Hypercalcemia and Elevated Serum 1.25‐Dihydroxyvitamin D in an End‐stage Renal Disease Patient with Pulmonary Cryptococcosis

Hypercalcemia occurs relatively often in dialysis patients. The most common cause of hypercalcemia in dialysis patients is the conventional therapy with calcium and calcitriol. Besides, secondary hyperparathyroidism, low turnover bone diseases, and immobilization are also common causes of hypercalcemia in dialysis patients. Fungal infection associated with hypercalcemia has been infrequently reported. We describe a 71‐year‐old female woman with end‐stage renal disease and diabetes mellitus, who developed severe hypercalcemia. Pulmonary cryptococcosis, with increased concentration of serum 1,25‐dihydroxyvitamin D (1,25(OH)₂D), was diagnosed. Her serum concentration of calcium and 1,25(OH)₂D returned to normal after antifungal treatment. Thus, hypercalcemia was mediated by extrarenal overproduction of 1,25(OH)₂D in this patient.     

Differences in vitamin D status and calcium intake: Possible explanations for the regional variations in the prevalence of hypercalcemia in tuberculosis

The prevalence of hypercalcemia in patients with untreated tuberculosis (TB) varies widely between countries. Since the vitamin D status and calcium intake are important determinants of hypercalcemia in TB, these two factors were compared among four populations (U.K., Hong Kong, Malaysia, Thailand) with a low prevalence (<3%) and two populations (Sweden, Australia) with a high prevalence (>25%). In the three Asian countries, the circulating vitamin D levels are abundant, but the calcium intakes are low. Subjects from the U.K. have the lowest circulating vitamin D level of all, although their calcium intake is high. In Sweden and Australia, both the circulating vitamin D levels and calcium intakes are high. Since serum 1,25(OH)₂D concentration will only be raised if its substance for extrarenal conversion, 25(OH)D, is plentiful and the effect of a given serum 1,25 (OH)₂D concentration on serum calcium is determined by the calcium intake, it is postulated that the regional variation in the prevalence of hypercalcemia in TB may be due to differences in the circulating vitamin D levels and calcium intakes in these populations. Received: 18 March 1996 / Accepted: 17 June 1996     

Abnormal calcium metabolism caused by increased circulating 1,25-dihydroxyvitamin D in a patient with rheumatoid arthritis

A 35-year-old white male with rheumatoid arthritis who had developed hypercalcemia, hypercalciuria, and nephrolithiasis was found to be abnormally sensitive to vitamin D as a result of lack of regulation of circulating 1,25-dihydroxyvitamin D (1,25-(OH)2D). An increase in daily intake of vitamin D from 10 micrograms (400 units) per day to 50 micrograms (2000 units) per day produced an abnormal elevation in serum 1,25-(OH)2D, hypercalcemia, and hypercalciuria which were corrected by prednisone. Serum 25-hydroxyvitamin D initially was abnormally low, and increased with vitamin D to values which were in the low normal range. There were significant positive correlations between serum 1,25-(OH)2D (p less than .05) and serum calcium and between serum 1,25-(OH)2D and urinary calcium (p less than .05). Serum immunoreactive parathyroid hormone, initially in the lower range of normal, decreased further during hypercalcemia. A radiograph of the chest, gallium scan, and serum angiotensin-converting enzyme activity were normal. No granulomas or evidence of lymphoma were found in biopsies of the liver and of several lymph nodes. It is concluded that the abnormal calcium metabolism in this patient resulted from increased circulating 1,25-(OH)2D and that the defect in vitamin D metabolism was not related to sarcoidosis, other granulomatous disease, Hodgkin's disease, or lymphoma. The relationship, if any, of the abnormal metabolism of vitamin D and calcium to rheumatoid arthritis remains to be established.     

Calcium and Vitamin D in Sarcoidosis: Is Supplementation Safe?

Granulomas in sarcoidosis express high levels of 1α‐hydroxylase, an enzyme that catalyzes the hydroxylation of 25‐OH vitamin D to its active form, 1,25(OH)₂ vitamin D. Overproduction of 1α‐hydroxylase is held responsible for the development of hypercalcemia in sarcoidosis patients. Corticosteroids are used as first‐line treatment in organ‐threatening sarcoidosis. In this light, osteoporosis prevention with calcium and vitamin D (CAD) supplementation is often warranted. However, sarcoidosis patients are at risk for hypercalcemia, and CAD supplementation affects the calcium metabolism. We studied calcium and vitamin D disorders in a large cohort of sarcoidosis patients and investigated if CAD supplementation is safe. Retrospectively, data of 301 sarcoidosis patients from July 1986 to June 2009 were analyzed for serum calcium, 25‐hydroxy vitamin D (25‐(OH)D), 1,25‐dihydroxy vitamin D (1,25(OH)₂D), and use of CAD supplementation. Disease activity of sarcoidosis was compared with serum levels of vitamin D. Hypercalcemia occurred in 8%. A significant negative correlation was found between 25‐(OH)D and disease activity of sarcoidosis measured by somatostatin receptor scintigraphy. In our study, 5 of the 104 CAD‐supplemented patients developed hypercalcemia, but CAD supplementation was not the cause of hypercalcemia. Patients without CAD supplementation were at higher risk for developing hypercalcemia. During CAD supplementation, no hypercalcemia developed as a result of supplementation. Hypovitaminosis D seems to be related with more disease activity of sarcoidosis and, therefore, could be a potential risk factor for disease activity of sarcoidosis. Thus, vitamin D–deficient sarcoidosis patients should be supplemented. © 2014 American Society for Bone and Mineral Research.     

The 'oral 1,25-dihydroxyvitamin D3 pulse therapy' in hemodialysis patients with severe secondary hyperparathyroidism

Many hemodialysis patients are still suffering from secondary hyperparathyroidism although 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been used to treat renal osteodystrophy for the last two decades. The main reason for its failure to correct the secondary hyperparathyroidism is that in patients, hypercalcemia occurs before adequate parathyroid hormone (PTH) suppression is obtained when a large daily dose of 1,25(OH)2D3 is started. In this study, the oral dose of 1,25(OH)2D3 (4.0 micrograms) was administered only twice a week at the end of hemodialysis ('oral 1,25(OH)2D3 pulse therapy'), in 19 patients with severe secondary hyperparathyroidism. Serum immunoreactive PTH started to decrease after 6 weeks of therapy, and the original level of 41.2 +/- 7.24 was reduced to 24.4 +/- 6.12 ng/ml by the end of the 6-month therapy (p less than 0.001). Serum alkaline phosphatase also was reduced by 64.4%. Three out of 19 patients suffered from hypercalcemia during the 4th month of therapy. Calcium supplement given to 6 other patients with severe secondary hyperparathyroidism did not lower serum PTH levels significantly after 6 weeks of therapy, although serum calcium levels increased and were sustained above 10 mg/dl for the last 5 weeks. These findings strongly suggest that the suppressive effect of the oral 1,25(OH)2D3 pulse therapy was attained by a direct action of 1,25(OH)2D3 on the parathyroid gland rather than by its ability to elevate serum calcium levels. In conclusion, the oral 1,25(OH)2D3 pulse therapy effectively lowered PTH levels in hemodialysis patients who cannot tolerate large daily doses of 1,25(OH)2D3.     

High ratio of 1,25-dihydroxyvitamin D3 to parathyroid hormone in serum of tuberculous patients with end-stage renal disease

AIM: Diagnosis of tuberculosis is sometimes difficult because of the low specificity of diagnostic procedures especially in patients on end-stage renal disease (ESRD). As abnormal vitamin D metabolism has been reported in tuberculosis, the aim of the present study was to determine whether serum concentration of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) may be a useful diagnostic indicator of tuberculosis in patients with ESRD. PATIENTS AND METHODS: Serum concentrations of 1,25-(OH)2D3, parathyroid hormone (PTH), and calcium were compared in 6 patients with ESRD and active tuberculosis (ESRD-TB group) and 110 patients with ESRD and no tuberculosis (ESRD group). These parameters were compared before and after treatment for tuberculosis in patients of ESRD-TB group. RESULTS: Hypercalcemia was observed in all 6 patients in the ESRD-TB group. Both higher serum concentration of 1,25-(OH)2D3 and lower serum concentration of PTH were observed in the ESRD-TB group relative to the ESRD group, suggesting enhanced extrarenal production of 1,25-(OH)2D3 and suppressed secretion of PTH by hypercalcemia in the ESRD-TB group. However, these parameters could not be used to distinguish the ESRD-TB group from the ESRD group. The ratio of 1,25-(OH)2D3 to PTH in serum was above 0.9 in the ESRD-TB group and below 0.9 in the ESRD group. Antituberculous treatment reduced this ratio to the range observed in the ESRD group. CONCLUSION: High ratio of 1,25-(OH)2D3 to PTH in serum is noted in active tuberculous patients with ESRD because of enhanced extrarenal production of 1,25-(OH)2D3.     

Hypercalcemia and elevated 1,25(OH)2D3 levels in a dialysis patient with disseminated tuberculosis

A 37-year-old diabetic patient with end-stage renal disease on maintenance dialysis developed widely disseminated tuberculosis. Tuberculosis was associated with hypercalcemia, inappropriately elevated serum levels of 1,25(OH)2D3, and consistently suppressed serum levels of iPTH. This case provides additional evidence that in granulomatous diseases extrarenal synthesis of 1,25(OH)2D3 may occur.     

Beneficial effect of intermittent cyclical etidronate therapy in hemiplegic patients following an acute stroke.

Significant decreases in bone mineral density (BMD) occur on the hemiplegic side in chronic stroke patients, which correlate with the degree of paralysis and hypovitaminosis D. In this double-blind, randomized, and prospective study of 98 patients with hemiplegia involving both an upper and lower extremity (55 males and 53 females; mean age, 71.4 +/- 0.6 years) after an acute stroke, 49 were given etidronate for 56 weeks and 49 received a placebo. The BMD was measured by computed X-ray densitometry (CXD) of the second metacarpal bone bilaterally. Forty age-matched control subjects were followed for 56 weeks. At baseline, both groups had 25-hydroxyvitamin D [25(OH)D] insufficiency, increased serum ionized calcium and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and low serum concentrations of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D], suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1,25(OH)2D. The BMD on the hemiplegic side decreased by 2.3% and 4.8% in the etidronate and placebo groups, respectively (p = 0.0003). After treatment, the serum 1,25(OH)2D concentration increased by 62.2% in the etidronate group and decreased by 12.4% in the placebo group. The etidronate group had significant decreases in the serum ionized calcium and ICTP and increases in PTH and bone Gla protein (BGP), whereas the placebo group had higher serum calcium and ICTP concentrations but stable PTH. These results suggest that etidronate can prevent decreases in the BMD in hemiplegic stroke patients because it decreases the serum calcium through inhibition of bone resorption and causes a subsequent increase in the serum 1,25(OH)2D concentration.     

Regulation of calcium absorption by 1,25,dihydroxy-vitamin D--studies of the effects of a bisphosphonate treatment

In 10 patients with Paget's disease of bone and 2 patients with osteoporosis, we studied the effects of hypocalcemia and hypophosphatemia induced by disodium-(3-amino-1-hydroxypropylidene)-1,-bisphosphonate (APD) treatment on the serum concentration of PTH and 1,25-dihydroxy-vitamin D [1,25(OH)2D3] and on calcium absorption and balance. The fall in serum calcium and phosphate was associated with a rise in the serum concentration of PTH and 1,25(OH)2D3, coupled with increases in net calcium absorption and calcium balance. The concentration of 1,25(OH)2D3 was significantly related (P less than 0.001) to the serum calcium (r = 0.66), the serum phosphate (r = 0.78), and the serum PTH (r = 0.71), confirming the interrelated control of these parameters on 1,25(OH)2D3 production. Moreover the rise in 1,25(OH)2D3 caused an appropriate rise in calcium absorption (r = 0.74) and calcium balance (r = 0.86), showing that this vitamin D metabolite contributes as a hormone to calcium homeostasis.     

Effect of immobilization upon renal synthesis of 1,25-dihydroxyvitamin D in disabled elderly stroke patients

A 1,25-dihydroxyvitamin D [1,25-(OH)2D] deficiency and immobilization-related increased serum calcium concentration have been observed in hemiplegic stroke patients. To elucidate the influence of increased serum calcium concentration on bone metabolism, we measured serum biochemical indices and bone mineral density (BMD) in the second metacarpals of 170 elderly subjects with hemiplegic stroke and 72 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D [25-(OH)D], 1,25-(OH)2D, ionized calcium, intact parathyroid hormone (PTH), intact bone Gla protein (BGP), and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were measured. An increased serum calcium concentration (mean 2.543 mEq/L) was observed in this population and correlated negatively with the Barthel index (mean 66), indicating immobilization-induced bone resorption with consequent increased serum calcium. Decreased serum concentrations of 1,25-(OH)2D (mean 25.0 pg/mL) and serum 25-OHD concentration (mean 11.6 ng/mL) were noted. Serum PTH was not increased (mean 34.8 pmol/L). Serum levels of BGP were decreased significantly, whereas serum ICTP concentrations were elevated (mean 15.2 ng/mL). A strong negative correlation was seen between the serum calcium concentration and 1,25-(OH)2D (p < 0.0001). BMD of the second metacarpal in patients was decreased significantly compared with control subjects and highly correlated with 25-(OH)D and 1,25-(OH)2D concentrations. Immobilization-related increased serum calcium levels may inhibit PTH secretion, and thus 1,25-(OH)2D production. In addition, 25-(OH)D insufficiency also may contribute to decreased concentration of 1,25-(OH)2D.     

Refractory Hypercalcemia in an Infant Secondary to Talc Pleurodesis Resolving After Renal Transplantation

Talc pleurodesis is the definitive therapy of recurrent pneumothorax and has not been associated with metabolic complications. We report an anephric male infant who developed severe hypercalcemia 6 months following talc pleurodesis for recurrent peritoneal dialysis-related hydrothorax. The etiology of hypercalcemia was related to persistently elevated 1,25-dihyroxyvitamin D₃ (1,25[OH]₂D) levels. The source appeared to be the extrarenal production of 1,25(OH)₂D from macrophages in a large thoracic talc granuloma. Hypercalcemia was controlled with a combination of a low calcium diet, low calcium dialysis, ketoconazole and hydroxychloroquine, but elevated 1,25(OH)₂D levels persisted. At 32 months of age the child underwent renal transplantation with alemtuzumab pre-conditioning. The hypercalcemia resolved immediately, with normalization of serum 1,25(OH)₂D levels and without hypercalciuria. This case demonstrates that hypercalcemia is a potential complication of talc pleurodesis from the extrarenal production of 1,25(OH)₂D and that alemtuzumab, a monoclonal antibody directed against the CD52 antigen (which is expressed on almost all macrophages), may have a role in the treatment of hypercalcemia associated with granulomatous conditions.     

Intravenous 1,25 dihydroxycholecalciferol corrects glucose intolerance in hemodialysis patients.

The effects of intravenous 1,25 dihydroxycholecalciferol [(OH)2D3] on glucose tolerance and insulin secretion were studied in eleven uremic patients on regular hemodialysis and compared with eleven healthy controls. Intravenous glucose tolerance tests (IVGTT) were used to assess glucose tolerance, and the hyperglycemic clamp technique was used to quantitate endogenous insulin secretion. Three days after they had discontinued oral 1,25(OH)2D3, the dialysis patients were then studied with (+D) and without (-D) a single intravenous dose of 1,25(OH)2D3 at 2 micrograms/m2, given two hours before the IVGTT or clamp studies. During the -D studies, the uremic patients were glucose intolerant but not hyperinsulinemic. Intravenous 1,25(OH)2D3 in dialysis patients increased glucose uptake (K values) during IVGTT by 38% (P less than 0.02) and increased early component of insulin secretion during hyperglycemic clamps by 48% (P less than 0.01) and the late component by 32% (P less than 0.01). After intravenous 1,25(OH)2D3, the dialysis patients became hyperinsulinemic and regained glucose tolerance. Intravenous 1,25(OH)2D3 did not change the K values during IVGTT nor the insulin secretion during hyperglycemic clamps in the control subjects. During the -D studies, serum concentrations of 1,25(OH)2D3 were significantly lower in uremic patients compared with controls. Serum 1,25(OH)2D3 during the +D studies increased to supraphysiological levels in both uremic patients and controls. Serum concentrations of intact parathyroid hormone, total and ionized calcium, magnesium, potassium, urea nitrogen and creatinine were not different between the +D and -D studies in neither the uremic patients nor the controls. These results suggest that 1,25(OH)2D3 deficiency, independent of parathyroid hormone and calcium, may contribute to the abnormalities in glucose tolerance and insulin secretion in dialysis patients.     

Three cases of urolithiasis associated with sarcoidosis: A review of Japanese cases

We report three cases of urolithiasis associated with sarcoidosis and reviewed the Japanese published reports. All cases had hypercalcemia, hyperuricemia, hypercalciuria and renal dysfunction. A serum level of 1,25-(OH)2D3 was elevated and intact parathyroid hormone (PTH) was decreased. Stone components were predominantly calcium oxalate. Abnormal calcium metabolism is a well-known feature of sarcoidosis and the reported prevalence of urolithiasis in patients with sarcoidosis was 1.3-14.0% in the English published reports. However, urolithiasis associated with sarcoidosis is uncommon in Japan and we could find only 16 documented cases including ours. Abnormal calcium metabolism is caused by an increase in serum concentration of 1,25-(OH)2D3, which is derived from endogenous overproduction in the pulmonary macrophages. If patients with urolithiasis have abnormal calcium metabolism, renal impairment and suppression of PTH, the possibility of sarcoidosis should be considered for a differential diagnosis. Also, it should be emphasized that the presence or developing of urolithiasis is to be monitored during follow up of patients with sarcoidosis.     

Acute effect of dialysate calcium concentration and intravenous vitamin D3 on the secretion of parathyroid hormone in hemodialysis patients.

We studied the suppression of intact parathyroid hormone (PTH) in ten patients on chronic hemodialysis using different calcium concentrations of dialysate. Secondly, giving i.v. vitamin D3 at commencement of dialysis we investigated whether 1 alpha (OH)D3 or 1,25(OH)2D3 acutely modifies the responsiveness of the parathyroid gland to the suppressive effect of increased serum calcium. Dialysis with high-calcium dialysate (1.75 mmol/l) reverted the plasma PTH to normal limits. Lower-calcium dialysate (1.5 mmol/l) induced only a partial suppression of hyperparathyroidism. We found no differences in the suppression of hyperparathyroidism whether 1 alpha (OH)D3 or 1,25(OH)2D3 was given at the beginning of the dialysis or not. We conclude that the suppressibility of hyperparathyroidism in dialysis patients can be evaluated by different calcium concentrations of dialysate, and that i.v. vitamin D3 does not acutely modify the responsiveness of the parathyroid gland to the effect of calcium.     

Intravenous 1,25(OH)2 vitamin D3 therapy in haemodialysis patients: evaluation of direct and calcium-mediated short-term effects on serum parathyroid hormone concentration

Eleven patients on chronic haemodialysis treatment thrice weekly received 1 microgram 1,25(OH)2D3 i.v. after each dialysis for 3 weeks. Phosphate binders were mainly CaCO3, supplemented in a few patients by moderate amounts of Al(OH)3. Ionised calcium was measured by ion-selective electrode, normal values being 1.28-1.42 mmol/l. PTH was estimated by an N-terminal-sensitive assay; normal values are less than 0.25 ng/ml. Results before and after 1,25(OH)2D3 were: ionised calcium before haemodialysis, 1.19 +/- 0.12 and 1.17 +/- 0.14; ionised calcium after haemodialysis, 1.33 +/- 0.07 and 1.30 +/- 0.09; PTH before haemodialysis, 1.39 +/- 0.71 and 1.38 +/- 0.69; PTH after haemodialysis, 0.64 +/- 0.22 and 0.60 +/- 0.17; Phosphate before haemodialysis, 1.85 +/- 0.48 and 2.18 +/- 0.43 (P less than 0.05). No change of PTH concentration and ionised calcium before and after haemodialysis treatment could be documented after i.v. 1,25(OH)2D3 treatment. Mild and severe hyperparathyroidism were indistinguishable. Increased serum calcium concentrations therefore appear to be required for the suppression of PTH secretion by i.v. 1,25(OH)2D3 therapy.     

Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency

Significant reduction in bone mineral density (BMD) occurs in patients with Parkinson's disease (PD), correlating with immobilization and with vitamin D deficiency, and increasing the risk of hip fracture, especially in elderly women. As a biological indicator of compromised vitamin K status, an increased serum concentration of undercarboxylated osteocalcin (Oc) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women. We evaluated treatment with vitamin K(2) (menatetrenone; MK-4) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD. In a random and prospective study of PD patients, 60 received 45 mg of MK-4 daily for 12 months, and the remaining 60 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K(1) deficiencies, high serum levels of ionized calcium, and glutaminic residue (Glu) Oc, and low levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D], indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion. BMD in the second metacarpals increased by 0.9% in the treated group and decreased by 4.3% in the untreated group (p < 0.0001). Vitamin K(2) level increased by 259.8% in the treated group. Correspondingly, significant decreases in Glu Oc and calcium were observed in the treated group, in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures (eight at the hip and two at other sites) in the untreated group, and one hip fracture occurred among treated patients (p = 0.0082; odds ratio = 11.5). The treatment with MK-4 can increase the BMD of vitamin D- and K-deficient bone by increasing vitamin K concentration, and it can also decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1,25-(OH)(2)D concentration.     

Decreased free 1,25-dihydroxycholecalciferol index in patients with the nephrotic syndrome

The serum concentrations of calcium, phosphorus, parathyroid hormone, vitamin D3 metabolites and their transport protein (DBP) were measured in 18 patients with the nephrotic syndrome (mean daily proteinuria 8.8 g). The glomerular filtration rate was normal in 13 patients while the remaining 5 had a mild degree of renal failure. The serum concentrations of total protein, albumin and DBP were significantly decreased in patients with the nephrotic syndrome. The serum calcium concentration was decreased but the calculated ionized calcium concentration remained normal. The serum concentrations of 25-hydroxycholecalciferol (5.3 +/- 3.1 micrograms/l) and 1,25-dihydroxycholecalciferol [1,25-(OH)2D3 (20 +/- 12 ng/l)] were significantly lower in patients with the nephrotic syndrome and normal glomerular filtration rates than in normal controls (14.4 +/- 4 micrograms/l and 42 +/- 13 ng/l, respectively). The free 1,25-(OH)2D3 index was also significantly below normal (0.9 +/- 0.4 vs. 1.8 +/- 0.4). Total and free 1,25-(OH)2D3 were still further reduced in patients with mild renal failure. The nephrotic syndrome thus results in mild vitamin D depletion with decreased free 1,25-(OH)2D3 concentrations but generally without secondary hyperparathyroidism.     

Losses of 1,25- and 24,25-dihydroxycholecalciferol in the peritoneal fluid of patients treated with continuous ambulatory peritoneal dialysis

We measured peritoneal losses of the active vitamin D metabolites 1,25(OH)2D3 and 24,25(OH)2D3 in patients receiving continuous ambulatory peritoneal dialysis (CAPD). The serum concentration of 24,25(OH)2D3 was considerably lower than in hemodialysis patients. The serum concentration of 1,25(OH)2D3 was undetectable and rose to levels similar to those in hemodialysis patients only after loading with much higher oral doses of 1-alpha-vitamin D3 than those received by hemodialysis patients. Losses of both metabolites in peritoneal fluid were considerable, averaging approximately 6-8% of the plasma pool per day. These losses lead to low serum levels of these active vitamin D metabolites in CAPD patients, which may be an important factor in exacerbating renal osteodystrophy. Our results indicate the need for increased replacement doses of vitamin D metabolites in CAPD patients.     

Novel nonsecosteroidal vitamin D receptor modulator inhibits the growth of LNCaP xenograft tumors in athymic mice without increased serum calcium.

BACKGROUND: We recently reported on novel vitamin D receptor (VDR) modulators that are structurally distinct from the secosteroid 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the endogenous activator of VDR. One of these compounds, LG190119, was tested for the ability to inhibit the growth of LNCaP human prostate cancer cell-derived tumors in athymic mice. METHODS: In one study, athymic mice with established LNCaP xenograft tumors were dosed orally every day with LG190119 (3 or 10 mg/kg) or with a synthetic analog of 1,25(OH)(2)D(3), EB1089 (1 microg/kg), for 15 days. In another study ("prevention mode"), oral administration (every other day) of 10 mg/kg LG190119 or a non-hypercalcemic dose of 1,25(OH)(2)D(3) (0.5 microg/kg) was initiated prior to tumor development and continued for 84 days. In both studies, tumor volumes, mouse weights, and serum calcium levels were measured. RESULTS: In the established tumor study, LG190119 at each dose resulted in significant tumor growth inhibition without hypercalcemia at both 10 and 15 days. EB1089 treatment resulted in significant tumor growth inhibition only at Day 10 and resulted in hypercalcemia at Day 15. In the prevention-mode study, LG190119 markedly slowed tumor growth without increased serum calcium in comparison with either vehicle or 1,25(OH)(2)D(3) treatment (P < 0.001). CONCLUSIONS: LG190119 effectively inhibited LNCaP xenograft tumor growth without increased serum calcium levels or any other apparent side effects. Compounds of this class may represent promising new therapeutics for treatment of prostate cancer and other cancers with fewer undesirable side effects than currently used drugs.     

Vitamin D metabolism and serum binding proteins in anorexia nervosa

Serum vitamin D metabolites and other parameters of mineral metabolism were measured in 12 patients with anorexia nervosa. Serum concentrations of calcium, phosphate, albumin, alkaline phosphatase, parathyroid hormone, calcitonin, osteocalcin, and 24-hours calcium excretion were normal. Serum 25-hydroxyvitamin D (25OHD) concentration was similar in patients and normal subjects, whereas 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were significantly reduced in patients (62 +/- 17 vs 82 +/- 17 pmol/l); p less than 0.05). The concentration of vitamin D-binding protein (DBP) in patients was normal, but serum binding capacity (Nmax) was diminished in anorectic patients (2.05 +/- 0.50 vs 2.53 +/- 0.51 mumol/l; p less than 0.05). The diminished serum binding capacity, in spite of normal concentrations of albumin and DBP, reflects the presence of qualitative rather than quantitative defects in serum transport proteins. Since the reduction in 1,25(OH)2D and serum binding capacity was quantitatively similar, it is likely that free 1,25(OH)2D levels would be normal.