Serum Calcitriol Levels Research Articles

OSR1-Sensitive Renal Tubular Phosphate Reabsorption

Background: The oxidative stress-responsive kinase 1 (OSR1) participates in the WNK-(with no K) kinase dependent regulation of renal salt excretion and blood pressure. Little is known, however, about the role of OSR1 in the regulation of further renal transport systems. The present study analyzed the effect of OSR1 on NaPiIIa, the major renal tubular phosphate transporter. Methods: Immunohistochemistry and confocal microscopy were employed to determine renal localization of OSR1 and NaPiIIa. To elucidate the effect of OSR on NaPiIIa activity, cRNA encoding NaPiIIa was injected into Xenopus oocytes with or without additional injection of cRNA encoding OSR1, and phosphate transport was estimated from phosphateinduced currents determined with dual electrode voltage clamp. To elucidate the in vivo significance of OSR1 serum phosphate and hormone concentrations as well as urinary phosphate output of mice carrying one allele of WNK-resistant OSR1 (osr1tg/⁺) were compared to the respective values of wild type mice (osr1^+/+). Results: NaPiIIa and OSR1 were both expressed in proximal renal tubule cells. Coexpression of OSR1 significantly up-regulated phosphate-induced currents in NaPiIIa-expressing Xenopus oocytes. Despite decreased serum phosphate concentration urinary phosphate excretion was significantly increased and NaPiIIa protein abundance in the brush border membrane significantly reduced in osr1tg/⁺ mice as compared to osr1^+/+ mice. Serum PTH and calcitriol levels were similar in osr1tg/⁺ mice and in osr1^+/+ mice, serum FGF23 concentration was, however, significantly higher in osr1tg/⁺ mice than in osr1^+/+ mice. Conclusions: OSR1 is expressed in proximal renal tubules and participates in the regulation of FGF23 release and renal tubular phosphate transport.

Novel Compound Heterozygous Mutations in the Vitamin D Receptor Gene in a Korean Girl with Hereditary Vitamin D Resistant Rickets

Hereditary vitamin D resistant rickets (HVDRR) is a rare genetic disorder caused by a mutation of vitamin D receptor (VDR) gene. A number of cases had been reported in many countries but not in Korea. We examined a three-year old Korean girl who had the typical clinical features of HVDRR including rickets, hypocalcemia, hypophosphatemia, elevated serum calcitriol level and secondary hyperparathyroidism. The girl and her father were both heterozygous for the 719 C-to-T (I146T) mutation in exon 4, whereas she and her mother were both heterozygous for 754 C-to-T (R154C) mutation in exon 5 of the VDR gene. In this familial study, we concluded that the girl had compound heterozygous mutations in her VDR gene which caused HVDRR. This is the first report of a unique mutation in the VDR gene in Korea.

Severe osteomalacia caused by short bowel syndrome in a patient on long-term hemodialysis after parathyroidectomy

In January 2009, a 70-year-old Japanese woman on long-term dialysis was admitted to our hospital for evaluation of a painful left leg. Maintenance dialysis was started in 1982, and parathyroidectomy was performed for secondary hyperparathyroidism in 2004. Most of her small intestine was resected because of superior mesenteric artery thrombosis in 2006, and the remaining small bowel only extended 50 cm distal to the ligament of Treitz. Parenteral nutrition was started after bowel resection. Fracture of her left leg occurred suddenly without any precipitating factors in January 2009, and iliac bone biopsy revealed severe osteomalacia with an increase of total osteoid volume (57.6%) (>15%) and no fibrous tissue (0%) (<0.5%). Although phosphorus and active vitamin D were administered intravenously to correct her hypophosphatemia and vitamin D deficiency, significant improvement was not achieved. This case indicates that when a patient on long-term dialysis with parathyroidectomy also suffers from short bowel syndrome, osteomalacia may become very severe. Lack of healing of the fracture, persistence of pain, and subsequent fracture even after vigorous treatment for low serum phosphate and calcitriol levels implied that these medications were not necessarily sufficient for this patient.

The effect of sevelamer carbonate and lanthanum carbonate on the pharmacokinetics of oral calcitriol

Background. Lanthanum carbonate and sevelamer carbonate are non-calcium-based phosphate binders used to manage hyperphosphataemia in patients with chronic kidney disease (CKD). Patients with CKD may require intravenous or oral active vitamin D. We investigated the effects of lanthanum carbonate and sevelamer carbonate on the bioavailability of oral calcitriol.Methods. This was a three-period, crossover study in healthy volunteers. Forty-one individuals were randomized to one of six possible sequences, each consisting of three treatment periods separated by washouts. The treatments were calcitriol (1 μg at lunch), calcitriol with lanthanum carbonate (3000 mg/day) and calcitriol with sevelamer carbonate (7200 mg/day). Serum calcitriol levels were assessed at baseline and throughout the study.Results. Co-administration of lanthanum carbonate with calcitriol had no significant effect on area under the curve over 48 h (AUC0–48) for serum exogenous calcitriol [least-squares (LS) mean, calcitriol with lanthanum carbonate vs calcitriol alone: 429 pg h/mL vs 318 pg h/mL, respectively; P = 0.171]. Similarly, there was no significant effect on maximum concentration (Cmax). In contrast, co-administration with sevelamer was associated with a significant reduction in bioavailability parameters for calcitriol (calcitriol with sevelamer carbonate vs calcitriol alone, LS mean AUC0–48: 137 pg h/mL vs 318 pg h/mL, respectively; P = 0.024; LS mean Cmax: 40.1 pg/mL vs 49.7 pg/mL, respectively; P < 0.001).Conclusions. Sevelamer carbonate significantly reduces serum concentrations of exogenous calcitriol when administered concomitantly with oral calcitriol, whereas lanthanum carbonate has no significant effect. This should be considered when treating CKD patients who require phosphate binders and oral vitamin D.

Estrogens and bone disease in chronic kidney disease: role of FGF23

To describe the direct and indirect effects of estrogen on bone with special emphasis on the analysis of the recent findings related to the putative role of FGF23 in the estrogen-dependent parathyroid hormone (PTH) suppression. Estrogens act directly on bone cells, downregulating osteoclast precursors and differentiation, increasing osteoclast apoptosis and stimulating osteoblast proliferation and differentiation. However, estrogens can also act indirectly on bone, modulating the calcium-phosphorus-vitamin D-PTH axis. It has been recently demonstrated that estrogens suppress PTH synthesis and secretion in a dose-dependent manner and reduce serum calcitriol and phosphorus levels by an indirect mechanism. In-vivo and in-vitro experiments demonstrated that FGF23 positively correlated, also in a dose-dependent manner, with the dose of estrogens and with the observed changes in calcitriol and phosphorus. These new findings support the importance of the indirect effects of estrogens on bone, suggesting a role for FGF23 in the regulation of PTH by estrogens.

Hypophosphatemic Rickets with Hypercalciuria due to Mutation inSLC34A3/Type IIc Sodium-Phosphate Cotransporter: Presentation as Hypercalciuria and Nephrolithiasis

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a metabolic disorder due to homozygous loss-of-function mutations in the SLC34A3 gene encoding the renal type IIc sodium-phosphate cotransporter (NaPi-IIc). The typical presentation is severe rickets and hypophosphatemia, and hypercalciuria is often discovered later or overlooked. We sought to determine the genetic basis for severe hypercalciuria and nephrolithiasis/nephrocalcinosis in an adolescent male with elevated serum levels of calcitriol but normal serum levels of calcium and phosphorus. We used PCR to analyze the SLC34A3 gene in the proband and members of his family. The proband was a compound heterozygote for two SLC34A3 missense mutations, a novel c.544C-->T in exon 6 that results in replacement of arginine at position 182 by tryptophan (R182W) and c.575C-->T in exon 7 that results in replacement of serine at position 192 by leucine (S192L). The R182W and S192L alleles were inherited from the mother and father, respectively, both of whom had hypercalciuria. A clinically unaffected brother was heterozygous for S192L. We report a novel mutation in the SLC34A3 gene in a patient with an unusual presentation of HHRH. This report emphasizes that moderate and severe hypercalciuria can be manifestations of heterozygous or homozygous loss-of-function mutations in the SLC34A3 gene, respectively, providing further evidence for a gene dosage effect in determining the phenotype. HHRH may be an underdiagnosed condition that can masquerade as idiopathic hypercalciuria or osteopenia.

Klotho Gene, Phosphocalcic Metabolism, and Survival in Dialysis

The discovery that two recently identified molecules, klotho and fibroblast growth factor 23 (FGF23), played an important role in calcium, phosphate, and vitamin D metabolism has transformed our traditional physiological view in which bone and mineral homeostasis was mainly regulated by parathyroid hormone, vitamin D, and calcitonin, according to mineral body needs. FGF23 is a 251-amino acid secreted protein produced by osteoblasts and osteocytes in bone following the stimulation by phosphate and vitamin D or the inhibition by dentin matrix protein 1. Originally isolated from tumoral cells of patients with tumor-induced osteomalacia and hypophosphatemia, FGF23 inhibits phosphate reabsorption in renal proximal tubular cells and 1alpha-hydroxylase activity, resulting in decreased synthesis of calcitriol. To exert these actions, FGF23 requires the conversion, by klotho, of the canonical FGF receptor 1 (IIIc) in a specific high affinity FGF23 receptor. On the other hand, klotho is a putative antiaging gene identified in 1997 when a particular mouse strain, created by random insertion mutagenesis, was found to be short-lived and displayed premature atherosclerosis, osteopenia, skin atrophy, pulmonary emphysema, hyperphosphatemia, hypercalcemia, and high serum calcitriol levels. The gene of klotho encodes a 1012-amino acid cell-surface protein with a short cytoplasmic tail and an extracellular domain that consists in tandem duplicated copies of a beta-glucuronidase-like sequence, which can be released into the circulation as soluble forms after being cleaved by metalloproteinases such as ADAM10 and ADAM17. By modulating FGF23 action, klotho regulates urinary phosphate excretion and calcitriol synthesis. By virtue of its beta-glucuronidase activity, klotho deglycosylates the calcium channel TRPV5 (transient receptor potential vallinoid-5) and regulates urinary calcium excretion. klotho also binds to Na(+),K(+)-ATPase in parathyroid cells and regulates calcium-stimulated PTH secretion. Finally, klotho extends life span via several mechanisms, including the reduction of calcitriol synthesis, serum calcium, and phosphorus levels; the induction of insulin resistance; and by increasing the resistance to oxidative stress.

Vitamin D–Resistant Diseases

Hereditary vitamin D receptor defects (HVDRDs) is a more appropriate and precise title for an inborn error of metabolism commonly known as pseudo-vitamin D deficiency or vitamin D dependency, type II. It is a rare autosomal recessive disorder, approximately 70 kindreds were described, but its main importance is elucidating the physiology of vitamin D and calcium homeostasis in humans. Patients usually develop the clinical and biochemical aberrations, identical to vitamin D deficiency, but with high serum levels of calcitriol, within the first year of life (i.e., muscle weakness, bone pain, deformities, and fractures). Defective calcium gut absorption leads to hypocalcemia, secondary hyperparathyroidism, hypophosphatemia, and defective mineralization of newly formed bone matrix. The disease is not cured by vitamin D replacement therapy, although some patients respond to very high doses of vitamin D or its metabolites. Cells derived from patients, mainly cultured skin fibroblasts, were used to assess steps in calcitriol action from cellular uptake to bioresponse and to elucidate the molecular aberrations in the vitamin D receptor (VDR). Point mutations in the VDR gene were identified in every patient examined, and the same defect was observed in the obligatory heterozygotes. The functional characterization of the patient's VDR reflected the localization of the mutation (18 different ones described to date), thus providing vital information about the structure-function relationship in the human VDR and the essentiality of the VDR as the mediator of vitamin D action.

UVB therapy increases 25(OH) vitamin D syntheses in postmenopausal women with psoriasis

Vitamin D3 is produced in the epidermis by ultraviolet (UV) radiation (290-315 nm) of 7-dehydrocholesterol. A similar range of 290-320 nm (broadband UVB) has been successfully used for years to treat psoriasis. The aim of this study was to investigate whether UVB therapy was able to influence vitamin D synthesis in psoriasis patients. Twenty-four postmenopausal, white Caucasian women, aged 69 +/- 5.9 (mean +/- SD), with active plaque psoriasis, were treated with broadband UVB two to three times per week for 8-12 weeks. The serum concentrations of calcidiol (25(OH)D3), calcitriol (1,25(OH)2D3), intact parathyroid hormone (PTH), thyroid hormones, osteocalcin, calcium and creatinine were measured before the first and after the last dose of radiation. Bone density was measured using Dual-Energy X-ray Absorptiometry (Hologic Delphi A) at the hip and lumbar spine. Serum levels of 25(OH)D3 increased from 36.8 +/- 17 ng/ml (mean +/- SD) to 59.6 +/- 18.7 ng/ml (P<0.001) after the UVB treatment period. Serum PTH decreased from 62.8 +/- 25.7 ng/l to 48.2 +/- 17.4 ng/l (P<0.001). Secondary hyperparathyroidism (PTH>65 ng/l) was revealed in seven patients (29%) in whom PTH values were suppressed by the UVB therapy. The serum levels of calcitriol, calcium, osteocalcin, thyroid hormones and creatinine were unaltered. UVB therapy in elderly psoriatic women improved psoriasis, increased serum 25(OH)D3 synthesis and reduced serum PTH concentrations.

A slowly enlarging painless nodule on the elbow

Conflict of interest: none declared A 13‐year‐old boy presented with a 3‐month history of a slowly enlarging nontender xanthomatous‐appearing nodule, 20 × 20 mm in size, on his left elbow (Fig. 1). There was no preceding history of trauma and he was otherwise fit and well. The nodule was well demarcated, round, smooth, firm and mobile within the skin, with no surface ulceration. No other abnormalities were detected on cutaneous examination. The lesion was excised under local anaesthetic with direct repair and sent for histopathological examination. ... Sections of the lesion were stained with haematoxylin and eosin, and revealed a dermal nodule composed of lobulated masses of calcified material and granular necrosis surrounded by fibrous septae (Fig. 2). The boy's serum urate, calcium, phosphate and calcitriol levels were normal. ... What is your diagnosis? Primary tumoral calcinosis. Primary tumoral calcinosis (PTC) is rare and appears to be more common in people of African descent. It typically presents with firm, enlarging, nontender, nonerythematous juxta‐articular nodules without involvement of the osseous elements. The aetiology is uncertain, although minor trauma is thought to be a possible trigger mechanism. Lesions may be solitary or multiple, ranging in size from 10 to 200 mm.

Monocyte fructose 1,6-bisphosphatase and cytidine deaminase enzyme activities: potential pharmacodynamic measures of calcitriol effects in cancer patients

To determine, in peripheral blood monocytes (PBM), whether the enzymatic activities of fructose 1,6-bisphosphatase (FBPase), cytidine deaminase (CDDase) and 24-hydroxylase (CYP24), enzymes regulated by calcitriol are useful pharmacodynamic (PD) measures of calcitriol effects in cancer patients. Cancer patients enrolled in a phase I clinical trial of calcitriol and carboplatin were studied. Baseline and calcitriol-induced changes in FBPase, CDDase and CYP24 activities were measured in PBM collected before, 6, 24, and 48 h after administration of calcitriol, prior to carboplatin, in doses ranging from 4 to 11 mug daily for 3 consecutive days (QDx3). Normal FBPase, CYP24 and CDDase activities were measured in PBM from untreated healthy volunteers. Baseline activities in PBM from cancer patients and healthy volunteers were (median and range): 1.0 (0.0-43.5) and 4.4 (3.1- 8.2) nmol/min/mg protein for FBPase (P = 0.002); 2.5 (0.9-9.3) and 0.8 (0.4-2.0) fmol/h/10(6) cells for CYP24 (P = 0.016), and 5.6 (2.5-22.3) and 6.6 (1.1-47.4) nmol/min/mg protein for CDDase (P > 0.05), respectively. All calcitriol doses achieved peak serum calcitriol levels > x3 the physiological levels, increased cancer patient PBM FBPase activity to normal levels and decreased CDDase activity to undetectable levels within 48 h, with no significant change in CYP24 activity. These enzyme activity changes were not associated with hypercalcemia. Calcitriol treatment-induced increase in FBPase and decrease in CDDase activities in cancer patient PBM are potential early and sensitive non-hypercalcemia PD measures of calcitriol effects.

25-hydroxyvitamin D levels and bone histomorphometry in hemodialysis renal osteodystrophy

The importance of 25-hydroxyvitamin D (25-OHD) serum levels in hemodialysis chronic renal failure has not been so far histologically evaluated. Information still lacking relate to the effect of 25-OHD deficiency on serum parathyroid hormone (PTH) levels and on bone and its relationship with calcitriol levels. This retrospective study has been performed on a cohort of 104 patients on hemodialysis from more than 12 months, subjected to transiliac bone biopsy for histologic, histomorphometric, and histodynamic evaluation. The patients, 61 males and 43 females, mean age 52.9 +/- 11.7 years, hemodialysis length 97.4 +/- 61.4 months, were treated with standard hemodialysis and did not receive any vitamin D supplementation. Treatment with calcitriol was not underway at the time of the biopsy. Transiliac bone biopsies were performed after double tetracycline labels. In addition, serum intact PTH (iPTH), alkaline phosphatase, and 25-OHD were measured. Calcitriol serum levels was also measured in a subset of patients (N= 53). The patients were divided according to serum 25-OHD levels in three groups: (1) 0 to 15 (15 patients), (2) 15 to 30 (38 patients), and (3) >30 ng/mL (51 patients). There was no significant difference in average age, hemodialysis age, serum PTH [490 +/- 494, 670 +/- 627, and 489 +/- 436 pg/mL, respectively (mean +/- SD)], alkaline phosphatase, and calcitriol between the three groups. The parameters double-labeled surface, trabecular mineralizing surface, and bone formation rate were significantly lower in group 1 than in the other groups (P < 0.03, < 0.03, and < 0.02, respectively). Osteoblast surface and adjusted apposition rate were borderline significantly lower in group 1 (P < 0.06 and < 0.10). There was no statistical difference in the biochemical and bone parameters between groups 2 and 3. A positive significant correlation was found between several bone static and dynamic parameters and 25-OHD levels in the range 0 to 30 ng/mL, showing a vitamin D dependence of bone turnover at these serum levels. However, actual evidence of an effect on bone of 25-OHD deficiency was found at serum levels below 20 ng/mL. With increasing 25-OHD levels beyond 40 ng/mL, a downslope of parameters of bone turnover was also observed. Since PTH serum levels are equally elevated in low and high 25-OHD patients, while calcitriol levels are constantly low, an effect of 25-OHD deficiency (group 1) on bone, consisting of a mineralization and bone formation defect, can be hypothesized. The effect of vitamin D deficiency or bone turnover is found below 20 ng/mL. The optimal level of 25-OHD appears to be in the order of 20 to 40 ng/mL. Levels of the D metabolite higher than 40 ng/mL are accompanied by a reduction of bone turnover.

Ultraviolet B radiation improves serum levels of vitamin D in patients with cystic fibrosis

Ultraviolet B (UVB) radiation can be used in the prevention and treatment of vitamin D deficiency.To investigate, in a controlled study of patients with cystic fibrosis (CF), whether regular UVB radiation would improve serum levels of calcidiol during the dark season (October-April).Thirty patients with mild to moderate disease were included (aged 9-40 y). All patients had cholecalciferol supplementation. One group (15 patients) was given UVB one to three times a week for 6 mo and one group (15 sex- and age-matched patients) served as controls. The radiation source consisted of three TL 12/40W UVB fluorescent lamps. Initial treatment duration was 1 min, subsequently increased by 0.5-1 min/treatment to a maximum of 10 min.The mean initial serum calcidiol levels were 21 ng/ml in the controls and 22 ng/ml in the intervention group. Serum calcidiol levels increased to 44 ng/ml after 8 wk and to 50 ng/ml after 24 wk of UVB radiation; the corresponding serum levels in the controls were 19 and 25 ng/ml, respectively. The mean serum calcitriol levels increased in the treated group and were unaltered in the control group.UVB radiation was effective in increasing vitamin D levels in patients with CF. The study results imply that UVB radiation is valuable in chronic conditions associated with vitamin D deficiency.

Ultraviolet B radiation improves serum levels of vitamin D in patients with cystic fibrosis

Ultraviolet B (UVB) radiation can be used in the prevention and treatment of vitamin D deficiency. To investigate, in a controlled study of patients with cystic fibrosis (CF), whether regular UVB radiation would improve serum levels of calcidiol during the dark season (October-April). Thirty patients with mild to moderate disease were included (aged 9-40 y). All patients had cholecalciferol supplementation. One group (15 patients) was given UVB one to three times a week for 6 mo and one group (15 sex- and age-matched patients) served as controls. The radiation source consisted of three TL 12/40W UVB fluorescent lamps. Initial treatment duration was 1 min, subsequently increased by 0.5-1 min/treatment to a maximum of 10 min. The mean initial serum calcidiol levels were 21 ng/ml in the controls and 22 ng/ml in the intervention group. Serum calcidiol levels increased to 44 ng/ml after 8 wk and to 50 ng/ml after 24 wk of UVB radiation; the corresponding serum levels in the controls were 19 and 25 ng/ml, respectively. The mean serum calcitriol levels increased in the treated group and were unaltered in the control group. UVB radiation was effective in increasing vitamin D levels in patients with CF. The study results imply that UVB radiation is valuable in chronic conditions associated with vitamin D deficiency.

Are new vitamin D analogues in renal bone disease superior to calcitriol?

Progression of chronic kidney disease is associated with an early reduction in serum calcitriol levels; thus, therapy with calcitriol should be initiated early in the course of chronic kidney disease to prevent the development of secondary hyperparathyroidism. Initial studies demonstrated a potential role of calcitriol in the prevention of growth retardation in children with chronic kidney disease prior to dialysis. But the optimal parathyroid hormone (PTH) levels that will maximize growth response during calcitriol treatment remain to be defined. Therapy with calcitriol has been shown to control the biochemical and skeletal manifestations of secondary hyperparathyroidism, but patients developed hypercalcemia, hyperphosphatemia and adynamic osteodystrophy. Thus, new vitamin D analogues with a lower hypercalcemic response have been developed. Although comparative studies are lacking, current evidence indicates that these new active vitamin D sterols (19-nor-paracalcitol and doxercalciferol) adequately control secondary hyperparathyroidism with minimal changes in serum calcium and phosphorus levels during treatment with calcium-containing binders. The long-term effect of such therapies on the skeleton and the process of vascular calcifications remain to be evaluated.

Fibroblast Growth Factor-23 Relationship to Dietary Phosphate and Renal Phosphate Handling in Healthy Young Men

The renal handling of inorganic phosphate (Pi) is controlled not only by PTH, but also by hitherto undetermined mechanisms dependent on phosphate intake. Recently, fibroblast growth factor (FGF)-23 was identified as a novel phosphaturic factor in tumor-induced osteomalacia and autosomal-dominant hypophosphatemic rickets. We hypothesized that phosphate intake could influence FGF-23 concomitantly to the changes in renal Pi handling. Twenty-nine healthy males were subjected to a 5-d low-phosphate diet and a phosphate binder, followed by a high-phosphate diet including supplements. Concomitant modifications in calcium intake allowed minimizing PTH changes in response to dietary phosphate. Serum FGF-23 levels significantly decreased on the low-phosphate diet, then increased with the oral phosphate load. Changes in FGF-23 were positively correlated with changes in 24-h urinary Pi excretion and negatively correlated with changes in the maximal tubular reabsorption of Pi and 1,25(OH)(2)D(3) (calcitriol), whereas PTH was not. In multivariate analysis, changes in FGF-23 remained the most significantly correlated to changes in 1,25(OH)(2)D(3) and maximal tubular reabsorption of Pi. Moreover, FGF-23 was positively correlated to serum osteocalcin, a marker of osteoblastic activity. In summary, FGF-23 was inversely related to renal Pi transport and serum calcitriol levels in healthy young men. These data suggest that FGF-23 may be implicated in the physiological regulation of Pi homeostasis in response to dietary phosphate changes, independent of PTH.

Bone disease in long-term adult kidney transplant patients with normal renal function

In successful renal transplantation, the degree of renal function recovery is usually incomplete and information is scarce about the abnormalities of mineral metabolism in long-term adult renal recipients with normal renal function. This study was designed to investigate bone mineral metabolism in patients with a long-term normal functioning kidney. Twenty-nine adult asymptomatic renal transplant (RT) recipients with stable graft function for more than 10 years and serum creatinine <2 mg/dL were studied. They were classified into two groups according to glomerular filtration rate: Group A (N = 12; nine men, three women)>70 mL/min (x: 126 +/- 55 mL/min) and Group B (N = 17; nine men, eight women) <70 mL/min (x: 56 +/- 11 mL/min). Circulating biochemical markers of bone remodelling, bone histomorphometry, and densitometry (lumbar spine and hip) were obtained to investigate bone disease in these patients. Serum PTH was slightly elevated in 10 patients (83%) in group A. Serum PTH levels were positively related to serum calcium, osteocalcin, BAP, telopeptide, OH-proline, and creatinine. There was no histologic data to support overactivity on bone in this group of patients, with only one showing high bone turnover. Mineralization was prolonged in 34% of patients. Twenty-two patients (75%) exhibited normal bone turnover. In the group with GFR>70 mL/min the prevalence of mineralization defect in the presence of normal serum levels of calcitriol suggested vitamin D resistance. Lumbar and femoral neck osteoporosis was present in 25% and 33% of patients in group A, and 23% and 53% in group B, respectively. T-score at lumbar spine was negatively correlated with months since transplantation. Patients under treatment with cyclosporine (CsA) showed increased concentrations of osteocalcin and D-pyr and higher lumbar bone mineral density (BMD), but bone histomorphometry was not influenced by CsA. Patients with long-term renal transplantation with normal renal function frequently present with slight increases in PTH, but without an effect on bone histology. CsA did not induce changes in bone histology and delayed mineralization was frequently observed.

Bone mineral density and urine calcium excretion among subjects with and without nephrolithiasis

Bone mineral density (BMD) is reduced among patients with idiopathic hypercalciuria (IH) and nephrolithiasis. To disentangle effects of diet, stone formation, and physiology upon BMD, we studied vertebral and femoral neck BMD among relatives of hypercalciuric stone formers, and contrasted those with to those without stones. Among 59 subjects from 11 families, vertebral and femoral neck BMD, diet calcium intake, urine excretions of calcium, sodium, ammonium, titratable acid, sulfate, urea nitrogen, and serum levels of calcitriol and markers of bone turnover were studied. Stone formers (SF) consumed less calcium than non-stone formers (NSF). Spine and femoral neck BMD z-scores varied inversely with urine calcium loss and urine ammonium excretion among SF but not NSF. No correlations of BMD z-score were found for bone markers, calcitriol, or any of the other measurements. SF consumed less calcium, presumably to prevent more stones, and displayed a bone mineral responsiveness to calcium loss and ammonium excretion not present among NSF, who ate more calcium. Lowered calcium consumption in IH, perhaps in response to stone formation, alters bone responses in a direction that can predispose to mineral loss and eventual fracture.

Effect of Low-Carbohydrate High-Protein Diets on Acid-Base Balance, Stone-Forming Propensity, and Calcium Metabolism

Diets that restrict carbohydrate intake but allow unlimited fat and protein, such as the Atkins' diet, are much in vogue today. Whether a low-carbohydrate, high-protein (LCHP) diet increases the risk of bone loss or kidney stone formation was the question asked in this study of 10 healthy individuals ranging in age from 21 to 52 years. Initially they took their usual diet for 2 weeks and then an Atkins'-type induction diet (with severely restricted carbohydrate) for 2 weeks. An Atkins' maintenance diet then was consumed for 4 weeks in the maintenance phase. In the last week, the participants ate constant metabolic meals. Both the induction and maintenance LCHP diets contained nearly twice as much protein and fat as the subjects' usual diets but significantly less carbohydrate. Intakes of calcium, potassium, magnesium, sodium, and chloride did not differ significantly. Both weight loss and increased blood urea nitrogen levels attested to compliance with the diet. None of the 10 dieters developed clinically apparent metabolic acidosis. Serum sodium levels dropped slightly, but there were no changes in levels of potassium, chloride, calcium, or phosphorus. Urinary pH and citrate fell significantly with the induction and maintenance diets. Urinary ammonium, titratable acidity, and net acid excretion rose nearly 2-fold, as did urinary sulfate levels. Urinary calcium and phosphorus levels increased by about 2.25 mmol and 12.5 mmol/day, respectively, during the LCHP diet periods. Urinary magnesium decreased, but uric acid, oxalate, sodium, and potassium excretion did not change measurably levels measured during the baseline diet. The urinary content of undissociated uric acid doubled. Calcium balance decreased during both LCHP diets. Serum alkaline phosphatase decreased, but the bone-specific fraction did not change. Serum osteocalcin was significantly lower when subjects were on the LCHP diets. Urinary levels of deoxypyridinoline and N-telopeptide tended to increase, but not to a significant degree, and serum levels of calcitriol and parathyroid hormone did not change significantly. Endogenous creatinine clearance rose significantly during both LCH diets. This short-term study suggests that intake of a LCHP weight reduction diet, through delivering an exaggerated acid load, may heighten the risk of both kidney stone formation and bone loss. This possibility should be evaluated in a long-term prospective trial.

Calcium homeostasis remains unaffected after 12 weeks' therapy with calcitriol 3 µg/g ointment; no correlation with extent of psoriasis

OBJECTIVE: To assess the systemic safety of calcitriol 3 µg/g ointment (Silkis ® ointment) in relation to body surface area (BSA) affected by chronic plaque psoriasis. METHODS: In this open-label, multicentre study, patients were divided into three parallel groups: 5% to <15% ( n =23), 15% to <25% ( n =18), 25% to 35% ( n =18) based on BSA involvement. Ointment was applied topically twice daily for 12 weeks; patients were followed up for a further 8 weeks. RESULTS: There was no alteration of calcium homeostasis: the mean values of albumin-adjusted serum total calcium, as well as 24-hour urinary calcium and serum calcitriol levels, remained within normal ranges throughout treatment. No changes in calcium or phosphate homeostasis related to the area of psoriasis being treated with calcitriol ointment were detected. CONCLUSIONS: Reductions in the global severity score and BSA involvement, as well as results of the assessment of improvement, attested to the clinical efficacy of calcitriol 3 µg/g ointment in psoriasis. The study confirms the systemic safety of calcitriol 3 µg/g in psoriatic patients with 5-35% BSA involvement.