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

A 49-year-old woman undergoing long-term hemodialysis and treated with deferoxamine (DFO) 1.5 g twice weekly for aluminum bone disease developed fever and bilateral calf pain caused by myonecrosis with gas gangrene. She had a rapidly fatal outcome. The cultures of blood and aspirates from both calf muscles demonstrated Aeromonas hydrophila. No obvious entry point could be traced. The in vitro growth of the patient's strain was found to be stimulated by the deferoxamine-iron complex in an iron-deprived medium. It is suggested that high-dose DFO therapy in this patient was responsible for promoting a bacterial infection by this microorganism.
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PMID:Fatal Aeromonas hydrophila bacteremia in a hemodialysis patient treated with deferoxamine. 862 37

Increasing use of medications designed specifically for intravenous administration during hemodialysis has dramatically improved the treatment of many comorbid conditions accompanying end-stage renal disease. Recombinant human erythropoietin has resulted in definitive treatment of the hypoproliferative anemia of uremia, while sustained response to this hormone has been facilitated by treatment with intravenous iron dextran. Simple and effective therapies for many gram-positive infections in end-stage renal disease patients have been realized through the favorable pharmacokinetics and low toxicity of vancomycin when administered during hemodialysis. Major improvements in the therapy of high-turnover bone disease have resulted from the increasing use of intravenous calcitriol during dialysis as well. The contributions of these four medications in improving patient care and the benefits of their administration during the dialysis procedure are reviewed.
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PMID:Injectable medications for hemodialysis patients. 871 68

Although the full mechanisms are not yet elucidated, research into the mechanism of toxicity of aluminum (Al) on bone formation and remodeling and on hematopoietic tissue is ongoing. In contrast little information exists on the interactive effects of systemic Al and the kidney. In bone, both clinically and experimentally, high doses of Al inhibit remodeling, slowing both osteoblast and osteoclast activities and producing osteomalacia and adynamic bone disease. In contrast, while very low levels of Al are mitogenic in bones of experimental animals, the effect of low levels of Al in humans is unknown. Aluminum has been shown to have its mitogenic action at the osteoblast, but whether the effect on resorption is viz osteoblast-directed changes in osteoclast activity has not yet been determined. Parathyroid hormone (PTH) levels are disrupted by Al in humans and animals. Whether altered PTH levels play a major or even a minor role in Al-dependent osteotoxicity requires clarification. In hematopoietic tissue, Al causes a microcytic anemia, not reversible by iron. Friend leukemia cells treated with Al have been reported to accumulate excess iron, without incorporating it into ferritin or heme. It is not yet known which steps in iron metabolism are disrupted by Al, if they involve a single mechanism of action, or even if this disruption in iron metabolism accounts for the anemia seen in Al toxicosis. In kidney, research is needed to evaluate Al nephrotoxicity; there are almost no studies in this area. Furthermore, research is needed to evaluate mechanisms of renal Al excretion, presently shown by one study to occur at the distal tubule. Such studies might well throw light on whether Al plays a role in aggravating renal insufficiency, or whether the role of the kidney in Al toxicosis is limited to the causative effect of renal compromise on Al accumulation. In summary, while a number of mechanisms have been proposed for the toxic action of Al, no single mechanism emerges to explain these diverse effects of systemic Al. Recommendations for future research are presented and summarized in Table 1.
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PMID:Systemic aluminum toxicity: effects on bone, hematopoietic tissue, and kidney. 877 4

That bone disease accompanies renal failure has been known for over 100 years. This bone disease (renal osteodystrophy) has been variously attributed to hyperparathyroidism, vitamin D deficiency, aluminium toxicity, iron toxicity, uraemia, and a host of other aetiologies. In addition, the form the bone disease takes has been variously described as osteitis fibrosa, osteomalacia, mixed uraemic osteodystrophy and the aplastic (adynamic) lesion. In this manuscript we will focus on the aetiology, consequences, diagnosis and possible management of the aplastic form of the disease. The renal osteodystrophy study was a prospective, cross-sectional study of renal bone disease in a largely unselected population of patients receiving dialysis in three hospitals in Toronto. A variety of non-invasive data (parathyroid hormone (PTH), aluminium, etc.) and bone histology were obtained and analysed to assess pathogenesis, diagnostic criteria and management. We have defined the aplastic lesion as having low bone formation without a marked increase in unmineralized osteoid (i.e. excluding osteomalacia). We have noted that it may be associated with increased aluminium or little to no aluminium. With increased aluminium the patients have a poorer prognosis both with regards to bone disease and mortality, and they should be managed appropriately to alleviate aluminium toxicity. With lesser amounts of aluminium, morbidity and mortality are less severely impacted, but not normal. We have shown that the low bone formation, of the aplastic lesion without aluminium may be "normalized' by increasing PTH levels. It is concluded that aplastic bone disease carries adverse consequences both in terms of bone problems and survival. In the absence of aluminium toxicity the stimulation of PTH effectively corrects the bone formation abnormality. Whether this will alleviate the adverse consequences will be difficult to study. Avoiding the problem by not over-suppressing PTH seems a reasonable approach at this point.
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PMID:The aplastic form of renal osteodystrophy. 884 Mar 8

The association of haemochromatosis and bone disease is well established, but osteoporotic fracture is an unusual presentation of the disease. We describe a male patient with osteoporotic fractures as a presenting feature of haemochromatosis. The bone histomorphometry showed a dramatic decrease in trabecular bone volume associated with a decrease in cortical bone thickness. Osteoblastic and osteoclastic activities were reduced without any sign of osteomalacia. Staining for iron with Perl's stain showed focal localization at the interface between mineralized trabecular bone and bone marrow. This observation leads us to review the possible mechanisms of osteoporosis.
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PMID:Spontaneous multiple vertebral fractures revealed primary haemochromatosis. 888 26

Renal osteodystrophy (ROD) is a multifactorial disease. Aluminium deposits have been implicated in its physiopathology but iron deposits have seldom been described. The purpose of this study was to investigate the presence of iron on the mineralization front, in 70 patients with ROD. Their mean age was 48+/-16 years, 36 were female, 34 male, 55 were admitted on peritoneal dialysis (78.5%) and 15 to haemodialysis (21.5%), for a period of 28+/-22 months. A bone biopsy was obtained from each patient after double tetracycline labelling. Blood samples were also obtained at the time of bone biopsy. The histomophometric analysis was performed following the criteria of Sherrard et al., with slight modifications; beside the usual stains, aluminium, iron and amyloid stainings were done on all bone specimens. Biochemical findings were: Ca 8.8+/-0.9 mg/dl, P 6.1+/-1.5 mg/dl; total alkaline phosphatase 197+/-258; PTHm 4.9+/-4.05ng/ml (normal 0.4-0.7 ng/ml), calcitonin 11+/-6 pg/ml (normal 1-26 pg/ml). Osteitis fibrosa was found in 31 patients (44.28%), mixed bone disease in two patients (2.28%); mild bone disease in 20 subjects (28.57%), adynamic bone lesion in 15 cases (21.42%) and osteomalacia in two patients (2.28%). Iron deposits were found on the mineralization front in 43 patients (61.4%); in 17, the percentage was <25 and, in 26, >25%. The iron deposits in the osteitis fibrosa group were highly significant (25/31). The aluminium deposit at the mineralization front was observed in eight patients (11.4%); in all but one, the percentage of this metal was <10%. Amyloid deposits were negative in all cases. The results show: (i) a Mexican population with ROD, present a highly significant incidence of siderosis on the bone mineralization front; (ii) in contrast, the aluminium deposits in this group of patients is lower than that reported in other series, and (iii) the spectrum of RO in this Mexican population is similar to that reported in other studies.
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PMID:High frequency of iron bone deposits in a Mexican population with renal osteodystrophy. 956 20

As thalassemia patients age, bone disease becomes a serious cause of morbidity. The frequency and type of bone disease is affected by the underlying type of thalassemia and its treatment. Problems include rickets, scoliosis, spinal deformities, nerve compression, fractures and severe osteoporosis. In early stages, patients may be asymptomatic but can present with back pain, a limp, dyspnea, neurological emergencies, or sudden fractures. The etiologies are often multifactorial, culminating with increased bone resorption and remodeling. They include hormonal deficiency, bone marrow expansion, nutritional deficiency, or desferal toxicity. Particular risk factors include older patients, low baseline hemoglobin, delayed puberty, hormonal failure, and high iron stores. Nutritional deficiencies may further compound the patient's risk for bone disease. Increasing evidence suggests that these complications and their associated long-term morbidity can be prevented if an annual screening is done, followed by long-term intervention. Patients treated with amino biphosphonates inhibit bone resorption and may demonstrate rapid healing. Intra-nasal calcitonin has also been successful in treating osteopenia. Early use of estrogen and testosterone appears to markedly lower the risk for selective patients. Both transfused and non-transfused patients should be educated about risk factors and early symptoms. All patients should be screened annually for bone disease. Once adolescence occurs, annual testing in selected cases should include bone density studies with X-ray absorptiometry.
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PMID:The morbidity of bone disease in thalassemia. 966 56

Cooley's original description of beta-thalassaemia major included marked bone deformities as a characteristic feature. These were thought to be due to expansion of haemopoiesis attempting to compensate for the congenital anaemia. Regular blood transfusions from infancy prevents these skeletal problems. Nevertheless, symptoms due to bone disease frequently occur in adult patients. Osteoporosis has not previously been reported as a cause of severe morbidity in thalassaemia major. The present study shows a high prevalence of low bone mass among thalassaemia major patients and analyses the predisposing causes. Bone density scans were performed in 82 patients with transfusion-dependent beta thalassaemia. Factors known to be associated with low bone mass such as gender, endocrine disorders and lifestyle activities, together with factors specific to the thalassaemia and its management, were included in a series of univariate analyses to ascertain any significant associations. 42 (51%) of the patients had severely low bone mass and a further 37 (45%) had low bone mass. The three factors showing a statistically significant association with severely low bone mass were male sex, 24/38 (63%) males had severely low bone mass, compared with 18/44 (41%) females, the lack of spontaneous puberty, 22/32 (69%) who required therapeutic induction of pubertal development had severely low bone mass, compared with 19/47 (40%) with spontaneous puberty and diabetes, 8/10 (80%) diabetic patients had severely low bone mass, compared with 23/56 (41%) with normal glucose tolerance. There was no association between the bone mineral density measurements and the haematological characteristics or treatment details of these patients. Severely low and low bone mass are common findings in patients with beta-thalassaemia major despite optimal transfusion and iron chelation. The associated features suggest that the severely low bone mass is due to endocrine abnormalities, in contrast to the haematological causes of bone disease characteristically seen in untreated thalassaemics.
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PMID:High prevalence of low bone mass in thalassaemia major. 988

Phosphate binders that contain aluminum or calcium are frequently prescribed to treat hyperphosphatemia in patients with end-stage renal disease (ESRD), but an accumulation of aluminum can lead to encephalopathy, aluminum-related bone disease (ARBD) such as osteomalacia, anaemia, and resistance to erythropoietin, and calcium accumulation can lead to hypercalcaemia. High phosphate concentrations are reduced in vitro and in vivo by a phosphate adsorption pill, which is synthesized by hydrolyzing ferrous sulfate in the presence of saccharides, to form an iron (III)-saccharide complex that is acid resistant and binds phosphate greater than iron (III) hydroxide alone. Under in vitro conditions, containing 3.26 mg P/dL, the iron (III)-sucrose complex showed the highest phosphate adsorption capacity at pH 2 with artificial gastric juice, 58.9 mg P/g binder. For the 7 day in vivo study, 0% (Group 1), 1% (Group 2), 4% (Group 3), and 8% (Group 4) iron (III)-sucrose complex was admixed into the rodent chow by weight and fed to 15 male Wistar rats. The weight and volume of the feces and urine, and the calcium, iron, and phosphorus excretions in the feces and urine samples were monitored for any signs of irregularity. Total urine outflow was collected during a 24-h period to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The fecal iron excretion was significantly effected by the amount of binder ingested throughout the study for Group 2 (p < 0.001), Group 3 (p < 0.01), and Group 4 (p < 0.001). The urinary calcium excretion (mg/rat/24-h) significantly increased by the 7th day for Group 2 (p < 0.05) and Group 4 (p < 0.01) in comparison to the control. Finally, after 7 days, there was a significant drop in the urinary phosphorus levels (mg P/rat/24-h) in a dose dependent manner for Group 2: from 7.82 +/- 1.46 to 1.98 +/- 0.10 mg P/rat/24-h (102 mg P/dL/24-h; p < 0.05); Group 3: from 6.70 +/- 1.14 to 0.16 +/- 0.09 mg P/rat/24-h (6.0 mg P/dL/24-h; p < 0.01); and Group 4: from 8.25 +/- 0.67 to 0.04 +/- 0.01 mg P/rat/24-h (0.9 mg P/dL/24-h; p < 0.01). The results show that this new adsorbent might provide an alternative to conventional aluminum and calcium containing phosphate-binding agents for combating hyperphosphataemia.
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PMID:Oral phosphate binders: phosphate binding capacity of iron (III) hydroxide complexes containing saccharides and their effect on the urinary excretion of calcium and phosphate in rats. 1051 89

Adynamic bone disease (ABD) has an increasing prevalence in the dialysis population, more so in peritoneal dialysis patients. Anemia in patients with high turnover bone disease and high intact parathyroid hormone (iPTH) tends to be resistant to recombinant human erythropoietin (rHuEPO). The same problem may occur in patients with ABD; however, data are scarce. This study evaluates the effectiveness of rHuEPO in 32 chronic peritoneal dialysis patients, 9 with iPTH levels below 100 pg/mL for more than 6 months (group A, with ABD) and 23 with iPTH levels above 100 pg/mL (group B, without ABD). In group A and group B respectively, the dosage of rHuEPO was 141.8 +/- 59 U/kg/week and 144.8 +/- 77 U/kg/week, and hematocrit was 33.2% +/- 4.3% and 31.7% +/- 4.5% (p > 0.05). Iron indices, nutritional parameters, and bone indices were similar, except that group A had lower alkaline phosphatase and serum ferritin levels. The data suggest that patients with ABD may not be resistant to rHuEPO, but may even have a slightly better hematocrit at a similar rHuEPO dosage. Further studies in a larger number of patients are needed to confirm these findings.
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PMID:Influence of adynamic bone disease on responsiveness to recombinant human erythropoietin in peritoneal dialysis patients. 1104 14


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