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)

The density of bone in the distal third of the radius is measured by I-125 photon absorptiometry in 38 RDT (Regular Dialysis Treatment) patients (19 mean and 19 women, age range from 17 to 65 years). In the majority of patients the bone density (BMC/W) is reduced. The clinical follow-up of dialysis patients demonstrates that the incidence and severity of clinical symtpoms do not always correlate closely with the bone density values, nor with the biochemistry and histopathological findings of bone disease associated with dialysis. Despite control of calcium and phosphorus metabolism, decreased mineralization of the appendicular skeleton persists. The advantages as well as disadvantages of bone density measurements in RDT patients are discussed.
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PMID:I-125 photon absorptiometric analysis of bone density in patients with regular dialysis treatment. 49 24

Osteopenia is frequently encountered in the course of idiopathic haemochromatosis. In order to establish the mechanism of this bone disorder, the following parameters were studied in nine diabetic patients wih idiopathic haemochromatosis: (i) the intestinal calcium absorption measured by using a double radiotracer technique; (ii) the bone mineral content (BMC, mg/cm2) determined on the forearm by the Cameron's absorptiometric technique, (iii) the plasma 25 hydroxyvitamin D (25-OH-D ng/ml) by a competitive protein-binding radioassay. The results were compared to those obtained in ten controls and in eight diabetics without haemochromatosis. The patients suffering from haemochromatosis had a significant fall in total fractional absorption of calcium and BMC as compared with controls and diabetics without haemochromatosis. Furthermore plasma 25-OH-D was significantly lower in haemochromatosis patients (5.1 +/- 0.6 ng/ml) than in controls (16.4 +/- 1.3 ng/ml, P less than 0.01) and in diabetics without haemochromatosis (14.2 +/- 1.4 ng/ml, P less than 0.02). These results indicate that haemochromatosis patients exhibit important disturbances in calcium homeostasis, i.e. low concentration of plasma 25-OH-D and reduced intestinal absorption of calcium. The latter abnormalities may well be related to the bone rarefaction observed in these patients.
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PMID:Evidence for 25-hydroxyvitamin D deficiency as a factor contributing to osteopenia in diabetic patients with idiopathic haemochromatosis. 678 13

The therapy of Paget's bone disease is essentially based on the use of calcitonin and diphosphonates: both drugs, if used in large doses for long periods, have shown themselves able to provoke particular side-effects. It was, therefore, decided to study the therapeutic efficacy of combined low-dosage treatment using synthetic salmon calcitonin and sodium-etidronate on a group of patients with Paget's osteodystrophy. A clear evident diminution in plasma alkaline phosphatase, hydroxyprolinuria and whole body retention (WBR) of MDP-Tc99m was observed, demonstrating a reduction of metabolic turnover in the bone. No changes in the bone mass (BMC), evaluated by bone mineral detector, were observed at the end of treatment. With this treatment the plateau effect was shown to be appreciably less than normally occurs when either calcitonin or sodium etidronate are used alone.
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PMID:[Effects of the combined calcitonin and sodium etidronate therapy in Paget's disease of bone]. 680 55

Bone scintigraphy and densitometry (iodine-125 photon absorptiometry) were performed in eight patients with symptomatic haemodialysis bone disease. The bone scintiscan showed either hot spots or hyperactivity as a feature of metabolic bone disease. The bone density (BMC/W) was reduced, but could not be distinguished from the degree of demineralisation found in asymptomatic patients on long-term haemodialysis. Therefore, bone density measurements require critical interpretation. Complementary bone scintigraphy should be used in symptomatic haemodialysis bone disease for assessing the extent of the disease.
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PMID:Bone scintigraphy and densitometry in symptomatic haemodialysis bone disease. 732 86

From a random sample of our institution's health maintenance organization (HMO), we recruited 250 white women and 112 black women, aged 55-75, all of whom were 10 or more years postmenospause with minimal estrogen exposure and free of osteoporosis, other metabolic bone disease, and medical, surgical, or therapeutic situations that may influence bone loss. Bone mass was measured in the radius, spine, and femur by DXA and in L1 by QCT. Serum samples were analyzed for parathyroid hormone, calcidiol, calcitriol, osteocalcin, and bone alkaline phosphatase and urine samples analyzed for creatinine, calcium, and hydroxyproline. Mean Z score, based on published reference data for forearm and femoral neck BMD in the white women, was not significantly different from zero, but mean Z score at the lumbar spine was 0.6 (p < 0.001), 17.2% of the individual values being > 2.0. In normal white women (BMI < 27.3, n = 143), Z score was still > 2.0 in 10.3%, suggesting that the upper bound of the published reference interval may be too low. After adjustment for body mass index, BMD was greater in the forearm (9.8%), spine (8.7%), and femoral neck (14.7%) in black women (p < 0.001 at all sites). At L1, adjusted BMC in the black women was 37.4% greater than in the white women (p < 0.001). Serum calcidiol was significantly lower and serum PTH and calcitriol significantly higher in the black women. Despite this, biochemical markers of bone resorption and formation were significantly lower in the black women. We conclude that skeletally healthy older black women have a greater bone mass and lower rates of bone remodeling than a comparable group of white women. These data can serve as reference intervals for the variables measured.
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PMID:Reference data for bone mass, calciotropic hormones, and biochemical markers of bone remodeling in older (55-75) postmenopausal white and black women. 797 9

Osteopenia is a common complication in primary biliary cirrhosis (PBC). In this follow-up study the authors investigated the metabolic bone disease in postmenopausal PBC patients. 17 Ca and vitamin D supplemented, postmenopausal female patients with PBC (stage II-IV, age: 41-84, mean: 52, each AMA M2 positive, without ascites) were followed-up for an average of 6.3 years. Bone mineral density (BMD) was measured yearly by dual energy x-ray absorptiometry (XR26, Norland) in lumbar spine (L2-4), femoral neck (FN), and radius BMC by single photon absorptiometry. Urinary pyridinoline/creatinine (Pyr/c) and deoxypyridinoline/creatinine ratio (D-Pyr/c) by HPLC, 25-OH-D3 level and standard liver function tests were monitored in all patients. At the beginning the BMD was decreased in 7 out of 17 patients (T-score < -2.5). The mean BMD was 0.885 SD +/- 0.26 g/cm2 in L2-4, 0.725 +/- 0.16 g/cm2 in FN and the BMC 0.703 +/- 0.14 g/cm in the radius. During follow-up the rate of annual bone loss was increased in patients with osteoporosis at the start of this study. There was a correlation between the urinary Pyr/c and D-pyr/c values and the annual rate of bone loss in patients with PBC (r: -0.79; p < 0.01). In patients with severe osteoporosis at the time of the diagnosis of PBC a more pronounced progression of bone loss was observed during the follow-up period.
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PMID:[Follow-up study of bone mineral density in postmenopausal patients with primary biliary cirrhosis]. 1128 76

BACKGROUND: Recently, radiopharmaceutical scanning with Tc-99m-MIBI was reported to depict areas with active bone disease in multiple myeloma (MM) with both high sensitivity and specificity. This observation was explained by the uptake of Tc-99m-MIBI by neoplastic cells. The present investigation evaluates whether Tc-99m-MIBI imaging and magnetic resonance imaging (MRI) perform equally well in detecting myelomatous bone marrow lesions. METHODS: In 21 patients with MM, MRIs of the vertebral region TH12 to S1 and whole body scans with Tc-99m-MIBI were done. RESULTS: Tc-99m-MIBI scanning missed bone marrow infiltration in 43 of 87 vertebrae (50.5%) in which MRI showed neoplastic bone marrow involvement. In patients with disease stage I+II, Tc-99m-MIBI scanning was negative in all of 24 vertebrae infiltrated according to MRI. In patients with disease stage III, Tc-99m-MIBI scanning detected 44 of 63 (70%) vertebrae involved by neoplastic disease. CONCLUSION: Tc-99m-MIBI scanning underestimated the extent of myelomatous bone marrow infiltration in the spine, especially in patients with low disease stage.
BMC Nucl Med 2003 Dec 11
PMID:Comparison of Technetium-99m-MIBI imaging with MRI for detection of spine involvement in patients with multiple myeloma. 1467 90

Bone mineral density (BMD) and content (BMC) were measured in 208 institutionalised patients with refractory epilepsy. BMD was in the osteoporotic range in 43% of males and 21% of females. BMC was reduced only in male patients. Apart from age and gender, no other factor or specific AED was particularly associated with reduced BMD or BMC. This study indicates the magnitude of the problem of bone disease in refractory epilepsy, in particular affecting young and male patients with chronic epilepsy.
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PMID:Bone mineral density in institutionalised patients with refractory epilepsy. 1740 80

Adults with beta thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, > or =6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X-ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty-one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1-75 yr), were studied. Spine and femur BMD Z-scores < -2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty-six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.
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PMID:Bone disease in thalassemia: a frequent and still unresolved problem. 1850 76

Chronic uremia is characterized by decreased levels of plasma 1,25(OH)2D3 due to decreased renal 1-hydroxylase activity and by decreased renal phosphate excretion. The consequence is an increased synthesis and secretion of parathyroid hormone--secondary hyperparathyroidism--due to the low levels of plasma calcium, low levels of plasma 1,25(OH)2D3 and high levels of phosphate. The association between renal bone disease and chronic renal failure is well described. Epidemiological studies have indicated that an association also exists between secondary hyperparathyroidism and increased mortality and cardiovascular calcifications in chronic uremic patients. Treatment of secondary hyperparathyroidism in chronic uremia focuses on avoiding hyperphosphatemia by the use of oral phosphate binders, which bind phosphate in the intestine and a concomitant substitution by a 1 alpha-hydroxylated vitamin D analog in order to compensate for the reduced renal hydroxylation. Additional treatment with aluminum containing phosphate binders to overcome phosphate absorption and retention was initiated already in the 1960s and used extensively until aluminum toxicity was disclosed in the mid-1980s. Instead calcium carbonate and calcium acetate were used as phosphate binders. Until recently, the most commonly used active vitamin D drug was either the natural 1,25(OH)2D3, or the 1 alpha-hydroxylated analog, 1alpha(OH)D3 which after 25-hydroxylation in the liver is converted to 1,25(OH)2D3. 1alpha(OH)D3 was produced by LEO Pharma in 1973. The two vitamin D analogs were used in different geographical areas: In Europe 1alpha(OH)D3 was mainly used, while 1,25(OH)2D3 was mainly used in the USA. 1,25(OH)2D3 increases the intestinal absorption of calcium and improves skeletal abnormalities. The combined treatment with calcium containing phosphate binders and active vitamin D induces an increase in plasma Ca 2+ and hypercalcemia became a clinical problem. Subsequently therefore, dialysis fluid with a reduced calcium concentration ("low-calcium") was introduced. In 1981 Madsen et al. [148] demonstrated for the first time a direct suppressive effect of intravenous 1,25(OH)2D3 on plasma PTH in acutely uremic patients. In 1984, Slatopolsky et al. [74] demonstrated that intravenous 1,25(OH)2D3 induces a marked suppression of plasma PTH with no increase in plasma Ca 2+ in chronic uremic patients. In the middle of the 1980s, 1alpha(OH)D3 became available not only as an oral, but also as an intravenous formulation. The main purpose of the present studies was to increase the knowledge of the action and effects of different treatment regimes with 1alpha(OH)D3, and thereby to improve the prophylaxis and treatment of secondary hyperparathyroidism in uremic patients on chronic dialysis. 168 patients on chronic dialysis treatment and six healthy volunteers were included in the seven studies included in this thesis. The first part of the studies, focused on short- (12 weeks) and long-term (103 weeks) effects of intravenous 1alpha(OH)D3 on plasma PTH and plasma Ca 2+ in relation to the doses of 1alpha(OH)D3 given. Further, it was examined whether the marked suppression of plasma PTH induced by 300 days of intermittent intravenous treatment with 1alpha(OH)D3, could be maintained when the administration was changed from intravenous to the oral route for 16 further weeks and then shifted back to intravenous administration for another 16 weeks. The second part focused on long-term effects (88 weeks in hemodialysis patients and 52 weeks in CAPD patients) of a treatment modality combining 1alpha(OH)D3, and CaCO3 as phosphate binders instead of aluminum containing compounds and a decreased calcium concentration in the dialysis fluid to 1.25 mmol/l in an attempt to avoid development of hypercalcemia. The third part focused upon the pharmacokinetic differences between intravenous and oral administration of 1,25(OH)2D3 and 1alpha(OH)D3 and upon the acute effects of different doses of the two compounds on the plasma levels of PTH, Ca 2+ and phosphate. Plasma PTH is a biochemical parameter most often used for the diagnosis and monitoring of bone disease in patients with chronic uremia. The level of plasma PTH measures depends on the assay used. More specific assays measuring only whole PTH 1-84 without co-measuring large C-terminal fragments have been developed. In this thesis, five different assays were used - one "N-terminal", one "C-terminal", two "Intact" and one "Whole" PTH assay. Each sample was analyzed by 1-3 different assays. Based on the results of my studies [1-7], it is concluded that: 1a. Intravenous administration of 1alpha(OH)D3 induces a marked suppression of plasma PTH without causing serious side-effects in patients on chronic hemodialysis. It is possible to prevent hypercalcemia by closely monitoring plasma Ca 2+ levels and by adjusting the dose of 1alpha(OH)D3 accordingly. 1b. Long-term intermittent intravenous treatment with 1alpha(OH)D3 was effective in suppressing plasma levels of Intact PTH. 1c. When plasma intact PTH was suppressed to a stable level by intravenous 1alpha(OH)D3 the suppression could be maintained by intermittent oral 1alpha(OH)D3 therapy. It was not examined whether a similar degree of suppression of severe secondary hyperparathyroidism could be induced by intermittent oral 1alpha(OH)D3 treatment alone. The responses following chronic intravenous or oral administration of 1alpha(OH)D3 on circulating levels of intact PTH and N- and C-terminal PTH fragments did not reveal any significant differences between the two routes of administration on the actions on the parathyroid glands. 2a. The combination of "low-calcium" hemodialysis fluid (1.25 mmol/l), CaCO3 as a phosphate binder, and intermittent intravenous 1alpha(OH)D3 prevented development of secondary hyperparathyroidism in uremic patients with normal PTH at the initiation of the study and induced a long-term suppression of PTH in patients with secondary hyperparathyroidism. No clinical or biochemical indications of development of adynamic bone disease were observed. Intravenous administration of 1alpha(OH)D3 prevented a decrease of BMC in the lumbar spine and femoral neck of hemodialysis patients both with normal and with elevated PTH levels. It was possible to use larger doses of CaCO3 and to reduce, but not exclude, the use of aluminum-containing phosphate binders in combination with intravenous administration of 1alpha(OH)D3. A decrease of plasma Ca 2+ was induced during dialysis, and special care had to be taken on the compliance of the patients as to the use of CaCO3 binders in order not to aggravate secondary hyperparathyroidism. 2b. In patients on CAPD, the use of low-calcium dialysis (1.25 mmol/l) made it possible to use larger doses of CaCO3 phosphate binders and to reduce, but not exclude, the use of aluminium containing phosphate binder in combination with oral pulses of 1alpha(OH)D3. A negative calcium balance was induced, and it is therefore recommended that a reduction of the calcium concentration in the dialysis fluid is only used in patients under strict control. 3a. The metabolic clearance rate of 1,25(OH)2D3 was 57% lower in uremic patients than in normal subjects (p < 0.03). The bioavailability of 1,25(OH)2D3 in both normal subjects and uremic patients was markedly lower following administration of 1alpha(OH)D3 both intravenously and orally than after administration of oral 1,25(OH)2D3. Despite lower plasma 1,25(OH)2D3 levels after administration of 1alpha(OH)D3 than after 1,25(OH)2D3, no significant difference was observed in the PTH suppressive effect in uremic patients of 4 mug intravenously of either of the two vitamin D analogs. 3b. A single intravenous high dose of 10 mug of 1alpha(OH)D3 or 1,25(OH)2D3 significantly suppressed plasma PTH. The acute suppressive effect of 1,25(OH)2D3 was three times greater than that of 1alpha(OH)D3.The increase in plasma Ca 2+ after intravenous administration of 10 mug 1,25(OH)2D3 was significantly higher than that of 1alpha(OH)D3. Due to the simultaneous effect on plasma Ca 2+ observed it was not possible to decide whether 1alpha(OH)D3 has a direct effect per se on the parathyroid glands or not. The study further did not give any further knowledge about the possible therapeutic equivalence of long-term treatment with 1alpha(OH)D3 or 1,25(OH)2D3. The PTH responses to acute administration of the 1alpha(OH)D3 and 1,25(OH)2D3 analogs were in principle the same when measured by one "whole" PTH and two "intact" PTH assays, namely mainly in a parallel shift of the PTH response curve. In this study on chronic uremic patients circulating levels of large C-terminal PTH fragments were not affected by differences in plasma Ca 2+ concentration or by the intravenous administration of 1alpha(OH)D3 or 1,25(OH)2D3. There is now a general agreement on the importance of carefully controlling plasma phosphate, normalize and avoid increases of plasma Ca 2+, and not to oversuppress PTH during treatment. Focus today is on the potential deleterious role of calcium overloading in the development of vascular calcifications in uremic patients. There is an urgent need for a development of an algorithm for the use of phosphate binders and vitamin D supplementation in combination with calcimimetics focusing upon long term morbidity and mortality in uremic patients.
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PMID:1alpha(OH)D3 One-alpha-hydroxy-cholecalciferol--an active vitamin D analog. Clinical studies on prophylaxis and treatment of secondary hyperparathyroidism in uremic patients on chronic dialysis. 1923 59


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