels. In addition, the study group had significantly increased serum hCAP-18 levels compared with control group. Correlation analysis showed a significant correlation between the percentage increase in serum hCAP-18 and 25(OH)D₃ levels.

CONCLUSIONS

Cholecalciferol, in combination with paricalcitol, additively lowers the iPTH levels in a significant number of patients after 16 weeks of supplementation. A dose of 5000 IU/week of cholecalciferol could maintain serum 25(OH)D₃ levels above 30 ng/dL as early as 8 weeks after beginning supplementation. Doubling of serum cathelicidin levels were noted after 16 weeks of cholecalciferol supplementation in 40% of study patients.

BACKGROUND

Bone and mineral metabolism is abnormal in most chronic haemodialysis patients and is associated with a high mortality risk. Because of possible pathogenic links between anaemia and intact parathyroid hormone (iPTH), the present study evaluated associations of mineral metabolism indicators with haemoglobin (Hb).

METHODS

Data were collected from 317 facilities (12 089 haemodialysis patients) in Australia, Belgium, Canada, France, Germany, Italy, Japan, New Zealand, Spain, Sweden, the United Kingdom and the United States by the Dialysis Outcomes and Practice Patterns Study (DOPPS). The major outcome studied was probability of haemodialysis patients having a target Hb, per guidelines, of>>/=11 g/dl at baseline. Major predictor variables were patient characteristics and laboratory markers of mineral metabolism: albumin-corrected serum calcium (calcium(Alb)), serum phosphorus (PO(4)) and iPTH. Analyses were adjusted for demographics, 15 comorbidity classes, baseline laboratory values, body mass index, years on dialysis, erythropoietin dose, vitamin D and catheter use, cause of end-stage renal disease and country.

RESULTS

The adjusted odds ratio (AOR) of having Hb>>/=11 g/dl was significantly higher (P<0.0001) in patients with higher calcium(Alb) (AOR = 1.32 per 1 mg/dl), higher PO(4) (AOR = 1.08 per 1 mg/dl) and lower iPTH (AOR = 0.96 per 100 pg/ml). Furthermore, 4 month intrapatient changes in Hb concentration were significantly (P<0.0001) related to 4 month changes in calcium(Alb) (0.17 g/dl Hb rise per 1 mg/dl higher calcium(Alb)) and PO(4) (0.11 g/dl Hb rise per 1 mg/dl higher PO(4)). Mean weekly recombinant human erythropoietin (rHuEpo) doses were higher for patients with high PO(4) or iPTH levels, but lower for patients with calcium(Alb) >9.5 mg/dl, after patient mix and Hb concentration adjustments.

CONCLUSIONS

The results of this study indicate that higher serum calcium(Alb) and PO(4) levels are each independently associated with better anaemia control. This relationship is independent of vitamin D use, PTH levels and prescribed rHuEpo dose. Despite this benefit of better anaemia control at higher serum calcium(Alb) and PO(4) concentrations, lower calcium and PO(4) levels, as recommended by the K/DOQI guidelines, should still serve as the long-term goal for HD patients in order to minimize tissue calcification and mortality risk.

BACKGROUND

PTH is a critical factor in mineral homeostasis, and chronic kidney disease mineral and bone metabolism disorder is a very important problem in patients with renal failure. Abnormal levels of PTH, serum phosphate, and calcium influence chronic kidney disease mineral and bone metabolism disorder, but there is little information about the influence of magnesium (Mg) on PTH.

OBJECTIVE

The aim of this study was to elucidate the correlation between magnesium and PTH levels in uremic patients just prior to beginning hemodialysis (HD) for the first time.

METHODS

We enrolled 1231 patients in nine Japanese facilities who had begun HD for end-stage renal disease. We investigated their serum Mg levels and the correlation between intact PTH (iPTH) and the serum Mg levels and other clinical parameters and medications.

RESULTS

The mean serum Mg was 2.2 ± 0.5 mg/dL, and hypermagnesemia was found in 663 patients (53.9%). Divided into two groups according to median iPTH level, the serum Mg levels were significantly higher in patients with low iPTH (2.3 ± 0.5 vs 2.1 ± 0.5, P < .01). Furthermore, divided into two groups according to the Mg level, iPTH levels were lower in patients with high Mg than in patients with normal serum Mg levels (277.9 ± 195.9 pg/mL vs 321.9 ± 203.7 pg/mL, P < .01). In the multiple regression analysis according to the effect of iPTH level, the serum Mg level was an independent variable after adjustment for other factors.

CONCLUSIONS

A high serum level of Mg is frequent in uremic patients with end-stage renal disease just prior to beginning HD. In the present set of patients, there was a significant correlation between the serum Mg and iPTH levels. Furthermore, the serum Mg level was an independent factor apart from the other factors regulating iPTH. These results suggest that serum Mg may be one of the factors regulating the serum PTH level in uremic patients.

BACKGROUND

There is limited data available especially in Indian Population about prevalence of reduced bone mineral density (BMD) and various factors associated with it in CKD patients not on dialysis.

METHODS

This study included 75 adult patients. Patients were divided into three groups depending upon GFR. Serum creatinine, albumin, calcium, phosphate (PO4), alkaline phosphatase, iPTH and Vitamin D were measured at baseline. BMD was measured by dual energy X-ray absorptiometry.

RESULTS

There were 51 male and 24 female patients. The mean serum phosphate, alkaline phosphatase and iPTH levels increased steadily as CKD progressed. On the other hand, mean corrected serum calcium and Vitamin D levels decreased progressively in group A, B and C. The mean serum PTH values in group A, B and C were 137.16 ± 109.85, 265.02 ± 132.03 and 328.14 ± 119.23 pg/mL, respectively and there was significant increase in mean PTH level from group A to group C (p < 0.05). The mean level of vitamin D showed a trend of declination from group A to C (p < 0.05). Z-score for group A, group B and group C was 1.11 ± 2.39, 0.87 ± 2.66 and -0.92 ± 1.59, respectively. Similarly, T score for the three groups were 0.47 ± 2.34, -0.4 ± 2.00 and -1.524 ± 1.42. Both T-score and Z-score positively correlated with GFR. There was negative correlation between Z-score and iPTH, and positive correlation with Vitamin D.

CONCLUSIONS

Reduced bone density was seen early in the course of CKD as estimated from reduced BMD levels, increased prevalence of osteoporosis and increased fracture risk and it worsened with the progression of CKD.

BACKGROUND

Hypocalcaemia after thyroidectomy is the most common postoperative complication, with a reported incidence from 0.5% to even 50% of the operated patients. Hypoparathyroidism could be a result of careless or inadequate preparation during the surgical procedure. There is a variety of proposed options for the prediction of the incidence of hypocalcaemia. The most effective of them are the peri-operative and intra-operative measurements of the parathyroid hormone (PTH) level.

METHODS

A prospective study was performed on 100 patients who underwent total thyroidectomy from January 2007 to June 2008. The total calcium level and intact human PTH (iPTH) levels were measured 24 hours before as well as 1 hour and 24 hours after the surgery.

OBJECTIVE

The goal of the study was to assess the potential correlation between the iPTH levels after the operation and the development of hypocalcaemia. The possible prediction value of postoperative iPTH levels was to be assessed.

RESULTS

We have presented a significant correlation between early iPTH measurement and the risk of hypocalcaemia. Moreover, a significant correlation between the iPTH level one hour after operation with the calcium level 24 hours after the operation was demonstrated.

CONCLUSIONS

Early postoperative assessment of iPTH levels can be used to identify the group of patients at risk of hypocalcaemia after thyroidectomy. Pre-emptive calcium supplementation can lead to the avoidance of complications causing prolonged hospital stay and most importantly to prevent severe hypocalcaemia.

BACKGROUND

The prevalence of insomnia in patients with symptomatic secondary hyperparathyroidism and the improvements of sleep disturbances after parathyroidectomy have not been previously reported.

METHODS

Thirty-one patients who had undergone successful total parathyroidectomy and autotransplantation for symptomatic secondary hyperparathyroidism were enrolled in the study. The symptoms of skin itching, bone pain, and general weakness were recorded. Preoperatively, serum levels of calcium, phosphorus, alkaline phosphatase (Alk-ptase), intact parathyroid hormone (iPTH), am melatonin (noon), and pm melatonin (midnight) were measured in association with a simple yes/no questionnaire of 5 items about sleep disturbances as described previously. The severity of insomnia was the sum of positive items of sleeping disturbances. The sleep hours per night and the habit of taking sleeping pills were also recorded. One week after surgery, serum levels of calcium, phosphorus, Alk-ptase, iPTH, am melatonin, and pm melatonin were measured again. Three months after surgery, symptoms of skin itching, bone pain, and general weakness were recorded, and serum levels of calcium, phosphorus, Alk-ptase and iPTH were measured in association with a yes/no questionnaire of sleep disturbances. The severity of insomnia, sleep hours per night, and the habit of taking sleeping pills were recorded again.

RESULTS

One week after parathyroidectomy, serum levels of calcium, phosphorus, and iPTH decreased significantly; serum levels of Alk-ptase and am melatonin increased significantly; serum levels of pm melatonin did not change significantly. Three months after parathyroidectomy, symptoms of skin itching, bone pain, and general weakness decreased significantly; serum levels of calcium, phosphorus, Alk-ptase, and iPTH decreased significantly; sleeping disturbances and severity of insomnia improved significantly in association with longer sleep hours per night. A significant reduction of the habit of taking sleeping pills was also noted. Preoperatively, the severity of insomnia was correlated with skin itching, general weakness, and levels of iPTH. Postoperatively, the severity of insomnia was correlated with skin itching, general weakness, and bone pain.

CONCLUSIONS

Preoperatively, a high prevalence of sleep disturbances (97%) was found in patients with symptomatic secondary hyperparathyroidism. We conclude that nocturnal melatonin levels do not change after parathyroidectomy; the improvements in sleep disturbance and the decreases in severity of insomnia are found 3 months after surgery in association with longer sleep hours per night. Decreases of symptoms such as skin itching, bone pain, and general weakness may be the reasons for the improvement in sleep and the decrease in insomnia.

The common intact parathyroid hormone (i-PTH) assay detects not only PTH (1-84) but also the PTH (7-84) fragment. Recently, it was reported that the PTH (7-84) fragment is an antagonist to the biological action of PTH (1-84). It was also reported that the accumulation of the PTH (7-84) fragment plays a role in skeletal resistance in haemodialysis (HD) patients. However, the role of accumulation of the PTH (7-84) fragment in continuous ambulatory peritoneal dialysis (CAPD) patients, with a different clearance rate from that of HD patients, is still unclear. Therefore, we have measured only the active form of PTH (1-84) using a new method of whole PTH (w-PTH) assay in 20 CAPD patients (15 male and five female; mean age 51.0+/-13.0 years). The mean w-PTH value was 88.5 +/-14.2 pg/ml in CAPD patients, which was 42.1% of i-PTH (152.6+/-23.6 pg/ml). The approximate value of w-PTH was calculated using the following formula (w-PTH=0.58 x iPTH-0.4, R(2)=0.94). PTH (7-84) fragment was calculated by the formula i-PTH-w-PTH. The PTH (7-84) fragment/w-PTH ratio as an index of skeletal resistance, and serum alkaline phosphatase activity as an osteoblastic marker were negatively correlated (P=0.02). From these results, we concluded that the i-PTH level as calculated using the common assay method might lead to an overestimation of parathyroid function and bone turnover in CAPD patients similarly to HD patients. The w-PTH assay may be useful for more precise evaluation of PTH activity in end-stage renal disease patients.

OBJECTIVE

The optimal vitamin D intake for nursing women is controversial. Deterioration, at least in bone mass, is reported during lactation. This study evaluated whether vitamin D supplementation during lactation enhances the maternal and infant's vitamin D status, bone mass and body composition.

METHODS

After term delivery, 174 healthy mothers were randomized to receive 1200 IU/d (800 IU/d+400 IU/d from multivitamins) or 400 IU/d (placebo+400 IU/d from multivitamins) of cholecalciferol for 6 months while breastfeeding. All infants received 400 IU/d of cholecalciferol. Serum 25-hydroxyvitamin D [25(OH)D], iPTH, calcium, urinary calcium, and densitometry were performed in mother-offspring pairs after delivery, and at 3 and 6 months later.

RESULTS

A total of 137 (79%) (n = 70; 1200 IU/d, n = 67; 400 IU/d) completed the study. 25(OH)D was similar in both groups at baseline (13.7 ng/ml vs. 16.1 ng/ml; P = 0.09) and at 3 months (25.7 ng/ml vs. 24.5 ng/ml; P = 0.09), but appeared higher in the 1200 IU/d group at 6 months of supplementation (25.6 ng/ml vs. 23.1 ng/ml; P = 0.009). The prevalence of 25(OH)D <20 ng/ml was comparable between groups at baseline (71% vs. 64%, P = 0.36) but lower in the 1200 IU/d group after 3 months (9% vs. 25%, P = 0.009) and 6 months (14% vs. 30%, P = 0.03). Maternal and infants' iPTH, calciuria, bone mass and body composition as well as infants' 25(OH)D levels were not significantly different between groups during the study. Significant negative correlations were noted between maternal 25(OH)D and fat mass (R = -0.49, P = 0.00001), android fat mass (R = -0.53, P = 0.00001), and gynoid fat mass (R = -0.43, P = 0.00001) after 6 months of supplementation.

CONCLUSIONS

Vitamin D supplementation at a dose of 400 IU/d was not sufficient to maintain 25(OH)D >20 ng/ml in nursing women, while 1200 IU/d appeared more effective, but had no effect on breastfed offspring vitamin D status, or changes in the bone mass and the body composition observed in both during breastfeeding.

BACKGROUND

ClinicalTrials.gov NCT01506557.

Many Arab women in the Gulf region cover their bodies for cultural and religious reasons, limiting the skin's exposure to sunlight and therefore its ability to synthesize vitamin D. The aim of this study is to determine whether the clothing style of Kuwaiti premenopausal women affects their vitamin D status, bone marker expression, and bone density. Three groups of healthy unmarried single Kuwaiti females (20-35 years old; n=30 per group) were recruited randomly from the general community: a control group who wear Western-style clothing (unveiled group), a group who wear a hejab that covers the whole body except for the face and hands (hejab group), and a group who wear a black veil with the entire body covered (veiled group). Bone mineral density (BMD), bone markers (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin, and β-CrossLaps), 25-hydroxy vitamin D, intact parathyroid hormone [iPTH], and calcitonin were measured. The bone marker osteocalcin was significantly higher in the hejab group compared to the control group, whereas P1NP and β-CrossLaps were significantly higher in the veiled group compared to the control group. 25-hydroxy vitamin D, iPTH, calcitonin, and BMD were not significantly different across the three groups despite the observed elevation in bone turnover markers. The majority of participants in all three groups exhibited vitamin D deficiency; however, the lowest vitamin D levels were observed among the hejab and veiled participants. These findings suggest that clothing style may contribute to vitamin D deficiency in young Kuwaiti women.

To study the influence of vitamin D receptor (VDR) gene polymorphism on parathyroid cell function in chronic renal failure, 85 patients who had serum PTH levels <12 pmol/L (the low intact PTH [iPTH] group) and 46 patients who had serum iPTH levels >60 pmol/L (the high iPTH group) were selected out of a total dialysis population of 170 individuals. As a result of subsequent exclusions based on several criteria in both groups (diabetic patients, serum aluminum levels, serum calcium levels, and time on dialysis), the final low iPTH group consisted of 34 patients and the final high iPTH included 32 patients. A healthy control population (n = 120) and 162 of the 170-patient dialysis population served as control groups. VDR gene polymorphism was determined by digestion with the BsmI enzyme and single-strand conformation polymorphism analysis of PCR amplified fragments. Serum iPTH levels were lower in patients with the BB genotype than in those with the Bb or bb genotype, both in the total dialysis population and when the various exclusion criteria were applied. No differences in genotypic and allelic frequencies were found between the healthy control population and the high iPTH group. However, the genotypic distribution was significantly different in the low iPTH group of patients before and after applying all exclusion criteria (P = 0.037 and P = 0.018, respectively). In the final selected population, the bb genotype was less frequent in the low iPTH group than in the total dialysis population (14.7% versus 36.4%; odds ratio, 0.3; confidence interval, 0.11 to 0.82; P = 0.01). Conversely, the BB genotype was over-represented in the low iPTH group (23.3% versus 19.7%; odds ratio, 1.9; confidence interval, 0.85 to 4.3; P = 0.1). In addition, the bb genotype and the b allele frequencies were lower in the low iPTH group than in the high iPTH group (14.7% versus 34.4%, P = 0.06, and 41.2% versus 60.9%, P = 0.02, respectively), and the BB genotype and the B allele were significantly more frequent in the low PTH group than in the high iPTH group (32.3% versus 12.5%, P = 0.05, and 58.8% versus 39.1%, P = 0.02, respectively). Thus, VDR gene polymorphism influences parathyroid function in chronic renal failure.

The majority of chronic hemodialysis patients have elevated serum iPTH levels and bone disease characterized by osteitis fibrosa. However, a small group of patients develop osteomalacic bone disease associated with normal or slightly elevated iPTH values and a tendency to hypercalcemia which occurs either spontaneously or after treatment with small doses of vitamin D sterols. To examine the causes of the relatively low iPTH levels, we evaluated the change in serum iPTH levels that occurred in response to acute hypocalcemia, produced by dialysis using a low calcium dialysate, in 11 patients with osteomalacia and 8 control hemodialysis patients. Dialysis against a dialysate free of calcium for 60 to 90 min led to a fall in serum calcium to 7.5 +/- 0.2 and 7.2 +/- 0.2 mg/dl in the osteomalacic and control patients, respectively. Serum iPTH rose in controls from 1380 +/- 287 to 1960 +/- 287 pg/ml (P less than 0.01), whereas in patients with osteomalacia it rose from 360 +/- 58 to 507 +/- 104 pg/ml (P less than 0.05), a value only slightly above normal for this PTH assay. These data suggest that the relatively low basal levels of serum iPTH do not arise as a consequence of physiologic suppression of parathyroid gland function. This reduction in parathyroid function could contribute to the pathogenesis of low turnover osteomalacia.

Recent interest in vitamin D has led to a substantial increase in the use of vitamin D supplements. Vitamin D intoxication may be a concern as hypervitaminosis D can result in irreversible calcification of soft tissues so that it is important to detect early markers of vitamin D intoxication. Our aim was to assess the simultaneous presence of biochemical markers of vitamin D toxicity (i.e. hypervitaminosis D, hypercalcemia) and determine the concentrations of 25-OH-vitamin D at which the risk of hypercalcemia, and thus toxicity, might begin.

We evaluated retrospectively a 6-year period during which 25.567 samples were assessed for 25-OH-vitamin D status by UHPLC. Hypervitaminosis D was defined at serum 25-OH-vitamin D >160 nmol/L. Serum and urine calcium, phosphorus and iPTH were also recorded, if available. Medical history revision was performed in subjects displaying simultaneously hypervitaminosis D and hypercalcemia.

Overall, hypervitaminosis D was found in 475 samples (1.86%) of which 51 displayed hypercalcemia (11.1%). A total of 382 samples were identified as the first record of hypervitaminosis D and 39 presented hypercalcemia (10.2%), most of them at 25-OH-vitamin D levels between 161 and 375 nmol/L. Only in 15 subjects, hypercalcemia could be directly attributed to vitamin D and serum 25-OH-vitamin D ranged between 164 and 1139 nmol/l. In no case, serum calcium achieved concentrations considered as critical values (>13 mg/dl).

Hypercalcemia due to vitamin D represented <4% of the total hypervitaminosis D detected and <0.1% of the tests performed. However, a highly variable response was observed and most subjects presented hypercalcemia at serum concentrations of 25-OH-vitamin D < 375 nmol/L.

OBJECTIVE

Fibroblast growth factor 23 (FGF23) and soluble α-Klotho are emerging potential biomarkers of phosphorus and vitamin D metabolism which change in concentration in early chronic kidney disease (CKD) in order to maintain normal phosphorus levels. Tubular reabsorption of phosphate (TRP) has been commonly used to assess renal tubular phosphate transport. The aim of this study was to evaluate the usefulness of TRP as a surrogate marker of parameters of CKD-mineral bone disease (CKD-MBD) in CKD.

METHODS

A cross-sectional study was performed in 93 stable patients with predialysis CKD stage 1-5. In all patients, TRP, estimated glomerular filtration rate (eGFR), calcium, phosphate, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, serum FGF23 and urine soluble α-Klotho levels were measured.

RESULTS

As renal function declined, TRP significantly decreased (P < 0.001; r = 0.763) and both iPTH and serum FGF23 increased (P < 0.001; r = -0.598, P < 0.001; r = -0.453, respectively). The prevalence of hyperphosphatemia, secondary hyperparathyroidism, FGF23 excess and abnormal TRP increased progressively with declining eGFR. Although TRP level changed later than FGF23, abnormal levels of both TRP and FGF23 were observed earlier than changes in iPTH and serum phosphate. Decreased TRP was found to be independently associated with decreased eGFR and increased iPTH but was not associated with urine soluble α-Klotho or serum FGF23 level in multiple linear regression analysis.

CONCLUSIONS

TRP is a simple, useful and cost-saving surrogate marker of the assessment of altered mineral metabolism in CKD patients and can be used as an alternative to serum FGF23, especially for mild to moderate renal insufficiency.

OBJECTIVE

To investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve the quality of life of MHD patients and reduce their mortality rate.

METHODS

This study was a prospective, randomized, controlled clinical trial. 100 MHD patients were selected and then randomly divided into two groups after four weeks of run-in period. Group 1 received HD alone 2 times a week and the combined treatment of HD with HP (HD+HP) once a week, whereas Group 2 was given HD alone 3 times a week. This study was followed up for a mean of 2 years. The primary outcome was the death of patients. Secondary end points included normal clinical data, leptin, high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), ß(2) microglobulin (ß(2)-MG), immunoreactive parathyroid hormone (iPTH), tumor necrosis factor-α (TNF-α) and the index of dimensions of Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36 Chinese Edition ).

RESULTS

At the end of the two-year observation, the serum concentration of leptin, hsCRP, iPTH, IL-6, ß(2)-MG and TNF-α, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), cardiothoracic ratio, left ventricular mass index (LVMI), the EPO doses and the types of antihypertensive drugs used were lower with Group 1 than with Group 2 (p<0.05); Group 1 had higher hemoglobin (Hb), ejection fraction (EF), and body mass index (BMI) (p<0.05). No statistical difference between the two groups was observed in terms of serum albumin, serum iron (SI), total iron binding capacity (TIBC), cardiac output (CO), Kt/V, early/atrial mitral inflow velocities (E/A) (p>0.05). Besides, the SF-36 indicated that the total score of overall dimentions of Group 1 was higher than Group 2 (p<0.05) and the quality of life of Group 1 was evidently better than Group 2. The Kaplan-Meier Survival Curves for the 2-year observation period showed that patients in Group 1 had obvious survival advantage while Log-rank test results showed p<0.05. No serious adverse incidents occurred during the HD+HP treatment.

CONCLUSIONS

HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body. These findings suggest a potential role for HD+HP in the treatment to improve the quality of life and survival rate of MHD patients.

CONCLUSIONS

Bone health assessed in three towns of Karachi, Pakistan in females showed poor calcium intake, vitamin D deficiency, secondary hyperparathyroidism, and high bone turnover. Correlates of high bone turnover included females residing in Saddar Town, underweight females less than 30 years of age from low socio-economic status, and secondary hyperparathyroidism.

OBJECTIVE

To assess bone health and association of dietary calcium and 25 hydroxy vitamin D with bone turnover in the community-dwelling females of Karachi.

METHODS

Bone health was assessed in three randomly selected towns of Karachi, Pakistan. One premenopausal female fulfilling the inclusion criteria from each household was included in the study. Dietary calcium was assessed through a food frequency questionnaire and biochemical markers including calcium, phosphates, albumin, magnesium, creatinine, and SGPT, intact parathyroid hormone, 25 hydroxy vitamin D, and N-telopeptide of type I collagen were measured to assess the bone health.

RESULTS

Three hundred and five females were included from three towns. Overall, 90.5% of females had vitamin D deficiency with 42.6 and 23.3% having secondary hyperparathyroidism and high bone turn over respectively. Prevalence of vitamin D deficiency, secondary hyperparathyroidism, and high bone turnover was significantly different among towns. Mean vitamin D levels were significantly low and iPTH levels significantly high in females with high bone turnover. Calcium intake was not significantly different among females with normal, high, and low bone turnover. Correlates of high bone turnover included females residing in Saddar Town, underweight females less than 30 years of age belonging to low socio-economic status, and secondary hyperparathyroidism.

CONCLUSIONS

Compromised bone health is seen in community-dwelling females of Karachi. There is a need to perform large-scale community-based studies in all age groups to understand the interplay of markers in our population to understand the impact of these variables translating into the risk of osteoporosis.

BACKGROUND

Recombinant leptin (metreleptin) treatment restores bone mineral density in women with hypothalamic amenorrhea (HA), a condition characterized by hypoleptinemia, which has adverse impact on bone health.

OBJECTIVE

The objective of the study was to investigate how metreleptin exerts its positive effect on bone metabolism in humans.

METHODS

This was a randomized, double-blinded, placebo-controlled study.

METHODS

The study was conducted at Beth Israel Deaconess Medical Center (Boston, Massachusetts).

METHODS

Women (n = 18) with HA and hypoleptinemia for at least 6 months were randomized to receive either metreleptin or placebo for 36 weeks. Serum samples were obtained at baseline and 12, 24, and 36 weeks of treatment.

METHODS

Circulating levels of leptin, intact PTH (iPTH), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), sclerostin, dickkopf-1, and fibroblast growth factor-23.

RESULTS

Metreleptin administration significantly increased leptin levels throughout the treatment period (P = .001). iPTH decreased over the 36 weeks of treatment (P = .01). There was a trend toward a decrease in serum RANKL and increase in serum OPG in the metreleptin-treated group. The RANKL to OPG ratio was significantly decreased within the metreleptin (P = .04) but not the placebo group. Metreleptin had no effect on serum sclerostin, dickkopf-1, and fibroblast growth factor-23.

CONCLUSIONS

Metreleptin treatment over 36 weeks decreases iPTH and RANKL to OPG ratio levels in hypoleptinemic women with HA.

OBJECTIVE

The objectives of this study were to (1) determine the prevalence of low bone mineral density (BMD) in a large prospective cohort of newly diagnosed patients with paediatric systemic lupus erythematosus (pSLE) and (2) identify risk factors associated with low BMD.

METHODS

Single-centre cohort study of 80 children and adolescents who underwent a dual-energy x-ray absorptiometry within 3 months of diagnosis. Low lumbar spine (LS) BMD was defined as z score ≤ -2.0. BMD was correlated with baseline demographic, clinical and laboratory markers of disease activity and biochemical markers of bone health. Risk factors of BMD were evaluated with univariable and multivariable linear and logistic regression analyses.

RESULTS

Low BMD at any site was found in 15% of newly diagnosed pSLE patients. LS BMD was associated with body mass index (BMI) z score and corrected calcium (r(2)=0.31, p<0.0001). Hip BMD was associated with BMI z score and intact parathyroid hormone (iPTH) (r(2)=0.26, p=0.002). Higher BMI z score was protective against low BMD at any site (OR 0.35).

CONCLUSIONS

One in six newly diagnosed pSLE patients had low BMD (at any site). Low BMI z score, low calcium and high iPTH identified children at risk for low BMD at diagnosis of pSLE.

The usefulness of double-phase parathyroid technetium-99m-MIBI scintigraphy for the detection of hyperplastic parathyroid tissue has been described. The aim of the present study was to establish the effectiveness of this new technique in the morphological and functional assessment of parathyroid glands in patients with different types of hyperparathyroidism. We performed 99mTc-MIBI scintigraphy (MIBI) and neck ultrasonography in 38 patients with primary (n=16) or secondary (n=22) hyperparathyroidism. All patients underwent surgical neck exploration, removing a total of 84 parathyroid glands. Before and after surgery, blood intact parathyroid hormone (iPTH) was measured peripherally and in both the right and left internal jugular veins. In patients with primary hyperparathyroidism, ultrasonography showed one enlarged gland in 11 cases (69%), while MIBI was positive in 15 (94%) (including two ectopic glands). The sensitivity of MIBI (93%) was greater than that of ultrasonography (68%), with a similar specificity (100 and 97%, respectively). In patients with secondary hyperparathyroidism, there was a discrepancy between both imaging modalities in 29 glands (33%). The sensitivity of both techniques was similar (41 and 54%, respectively), with the same specificity (89%). There were more difficulties in detecting the upper than the lower pathological glands. MIBI reflected more accurately the functionality of the glands, and ultrasonography has a better correlation with the volume and weight. In conclusion, Tc-99m-MIBI scintigraphy is a good technique to identify parathyroid hyperfunctioning tissue in cases of primary hyperparathyroidism and to detect ectopic glands, but it does not give significantly better results than conventional ultrasonography in patients with secondary hyperparathyroidism.

OBJECTIVE

Patients taking antiepileptic drugs (AEDs) have an increased incidence of fractures. This study investigated chronic AED use and physical contributors to falls risk using an AED-discordant, twin and sibling matched-pair approach, and assessed clinically relevant subgroups: AED polytherapy; longer-duration AED; and falls history.

METHODS

Twenty-nine same-sex (mean age 44.9 years, 59% female), ambulatory, community-dwelling twin and sibling pairs, discordant for AED exposure (and AED-indication), were recruited. Validated clinical and laboratory tests of strength, gait, and balance were performed. Relevant AED levels, and fasting serum samples for 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and immunoreactive parathyroid hormone (iPTH) levels were taken.

RESULTS

There were significant mean within-pair differences in tests of static and dynamic balance, with the AED user having poorer balance function than the AED nonuser. No difference was seen in lower limb strength or gait measures. Increased duration of AED therapy and AED polytherapy were independent predictors of increased sway. No significant within-pair differences were seen in fasting serum levels of 1,25(OH)(2)D, 25OHD and iPTH after Bonferroni correction.

CONCLUSIONS

Balance performance is impaired in AED users compared to their matched nonuser siblings. Pairs where the AED users took AED polytherapy, or had a longer duration of AED use, had more impaired balance performance. These balance deficits may contribute to the increased rate of fractures in this population.