vitamin-d-2 and Bone-Diseases--Metabolic

Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates. This is an update of a review first published in 2010.. This review aimed to examine the benefits (improved growth rates, reduced risk of bone fractures and deformities, reduction in PTH levels) and harms (hypercalcaemia, blood vessel calcification, deterioration in kidney function) of interventions (including vitamin D preparations and phosphate binders) for the prevention and treatment of metabolic bone disease in children with CKD.. We searched the Cochrane Kidney and Transplant Specialised Register to 8 September 2015 through contact with the Trial's Search Co-ordinator using search terms relevant for this review.. We included randomised controlled trials (RCTs) comparing different interventions used to prevent or treat bone disease in children with CKD stages 2 to 5D.. Data were assessed for study eligibility, risk of bias and extracted independently by two authors. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model.. This review included 18 studies (576 children); three new studies were added for this update. Adequate sequence generation and allocation concealment were reported in 12 and 11 studies respectively. Only four studies reported blinding of children, investigators or outcome assessors. Nine studies were at low risk of attrition bias and 12 studies were at low risk of selective reporting bias.Eight different interventions were compared. Two studies compared intraperitoneal (IP) with oral calcitriol. PTH levels were significantly lower with IP compared with oral calcitriol (1 study: MD -501.00 pg/mL, 95% CI -721.54 to -280.46) but the number of children with abnormal bone histology did not differ between treatments. Three studies compared intermittent with daily oral calcitriol. The change in mean height SDS (1 study: MD 0.13, 95% CI -0.22 to 0.48) and the percentage fall in parathyroid hormone (PTH) levels at eight weeks (1 study: MD -5.50%, 95% CI -32.37 to 21.37) and 12 months (1 study: MD -6.00% 95% CI -25.27 to 13.27) did not differ between treatments.Four studies compared active vitamin D preparations (calcitriol, paricalcitol, 1α-hydroxyvitamin D) with placebo or no specific treatment. One study reported vitamin D preparations significantly reduced PTH levels (-55.00 pmol/L, 95% CI -83.03 to -26.97). There was no significant difference in hypercalcaemia risk with vitamin D preparations compared with placebo or no specific treatment (4 studies, 103 children: RD 0.08 mg/dL, 95% CI -0.08 to 0.24). However, there was heterogeneity (I(2) = 55%) with one study showing a significantly greater risk of hypercalcaemia with intravenous (IV) calcitriol administration. Two studies (97 children) compared calcitriol with other vitamin D preparations and both found no significant differences in growth between preparations.Two studies compared ergocalciferol in patients with CKD and vitamin D deficiency. Elevated PTH levels developed significantly later in ergocalciferol treated children (1 study: hazard ratio 0.30, 95% CI 0.09 to 0.93) though the number with elevated PTH levels did not differ between groups (1 study, 40 children: RR 0.33, 95% CI 0.11 to 1.05).Two studies compared calcium carbonate with aluminium hydroxide as phosphate binders. One study (17 children: MD -0.86 SDS, 95% CI -2.24 to 0.52) reported no significant difference in mean final height SDS between treatments. Three studies compared sevelamer with calcium-containing phosphate binders. There were no. Bone disease, assessed by changes in PTH levels, is improved by all vitamin D preparations. However, no consistent differences between routes of administration, frequencies of dosing or vitamin D preparations were demonstrated. Although fewer episodes of high calcium levels occurred with the non-calcium-containing phosphate binder, sevelamer, compared with calcium-containing binders, there were no differences in serum phosphorus and calcium overall and phosphorus values were reduced to similar extents. All studies were small with few data available on patient-centred outcomes (growth, bone deformities) and limited data on biochemical parameters or bone histology resulting in considerable imprecision of results thus limiting the applicability to the care of children with CKD.

Topics: Aluminum Hydroxide; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcitriol; Calcium; Calcium Carbonate; Child; Chronic Disease; Ergocalciferols; Humans; Kidney Diseases; Parathyroid Hormone; Phosphorus; Polyamines; Randomized Controlled Trials as Topic; Sevelamer; Vitamin D

Chronic kidney disease mineral bone disorders (CKD-MBD) encompass laboratory, vascular and bone abnormalities that might portend a poor prognosis in CKD. In spite of a great effort in elucidating the CKD-MBD natural history and pathogenesis, the underlying mechanisms are still largely unknown. However, a deficit in vitamin D is commonly reported as one of the first steps in CKD-MBD, and numerous epidemiological studies have associated serum vitamin D levels with different markers of cardiovascular disease and the risk of death in different populations. We herein summarize current evidence that links vitamin D deficiency to an adverse outcome and the results of the most recent clinical trials that have investigated the impact of paricalcitol supplementation on hard outcome in CKD patients.

Topics: Bone Density Conservation Agents; Bone Diseases, Metabolic; Cardiovascular Diseases; Ergocalciferols; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Treatment Outcome; Vitamin D

The treatment of chronic kidney disease-mineral bone disorder (CKD-MBD) has traditionally focused on improvement in biochemical parameters of the disease. However, studies evaluating hard clinical end points or surrogate end points are limited.. Two randomized controlled trials have recently been published. In the EVOLVE study (Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events), cinacalcet was compared with placebo in 3883 haemodialysis patients with secondary hyperparathyroidism. The primary end point (death, myocardial infarction, unstable angina, heart failure or peripheral vascular disease) in an unadjusted intention-to-treat analysis was not significant [hazard ratio 0.93; 95% confidence interval (CI) 0.85-1.02, P=0.11]. However, the pre-specified secondary end points of an adjusted intention-to-treat analysis (hazard ratio 0.88; 95% CI 0.79-0.97, P=0.008) were significant. In the PRIMO (Paricalcitol Capsule Benefits in Renal Failure Induced Cardiac Morbidity) trial, 227 patients with CKD stage 3-4 and left ventricular hypertrophy by echocardiography were randomized to paricalcitol or placebo. The primary end point of change in left ventricular mass index by MRI after 12 months was not different between the two groups, but the prespecified end point of cardiovascular-related hospitalizations was reduced in the paricalcitol-treated group (P=0.04).. The results of these two randomized controlled trials have negative primary end points but significant secondary end points and thus require physicians to individualize therapies for the treatment of secondary hyperparathyroidism.

Topics: Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcimimetic Agents; Cardiovascular Diseases; Cinacalcet; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Naphthalenes; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic

Reduction in serum 1,25 (OH) (2)D level plays an important role in the pathophysiology of altered bone and mineral metabolism among patients with advanced stages of CKD. The use of vitamin D receptor activators (VDRA) has brought great progress in medical management of CKD-MBD. A number of observational studies have shown that the nonuse of VDRA, and low serum concentrations of 1,25 (OH) (2)D or 25 (OH) D are the predictors of poor clinical outcomes in CKD patients including dialysis patients, raising a possibility that the pleiotropic actions of vitamin D may be systemically involved in the poor survival of patients with CKD-MBD. Randomized controlled trials are needed to clarify whether or not VDRA could be beneficial in the protection of the cardiovascular system and good longevity.

Topics: Bone Diseases, Metabolic; Cardiovascular Diseases; Cholecalciferol; Chronic Disease; Ergocalciferols; Humans; Kidney Diseases; Minerals; Randomized Controlled Trials as Topic; Receptors, Calcitriol; Risk; Vitamin D

Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D(3) (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D. Rickets appeared to have been conquered with vitamin D intake, and many health care professionals thought the major health problems resulting from vitamin D deficiency had been resolved. However, rickets can be considered the tip of the vitamin D deficiency iceberg. In fact, vitamin D deficiency remains common in children and adults. An individual's vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D (25(OH)D3) concentration. There is increasing agreement that the optimal circulating 25(OH)D3 level should be approximately 30 ng/mL or above. Using this definition, it has been estimated that approximately three-quarters of all adults have low levels. In utero and during childhood, vitamin D deficiency can cause growth retardation and skeletal deformities and may increase the risk of hip fracture later in life. Vitamin D deficiency in adults can exacerbate osteopenia and osteoporosis, cause osteomalacia and muscle weakness, and increase the risk of fracture. More recently, associations between low vitamin D status and increased risk for various non-skeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. The discovery that most tissues and cells in the body have vitamin D receptors and that several possess the enzymatic machinery to convert the 25-hydroxyvitamin D3, to the active form, 1,25-dihydroxyvitamin D3, has provided new insights into the function of this vitamin. Of great interest is its role in decreasing the risk of many chronic illnesses, including common cancers, autoimmune diseases, infectious diseases, and cardiovascular disease. In this review I consider the nature of vitamin D deficiency, discuss its role in skeletal and non-skeletal health, and suggest strategies for prevention and treatment.

Topics: Asthma; Biomarkers; Bone Density Conservation Agents; Bone Diseases, Metabolic; Cholecalciferol; Dietary Supplements; Ergocalciferols; Humans; Metabolic Syndrome; Nervous System Diseases; Parathyroid Hormone; Rickets; Risk Factors; Sunlight; Vitamin D; Vitamin D Deficiency

Decline in renal function is related directly to cardiovascular mortality. However, traditional risk factors do not fully account for the high mortality in these patients. Activated vitamin D, a hormone produced by the proximal convoluted tubule of the kidney, appears to have beneficial effects beyond suppressing parathyroid hormone (PTH). However, activated vitamin D also can cause hypercalcemia and hyperphosphatemia in chronic kidney disease. Newer agents such as vitamin D receptor activators (eg, paricalcitol) suppress PTH with reduced risk of hypercalcemia and hyperphosphatemia. Recent evidence from animal and preliminary human studies supports an association between vitamin D receptor activators and reduced risk of cardiovascular disease deaths, irrespective of PTH levels. New pathways of vitamin D regulation also have been discovered, involving fibroblast growth factor-23 and klotho. Although considerable work has been performed to advance our understanding of the effects of vitamin D in health and chronic kidney disease, more investigations and randomized trials need to be performed to elucidate the mechanistic underpinnings of these effects.

Topics: Animals; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcitriol; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Prognosis; Renal Dialysis; Vitamin D

In patients with primary hyperparathyroidism, a definite diagnosis is the first step in the management strategy and relies on appropriately selected and carefully interpreted laboratory tests. Parathyroid hormone assays are being increasingly performed as part of the routine evaluation of osteoporosis. In this setting, laboratory tests are often consistent with primary hyperparathyroidism but should be interpreted with caution. Bone mineral density measurements are useful for assessing the impact of primary hyperparathyroidism. The recommended bone mineral density cutoffs for selecting patients requiring parathyroidectomy were lowered in 2003, and the number of surgically treated patients has increased as a result. Parathyroidectomy remains the treatment of choice given the low mortality associated with this procedure and the absence of pharmacological alternatives suitable for long-term use.

Topics: Bone Density; Bone Diseases, Metabolic; Ergocalciferols; Humans; Hypercalcemia; Hyperparathyroidism; Osteoporosis; Parathyroidectomy; Postoperative Period

Patients receiving long-term treatment with total parenteral nutrition often develop bony abnormalities characterized by patchy osteomalacia and low bone turnover. The patients present evidence of physiologic hypoparathyroidism, although low levels of iPTH cannot entirely explain the osteomalacia. Abnormally low serum levels of 1,25(OH)2-vitamin D have been demonstrated, but the significance of these reduced levels in the pathogenesis of the bone lesions is not defined. Aluminum has been detected in large quantities in the plasma, urine, and bone of some patients treated with TPN, and there is mounting evidence that aluminum may be associated with skeletal pathology, particularly osteomalacia. There is, however, no clear documentation that aluminum accumulation produces the skeletal lesions observed, although it could be a contributing factor. There has been the unusual empiric observation that the removal of vitamin D2 from the infusate is associated with a decrease in the quantity of unmineralized osteoid in TPN patients. A possible role of vitamin D2 in producing osteomalacia is not easy to understand since normal serum levels of 25(OH)-D2, the circulating form of vitamin D2, have been reported. The long-term consequences of intravenous nutritional support for many aspects of metabolism remain unknown. Administration into the systemic circulation of predetermined quantities of calcium and phosphorus via a route that bypasses their passage across the intestinal mucosa, the portal system and the liver may have adverse consequences. It is possible that bypassing homeostatic mechanisms may affect bone formation and metabolism or lead to alterations in vitamin D sterols. Alternatively, a deficiency of an essential trace metal or the accumulation of a toxic trace substance could be responsible for the bony abnormalities. Much remains to be clarified concerning calcium homeostasis and bone disease during total parenteral nutrition. Among various possible factors, it seems likely that the significance of the low levels of 1,25(OH)2-vitamin D and of the accumulation of aluminum in this condition will soon be clarified.

Topics: Adult; Aged; Aluminum; Bone and Bones; Bone Diseases, Metabolic; Bone Resorption; Calcitriol; Calcium; Ergocalciferols; Female; Humans; Infant; Male; Middle Aged; Minerals; Pain; Parathyroid Hormone; Parenteral Nutrition; Parenteral Nutrition, Total; Phosphates; Prospective Studies; Rickets; Trace Elements; Vitamin D

In this Phase 4 international study, efficacy and safety of paricalcitol-centred therapy were compared with that of cinacalcet-centred therapy for the treatment of chronic kidney disease (CKD)-associated secondary hyperparathyroidism (SHPT) in patients undergoing haemodialysis (ClinicalTrials.gov identifier NCT00977080).. Patients ≥ 18 years of age with Stage 5 CKD and SHPT [intact parathyroid hormone (iPTH) level of 300-800 pg/mL, calcium level of 8.4-10.0 mg/dL and phosphate concentration of ≤ 6.5 mg/dL] who were undergoing haemodialysis were included. Patients were randomized by mode of paricalcitol administration [i.e. intravenous (IV) or oral strata] to receive paricalcitol- or cinacalcet-centred therapy for ≤ 28 weeks. Changes in metabolic markers [total alkaline phosphatase (AP), bone-specific AP and fibroblast growth factor-23 (FGF-23)] and the proportion of patients in each treatment group who achieved an iPTH level of 150-300 pg/mL during Weeks 8, 16 and 21-28 as a composite value were evaluated.. Compared with cinacalcet-centred therapy, levels of both bone turnover markers were significantly reduced from baseline with IV and oral paricalcitol-centred treatment (P < 0.05 for both dosing strata) at Weeks 8, 16 and 28. Levels of FGF-23 were increased with paricalcitol versus cinacalcet-centred treatment. A greater proportion of patients receiving paricalcitol-centred therapy achieved target iPTH levels (i.e. 150-300 pg/mL) throughout the study in the IV and oral dosing strata compared with patients receiving cinacalcet-centred treatment.. In patients with CKD and SHPT undergoing haemodialysis, paricalcitol-centred therapy reduced circulating bone turnover markers and iPTH levels and increased FGF-23 levels compared with cinacalcet-centred treatment.. ClinicalTrials.gov identifier NCT00977080.

Topics: Aged; Biomarkers; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcium; Cinacalcet; Dose-Response Relationship, Drug; Ergocalciferols; Female; Fibroblast Growth Factor-23; Follow-Up Studies; Humans; Hyperparathyroidism, Secondary; Injections, Intravenous; Male; Middle Aged; Naphthalenes; Parathyroid Hormone; Phosphorus; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome

Assessment of the effectiveness and safety of high daily 125 microg (5,000 IU) or 250 microg (10,000IU) doses of vitamin D(2) during 3 months, in rapidly obtaining adequate 25 hydroxyvitamin D (25OHD) levels.. Longitudinal study.. Postmenopausal osteopenic/osteoporotic women (n = 38) were studied during winter and spring. Median age (25-75th percentile) was 61.5 (57.00-66.25) years, and mean bone mineral density (BMD) was 0.902 (0.800-1.042)g/cm(2). Subjects were randomly divided into three groups: control group (n=13): no vitamin D(2), 125 mug/day (n=13) and 250 microg/day (n=12) of vitamin D(2) groups, all receiving 500 mg calcium/day. Serum calcium, phosphate, bone alkaline phosphatase (BAP), C-telopeptide (CTX), 25OHD, mid-molecule parathyroid hormone (mmPTH), daily urinary calcium and creatinine excretion were determined at baseline and monthly.. For all subjects (n=38), the median baseline 25 hydroxyvitamin D (25OHD) level was 36.25 (27.5-48.12) nmol/l. After 3 months, 8% of the patients in the control group, 50% in the 125 microg/day group and 75% in the 250 microg/day group had 25OHD values above 85 nmol/l (34 ng/ml). Considering both vitamin D(2) groups together, mmPTH and BAP levels diminished significantly after 3 months (P<0.02), unlike those of CTX. Serum calcium remained within normal range during the follow-up.. The oral dose of vitamin D(2) required to rapidly achieve adequate levels of 25OHD is seemingly much higher than the usual recommended vitamin D(3) dose (20 mug/day). During 3 months, 250 microg/day of vitamin D(2) most effectively raised 25OHD levels to 85 nmol/l in 75% of the postmenopausal osteopenic/osteoporotic women treated.

Topics: Aged; Alkaline Phosphatase; Bone Density; Bone Diseases, Metabolic; Calcium; Collagen Type I; Creatinine; Dose-Response Relationship, Drug; Ergocalciferols; Female; Humans; Longitudinal Studies; Middle Aged; Nutritional Requirements; Osteoporosis, Postmenopausal; Parathyroid Hormone; Peptides; Phosphates; Safety; Seasons; Vitamin D; Vitamin D Deficiency

This study is the first reported administration of 1 alpha-hydroxyvitamin D2 (1 alpha-OHD2) to human subjects. A total of 15 postmenopausal osteopenic women were given increasing oral doses of 1 alpha-OHD2, beginning with a low dose of 0.5 microgram/day. In 15 subjects, the doses were raised at weekly intervals to 1.0, 2.0, 4.0, and 5.0 micrograms/day, and in 5 of these subjects, the dose was further increased to 8.0 or 10.0 micrograms/day. Mean urine calcium +/- SEM showed a dose-related increase from 134 +/- 17 mg/24 h on 0.5 microgram/day to 198 +/- 21 mg/24 h on 4.0 micrograms/day (p < 0.05) and to 241 +/- 35 mg/24 h on 5.0 micrograms/day (p < 0.05). No subjects had hypercalciuria (> 350 mg/24 h, the upper limit of the laboratory normal range) at doses less than 5.0 micrograms/day; 5 subjects had hypercalciuria at or above 5.0 micrograms/day (3 at 5.0 micrograms/day, 1 at 8.0 micrograms/day, and 1 at 10.0 micrograms/day). Mean serum calcium increased slightly on the 4.0 micrograms dose only (p < 0.05) but remained well within the normal range. Mean creatinine clearance and BUN, used as measures of renal function, showed no significant changes. Routine blood and urine assays also showed no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Aged; Bone Density; Bone Diseases, Metabolic; Calcium; Dose-Response Relationship, Drug; Ergocalciferols; Female; Homeostasis; Humans; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal

Children with hyperprostaglandin E syndrome, a neonatal variant of Bartter syndrome with enhanced renal and systemic formation of prostaglandin E2, have hypercalciuria, nephrocalcinosis, and osteopenia. Because prostaglandin E2 affects tubular calcium handling, stimulates the formation of calcitriol in vitro, and has osteolytic activity, we studied calcium homeostasis and the influence of prostaglandin E2 formation on hypercalciuria in nine patients with hyperprostaglandin E syndrome during long-term indomethacin treatment and after its withdrawal. Suppression of prostaglandin E2 formation by indomethacin resulted in improvement of biochemical and clinical features of hyperprostaglandin E syndrome. However, hypercalciuria, osteopenia, and nephrocalcinosis did not completely resolve. Despite a low calcium diet, daily urinary calcium excretion was enhanced during and after withdrawal of indomethacin treatment (median 6.3, range 5.3 to 14, and median 9.4, range 4.4 to 38 mg/kg per day, respectively). Daily urinary calcium excretion was greater after withdrawal than during indomethacin treatment. Urinary calcium excretion was not correlated with urinary prostaglandin E2 excretion. Plasma levels of intact parathyroid hormone (median 11, range 6.8 to 12 pmol/L) and calcitriol (median 157, range 108 to 236 pg/ml) were elevated during indomethacin treatment and decreased after withdrawal of indomethacin. These data suggest that hypercalciuria in hyperprostaglandin E syndrome is mainly due to a renal leak of calcium, which is caused by enhanced renal formation of prostaglandin E2 and a tubular defect not related to prostaglandin E2 formation. There is no evidence for prostaglandin-stimulated calcitriol formation. Decreasing plasma levels of parathyroid hormone in the presence of renal calcium losses after withdrawal of indomethacin treatment may be due to a bone resorption process caused by systemic prostaglandin formation; the process may contribute to hypercalciuria in the patient not receiving indomethacin.

Topics: Bone Diseases, Metabolic; Calcitriol; Calcium; Calcium Metabolism Disorders; Calcium, Dietary; Child; Child, Preschool; Dinoprostone; Ergocalciferols; Female; Homeostasis; Humans; Indomethacin; Infant, Newborn; Male; Nephrocalcinosis; Parathyroid Hormone; Phosphates; Renin; Syndrome

Bone mineral content(BMC), serum calcium, phosphorus and AKP were measured in 64 epileptic patients on long-term treatment with antiepileptics and in 14 epileptic patients not taking antiepileptics. All these indices were also measured in a group of healthy controls. In the epileptic patients taking antiepileptics BMC was significantly lower than that in the control group. Serum calcium and phosphorus were also lower than normal, while AKP was elevated. In the epileptic patients not taking antiepileptics BMC was not significantly different from that in the control group. Serum calcium, phosphorus and AKP were all normal. After 3 months of treatment with vitamin D2, BMC and serum calcium level returned to normal, but AKP was still significantly lowered.

Topics: Adolescent; Adult; Anticonvulsants; Bone Density; Bone Diseases, Metabolic; Child; Child, Preschool; Epilepsy; Ergocalciferols; Female; Humans; Male; Middle Aged

We evaluated low-dose calcitriol (0.25 microgram b.i.d.) in combination with 1 g of supplemental calcium therapy as treatment for osteopenic women over 60 years of age (n = 4). Control patients (n = 6) received ergocalciferol (50,000 units twice a week) and 1 g of supplemental calcium. Bone biopsies and CT-determined bone mineral density were done initially and after 1 year of therapy. Bone mineral density increased from 77 +/- 18 to 88 +/- 9 mg/ml (NS) in the calcitriol-treated group and from 87 +/- 13 to 112 +/- 30 mg/ml (NS) in the ergocalciferol-treated group. There was also no significant change in bone volume, as determined by bone biopsy in either group. No compression fractures occurred in either treatment group. After 1 year of therapy, urinary calcium excretion was increased significantly above that observed in age-matched untreated women. Creatinine clearance did not change significantly. Hypercalcemia was rare. In summary, we found calcitriol was not superior to ergocalciferol in preventing progressive bone loss and fractures. Both therapies were associated with significant hypercalciuria.

Topics: Bone Density; Bone Diseases, Metabolic; Calcitriol; Calcium; Creatinine; Drug Therapy, Combination; Ergocalciferols; Female; Humans; Middle Aged; Vitamin D

A 50-year-old man with a history of prostate cancer with extensive bone metastasis and hypocalcaemia presented with muscle aches and cramps. Physical exam was significant for Chvostek's and Trousseau's sign. Laboratory assessment was consistent with profound hypocalcaemia. This was believed to be due to hungry bone syndrome secondary to advanced prostate cancer. He was treated with intravenous calcium, vitamin D and calcitriol. He also received three doses of radium

Topics: Antineoplastic Agents; Bone Density Conservation Agents; Bone Diseases, Metabolic; Bone Neoplasms; Calcium Carbonate; Ergocalciferols; Humans; Hypocalcemia; Male; Middle Aged; Prostatic Neoplasms; Radioisotopes; Radium; Whole Body Imaging

Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism.. A retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period.. A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2 ± 0.9 mg/dl y GFR-MDRD was 36 ± 20 ml/min/1.73 m(2). Paricalcitol doses were gradually increased during the study: baseline 3.8 ± 1.9 μg/week, 12 months 5.2 ± 2.4 μg/week; 24 months 6.0 ± 2.9 μg/week (P<.001). Serum PTH levels showed a significant fast decline: baseline 288 ± 152 pg/ml; 6 months 226 ± 184 pg/ml; 12 months 207 ± 120; 24 months 193 ± 119 pg/ml (P<.001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92 ± 50 IU/l; 6 months 85 ± 36 IU/l, 12 months 81 ± 39 IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5-0.6 mg/dl) but still within normal range, whereas patients with baseline calcium>10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar.. Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet.

Topics: Adult; Aged; Alkaline Phosphatase; Bone and Bones; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcitriol; Calcium; Cinacalcet; Drug Substitution; Drug Therapy, Combination; Ergocalciferols; Female; Follow-Up Studies; Humans; Hyperparathyroidism, Secondary; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Postoperative Complications; Retrospective Studies

Secondary hyperparathyroidism (SHPT) is a common problem among patients with chronic kidney disease (CKD) on haemodialysis. This study was conducted to assess the use, effectiveness and safety of intravenous paricalcitol in haemodialysis patients with various degrees of SHPT.. This observational, multicentre, prospective study was conducted in 14 Swedish dialysis centres from May 2007 to June 2008 and included 92 haemodialysis patients with a diagnosis of SHPT associated with CKD. The decision to initiate treatment with intravenous paricalcitol was made by the treating physician. No treatment algorithms were provided.. Mean patient age was 64 years. Of the 92 patients included, 74 had an intact parathyroid hormone (iPTH) level of >300 pg/ml at baseline. Median iPTH was 584 pg/ml in patients with a baseline PTH of >300 pg/ml. During follow-up there was a decrease in iPTH to 323 pg/ml at 6 months (-45%, p < 0.0001). In parallel, there was a small increase in serum calcium, but serum phosphorus and the calcium × phosphorus product remained unchanged.. This study showed that intravenous paricalcitol substantially and safely decreased iPTH in haemodialysis patients with a baseline iPTH above the Kidney Disease Outcomes Quality Initiative recommended target range (150-300 pg/ml) and had minimal impact on serum minerals.

Topics: Aged; Biomarkers, Pharmacological; Bone and Bones; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcium; Chronic Disease; Ergocalciferols; Female; Humans; Hyperparathyroidism, Secondary; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Observation; Parathyroid Hormone; Phosphorus; Prospective Studies; Renal Dialysis; Sweden

Topics: Adult; Bone and Bones; Bone Diseases, Metabolic; Bone Neoplasms; Celiac Disease; Diagnosis, Differential; Diet, Gluten-Free; Ergocalciferols; Female; Humans; Neoplasms, Unknown Primary; Radiography; Radionuclide Imaging

Intravenous vitamin D is standard therapy for secondary hyperparathyroidism in hemodialysis (HD) patients. In for-profit dialysis clinics, mortality was higher for patients on calcitriol compared to paricalcitol. Doxercalciferol, a second vitamin D2 analog, is currently available. We assessed mortality associated with each vitamin D analog and with lack of vitamin D therapy in patients who began HD at Dialysis Clinic Inc. (DCI), a not-for-profit dialysis provider. During the 1999-2004 study period we studied 7731 patients (calcitriol: n=3212; paricalcitol: n=2087; doxercalciferol: n=2432). Median follow-up was 37 weeks. Mortality rates (deaths/100 patient-years) were identical in patients on doxercalciferol (15.4, 95% confidence interval (13.6-17.1)) and paricalcitol (15.3 (13.6-16.9)) and higher in patients on calcitriol (19.6 (18.2-21.1)) (P<0.0001). In all models mortality was similar for paricalcitol versus doxercalciferol (hazard ratios=1.0). In unadjusted models, mortality was lower in patients on doxercalciferol (0.80 (0.66, 0.96)) and paricalcitol (0.79 (0.68, 0.92)) versus calcitriol (P<0.05). In adjusted models, this difference was not statistically significant. In all models mortality was higher for patients who did not receive vitamin D versus those who did (1.2 (1.1-1.3)). Mortality in doxercalciferol- and paricalcitol-treated patients was virtually identical. Differences in survival between vitamin D2 and D3 may be smaller than previously reported.

Topics: Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcitriol; Calcium; Ergocalciferols; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Renal Dialysis; Retrospective Studies; Risk Factors; Survival Analysis; Vitamin D

Topics: Aged; Bone Diseases, Metabolic; Calcium Carbonate; Dietary Supplements; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism

Cyclosporine A (CsA), a potent immunosuppressant used in transplantation, induces increased formation with excess resorption in the rat with resultant osteopenia. These findings are confirmed in the human model. Transforming growth factor-beta (TGF-beta) is reported to be involved in the coupling of bone formation with resorption and in vivo and in vitro stimulates osteoblasts, and in vitro inhibits osteoclasts. CsA stimulates secretion of TGF-beta1 in humans, which, while improving immunosuppression, may also contribute to renal toxicity. This study was performed determine whether exogenously administered TGF-beta would modify the bone effects of CsA. Male Sprague-Dawley rats, 6 months of age, were randomized to receive: TGF-beta and CsA vehicle (group A); TGF-beta 5 microg/kg three times per week and CsA vehicle (group B); TGF-beta vehicle and CsA 10 mg/kg (group C); or TGF-beta 5 microg/kg three times per week and CsA 10 mg/kg (group D). These were compared with control over 28 days. CsA, but not TGF-beta, increased serum 1,25(OH)(2)D levels throughout the study. CsA increased osteocalcin (BGP), but TGF-beta negated this effect. Histomorphometry confirmed the known effects of CsA, whereas TGF-beta alone had no effect. However, in combination, TGF-beta blocked CsA's effect and increased osteoblast recruitment and activity, as reflected by increased percent mineralizing surface, percent osteoid perimeter, bone formation rate (bone volume referent), and activation frequency. Thus, it appears as if TGF-beta administration may have potential in modulating the deleterious bone effects of CsA.

Topics: Animals; Bone Diseases, Metabolic; Bone Resorption; Cyclosporine; Ergocalciferols; Male; Osteocalcin; Parathyroid Hormone; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta

Vitamin D insufficiency is characterized biochemically by the presence of secondary hyperparathyroidism, which can contribute to bone loss in osteopenic patients. Over a 2-yr period of evaluation of 118 consecutive, free living patients with osteopenia or osteoporosis, we identified 18 subjects with depressed serum 25-hydroxyvitamin D (250HD; < or = 14 ng/mL). Twelve of these subjects harbored a low 25OHD level and consented to undergo replacement with 50,000 IU vitamin D2 twice weekly for 5 weeks. Five hundred thousand units of oral vitamin D2 resulted in significant increases in 25OHD (+24.3+/-16.9 ng/mL; P < 0.001) and the fasting urinary calcium/creatinine excretion ratio (+0.06+/-0.004; P = 0.01) and significant decreases in the serum concentration of PTH (-32.9+/-36.9 pg/mL; P < 0.001) and osteocalcin (-4.9+/-2.4 ng/mL; P < 0.001). Vitamin D repletion was associated with a significant 4-5% annualized increase in bone mineral density at both the lumbar spine (P < 0.001) and the femoral neck (P = 0.03), indicating that resolution of vitamin D insufficiency in a population of patients with low bone mass results in a rapid rebound increase in bone mineral density.

Topics: Adult; Aged; Bone Density; Bone Diseases, Metabolic; Calcifediol; Ergocalciferols; Female; Humans; Male; Middle Aged; Parathyroid Hormone; Vitamin D Deficiency

Bone disease with total parenteral nutrition (TPN) has been attributed to aluminum loading or vitamin D therapy. We studied 17 patients who first received TPN containing casein hydrolysate with high Al and ergocalciferol (25 micrograms/d) for 6-72 mo followed by TPN containing amino acids with reduced Al and ergocalciferol (5 micrograms/d) for 9-58 mo. We also did a cross-sectional study of 22 patients receiving casein and ergocalciferol (25 micrograms/d) compared with 46 patients receiving amino acids and ergocalciferol (5 micrograms/d) for 6-58 mo. Bone formation was higher and osteoid area, bone-surface stainable Al and total bone Al were lower with amino acid TPN than with casein TPN. Bone formation varied inversely with both plasma Al and bone-surface Al, suggesting that plasma or bone-surface Al, acquired during TPN, can reduce bone formation and lead to patchy osteomalacia. Serum levels of iPTH and 1,25-dihydroxyvitamin D were higher with amino acid TPN.

Topics: Aluminum; Amino Acids; Bone and Bones; Bone Development; Bone Diseases, Metabolic; Calcium; Caseins; Creatinine; Ergocalciferols; Humans; Metabolic Clearance Rate; Osteomalacia; Parenteral Nutrition, Total; Protein Hydrolysates

Topics: Adult; Bone Diseases, Metabolic; Child; Ergocalciferols; Humans; Rickets

Fifteen female patients with primary biliary cirrhosis were evaluated for vitamin D status and evidence of metabolic bone disease. Full-thickness iliac crest bone biopsy specimens with histomorphometric analysis after double tetracycline labeling were performed before and after 1 yr of treatment with oral 25-hydroxyvitamin D (100 micrograms/day). Initially, serum 25-hydroxyvitamin D levels were low (less than 15 ng/ml) in 11 of the 15 patients and were increased to normal (greater than 25 ng/ml) in all patients within 3 mo. Serum parathyroid hormone levels were low normal or not detectable in all patients and did not change with therapy. No patient had a fracture during the treatment. No evidence of osteomalacia was found initially or in follow-up study in any patient. Follow-up histomorphometric analysis at the end of the 1-yr treatment showed that bone volume decreased during the study interval despite therapy (p less than 0.001). Photon beam densitometry confirmed the loss in trabecular density of the radius over the study interval (p less than 0.03). The mean fractional osteoid surface was not increased initially and did not change with therapy. The mean linear bone appositional rate as measured by double tetracycline labeling was not decreased initially and did not change with therapy. It was concluded that in moderate to severe primary ciliary cirrhosis, initial 25-hydroxyvitamin D levels are low and are rapidly corrected by oral 25-hydroxyvitamin D. These patients have significant osteoporosis which progresses despite 25-hydroxyvitamin D.

Topics: 25-Hydroxyvitamin D 2; Adult; Bone and Bones; Bone Diseases, Metabolic; Ergocalciferols; Female; Humans; Liver Cirrhosis, Biliary; Middle Aged

The prevalence of vitamin D deficiency in Crohn's disease and the relationship of vitamin D status to metabolic bone disease have not been fully characterized. Serum 25-hydroxyvitamin D was measured in 82 patients with Crohn's disease; 65% of Crohn's disease patients had a low serum 25-hydroxyvitamin D concentration; 25% had deficient levels (less than 10 ng/ml). The lowest 25-hydroxyvitamin D levels were observed in patients with previous ileal resections. Nine patients were studied in detail including transiliac needle bone biopsies; 6 had osteomalacia and 3 osteoporosis. Six patients had repeat bone biopsies 9 to 18 mo after vitamin D treatment. Three patients with osteomalacia and low serum 25-hydroxyvitamin D levels showed histologic improvement after therapy with oral vitamin D restored serum 25-hydroxyvitamin D levels to normal. The adequacy of therapy was assessed accurately by monitoring serum 25-hydroxyvitamin D concentration. Three patients with metabolic bone disease with normal serum 25-hydroxyvitamin D levels at diagnosis did not show histologic improvement after receiving vitamin D.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Bone and Bones; Bone Diseases, Metabolic; Crohn Disease; Ergocalciferols; Female; Humans; Male; Middle Aged; Osteomalacia; Vitamin D; Vitamin D Deficiency

Research over the last fifteen years has led to the identification of several metabolites of vitamin D, elucidation of their mechanism of action, clarification of the pathogenesis of several metabolic bone diseases, and development of new diagnostic tests and more effective and safe treatment. 1, 25(OH)2 D, the most active metabolite, can be regarded as a highly potent steroid hormone, with its formation from its precursors tightly coupled to physiological need by a variety of ionic and hormonal regulating mechanisms.

Topics: Animals; Bone Diseases, Metabolic; Calcium; Cholecalciferol; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hydroxycholecalciferols; Intestinal Absorption; Kidney; Phosphorus

Patients receiving long term parenteral nutrition may develop metabolic bone disease. In all 11 patients studied, histologic studies of bone showed excessive unmineralized bone tissue despite normal plasma 25-hydroxyvitamin D levels. Three patients also had bone pain and fractures and severe urinary loss of calcium and phosphate. Withdrawal of vitamin D from parenteral nutrition solutions was associated with improved histologic findings of bone in all patients, shown by a decrease in osteoid tissue and an increase in tetracycline uptake. In the three patients with symptoms, bone pain subsided, fractures healed, and urinary loss of calcium and phosphate decreased. Thus, vitamin D may be a factor in the genesis of parenteral nutrition-induced metabolic bone disease.

Topics: 25-Hydroxyvitamin D 2; Adult; Bone and Bones; Bone Diseases, Metabolic; Calcium; Dihydroxycholecalciferols; Ergocalciferols; Female; Fluorides; Humans; Male; Middle Aged; Osteomalacia; Parenteral Nutrition; Parenteral Nutrition, Total; Phosphates