Increased Serum 1,25-Dihydroxyvitamin D after Growth Hormone Administration is not Parathyroid Hormone-Mediated

To assess the effects of growth hormone (GH) on serum 1,25-dihydroxyvitamin D [1,25(OH)₂D], we performed the following prospective crossover study in six healthy, young, adult, white men. During each of two admissions for 2? days to a general clinical research center, subjects were placed on a daily dietary calcium intake of 400 mg. Serum calcium, phosphorus, 1,25(OH)₂D, immunoreactive intact parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP3), tubular reabsorption of phosphate (TRP), and maximum tubular reabsorption of phosphate (TMP/GFR) were measured. Recombinant human GH (rhGH, Humatrope) (25 μg/kg/day subcutaneously for 1 week) was administered prior to and during one of the admissions. Results are expressed as mean ± SEM. Whereas serum 1,25(OH)₂D (58.9 ± 7.7 versus 51.6 ± 7.4 pg/ml, P < 0.01), serum phosphorus (4.5 ± 0.1 versus 3.7 ± 0.1 mg/dl, P < 0.01), TRP (92.0 ± 0.5 versus 87.8 ± 0.7 mg/dl, P < 0.005), TMP/GFR (4.6 ± 0.1 versus 3.5 ± 0.2, P < 0.005), and urinary calcium (602 ± 49 versus 346 ± 25 mg/day, P < 0.001) increased significantly, serum PTH decreased significantly (19.9 ± 1.9 versus 26.8 ± 4.0 pg/ml, P < 0.05) and serum calcium did not change when subjects received rhGH. These findings indicate that in humans, GH affects serum 1,25(OH)₂D independently of circulating PTH and that this effect is mediated by IGF-I. We propose, therefore, that one potential mechanism by which GH stimulates increases in bone mass is via modest increases in serum 1,25(OH)₂D. Received: 2 May 1996 / Accepted: 18 October 1996     

Effects of hPTH(1‐34) Infusion on Circulating Serum Phosphate, 1,25‐Dihydroxyvitamin D,and FGF23 Levels in Healthy Men

Fibroblast growth factor 23 (FGF23) promotes phosphaturia and suppresses 1,25‐dihydroxyvitamin D [1,25(OH)₂D] production. PTH also promotes phosphaturia, but, in contrast, stimulates 1,25(OH)₂D production. The relationship between FGF23 and PTH is unclear, and the acute effect of pharmacologically dosed PTH on FGF23 secretion is unknown. Twenty healthy men were infused with human PTH(1‐34) [hPTH(1‐34)] at 44 ng/kg/h for 24 h. Compared with baseline, FGF23, 1,25(OH)₂D, ionized calcium (iCa), and serum N‐telopeptide (NTX) increased significantly over the 18‐h hPTH(1‐34) infusion (p < 0.0001), whereas serum phosphate (PO₄) transiently increased and then returned to baseline. FGF23 increased from 35 ± 10 pg/ml at baseline to 53 ± 20 pg/ml at 18 h (p = 0.0002); 1,25(OH)₂D increased from 36 ± 16 pg/ml at baseline to 80 ± 33 pg/ml at 18 h (p < 0.0001); iCa increased from 1.23 ± 0.03 mM at baseline to 1.46 ± 0.05 mM at hour 18 (p < 0.0001); and NTX increased from 17 ± 4 nM BCE at baseline to 28 ± 8 nM BCE at peak (p < 0.0001). PO₄ was 3.3 ± 0.6 mg/dl at baseline, transiently rose to 3.7 ± 0.4 mg/dl at hour 6 (p = 0.016), and then returned to 3.4 ± 0.5 mg/dl at hour 12 (p = 0.651). hPTH(1‐34) infusion increases endogenous 1,25(OH)₂D and FGF23 within 18 h in healthy men. Whereas it is possible that the rise in PO₄ contributed to the observed increase in FGF23, the increase in 1,25(OH)₂D was more substantial and longer sustained than the change in serum phosphate. Given prior data that suggest that neither PTH nor calcium stimulate FGF23 secretion, these data support the assertion that 1,25(OH)₂D is a potent physiologic stimulator of FGF23 secretion.     

Reduction of dietary magnesium by only 50% in the rat disrupts bone and mineral metabolism

Introduction The objective of this study was to determine the effect of a moderate reduction of dietary magnesium [50% of nutrient requirement (50% NR)] on bone and mineral metabolism in the rat, and to explore possible mechanisms for the resultant reduced bone mass. Methods Female rats were 6 weeks of age at the start of study. Serum magnesium (Mg), calcium (Ca), parathyroid hormone (PTH), 1,25(OH)₂-vitamin D, alkaline phosphatase, osteocalcin, and pyridinoline were measured during the study at 3- and 6-month time points in control (dietary Mg of 100% NR) and Mg-deficient animals (dietary Mg at 50% NR). Femurs and tibias were also collected for mineral content analyses, micro-computerized tomography, histomorphometry, and immunohistochemical localization of substance P, TNFα, and IL-1β at 3 and 6 months. Results Although no significant change in serum Mg was observed, Mg deficiency developed, as assessed by the reduction in bone Mg content at the 3- and 6-month time points (0.69±0.05 and 0.62±0.04% ash, respectively, in the Mg depletion group compared to 0.74±0.04 and 0.67±0.04% ash, respectively, in the control group; p=0.0009). Hypercalcemia did not develop. Although serum Ca level remained in the normal range, it fell significantly with Mg depletion at 3 and 6 months (10.4±0.3 and 9.6±0.3 mg/dl, respectively, compared to 10.5±0.4 and 10.1±0.6 mg/dl, respectively, in the control group; p=0.0076). The fall in serum Ca in the Mg-depleted animals was associated with a fall in serum PTH concentration between 3 and 6 months (603±286 and 505±302 pg/ml, respectively, although it was still higher than the control). The serum 1,25(OH)₂-vitamin D level was significantly lower in the Mg depletion group at 6 months (10.6±7.1 pg/ml) than in the control (23.5± 12.7 pg/ml) (p<0.01 by the t-test). In Mg-deficient animals, no difference was noted in markers of bone turnover. Trabecular bone mineral content gain was less over time in the distal femur with Mg deficiency at 3 and 6 months (0.028±0.005 and 0.038±0.007 g, respectively, compared to 0.027±0.004 and 0.048±0.006 g, respectively, in the control group; p<0.005). Histomorphometry at these time points demonstrated decreased trabecular bone volume (15.76±1.93 and 14.19±1.85%, respectively, compared to 19.24±3.10 and 17.30±2.59%, respectively, in the control group; p=0.001). Osteoclast number was also significantly increased with Mg depletion (9.07±1.21 and 13.84±2.06, respectively, compared to 7.02±1.89 and 10.47±1.33, respectively, in the control group; p=0.0003). Relative to the control, immunohistochemical staining intensity of the neurotransmitter substance P and of the cytokines TNFα and IL-1β was increased in cells of the bone microenvironment in the Mg depletion group, suggesting that inflammatory cytokines may contribute to bone loss. Conclusion These data demonstrate that Mg intake of 50% NR in the rat causes a reduced bone mineral content and reduced volume of the distal femur. These changes may be related to altered PTH and 1,25(OH)₂-vitamin D formation or action as well as to an increase release of substance P and the inflammatory cytokines TNFα and IL-1β.     

Vitamin D deficiency, insulin resistance, serum adipokine, and leptin levels in peritoneal dialysis patients

Objective

Associations between 25 hydroxy vitamin D [25(OH)D], adipokines levels, and insulin resistance have been reported. The aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, insulin resistance, leptin, and adiponectin levels in vitamin D-deficient peritoneal dialysis (PD) patients.

Methods

In nineteen vitamin D-deficient PD patients, who were treated with cholecalciferol, fasting serum glucose, insulin, adiponectin, leptin, 25(OH)D and parathyroid hormone (PTH) were measured before and after cholecalciferol replacement therapy. Eighteen (94.7 %) PD patients with vitamin D deficiency were receiving active vitamin D compounds (alphacalciferol) for PTH control. Alphacalciferol dosing was kept constant during treatment with cholecalciferol.

Results

While mean 25(OH)D significantly increased from (10.2 ± 4.9 ng/ml) to (82.9 ± 56.5 ng/ml) (p < 0.05), mean homeostatic model assessment-insulin resistance index significantly decreased from (4.6 ± 3.6) to (2.8 ± 2.0) after cholecalciferol replacement therapy (p < 0.05). Serum leptin levels (12.9 ± 17.6 ng/ml) significantly increased (18.1 ± 19.5 ng/ml) (p < 0.05), while there was no change in serum adiponectin, calcium, and phosphate after vitamin D replacement. Serum PTH levels significantly decreased from 551.9 ± 276.6 pg/ml to 434.0 ± 273.4 ng/ml.

Conclusions

Cholecalciferol replacement therapy significantly decreases PTH levels and insulin resistance. The results of this study need to be confirmed in larger clinical trials.     

Response of different PTH assays to therapy with sevelamer or CaCO<Subscript>3</Subscript> and active vitamin D sterols

Amino-terminally truncated parathyroid hormone (PTH) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays (PTH-IMAs), and acute changes in serum calcium affect the proportion of these fragments in circulation. However, the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined. In this study, 60 pediatric dialysis patients, aged 13.9 ± 0.7 years, with secondary hyperparathyroidism were randomized to 8 months of therapy with oral vitamin D combined with either calcium carbonate (CaCO₃) or sevelamer. Serum phosphorus levels did not differ between groups. Serum calcium levels rose from 9.3 ± 0.1 to 9.7 ± 0.1 mg/dl during CaCO₃ therapy (p < 0.01 from baseline) but remained unchanged during sevelamer therapy. In the CaCO₃ and sevelamer groups, baseline serum PTH levels (1st PTH-IMA; Nichols Institute Diagnostics, San Clemente, CA) were 964 ± 75 and 932 ± 89 pg/ml, and levels declined to 491 ± 55 and 543 ± 59 pg/ml, respectively (nonsignificant between groups). Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO₃. The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs, despite differences in serum calcium levels.     

Potential factors regulating serum parathyroid hormone in maintenance hemodialysis patients: 4-year retrospective study

Background. This study was carried out to evaluate potential factors affecting long-term parathyroid function in patients on maintenance hemodialysis. Methods. Biochemical parameters, including intact parathyroid hormone (i-PTH) and intact osteocalcin (i-OC) were analyzed retrospectively in 120 outpatients receiving hemodialysis, for the 4 years between 1992 and 1996. Patients were classified into the following three groups according to their serum i-PTH levels in 1996: low PTH (<100 pg/ml), normal PTH (100–450 pg/ml), and high PTH (≧450 pg/ml). Results. Among the three PTH groups, no differences were found in age, sex, duration of dialysis, and laboratory parameters, except for serum levels of alkaline phosphatase (ALP), i-PTH, and i-OC. The percentage of diabetic patients was higher in the low PTH group than in the other two PTH groups. Both serum ALP and i-PTH levels increased in the high PTH group, and serum i-PTH level decreased in the low PTH group during the 4 years. The change in serum calcium (Ca) level was negatively correlated with that in serum i-PTH level (1994–1996, r = −0.623, 1992–1996, r = −0.565; P <0.0001). A higher correlation coefficient was observed in the low PTH group than in the other PTH groups, although the difference was not significant. A weak positive correlation of the changes in serum inorganic phosphorus (IP) level (1994–1996) and i-PTH level (1994–1996) was found in the high PTH group (r = 0.379, P < 0.05). Conclusion. Serum Ca level may play a determinant role in suppressing serum i-PTH level in hemodialysis patients. Serum IP level may stimulate serum i-PTH level in patients with hyperparathyroidism, although the physiological role of serum IP is yet to be established. Received: March 23, 1999 / Accepted: September 1, 1999     

Bone Metabolism and Gonad Function in Male Patients Undergoing Liver Transplantation: A Two-Year Longitudinal Study

Osteodystrophy is a major complication of end-stage liver disease, especially in postmenopausal women. Our aim in this study was to evaluate bone metabolism and gonad function in men undergoing orthotopic liver transplantation (OLTx). Twenty-three consecutive men (mean age 48 ± 13 years) evaluated for OLTx were studied, assessing the following parameters at baseline and 3, 6, 12 and 24 months after OLTx: lumbar spine (L2–L4) bone mineral density (BMD), parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D (25OHD), free testosterone (FT) and gonadotropins (FSH, LH). At baseline, 12 patients (52%) had a T-score <–2.5 SD and the mean BMD was 0.806 ± 0.11 g/cm² (range 0.470–1.045 g/cm²). The BMD was lower 3 months after OLTx and significantly higher 12 and 24 months after OLTx. A significant increase in serum BGP was observed at 6, 12 (p<0.05) and 24 months (p<0.005) after OLTx. The mean serum PTH level was 26.6 ± 3.1 pg/ml at baseline and increased significantly at 12 and 24 months (to 49.4 ± 9.9 and 61.2 ± 10.1 pg/ml, respectively; p<0.05). 25OHD serum levels were low at baseline and returned to the normal range after 12 and 24 months (baseline, 8.73 ± 1.54 ng/ml; 12 months, 16.4 ± 2.6 ng/ml; 24 months, 17.67 ± 3.1 ng/ml; p<0.05). FT was significantly lower at baseline than in a group of 10 healthy controls (5.09 ± 10.99, vs 10.3 ± 1.1 pg/ml; p<0.0001). After OLTx a significant increase in FT was recorded at 6, 12 (p<0.05) and 24 months (p<0.005). FT was not correlated with BMD, however. After OLTx an increase in FSH and LH was observed (but failed to reach statistical significance) at 3 and 6 months, followed by a slight reduction at 12 and 24 months. Thus a high proportion of men with end-stage liver disease do have osteoporosis. After OLTx, an early recovery of gonad function is observed, followed by an increase in bone mass, which occurs from the sixth month onward. Received: 3 October 2000 / Accepted: 21 March 2001     

Evidence for abnormal regulation of circulating 1α,25-dihydroxyvitamin D in patients with pulmonary tuberculosis and normal calcium metabolism

Summary Available evidence indicates that hypercalcemia in pulmonary tuberculosis results from increases in circulating 1α,25-dihydroxyvitamin D [1α,25(OH)₂D]. To further characterize vitamin D metabolism in this disorder, the effects of vitamin D, 100,000 units a day for 4 days, were compared in 25 normal subjects and 11 patients with active pulmonary tuberculosis who were normocalcemic and had not had hypercalcemia. Serum calcium, phosphorus, 25-hydroxyvitamin D (25-OHD) and 1α,25(OH)₂D were measured. Whereas vitamin D increased mean serum 25-OHD from 20±2 (±SE) to 40±5 ng/ml (P<0.001) and did not change mean serum 1α,25(OH)₂D in the normals (33±2 vs. 31±2 pg/ml), it increased mean serum 25-OHD from 21±4 to 55±13 ng/ml (P<0.05) and mean serum 1α,25(OH)₂D from 28±2 to 35±3 pg/ml (P<0.05) in the patients. Serum calcium was normal and remained within the normal range in all subjects and patients. The findings indicate that there is a modest but significant abnormality in the regulation of circulating 1α,25(OH)₂D in normocalcemic patients with pulmonary tuberculosis. The results are similar to those previously reported by us in normocalcemic patients with sarcoidosis.     

Effect of Chronic Vitamin D Infusion Upon In Vivo Glucose Disposal

We have previously demonstrated that parathyroid hormone (PTH) infusion decreases glucose disappearance rate (K_g) in vivo. Because in the rodent model used it was not possible to determine whether the PTH itself, the induced hypercalcemia, or both contributed to the glucose intolerance, we examined the effect of vitamin D infusion on insulin-mediated glucose disposal. In this model also hypercalcemia is induced but PTH levels are suppressed. Thirty male Sprague Dawley rats were continuously infused with vit D for 5 days using an Alzet miniosmotic pump, at a rate of 9.7 pmol/hour. Thirty controls were infused with the vehicle alone. On the 5th day, glucose 700 mg/kg and insulin 0.35 U/kg were given as a bolus through the left femoral vein and blood samples were obtained from the right femoral vein just prior to and at 2, 5, 10, and 20 minutes post-glucose/insulin infusion. At the end of 5 days, plasma calcium levels were higher in the vit D-infused rats than in the control rats (12.8 ± 0.1 versus 10.0 ± 0.1 mg/dL, P < 0.01) and rat PTH levels were suppressed (2.1 ± 0.1 versus 62 ± 12 pg/ml, P < 0.01). Glucose levels were higher in the vit D animals only at 5 minutes following glucose/insulin bolus (375 ± 7 versus 350 ± 6 mg/dL, P < 0.01) but at no other time. There were no differences between serum insulin levels at any time. Unlike previous findings in PTH-infused rats, K_g (measured from 2 to 20 minutes following glucose/insulin bolus) was not different between groups (4.5 ± 0.3 versus 4.7 ± 0.2, P= 0.92.) A positive correlation between serum calcium and serum glucose was found only at 5 minutes (r = 0.55, P < 0.01) and only in the vit D animals. The areas under the glucose curves approached statistically significant differences (vit D-infused 5258 ± 142 mg/dL/18 minutes versus control 4947 ± 127, P= 0.06.) Analysis of serum glucose data by two-factor analysis of variance (ANOVA) suggests that the two groups differ slightly in glucose values (P= 0.03) but have parallel K_g. In order to define whether different effects of PTH (1–34) and vit D on intracellular calcium [Ca²⁺]_i levels could partly explain the different effects of PTH and vit D infusion on glucose disposal, we investigated the effect of PTH and vit D infusions on basal and concanavalin A (con A)-stimulated changes in mononuclear [Ca⁺²]_i levels. Following 5 days of PTH, vit D, or control infusion, peripheral mononuclear cells were incubated with 50 μg/ml con A. Changes in [Ca⁺²]_i over 5 minutes were calculated by flow cytometric measurement of the calcium sensitive fluo-3 AM dye. Despite achieving significant and comparable degrees of hypercalcemia in the PTH and vit D infused animals, there were no differences in basal or con A-stimulated [Ca⁺²]_i levels from control. Consequently, we conclude that vit D-induced hypercalcemia associated with suppressed PTH levels has mild affects on glucose homeostasis but does not affect glucose disappearance rate in vivo (K_g) as does hypercalcemia induced by PTH infusion, and that neither chronic PTH infusion nor chronic vit D infusion are associated with long-standing changes in [Ca²⁺]_i levels. Received: 24 March 1998 / Accepted: 29 June 1998     

Alteration in osteoblast activity and nutritional vitamin-D deficiency in non-hypercalcemic malignancy

Summary The biochemical parameters of bone mineral metabolism in patients with nonhypercalcemic malignancy have not been extensively investigated. Therefore, a group of 29 such patients with different types of malignancy was studied. Ten patients received corticosteroids. In the entire group, serum ionized calcium (Ca²⁺), bone gla protein (BGP), 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D (1,25(OH)₂D) were all lower than in age-matched controls, and carboxy-terminal parathyroid hormone (CPTH) was higher. Although both corticosteroid- and noncorticosteroid-treated patients had decreased BGP values, the corticosteroid-treated patients had lower BGP levels than those not on steroids (4.24±0.70 SE vs. 11.50±2.20 ng/ml;P<0.005). Patients on corticosteroids had lower 1,25(OH)₂D values than controls (18.81 ±2.71 vs. 27.83±1.17 pg/ml;P<0.01), whereas those not on corticosteroids had normal 1,25(OH)₂D values. These results suggest that patients with nonhydpercalcemic malignancy have nutritional vitamin-D deficiency and secondary hyperparathyroidism with perhaps corticosteroid-induced suppression of serum 1,25(OH)₂D and BGP. The decreased levels of serum BGP in the nonsteroid-treated patients suggest, in addition, a defect in osteoblast function.     

Serum 25-hydroxyvitamin D, parathyroid hormone, and bone mineral density in men: the Rancho Bernardo study

Introduction This study examined the distribution and determinants of serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) and their associations with bone mineral density (BMD) at the hip and spine in 414 older men (mean age 74 years) living in southern California.Methods At a clinic visit (1997–2000), demographic and lifestyle information, fracture history, and medication use were recorded; venous blood for serum 25OHD and PTH was obtained; and BMD was measured at the hip and spine.Results Only one man had vitamin D deficiency (25OHD <20 nmol/l), but 15.5% of the men had high parathyroid levels (PTH ≥65 pg/ml). The mean 25OHD and PTH levels were 109.0 nmol/l and 50.3 pg/ml, respectively. Overall, 21.5% used calcium and 9.7% used vitamin D supplements. Serum 25OHD decreased with age and was lowest in the winter; levels were higher in supplement users (vitamin D and/or calcium; p<0.01). Serum PTH did not vary by age or season, and it was lower in supplement users (p<0.01). After excluding 12 men who were outliers for serum 25OHD and PTH, there was no significant correlation between serum 25OHD and PTH (r=−0.05, p=0.3). In multiple adjusted models, serum 25OHD was positively associated with BMD at the hip (p=0.01) and spine (p=0.001). Serum PTH was moderately and inversely associated with BMD at the hip (p=0.04) but not at the spine (p=0.77).Conclusion We conclude that serum 25OHD is associated with bone health in older, community-dwelling men.     

Bone mineral density in patients with predialysis chronic kidney disease

Abstract

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. Material: 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. Conclusion: 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.     

Circulating interleukin-1 receptor antagonist (IL-1RA) serum levels in patients undergoing orthotopic heart transplantation

In a pilot study we determined the serum levels of circulating interleukin-1 receptor antagonist (IL-1ra) in patients undergoing orthotopic heart transplantation and in control patients scheduled for open heart surgery without allograft transplantation. Blood samples were obtained from 12 transplant recipients and 7 controls prior to the operative procedures to determine baseline values. Serum levels of IL-1ra were measured within 12 h of decrossclamping of the aorta and every 24 h for the following 14 days. Endomyocardial biopsies were obtained weekly for the 1st month after transplantation. Compared to baseline values, IL-1ra serum levels 12 h after decrossclamping of the aorta were significantly higher both in the control group (507 ± 165 vs 3980 ± 452 pg/ml, P < 0.01) and among the transplant recipients (413 ± 180 vs 4117 ± 459 pg/ml, P < 0.01) IL-1ra levels remained significantly elevated for 2 and 5 days, respectively. There were no significant differences in the IL-1ra serum levels between the two groups throughout the observation period. Endomyocardial biopsies of two patients showed acute allograft rejection, Billingham grade III a and III b, respectively. In both cases, the rejection episodes were accompanied by a renewed and more pronounced elevation in the IL-1ra serum levels beyond 4000 pg/ml for at least 2 days. These preliminary results indicate that IL-1ra may be a nonspecific immune marker during the first few days after orthotopic heart transplantation and cardiopulmonary bypass. Moreover, renewed, prolonged increases in IL-1ra appear to be associated with rejection. Further studies are needed to confirm the predictive value of IL-1ra in the detection of acute allograft rejection. Received: 26 May 1998 Received after revision: 21 August 1998 Accepted: 21 August 1998     

Calcidiol and PTH Levels in Women Attending an Osteoporosis Program

We performed a retrospective study of 237 patients attending a specialty osteoporosis practice. Secondary causes for reduced bone mineral density (BMD) were evaluated in 196 postmenopausal women and 41 premenopausal women; mean age was 56 ± 13.8 years (mean ± SD). BMD was measured by dual-energy X-ray absorptiometry (DXA) (QDR 1000W/2000 Hologic). Levels of intact parathyroid hormone (iPTH), calcidiol [25(OH)D], thyroid-stimulating hormone, and 24-hour urinary calcium were measured, and serum and urine protein (SPEP and UPEP) electrophoresis were performed. Overall, 16% of our patients had 25(OH)D levels <15 ng/ml, the lowest acceptable vitamin D level without a concomitant rise in iPTH levels. Among the osteoporotic patients (T score <−2.5 SD), 17% had 25(OH)D levels <15 ng/ml and 7% <10 ng/ml. Among the osteopenic patients (−2.5 < T < −1.0 SD), 11% had 25(OH)D levels <15 ng/ml. Seventeen percent of patients with Z score ≤−1.0 SD (low range normal value) had 25(OH)D levels <15 ng/ml. Low 25(OH)D levels were inversely related to high iPTH values (r = 0.30, P < 0.0001). Hypercalciuria was present in 15% of our patients, elevations of PTH levels (>65 pg/ml, upper normal limit of assay) were present in 11.5%, and hyperthyroidism in 4%. A 25(OH)D level of <25 ng/ml in women (n = 86) with no known secondary causes of low BMD was associated with an iPTH level above 49 pg/ml. The measurement of 25(OH)D levels is recommended in the evaluation of secondary causes for reduced BMD. Supplementation with vitamin D appears needed to keep 25(OH)D above 25 ng/ml, the level required to prevent increments in iPTH levels. Received: 9 February 1998 / Accepted: 1 October 1998     

1.25 (OH)2 cholecalciferol pulse therapy and the effects of different dialysis membranes on serum PTH levels of haemodialysis patients

Either oral, intravenous or subcutaneous 1.25 (OH)₂ cholecalciferol is used in the therapy of hyperparathyroidism, which is a serious complication in patients on haemodialysis. We studied a total of 30 patients (10 women and 20 men) and divided them into two groups depending on the different types of dialysis membranes used. In the poly sulfone group, mean age was 43.7±0.97 years and the average dialysis period lasted 29.9±1.23 months. For the 15 cases in which we used cuprophane membrane the mean age was 40.2±1.31 years and the average dialysis period lasted 16.2±0.86 months. The calcium level of the dialysate in both groups was 1.5 mmol/l. According to the study protocol, the determined oral calcitriol dose was 0.07 mg/kg and it was administered intermittently. After one month on high dose calcitriol therapy, treatment was continued with a maintenance dose of 0.03 mg/kg for a further six months. As a phosphate binding agent, daily 3 g calcium carbonate was administered. Before starting this treatment protocol, patients went on a 1 mg/day calcitriol therapy, although the mean PTH level was 424.63 pg/ml and the mean serum alkaline phosphatase level was 290.2 U/l. During the pretreatment period, levels of PTH, alkaline phosphatase, ionized calcium, and total calcium remained significantly within normal limits as a result of the new therapy protocol applied. PTH and phosphorus clearance rates were compared in the patient groups in which different dialysis membranes had been used. PTH and phosphorus clearances were 15.2±3 ml/min and 239.1±19.2 ml/min, respectively, in the polysulfone membrane group, and 1.1±0.3 ml/min and 112.8±9.88 ml/min, respectively, in the cuprophane membrane group (p<0.05).     

Effects of oral phosphorus supplementation on mineral metabolism of renal transplant recipients

Background. Persistent hyperparathyroidism (HPT) is frequently observed in kidney transplant recipients. Hypophosphataemia is a common biochemical consequence of HPT. Theoretically, oral phosphorus administration may induce negative effects on the control of HPT, though this point has never been demonstrated in kidney-transplant recipients. This study was designed to evaluate the effects of oral phosphorus supplementation on the mineral metabolism of successful kidney transplant recipients. Methods. Thirty-two kidney transplant recipients with serum creatinine <2 mg/dl and serum phosphate levels <3.5 mg/dl were included in the study. After a wash-out period in which oral phosphorus supplementation was discontinued, the following parameters were determined (F0 period): serum calcium, phosphate, alkaline phosphatase, uric acid, bicarbonate, PTH, 1,25-dihydroxyvitamin D3 (1,25(OH)2D) and 25-hydroxyvitamin D3 (250HD). Creatinine clearance, calcium, and phosphate excretion were determined from a 24-h urine sample. The same determinations were repeated (F1 period) after all patients received 1.5 g of oral phosphorus for 15 days. For data analysis, patients were divided into two subgroups (optimal and suboptimal) according to allograft function (Ccr>or<70 ml/min/1.73 m²). Results. In the F0 period, only nine of 32 patients had PTH levels within the normal range (<65 pg/ml). The mean concentrations of PTH, 1,25(OH)2D and 25OHD were 132±97 pg/ml, 40.5+16 pg/ml and 12.5±8.2 ng/ml respectively. Phosphorus supplementation led to significant reductions in serum calcium and 1,25(OH)2D concentrations, as well as in urinary calcium excretion in the whole group. On the contrary, serum phosphate, PTH, and urinary phosphate excretion increased significantly. The percentage increase in PTH concentrations after phosphorus supplementation were similar in patients with optimal and suboptimal allograft function (33 vs 36%). The reduction of 1,25(OH)2D concentrations after phosphorus supplementation was observed mainly in the subgroup with optimal allograft function (21% reduction with respect to baseline values), while the mean 1,25(OH)2D concentrations in patients with suboptimal allograft function scarcely changed (1.4% increase). Changes in 1,25(OH)2D concentrations after phosphorus supplementation, expressed as a percentage of the initial concentrations, correlated positively with the percentage changes in PTH concentrations for the whole group, as well as for each subgroup. The best determinants for the percentage and the absolute increase in PTH concentration after phosphorus supplementation was the final serum phosphate concentration (F=4.84, r=0.37, P=0.035) and the increase in serum phosphate (F=7.69, r=0.45, P=0.009) respectively. Conclusions. Oral phosphorus supplementation led to a significant increase in the PTH concentration of kidney transplant recipients. The mean 1,25(OH)2D concentration decreased mainly in recipients with optimal allograft function. The counterbalance effect of PTH on 1,25(OH)2D production may account for the relative preservation of 1,25(OH)2D levels in recipients with suboptimal allograft function.     

Secondary hyperparathyroidism and acute tubular necrosis following renal transplantation

In the present study we investigated the relationship betweensecondary hyperparathyroidism in renal graft recipients andpost-transplantation acute tubular necrosis (ATN). Patientswere divided into two groups according to graft function: groupA consisted of 28 patients who had an uneventful postoperativeperiod and did not require haemodialysis. Group B comprised26 patients with primary non-function of the graft due to biopsy-provenATN who required continued haemodialysis for the first postoperativeweek or longer (mean 14.2 ±8.7 days). Both groups hadcomparable donor characteristics, HLA-matching and ischaemiatimes. All patients were given cyclospo-rin and low-dose prednisolonefor immunosuppression. Pretransplant levels of intact PTH weresignificantly greater in group B than in group A (203.5 ±193.1pg/ml versus 81.7±45.2 pg/ml, P<0.01). Group B patientshad more transplant biopsies (50 versus 7) and a longer hospitalizationtime (33.4 ± 10.9 days versus 21.9 ± 11.9 days,P<0.01), although serum creatinine on the day of dischargewas higher in group B (1.77 ± 0.51 mg/dl versus 1.5±0.45mg/dl, P<0.05). We conclude that patients with secondaryhyperparathyroidism as assessed by measuring circulating levelsof intact PTH have an increased incidence of ATN.     

Impact of calcium and vitamin D insufficiencies on serum parathyroid hormone and bone mineral density: Analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV‐3, 2009 and KNHANES V‐1, 2010)

The relative contributions of calcium and vitamin D to calcium metabolism and bone mineral density (BMD) have been examined previously, but not in a population with very low calcium intake. To determine the relative importance of dietary calcium intake and serum 25‐hydroxyvitamin D [25(OH)D] concentration to calcium metabolism and bone mass in a population with low calcium intake, a total of 4662 adults (2567 men and 2095 women) ≥50 years of age from the 2009–2010 Korea National Health and Nutrition Examination Survey (KNHANES) were divided into groups according to dietary calcium intakes (quintiles means: 154, 278, 400, 557, and 951 mg/d) and serum 25(OH)D concentrations (<50, 50–75, and >75 nmol/L). Serum intact parathyroid hormone (PTH) and femoral neck and lumbar spine BMD were evaluated according to dietary calcium intake and serum 25(OH)D. Mean calcium intake was 485 mg/d; mean serum 25(OH)D concentration was 48.1 nmol/L; PTH was 68.4 pg/mL; femoral neck BMD was 0.692 g/cm²; and lumbar spine BMD was 0.881 g/cm². Lower dietary calcium intakes were significantly associated with higher serum PTH concentrations and lower femoral neck BMD, not only at lower (<50 nmol/L) but also at higher (>75 nmol/L) serum 25(OH)D concentrations. Serum PTH was highest and femoral neck BMD was lowest in the group, with a serum 25(OH)D less than 50 nmol/L. In this low‐intake population, calcium intake is a significant determinant of serum PTH and BMD at higher as well as lower 25(OH)D levels. This finding indicates that low calcium intake cannot be compensated for with higher 25(OH)D levels alone. As expected, serum 25(OH)D levels were inversely associated with serum PTH and BMD. A calcium intake of at least 668 mg/d and a serum 25(OH)D level of at least 50 nmol/L may be needed to maintain bone mass in this calcium deficient population. © 2013 American Society for Bone and Mineral Research.     

Vitamin D insufficiency and effect of cholecalciferol in children with chronic kidney disease

Vitamin D insufficiency is common in patients with chronic kidney disease (CKD) and may contribute to mineral bone disease. In a prospective interventional study, we estimated the prevalence of vitamin D insufficiency (serum 25-hydroxyvitamin D3 [25OHD] < 30 ng/ml), and examined the effect of high-dose (600,000 IU) cholecalciferol supplementation after 6 weeks on serum 25OHD and parathyroid hormone (PTH) levels in children with CKD stages 2–4. Forty-two children (86% boys) with a mean age of 7.7 ± 3.8 (range 2-–5) years were studied. Thirty-seven children (82.1%) had vitamin D insufficiency; 18 (42.8%) had 25OHD < 16 ng/ml. The median 25OHD increased significantly from 16.7 (95% CI 11.3, 19.8) to 46.2 (34.5, 44.6) ng/ml in patients with vitamin D insufficiency (P <0.001). The median PTH decreased significantly from 51.3 (95% CI 46.7, 71.5) to 37.1 (29.0, 54.6) pg/ml (P = 0.003). Nineteen patients (47.5%) had >30% reduction in the PTH after supplementation. Serum calcium, phosphorus, and estimated GFR did not change significantly. We conclude that vitamin D insufficiency is highly prevalent in children with CKD stages 2–4. High-dose cholecalciferol is safe and effective in correcting vitamin D insufficiency and results in a significant reduction in PTH levels in vitamin D-insufficient children.     

Diurnal rhythm in serum osteocalcin: Relation with sleep,growth hormone,and PTH(1–84)

Summary We examined the role of sleep, growth hormone (GH), and parathyroid hormone [PTH(1–84)] as regulators of the diurnal rhythm of the osteoblastic bone marker, serum osteocalcin (OC). Nine normal subjects were followed with hourly blood sampling during one 24-hour period with norsleep deprivation. We found that the rhythm in serum OC did not exhibit significant changes (P>0.50). Serum OC (mean±SE) was 30.9±2.5 μg/liter during sleep (2330-0730 hours) versus 29.9±4.9 μg/liter during sleep deprivation (not significantly different). The serum GH rhythm was significantly different on the two occasions (P<0.01). A maximum GH peak (mean±SE) of 10.3±2.4 μg/liter occurred at 0136 hours±6 minutes during sleep compared with a maximal peak of 7.6±1.2 μg/liter (P<0.01) at 0245 hours ±20 minutes (P<0.01) during sleep deprivation. During sleep (2330-0730 hours), mean serum GH was 3.61±0.60 μg/liter compared with 2.39±0.40 μg/liter during sleep deprivation (P<0.005). Small insignificant changes occurred in serum PTH(1–84) and serum ionized calcium during the two occasions. We conclude that sleep and GH are not acute controlling factors of the diurnal rhythm in serum OC and the role of serum PTH(1–84) remains unsettled.