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 marked direct suppression of primary hyperparathyroidism with osteitis fibrosa cystica has been achieved by the intravenous administration of 1,25-dihydroxycholecalciferol [1,25(OH)2D]. In a recent survey of 306 patients with primary hyperparathyroidism (PHPT), we hypothesized that the far higher degree of parathyroid hormone (PTH) hypersecretion in PHPT with osteitis fibrosa cystica than in PHPT without overt bone disease might be due to the absence of suppression of hormonal hypersecretion by the low-to-normal circulating 1,25(OH)2D reflecting a relative vitamin D deficiency. To test this hypothesis, a patient having hypercalcemic PHPT with florid osteitis fibrosa cystica and normal serum 1,25(OH)2D was given increasing daily doses of intravenous calcitriol (0.5-2 micrograms) for several days. Doubling the level of circulating 1,25(OH)2D from 48 to 100-114 pg/ml was accompanied by a marked decline (46%) in serum iPTH(1-84), without a change in the serum calcium concentration. A lowered set point of parathyroid cells for calcium, and a diminished maximum secretory rate of PTH, may contribute to the marked suppression of PHPT.
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PMID:Marked direct suppression of primary hyperparathyroidism with osteitis fibrosa cystica by intravenous administration of 1,25-dihydroxycholecalciferol. 261 19

This study represents the first randomized prospective, double-blind, placebo-controlled trial of the efficacy of 1,25(OH)2D3 on bone histology and serum biochemistry in patients with mild to moderate renal failure. Sixteen patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min) received either 1,25(OH)2D3, at a dose of 0.25 to 0.5 microgram daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. 1,25(OH)2D3 treatment was associated with a significant fall in serum phosphorus and alkaline phosphatase concentrations as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of 1,25(OH)2D3 was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.
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PMID:1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial. 265 58

Major contributions to and confirmations of osteoclast biology have been made by experimental investigations of the osteopetrotic mutations in mammals. Congenital osteopetrosis is a bone disease characterized by a generalized increase in skeletal mass due to decreased osteoclast function. Abnormalities of skeletal growth and the failures of marrow cavity development and tooth eruption are secondary to reduced bone resorption of heterogeneous cause. Elucidation of pathogenetic pathways and unraveling of the cell biology of the osteoclast have proceeded hand-in-hand. This is illustrated by the variable differentiation and activation of osteoclasts among mutations and by demonstrations that the disease in certain animals and children can be cured by providing competent stem cells for osteoclasts via bone marrow transplantation. Congenital absence of carbonic anhydrase II (CA II) in children results in a syndrome that included osteopetrosis because osteoclasts are unable to function in the absence of CA II. The resistance of all mutations to the hypercalcemic effects of parathyroid hormone and recent reports of elevated blood levels of 1,25 dihydroxyvitamin D have broadened the scope of pathogenetic possibilities for osteopetrosis and regulatory possibilities for osteoclasts. Immunological effects including reductions in natural killer cell activity, superoxide and interleukin-2 production make osteopetrotic mutants potential models for studying the role of the immune system in osteoclast biology. Furthermore, coexistence of osteopetrosis with rickets and osteoblast abnormalities and the failure of cell transplants to cure the disease in some mutations illustrate the utility of the osteopetroses for exploring the role of matrix as mentor in osteoclast biology. Thus, understanding congenital osteopetrosis and osteoclast biology are likely to continue together.
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PMID:Osteoclast biology: lessons from mammalian mutations. 268 80

The value of calcitriol administration in the management and prevention of renal bone disease was studied in a prospective double-blind manner in 16 patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min). They were given either calcitriol at a dose of 0.25 to 0.5 micrograms daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had biochemical or radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. Calcitriol treatment was associated with a significant fall in serum phosphorus concentrations and alkaline phosphatase levels as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of calcitriol was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.
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PMID:Early therapy of renal bone disease with calcitriol: a prospective double-blind study. 269 94

In 23 very low birth weight infants the influence of mineral supplementation with 0.4 mmol calciumgluconate and 0.2 mmol glucose-1-phosphate/dl human milk on concentrations of 25-OH-D3, parathyroid hormone, calcitonine, calcium, phosphorus and activity of alkaline phosphatase was studied on days 3, 8, 28 and 56. On days 28 and 56 respectively, degree of bone mineralisation was classified. 8 preterm infants received supplementation before day 28, 7 infants after day 28, 8 infants had no supplementation. All preterm infants received beginning with day 7 vitamin D3 1000 IU/day. In all preterms mean concentrations of 25-OH-D3 were normal and increasing with age. Concentrations of parathyroid hormone and calcitonine were first of all increased and decreased with age, especially in supplemented infants. Light metabolic bone disease without fractures occurred in 4 infants of supplemented groups. Non-supplemented group contains 5 infants with severe metabolic bone disease without fractures. Results indicate intact metabolism and secretion of 25-OH-D3, parathyroid hormone and calcitonine. Decrease of calcitonine concentration in mineral supplemented preterms is a reference to a better mineral supply. Mineral supplementation is followed by an increase in bone mineralisation with prevention of severe metabolic bone disease.
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PMID:[The effect of osteopenia prevention in very small premature infants on hormonal parameters of calcium metabolism and bone mineralization]. 273 43

Although hypercalcaemia in young children or adolescents immobilized by fractures or spinal cord injury is well recognized, hypercalcaemia in adult immobilized patients is rare without a pre-existing bone disease. To our knowledge, hypercalcaemia in a head-injured, immobilized patient has not been previously reported. We report here a case where a previously normocalcaemic, immobilized, head-injured adult patient developed cognitive decline secondary to hypercalcaemia five months after injury, when transient interruption of enteral feedings led to mild dehydration. Indices of bone turnover were elevated and parathyroid hormone was appropriately suppressed. Possible predisposing factors in our patient included a severe degree of immobilization and a very high level of athletic activity prior to injury. Careful fluid management and specific monitoring of calcium levels, even several months post-injury, should be performed to avoid the added complications of hypercalcaemia in head-injured patients.
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PMID:Hypercalcaemia causing declining cognitive function in a head injured patient. 275 93

Aluminum toxicity in dialysis patients is associated with decreased bone turnover and a relative parathyroid hormone (PTH) deficiency. Desferrioxamine (DFO), a chelating agent, has been reported to improve bone histology in aluminum associated, low turnover bone disease in dialysis patients not subjected to parathyroidectomy. Information on the effect of DFO therapy on parathyroid gland function is lacking. In the present study, in addition to changes in bone histology, parathyroid gland function was evaluated in 18 hemodialysis patients with aluminum associated, low turnover bone disease (osteomalacia and aplastic bone disease) before and after one year of DFO treatment (1 to 6 g/week). Parathyroid gland function was assessed by using a calcium free and high calcium (3.5 to 4 mEq/liter) hemodialysis bath.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Desferrioxamine therapy in hemodialysis patients with aluminum-associated bone disease. 277 Jan 15

Osteocalcin (OC), also called Bone Gla Protein (BGP), is a bone matrix protein of 5800 MW synthesized by osteoblasts. Since OC is mainly metabolized in the kidney, its blood concentration is altered in renal failure. The relationship between OC and the calcium-phosphorus regulating hormones (parathyroid hormone, calcitonin) and the biochemical parameters of bone metabolism (serum calcium, serum phosphorus and serum alkaline phosphatase) was studied in 30 patients on chronic hemodialysis (mean age: 51 years; mean duration of dialysis treatment: 39 months). OC levels were significantly elevated in all patients on chronic hemodialysis (34.7 +/- 31.5 ng/ml) when compared to healthy subjects (6.25 +/- 1.39 ng/ml, p less than 0.001). In 2 patients the OC levels were excessively high (127.54 ng/ml; 148.02 ng/ml), which was associated with severe renal osteodystrophy due to secondary hyperparathyroidism. When divided into 2 groups in the patients with secondary hyperparathyroidism the mean OC value was markedly elevated (50.5 +/- 12.7 ng/ml) compared to the patients without secondary hyperparathyroidism (24.1 +/- 2.8 ng/ml) (p less than 0.05). 70 per cent of the patients on chronic hemodialysis with OC levels greater than 30 ng/ml showed moderate to severe scintigraphic findings of bone disease. In neither of the 2 groups could a correlation between OC and serum alkaline phosphatase be demonstrated. The results indicate, that OC levels could be useful additional parameter in hemodialyzed patients with secondary hyperparathyroidism and OC levels could reflect bone formation in these patients.
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PMID:[Osteocalcin in chronic hemodialysis patients as an additional parameter in the diagnosis of advanced secondary hyperparathyroidism]. 278 25

The treatment of premature infants with the diuretic furosemide appears to be a contributory factor in the development of metabolic bone disease presumably because of furosemide-induced hypercalciuria. In this study, we measured calcium and phosphorus balance in furosemide-treated very low birth weight infants (VLBW) infants with bronchopulmonary dysplasia (BPD) who were fed a specialized premature formula containing increased amounts of calcium and phosphorus. Furosemide-treated infants received 166 +/- 37 mg/kg/day and retained 80 +/- 34 mg/kg/day of calcium, and 87 +/- 19 mg/kg/day and retained 52 +/- 14 mg/kg/day of phosphorus. The amounts retained were approximately 65% of the calcium and 72% of the phosphorus requirements for in utero mineral accretion. Compared to a group of similarly fed VLBW infants without BPD and not treated with the diuretic, the furosemide-treated infants excreted a larger percent of the calcium intake in the urine but had similar total urinary calcium and phosphorus losses (mg/kg/day) and serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) levels. From the latter two findings, we suggest that the extra mineral content of the formula may have promoted bone mineralization and prevented the occurrence of secondary hyperparathyroidism.
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PMID:Effect of high calcium and phosphorus intake on mineral retention in very low birth weight infants chronically treated with furosemide. 280 41

It has been shown in vitro that verapamil inhibits parathyroid hormone-induced bone resorption. To determine the effect of verapamil administration on bone histology in rats with chronic renal failure, male Wistar rats were divided into three groups: subtotally nephrectomized (SNX), SNX treated with verapamil, 8 mg/kg/day p.o. (SNX-V) and control (C). Thirteen weeks later, the mandibular condyle bone was studied by histomorphometry. When compared to C rats, SNX rats had active bone disease, with increased resorption parameters (resorption surface, active resorption surface, osteoclast number) and accelerated mineral appositional rate. These parameters improved with verapamil administration. When compared to C rats, SNX-V rats had decreased osteoid seam width and mineral appositional rate. Serum parathyroid hormone was similarly elevated in both uremic groups. These data suggest that verapamil administration improves active bone disease in rats with chronic renal failure and decreases bone formation.
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PMID:Effect of verapamil on bone resorption and formation in uremic rats. 281 87


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