Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There has been much progress in our understanding of the metabolism of vitamin D. It is now clear that vitamin D3 can be produced in the skin or ingested in the diet. It accumulates very rapidly in the liver where it undergoes 25-hydroxylation, yielding 25-OH-D3, the major circulating metabolite of the vitamin. 25-OH-D3 proceeds to the kidney where it undergoes one of two hydroxylations. If there is a biological need for calcium or for phosphate the kidney is stimulated to convert 25-OH-D3 to the 1,25-(OH)2-D3, a calcium and phosphate mobilizing hormone. If, however, the animal has sufficient supplies of calcium and phosphate, the l-hydroxylase is shut down and instead the 25-OH-D3 is converted to a 24,25-(OH)2D3. The role of the 24,25-(OH)2D3 remains unknown; it may be an intermediate in the inactivation-excretion mechanism. 1,25-(OH)2D3 proceeds to the intestine where it stimulates intestinal calcium transport and intestinal phosphate transport. It also stimulates bone calcium mobilization and probably has other effects yet to be discovered in such tissues as muscle. The 25-OH-D3-l-hydroxylase, which is located exclusively in renal mitochondria, has been shown to be a three component system involving a flavoprotein, an iron-sulfur protein (renal ferredoxin), and a cytochrome P-450. This system has been successfully solubilized, the components isolated, and reconstituted. The 24-hydroxylase, however, has not yet been thoroughly studied. 1,25-(OH)2D3 is necessary for the appearance of the 24-hydroxylase; parathyroid hormone represses 24-hydroxylation. It is possible that the 24-hydroxylase represents the major regulated enzyme, so that its presence or absence may determine whether 1,25-(OH)2D3 is produced. Two metabolic pathways for 1,25-(OH)2D3 are known, conversion by the 24-hydroxylase to 1,24,25-(OH)3D3, and conversion of 1,25-(OH)2D3 to an unknown substance. In the latter instance, there occurs loss of a side chain piece, including at least one of the 26 and 27 carbons. Whether 1,25-(OH)2D3 must be metabolized further before it carries out all of its functions has yet to be established. The primary excretion route of vitamin D3 is via the bile into the feces. Urinary excretion appears small in magnitude and no excretion products have yet been identified positively. Much remains to be learned concerning the metabolism and function of vitamin D and its metabolites. This should therefore, prove to be a fruitful area of investigation for many years to come, especially since 1,25-(OH)2D3, 25-OH-D3, and lalpha-OH-D3 have been shown to be effective in a number of metabolic bone disease states.
 ...
PMID:Metabolism of vitamin D: current status. 18 53

Intakes of calcium, iron, potassium, and magnesium are reported for 77 men and 187 women aged 65 and over and living at home in N. Glasgow. Calcium intakes were below the national average. The importance of milk as a source of calcium and the relevance of calcium intake to bone disease in old age are discussed. Iron intakes were probably adequate, but those of potassium and magnesium may well be below optimum levels.
 ...
PMID:Nutrition of the elderly at home. III. Intakes of minerals. 117 7

Recent advances in renal osteodystrophy deal with the pathogenesis of the disease, in particular in early renal failure, with the mechanisms of skeletal resistance to parathyroid hormone, with the potential role of iron, and with increased knowledge of adynamic bone disease. For the control of phosphatemia, aluminum-containing phosphate binders are more and more avoided, whereas calcium acetate or carbonate are more and more prescribed. X-linked hyphophosphatemia continue to cause great interest as well as the various iatrogenic osteomalacias.
 ...
PMID:Renal osteodystrophy, disorders of vitamin D metabolism, and hypophosphatasia. 159 20

Aluminum (Al) retention in the body can cause metabolic bone disease. This disorder is characterized by reductions in the number of osteoblasts, a feature that suggests a disturbance in bone cell proliferation or differentiation. Because Al as well as iron (Fe) can bind to transferrin (TF) in plasma, the role of TF as a modifier of osteoblast proliferation was examined in UMR-106-01 osteoblast-like cells by measuring the incorporation of tritiated thymidine ([3H]-TdR) into DNA (counts.min-1.microgram cell protein-1, means +/- SE) during 48-h incubations in serum-free medium (SFM). In the absence of TF, DNA synthesis decreased when media levels of Al exceeded 6-10 microM. The mitogenic response to physiological levels of unsaturated TF (apo-TF) was attenuated however during incubations with TF that was partially saturated with Al (Al-TF). A similar inhibitory response was seen in cells incubated with the antiproliferative agent gallium (Ga) when added to SFM as partially saturated Ga-TF. TF produced a shift to the left in the inhibitory dose-response curve to Al in osteoblast-like cells; thus, DNA synthesis decreased at substantially lower media concentrations of Al in cells grown in SFM containing partially saturated Al-TF. The results indicate that TF is an important determinant of the inhibitory effect of Al on DNA synthesis by osteoblast-like cells at the micromolar levels of Al that can occur in plasma in vivo.
 ...
PMID:Transferrin enhances the antiproliferative effect of aluminum on osteoblast-like cells. 201 19

Bone pathology was studied in 27 patients showing either iron or aluminium accumulation in bone. These patients belonged to a group of 120 unselected chronic haemodialysis patients in whom transiliac bone biopsies had been obtained. Group A consisted of 12 patients with bone iron deposits (positive Perls' staining at the calcified bone boundary, CBB) and only minimal aluminium accumulation (bone aluminium below 20 micrograms/g wet weight). Group B included 15 patients with pronounced aluminium accumulation (positive aluminium staining at the CBB and bone aluminium of 20 micrograms/g wet weight or more) and without significant bone iron deposition (negative Perls' staining at the CBB). Bone diseases were classified as early hyperparathyroidism, osteitis fibrosa, mixed disease, osteomalacia, adynamic bone disease or other bone condition using osteoid volume, relative osteoblastic activity (ROBA%), and the presence of fibrosis, as criteria. In group A, 5 of 12 patients showed adynamic bone disease, a fairly uncommon condition in the general population of non-parathyroidectomised dialysis patients. In fact, in a control group of 80 patients without iron and without aluminium overload, only five patients showed adynamic bone disease. In group B, 8 of 15 patients showed osteomalacia, and 2 of 15 presented with mixed disease, which is in agreement with the established relationship between bone aluminium accumulation and the occurrence of defective bone mineralisation. It is concluded that iron overload in dialysis patients is associated with an increased frequency of adynamic bone disease.
 ...
PMID:Iron overload and bone disease in chronic dialysis patients. 212 51

The histological features of thalassemic bone are imperfectly known, and the roles of bone marrow hyperactivity, iron overload or vitamin D deficiency in the pathogenesis of the disease are not clearly identified. In this study we examined iliac crest biopsies from 17 transfusion-dependent children with homozygous beta-thalassemia and severe radiological skeletal thalassemic changes, including widening of medullary spaces and osteoporosis. Rachitic lesions were not observed. Serum ferritin concentrations were increased in all but one subject. Iron deposits were histochemically detected in bone marrow, at the marrow-bone interface, along cement lines and mineralizing perimeters. Minor changes were present in trabecular bone, and osteomalacia was absent. By contrast, cortical bone exhibited severe changes including fissures and focal mineralization defects. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations measured during the winter (December-May, 6.5 +/- 4.9 ng/ml, mean +/- SD, n = 6) and during the summer (June-November, 13.8 +/- 8.4 ng/ml, n = 9) did not differ from those of age-matched children living in the same country. Seven patients had moderate hypocalcemia but no biological signs suggestive of vitamin D deficiency: all had normal alkaline phosphatase activity, normal or slightly elevated plasma phosphate, only two had low plasma 25(OH)D concentrations and two others supranormal values of plasma immunoreactive parathyroid hormone. These results show that iron overload and vitamin D deficiency do not seem to play an important role in the pathogenesis of thalassemic bone disease, which is characterized by cortical lesions probably related to marrow hyperactivity.
 ...
PMID:Bone disease in children with homozygous beta-thalassemia. 230 56

The accumulation of iron or aluminum can cause metabolic bone disease, but the mechanisms by which these agents affect bone metabolism remain uncertain. Since transferrin (Tf) can bind several different metals in plasma, equilibrium radioligand binding studies were performed to identify and characterize the Tf receptor in UMR-106-01 osteoblast-like cells; the role of Tf as a modifier of metal-induced changes in cell proliferation was also examined. Osteoblast-like cells grown in serum-free medium have approximately 40,000 Tf receptors on the cell membrane. Tf receptor expression increases during iron depletion and decreases with iron supplementation; the number of Tf receptors was also inversely related to both cell density and the rate of cell proliferation in vitro. Physiological levels of unsaturated Tf (5 microM) enhanced DNA synthesis in osteoblast-like cells maintained in serum-free medium, as measured by the incorporation of tritiated thymidine into DNA. Although neither 10 microM iron (Fe) nor 10 microM gallium (Ga), a known antiproliferative agent, altered DNA synthesis in UMR-106-01 cells during 48-h incubations in serum-free medium, both agents reduced the rate of DNA synthesis when added to serum-free medium containing 5 microM apo-Tf. Decreases in the incorporation of [3H] thymidine into DNA were also noted in osteoblast-like cells incubated for 48 h with 3 microM partially saturated iron Tf or gallium Tf. The results indicate that osteoblast-like cells have a single class of membrane receptors for Tf and that the regulation of Tf receptor expression in UMR-106-01 cells is similar to that in other cell types. The uptake of iron and gallium via the Tf-receptor complex can affect osteoblast proliferation, and such a mechanism may contribute to the bone cell toxicity of various metals.
 ...
PMID:Characterization of the transferrin receptor in UMR-106-01 osteoblast-like cells. 230 25

Cobalamin deficiency has well-known hematologic and neurologic effects, but little is known about its other effects. We therefore studied the effect of cobalamin on osteoblast-related proteins. We found that mean (+/- 1 SD) levels of skeletal alkaline phosphatase in the blood were lower in 12 cobalamin-deficient patients (3.89 +/- 2.19 units per liter) than in 5 nondeficient and 5 iron-deficient control subjects (7.55 +/- 3.99 units per liter). The degree of the megaloblastic anemia correlated with the reduction in skeletal alkaline phosphatase levels (r = 0.67, P less than 0.01). With cobalamin therapy, levels of skeletal alkaline phosphatase rose in 11 of the 12 cobalamin-deficient subjects but not in the controls. The cobalamin-deficient patients also had significantly lower osteocalcin levels than the control subjects (1.11 +/- 0.77 vs. 1.84 +/- 0.49 nmol per liter). During cobalamin therapy, these levels rose in the cobalamin-deficient patients but not in the controls. In contrast to the levels of osteoblast-related proteins, hepatic alkaline phosphatase levels were similar in the patients and controls and were usually unaffected by cobalamin therapy. In vitro studies of calvarial cells from chicken embryos showed that their alkaline phosphatase content was cobalamin-dependent, thus supporting our in vivo observations in humans. Our findings suggest that osteoblast activity depends on cobalamin and that bone metabolism is affected by cobalamin deficiency, but we do not yet know whether cobalamin deficiency produces clinically important bone disease.
 ...
PMID:Cobalamin and osteoblast-specific proteins. 326 8

Only rather recently has the biologic and pathogenetic relevance of aluminum, this most common metal come under serious scientific scrutiny. Various laboratory findings of accumulations of aluminum in the brain, kidney, liver, parathyroid glands, skeletal muscle, heart, lungs, pancreas and spleen as well as stainable aluminum in bone have spurred widespread interest in aluminum absorption and toxicity and in the mechanisms involved in the metabolism of aluminum. Since the kidney is the major excretory organ for aluminum, this report focuses on the abnormalities occurring with aluminum accumulation in the bone of patients with renal failure to determine the metabolic interrelationships of aluminum, parathyroid hormone, vitamin D, iron, and calcium. This editorial presents an overview of the most recent investigations of aluminum accumulation in humans, experimental animal models, and at the cellular level, presents the metabolic relationships known to exist as well as those strongly suggested in documented studies, and identifies those aspects of aluminum-related bone disease awaiting study in this increasingly important field of inquiry. The study outlines the metabolism of aluminum, the pathogenesis, prevalence, morbidity and mortality of aluminum-related bone disease, the histopathology of bone with aluminum accumulation, the recognized difficulties inherent in the diagnosis of aluminum-related bone disease, and the current understanding as relates to prevention and therapy.
 ...
PMID:Aluminum-related bone disease. 334 41

During a 19-month period we determined the incidence of bacterial infection among 39 patients treated with desferrioxamine who had end-stage renal disease and were undergoing maintenance hemodialysis. Twenty-three received desferrioxamine because of aluminum-related bone disease, and 16 because of iron overload. A control group of 193 patients on maintenance hemodialysis but without desferrioxamine was used. No difference was found in the incidence of septicemia or of all bacterial infections between the patients with aluminum-related bone disease treated with desferrioxamine and the control patients (0.12 vs. 0.12 septicemia per patient-therapy-year, p greater than 0.05; 0.23 vs. 0.26 bacterial infections per patient-therapy-year, p greater than 0.05). The incidence of septicemia in patients treated with desferrioxamine for iron overload, however, was almost three times that in the control patients (0.36 vs. 0.12 septicemia per patient-therapy-year, p less than 0.01). To assess the effect of iron overload itself, we determined the frequency of bacterial infection in patients on regular hemodialysis who have never received desferrioxamine. These were subdivided into three groups according to serum ferritin level which indicated normal or low iron stores (Group I: serum ferritin 10-330 micrograms/l, n = 125), moderate (Group II: serum ferritin 331-1000 micrograms/l, n = 49) or more advanced iron overload (Group III: serum ferritin 1001-2000 micrograms/l, n = 10). Compared to patients with normal or low serum ferritin levels (Group I), we found a significantly higher rate of bacterial infection among patients in Group II compared with Group I (0.18 vs. 0.34 infections per patient-therapy-year, p less than 0.05) and Group III compared with Group I (0.18 vs. 0.58 infections per patient-therapy-year, p less than 0.01). These results suggest that treatment with desferrioxamine does not favour the development of septicemia or bacterial infection independently of iron overload and that iron overload itself may predispose patients on regular hemodialysis to bacterial infection.
 ...
PMID:Iron overload, but not treatment with desferrioxamine favours the development of septicemia in patients on maintenance hemodialysis. 345 53


1 2 3 4 5 6 7 8 9 Next >>