dihydrotachysterol and Uremia

Topics: Bone and Bones; Bone Diseases; Calcium; Cholecalciferol; Dihydrotachysterol; Homeostasis; Intestinal Absorption; Kidney; Kidney Failure, Chronic; Uremia; Vitamin D

The usefulness of 99mTc-Pyrophosphate (99mTc-PPi) bone scintigraphy was evaluated in the follow up of 21 haemodialysed patients without clinical or radiological evidence of osteodystrophy. 99mTc-PPi bone scintigraphy was semi-quantitatively analysed using Fogelman's score. Patients were randomised to receive vitamin D analogues (1 alpha hydroxyvitamin D3 or dihydrotachysterol, n = 12) or to serve as controls (n = 9), both groups being given oral calcium supplements. Bone scintigraphy deteriorated in patients only on calcium therapy but not in patients treated by vitamin D-analogues. Vitamin D therapy reduced secondary hyperparathyroidism in all cases but induced rapid intoxication with normal doses in 4 of the 12 treated patients. Since intoxicated patients had significantly lower Fogelman's score than the patients who tolerated the treatment well, 99mTc-PPi bone scintigraphy is proposed as a screening test before vitamin D-analogues trials.

Topics: Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Diphosphates; Humans; Hydroxycholecalciferols; Radionuclide Imaging; Renal Dialysis; Technetium; Technetium Tc 99m Pyrophosphate; Uremia

The use of calcitriol in the treatment of uremic hyperparathyroidism and renal osteodystrophy is limited in many patients by hypercalcemic side-effects. New less calcemic analogues of calcitriol are being developed, and some are under clinical evaluation. To investigate whether these compounds possess important differences in their action on bone cells, we have studied their effects [with and without parathyroid hormone (PTH)] on the release and synthesis of the resorptive osteotropic cytokine, interleukin-6 (IL-6).. MG 63 and SaOS-2 human osteoblastic cell lines were cultured for 6 or 24 hours in media containing calcitriol, the sterols of interest, or 1-34 synthetic PTH. IL-6 release was assayed by commercially available enzyme-linked immunosorbent assay. IL-6 mRNA levels were assessed by reverse transcriptase-polymerase chain reaction.. We found that calcitriol and paricalcitol behaved in a similar fashion, resulting in increased IL-6 release only at higher concentrations (10(-7) to 10(-9) M). In contrast, 22-oxacalcitriol and 1,25-dihydroxydihydrotachysterol2 stimulated release to a similar extent but at concentrations three to four orders of magnitude lower (10(-11) to 10(-13) M), despite being less potent as suppressers of parathyroid function than calcitriol. Studies of IL-6 mRNA showed a similar pattern of concentration and cell line-dependent transcription.. Compounds stimulating IL-6 release at concentrations achievable during the treatment of uremic hyperparathyroidism might favor continuing linked bone formation and resorption and thereby avoid adynamic bone disease while still allowing profound suppression of PTH.

Topics: Bone Diseases; Calcitriol; Cell Line; Dihydrotachysterol; Ergocalciferols; Humans; Interleukin-1; Osteoblasts; Parathyroid Hormone; RNA, Messenger; Uremia; Vitamin D

The effect of intravenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] therapy on insulin and lipid metabolism was examined in patients on maintenance hemodialysis (HD). Eight patients (Group I, 19 +/- 1 years old) were studied before and after four weeks of intravenous 1,25 (OH)2D3 therapy (1.8 +/- 0.3 micrograms), during which time the serum parathyroid hormone (PTH) concentrations did not change. Another eight patients (Group II, 18 +/- 1 years old) were studied before and after four weeks of oral dihydrotachysterol (0.8 +/- 0.1 mg). Serum PTH also did not change in Group II. Serum glucose concentrations during an oral glucose tolerance test (OGTT) were higher in Group I before 1,25(OH)2D3 compared with controls and these normalized following four weeks of intravenous 1,25(OH)2D3. Serum glucose concentrations during OGTT were also higher in Group II before DHT compared with controls and did not change following four weeks of oral DHT. Insulin sensitivity during euglycemic clamp studies in Group I before 1,25(OH)2D3 (223 +/- 20 mg/m2/min; P < 0.01) was low compared with controls (320 +/- 26 mg/m2/min) and was normalized following therapy (315 +/- 25 mg/m2/min). Insulin sensitivity was also low in Group II at the beginning of the study and did not change at the end of the four week period. Both early-phase and late-phase insulin secretion were low in Group I before 1,25(OH)2D3 compared with controls and normalized following intravenous 1,25(OH)2D3 therapy. Both early-phase and late-phase insulin secretion were also low in Group II at the beginning of the study and did not change at the end of the four week period of DHT treatment. Plasma triglycerides were elevated in Group I patients before treatment (198 +/- 16 mg/dl; P < 0.01) compared with controls (139 +/- 12 mg/dl) and were normalized (148 +/- 13 mg/dl) following intravenous 1,25(OH)2D3 therapy. Plasma total cholesterol and high density lipoprotein cholesterol were normal before treatment compared with controls and did not change following Intravenous 1,25(OH)2D3 therapy. Plasma triglycerides, total cholesterol and high density lipoprotein cholesterol did not change in Group II during the study period. Thus, intravenous 1,25(OH)2D3 therapy corrected glucose intolerance, insulin resistance, hypoinsulinemia as well as hypertriglyceridemia in patients on HD, in the absence of PTH suppression.

Topics: Adolescent; Adult; Blood Glucose; Calcitriol; Dihydrotachysterol; Glucose Clamp Technique; Humans; Injections, Intravenous; Insulin; Insulin Resistance; Lipids; Parathyroid Hormone; Renal Dialysis; Triglycerides; Uremia

Topics: Adolescent; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Follow-Up Studies; Humans; Uremia

Topics: Adolescent; Adult; Calcium; Child; Dihydrotachysterol; Humans; Intestinal Absorption; Uremia

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Middle Aged; Uremia

Topics: Animals; Bone Diseases; Calcium; Chemical Phenomena; Chemistry; Cholecalciferol; Dihydrotachysterol; Dihydroxycholecalciferols; Disease Models, Animal; Humans; Hydroxycholecalciferols; Isomerism; Kidney Failure, Chronic; Microradiography; Osteitis Fibrosa Cystica; Osteomalacia; Phosphates; Rats; Renal Dialysis; Uremia; Vitamin D

Topics: Administration, Oral; Adolescent; Adult; Aged; Aluminum Hydroxide; Calcium; Calcium, Dietary; Diet; Dihydrotachysterol; Feces; Glomerulonephritis; Humans; Kidney Failure, Chronic; Middle Aged; Nephrotic Syndrome; Phosphorus; Polycystic Kidney Diseases; Potassium; Uremia

Topics: Bone Diseases; Dihydrotachysterol; Humans; Kidney Failure, Chronic; Renal Dialysis; Uremia

Topics: Adult; Aged; Calcium; Calcium Isotopes; Dihydrotachysterol; Feces; Humans; Intestinal Absorption; Middle Aged; Phosphorus; Renal Dialysis; Uremia