dihydrotachysterol and Chronic-Kidney-Disease-Mineral-and-Bone-Disorder

Topics: 25-Hydroxyvitamin D 2; Calcitriol; Calcium; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Ergocalciferols; Humans; Intestinal Absorption; Osteomalacia; Parathyroid Hormone; Vitamin D

Dihydrotachysterol which was developed already 50 years ago is above all used in the substitution therapy of hypoparathyroidism. Its parathyreomimetic effectivity has led to an enlargement of the spectrum of indication during the last years; it allows the prophylactic use of dihydrotachysterol in chronic nephropathy in order to prevent by this means the risk of reactive hyperparathyroidism as well as its sequelae. On the basis of own experimental results the pathophysiologic prerequisites of this new form of treatment are discussed.

Topics: Chronic Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Hyperparathyroidism; Parathyroid Glands

Topics: Animals; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Hypophosphatemia, Familial; Rats; Rickets; Vitamin D; Vitamin D Deficiency

Topics: Aluminum; Bone Regeneration; Calcium; Calcium Carbonate; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hydroxycholecalciferols; Intestinal Absorption; Osteitis Fibrosa Cystica; Osteomalacia; Parathyroid Glands; Phosphorus; Secretory Rate; Vitamin D

Topics: Anthropometry; Calcitriol; Child; Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Clinical Protocols; Dihydrotachysterol; Double-Blind Method; Growth Disorders; Humans; Infant; Multicenter Studies as Topic; Nutritional Status; Radiography

Topics: Anthropometry; Calcitriol; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Clinical Protocols; Dihydrotachysterol; Growth Disorders; Humans; Multicenter Studies as Topic; Nutritional Status; Program Evaluation

Topics: Calcitriol; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Growth Disorders; Humans; Multicenter Studies as Topic; National Institutes of Health (U.S.); Randomized Controlled Trials as Topic; United States

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

Many clinicians continue to prefer dihydrotachysterol (DHT) as the initial vitamin D agent of choice in hypoparathyroidism and renal osteodystrophy because of its long history of efficacy and safety. Assessment of the factors influencing the clinical response to DHT treatment should include measurement of vitamin D metabolite profiles, but investigators have heretofore been unable to measure 1,25(OH)2D because levels have been found to be falsely elevated when employing the chick intestinal cytosol receptor assay. After converting from the chick cytosol receptor assay to the calf thymus receptor assay for measuring 1,25(OH)2D, we did not note falsely elevated levels of 1,25(OH)2D in DHT-treated patients. The design of this study, therefore, was aimed at determining whether or not the calf thymus receptor measured authentic 1,25(OH)2D in such patients. We controlled for the possibility that freezing and thawing or prolonged storage might have either lowered 1,25(OH)2D levels or degraded a metabolite(s) of DHT that would have otherwise been recognized as "1,25(OH)2D" by the calf receptor. Similarly, technical differences between the two assays, source of thymus, and potential interference by other cytosolic proteins were eliminated as causes for the difference between the 1,25(OH)2D levels in the two assays. Our experiments do not provide an explanation for why the thymus receptor does not "see" the interfering metabolite(s) of DHT. This could reflect either a tissue difference or perhaps a species difference. Our results do provide the first opportunity to expand the investigation of the metabolic effects of DHT therapy to include changes in intrinsic 1,25(OH)2D metabolism.

Topics: Biological Assay; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Hypoparathyroidism; Receptors, Calcitriol; Receptors, Steroid; Thymus Gland

Topics: Adult; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

The effect of administration of 25 micrograms 24,25-dihydroxyvitamin D3 (24,25(OH)2D) combined with dihydrotachysterol (DHT2) on clinical, radiological, biochemical and bone histological parameters was assessed in ten children on chronic hemodialysis. Eight children had been treated with DHT2 prior to administration of 24,25(OH)2D. Addition of 24,25(OH)2D to the treatment resulted in a decrease in serum calcium values. Therefore higher doses of DHT2 were required to maintain serum-calcium levels between 2.4-2.8 mmol/l. Administration of 24,25(OH)2D did not modify the quality of bone, but histomorphometric investigation did show a significant reduction of the surface percentage of bone trabecula, in the iliac crest, covered with osteoclasts (oc%). Following the administration of 24,25(OH)2D an increase in bone mineralization was shown by X-rays of the wrists and measured by dual photonabsorptiometry. Addition of 24,25(OH)2D to the DHT2 treatment resulted in an increase in serum concentration of 24,25(OH)2D and a decrease in DHT2 levels. The present study suggests that administered 24,25(OH)2D interferes with DHT2 metabolism and increases DHT2 tolerance. Increased bone mineralization may be related to 24,25(OH)2D, a higher dose of DHT2 or both.

Topics: 24,25-Dihydroxyvitamin D 3; Adolescent; Bone and Bones; Calcium; Child; Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Dihydroxycholecalciferols; Drug Therapy, Combination; Female; Humans; Kidney Failure, Chronic; Male; Minerals; Renal Dialysis

16 patients with advanced renal failure and histologic evidence of renal osteodystrophy were treated with dihydrotachysterol (DHT) in a dose of 0.125-0.375 mg/day. All patients had creatinine clearances of less than 22 ml/min, but none were undergoing dialysis. The rate of deterioration in renal function was determined by serial measurements of the serum creatinine and by plotting the reciprocal of the serum creatinine against time. The duration of follow-up was 17.0 +/- 8.6 months. There was no significant deterioration in renal function in 12 patients. The remaining 4 patients showed acceleration in the rate of deterioration, but the relationship to DHT therapy was unclear.

Topics: Alkaline Phosphatase; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Creatinine; Dihydrotachysterol; Drug Evaluation; Humans; Kidney; Kidney Failure, Chronic; Metabolic Clearance Rate; Phosphates; Retrospective Studies; Time Factors

We treated 24 patients who had chronic renal insufficiency and renal osteodystrophy with either calcitriol (1,25-dihydroxyvitamin D3) or dihydrotachysterol. Renal function was evaluated before and during treatment to determine if these vitamin D analogues caused an accelerated rate of renal function deterioration. An accelerated rate of increase in the serum creatinine level was found in three of 12 patients in each treatment group after therapy was started, but the mean rate of increase during treatment did not differ significantly from the rate during the pretreatment control period in either group. The occurrence of hypercalcemia or an excessive serum calcium x phosphorus-product did not correlate with the rate of change in renal function during treatment with either drug. We concluded that children receiving calcitriol are not at greater risk for an accelerated rate of renal function deterioration than are children treated with dihydrotachysterol. Furthermore, neither vitamin D analogue could be directly implicated as a cause of an accelerated rate of renal function deterioration when episodes of hypercalcemia were transient and occurred infrequently.

Topics: Adolescent; Adult; Calcitriol; Calcium; Child; Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Creatinine; Dihydrotachysterol; Humans; Hypercalcemia; Infant; Kidney; Kidney Failure, Chronic; Phosphorus; Retrospective Studies; Risk

In 25 (33.8%) of 74 chronically haemodialysed patients a distinct osteopathy with bone pain, spontaneous fractures, arthralgias and weakness of the muscles due to dialysis was present. In comparison to a group without complaints the duration of the dialysis was longer by 6 months, the mineral contents of the bones was decreased in 38%, in the comparative group in 22%. A progressive demineralisation was found in 46%, in the comparative group in 20%. Hypercalcaemias under vitamin D2 caused a therapy resistance. In 1 exemplary case (type IIc, PTH 0.3 micrograms/l) in the 3rd year of dialysis a fracture of the neck of the femur took place and an endoprosthesis was implanted. There was a progressive demineralisation of about 16%. The suspicion of a typical combination with an encephalopathy due to dialysis did not confirm itself. A pseudocyst in the brain was found. The differential diagnosis to the hypercalcaemia-induced psychosis in the osteopathy due to dialysis is discussed. In a prophylactic application dihydrotachysterine proved favourable for avoidance of an osteopathy due to dialysis. Parallel to the clinical progressing of the osteopathy due to dialysis a progressive demineralisation could be demonstrated at the peripheral mineral contents of the bones. Extreme losses of minerals appeared from the 4th to the 59th month of dialysis from - 16% to - 37% and from the 22nd to the 87th month from plus 11% to minus 14% of the age-and-sex-specific normal values. Successful transplantations led to the stagnation of the progressive demineralisation, unsucessful transplantations increase them. The influence of the non-refined water for the production of dialysate by possible aluminium intoxications on the development of the osteopathy due to dialysis is discussed.

Topics: Aluminum Hydroxide; Bone and Bones; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Ergocalciferols; Fractures, Spontaneous; Humans; Kidney Transplantation; Minerals; Prognosis; Renal Dialysis; Ultraviolet Therapy

Topics: Calcifediol; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Osteitis Fibrosa Cystica; Osteomalacia; Renal Dialysis; Vitamin D

Renal osteodystrophy in part due to secondary hyperparathyroidism, is one of the major unresolved problems affecting patients on chronic hemodialysis. In addition, evidence has shown that parathyroid hormone (PTH) is toxic to other organ systems besides bone. The results of a prospective study on the effect of propranolol in reducing PTH levels in chronic renal failure patients on hemodialysis are reported. Propranolol administration reduced PTH levels by over 50-75%. The levels of calcium, phosphorus, alkaline phosphatase and hematocrit were variable, but patients with severe derangements in these measurements also seemed to benefit from propranolol. It should now be determined by larger and longer studies whether these biochemical improvements can be translated into clinical benefits.

Topics: Alkaline Phosphatase; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Parathyroid Hormone; Propranolol; Renal Dialysis

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

Two non-dialyzed patients with severe uremic bone disease were treated successfully with dihydrotachysterol (DHT). In each case, dramatic clinical improvement was noted in several weeks and this was verified by biochemical, radiologic and histologic measurements. Although DHT has been utilized previously in combination with dialysis, its documented effectiveness in the absence of the latter therapy has not previously been reported.

Topics: Adult; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Female; Hand; Humans; Middle Aged; Radiography; Skull

Topics: Adolescent; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Male; Phosphates; Puberty

The morphologic and morphometric study of the femoral bones of rats with experimental renal insufficiency induced by the removal of the 5/6 of the renal tissue amount has been carried out. The administration of dihydrotachysterol to the animals reduced the incidence and severity of changes (nephrogenic osteodystrophy) in the examined parts of the rat skeleton.

Topics: Animals; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Kidney Failure, Chronic; Male; Rats

Topics: Alkaline Phosphatase; Bicarbonates; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Phosphates; Renal Dialysis; Vitamin D

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

Topics: Child; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Drug Evaluation; Humans; Hydroxycholecalciferols; Pennsylvania; Prospective Studies

Topics: Adolescent; Age Factors; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Kidney Failure, Chronic

Topics: Adult; Alkaline Phosphatase; Aluminum Hydroxide; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Female; Humans; Hydroxyproline; Kidney Failure, Chronic; Male; Osteomalacia; Parathyroid Hormone; Phosphates; Renal Dialysis

Nine of 24 patients undergoing long-term hemodialysis were found to have evidence of moderate to severe bone disease. Two had bone pain and muscle weakness and two had pseudofractures. Eight of the nine were treated with dihydrotachysterol (DHT), 0.25 to 0.375 mg/d initially, but four required doses between 0.5 and 1.0 mg/d. Ther serum alkaline phosphatase value decreased in all patients and returned to normal in six. The bone pain and muscle weakness resolved and the pseudofractures healed. Bone biopsies in six patients before and after initiation of treatment with DHT showed that the osteoid area decreased significantly from 29.6 +/- 22.8% (mean +/- standard deviation) to 11.5 +/- 7.5% (P less than 0.025) and the resorptive surface decreased in all patients. DHT, in doses of up to 1.0 mg/d, is effective in treating both the osteitis fibrosa and the osteomalacic components of bone disease in patients undergoing hemodialysis.

Topics: Bone and Bones; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Osteomalacia; Radiography; Renal Dialysis

Topics: Adolescent; Adult; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Dihydroxycholecalciferols; Female; Femur; Humans; Hydroxycholecalciferols; Kidney Transplantation; Male; Minerals; Renal Dialysis; Transplantation, Homologous

21 hypocalcemic patients on regular hemodialysis were treated for 2 months with 0.2 mg and for a further 2 months with 0.46 mg dihydrotachysterol daily. 8 normocalcemic patients served as a control group. Radiological and radiodensitometric investigations were undertaken in all patients at regular intervals. Slight signs of renal osteopathy with a predominant osteomalacic component could be established in the skeletal X-ray in 55% of all patients. Compared with a healthy collective, all dialysis patients showed a small but significant reduction of bone mineralisation radiodensitometrically before the beginning of treatment. During treatment with dihydrotachysterol, the patients showed a significant demineralisation of the skeleton. In four cases the characteristics of the osteopathy also increased in the skeletal radiography. During the same period of observation, none of the untreated patients showed any change of the bone mineralisation.

Topics: Absorptiometry, Photon; Adolescent; Adult; Alkaline Phosphatase; Bone and Bones; Bone Resorption; Calcinosis; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Creatinine; Dihydrotachysterol; Dose-Response Relationship, Drug; Drug Synergism; Female; Humans; Kidney Failure, Chronic; Long-Term Care; Male; Middle Aged; Parathyroid Hormone; Phosphates; Renal Dialysis

Nine out of 24 patients on chronic hemodialysis were found to have biochemical, radiologic and bone biopsy evidence of moderate to severe bone disease. Two patients had bone pain and muscle weakness, 2 had pseudofractures, and one patient had a pathologic fracture of the neck of the femur. Eight patients were treated with dihydrotachysterol (D.H.T.), 0.25 to 0.37 mg/day initially. Four patients required doses between 0.5 and 1.0 mg daily. The alkaline phosphatase decreased in all patients, returning to normal in 6 patients. The symptoms of bone pain and muscle weakness resolved, and the pseudofractures healed. Repeat bone biopsies were performed in 6 patients 12 mos or more after treatment with D.H.T. The osteoid area fell from 29.6 +/- 22.8 to 11.5 +/- 7.5% (p less than 0.025). Resorptive surface decreased in all patients. D.H.T., in doses of up to 1.0 mg/day, is effective in the treatment of both the osteitis fibrosa and the osteomalacic component of bone disease in patients on hemodialysis.

Topics: Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Osteomalacia; Renal Dialysis

Topics: Chemical Phenomena; Chemistry; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Epilepsy; Humans; Hydroxycholecalciferols; Hypophosphatemia, Familial; Osteomalacia; Rickets; Vitamin D; Vitamin D Deficiency

Immobilization of normal people causes reabsorption of calcium from bone, a small rise in serum ionized calcium, and, rarely, frank hypercalcaemia. The hazard is increased when patients with renal osteodystrophy are immobilized because of pathological fractures.

Topics: Adult; Calcium Carbonate; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Female; Humans; Hypercalcemia; Immobilization; Male; Middle Aged; Renal Dialysis

Topics: Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Kidney Failure, Chronic; Renal Dialysis

Topics: Alkaline Phosphatase; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Hypophosphatemia; Kidney; Osteomalacia; Phosphates; Phosphorus; Phosphorus Metabolism Disorders; Renal Tubular Transport, Inborn Errors; Rickets; Urine; Vitamin D

Topics: Calcium Metabolism Disorders; Chronic Kidney Disease-Mineral and Bone Disorder; Diet; Diet Therapy; Dihydrotachysterol; Humans; Kidney; Rickets; Testosterone

Topics: Amino Acid Metabolism, Inborn Errors; Amino Acids; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Hydromorphone; Osteoporosis; Rickets