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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal bone disease is an important cause of morbidity in patients on dialysis. The prevalence of renal bone disease, especially aluminium related bone disease, has not been studied in the Singapore dialysis population. As such, we studied 45 haemodialysis patients for renal bone disease using biochemical and radiological parameters. Selected patients underwent a renal biopsy. There were 29 males and 16 females, mean (+/- SEM) age, 44.6 +/- 13.4 years. The duration of haemodialysis ranged from two months to ten years, mean 18.5 months. 75.4% of patients had hyperphosphatasemia, 24.4% had hypocalcemia and two patients had hypercalcemia. There was a wide range in the serum parathyroid hormone levels and 55.4% of patients had serum parathyroid hormone levels > 1000 pmol/L. Patients with symptoms and radiological abnormalities had significantly higher serum parathyroid hormone and alkaline phosphatase levels than those without (P < 0.005). The desferrioxamine infusion test was positive, with an increment in serum aluminium (DL) > 100 mg/L in five patients. Skeletal survey was positive for renal bone disease in 24.4% of patients. There was a significant correlation between the serum parathyroid hormone level, DA1 and the duration of dialysis (r = 0.752, p < 0.001 and r = 0.837, p < 0.001 respectively). There was no correlation between serum parathyroid hormone, calcium, phosphate levels and DA1. The serum haemoglobin concentration and ferritin levels did not show a correlation with DA1. Bone biopsy revealed hyperparathyroid bone disease in two patients, aluminium-related bone disease in one patient and mixed uraemic osteodystrophy in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal bone disease in patients on haemodialysis: biochemical and radiological assessment. 129 14

In experimental and clinical studies, conflicting results regarding the effect of oral anticoagulant therapy on bone metabolism have been reported. To measure a possible influence of long-term anticoagulant therapy with phenprocoumon on peripheral bone mass, measurements of peripheral bone mineral content (BMC) and serum osteocalcin levels were performed with single photon absorptiometry in a total of 78 patients on anticoagulant treatment. We studied 43 women (mean age 66 years +/- 2 SEM) and 35 men (mean age 65 years +/- 2 SEM) with a median duration of phenprocoumon therapy of 1 year (1-9 years). In all patients, the medical history gave no symptoms of metabolic bone disease, or diseases or medications causing osteoporosis. Both in the male and female groups, mean peripheral BMC was significantly decreased (male: P less than 0.01, female: P less than 0.003) when compared with corresponding controls. Serum OC-levels measured in 16 patients were also significantly lower than those of the controls (P less than 0.02). Our data of decreased BMC and low serum OC-levels indicate reduced bone mass in patients on long-term anticoagulant therapy with phenprocoumon. This may imply an influence of anticoagulants on bone metabolism resulting in decreased bone formation.
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PMID:Decreased peripheral bone mineral content in patients under anticoagulant therapy with phenprocoumon. 204 Mar 27

A freely mobile jacket and tether system was developed for the investigation of total parenteral nutrition (TPN)-induced metabolic bone disease and complications of prolonged TPN in 12 Macaca fascicularis nonhuman primates. The animals received TPN for 49 +/- 7 d (means +/- SEM), providing 82 +/- 2 kcal.kg-1.d-1. Serum glucose increased from 3.6 +/- 0.2 mmol/L at baseline to 8.3 +/- 1.9 mmol/L (p less than 0.01) during TPN, and serum albumin decreased from 38 +/- 1 g/L at baseline to 29 +/- 1 g/L (p less than 0.001) during 2.75% amino acid TPN and 30 +/- 2 g/L (p less than 0.01) during 5% amino acid TPN infusion. No significant changes were seen in serum prealbumin, total protein, bilirubin, alanine aminotransferase, and 5'-nucleotidase during TPN infusion. Major complications included catheter sepsis, hyperglycemia, diarrhea, and premature death in six animals. Thus, metabolic complications of prolonged TPN support may be investigated in a freely mobile nonhuman primate.
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PMID:Long-term parenteral nutrition in unrestrained nonhuman primates: an experimental model. 210 76

In maintenance dialysis patients, low-turnover osteomalacia and aplastic bone disease are generally attributed to aluminum toxicity. Both groups of patients have a relative deficiency of PTH. The reason for the development of osteomalacia versus aplastic bone disease is unclear. The present study was performed to evaluate whether parathyroidectomy (PTX) modifies the effect of aluminum administration on bone histology in renal failure. Seven groups of pair-fed rats were studied: normals (N); renal failure (RF); RF + PTX; PTX; RF + aluminum (AL); RF + PTX + AL; and PTX + AL. Aluminum was administered intraperitoneally 5 days/week for 6 weeks. All groups were sacrificed at 6 weeks. Renal failure increased the serum calcium in both the parathyroid intact (RF versus N, 11 +/- 0.1 versus 10 +/- 0.3 mg/dl, X +/- SEM, P less than 0.05) and calcium-supplemented PTX groups (PTX + RF versus PTX, 9.7 +/- 0.2 versus 9.2 +/- 0.2 mg/dl, P less than 0.05). After PTX, aluminum administration increased the serum calcium (PTX + AL versus PTX, 9.8 +/- 0.3 versus 9.2 +/- 0.2, P less than 0.05, and PTX + RF + AL versus PTX + RF, 10.8 +/- 0.1 versus 9.7 +/- 0.2 mg/dl, P less than 0.05). In rats with renal failure receiving aluminum, PTX decreased osteoid volume and surface but not osteoid thickness. Rats receiving aluminum did not mineralize bone. Additionally, in PTX rats receiving aluminum, renal failure per se increased osteoblast surface, osteoid surface, osteoid volume, and osteoclast number.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of parathyroidectomy on aluminum toxicity and azotemic bone disease in the rat. 234 77

Serial bone biopsies obtained from 19 chronic hemodialysis patients asymptomatic for bone disease were examined retrospectively. We found only modest amounts of stainable bone aluminum after the first few years of hemodialysis therapy. Over the ensuing 5 to 15 years, there was a progressive increase in stainable bone aluminum (% of total bone surface): 0 to 4.9 years, 19.9 +/- 3.8% (mean +/- SEM); 5.0 to 9.9 years, 28.4 +/- 5.3%; and greater than or equal to 10.0 years, 58.0 +/- 7.7%. At final biopsy, the extent of bone surface aluminum was significantly correlated with duration of hemodialysis therapy (r = 0.54) and with bone formation rate (BFR) (r = -0.54). Patients who developed aluminum-associated bone disease did not differ from other patients in duration of hemodialysis, intake of 1-hydroxylated vitamin D3 compounds, or the findings on early bone biopsy. High-turnover renal osteodystrophy remains the dominant bone lesion throughout the course of hemodialysis in patients with intact parathyroid glands. In individual patients, bone histology frequently changes over time and in some patients, aluminum-associated bone disease may improve spontaneously. Bone biopsy in an asymptomatic patient who has received hemodialysis therapy for less than 5 years does not appear to be useful in predicting the subsequent appearance of aluminum-associated bone disease.
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PMID:Bone aluminum accumulation in hemodialysis patients: a longitudinal perspective. 341 77

To study the value of bone Gla protein (BGP) as a biochemical marker of normal bone physiology and metabolic bone disorders, we have developed a radioimmunoassay (RIA) for the detection of BGP in human plasma. Antibodies were generated in rabbits immunized with purified calf BGP conjugated to thyroglobulin. Human plasma BGP reacted identically with the calf BGP standard, thus demonstrating the suitability of the assay to measure plasma BGP levels in man. The RIA is sensitive, accurate, and technically simple. Plasma BGP levels were determined in normal subjects (N = 35) and in patients with hypothyroidism (N = 10), hyperthyroidism (N = 22) and chronic renal failure (N = 35). The mean (+/- 1 SEM) concentration of plasma BGP in normal subjects was 1.27 +/- 0.07 nmol/l. Plasma BGP was significantly increased in patients with hyperthyroidism, 4.04 +/- 0.78 nmol/l (P less than 0.001) and chronic renal failure, 10.17 +/- 2.47 nmol/l (P less than 0.001). Low concentrations were found in patients with hypothyroidism, 0.74 +/- 0.11 nmol/l (P less than 0.01). Our studies indicate that plasma BGP provides a useful technique in the diagnosis of patients with bone disease.
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PMID:A radioimmunoassay for bone Gla protein (BGP) in human plasma. 349 71

The bone histology in patients with chronic renal failure and aluminum-related bone disease does not always show the excess accumulation of unmineralized osteoid (matrix) characteristic of osteomalacia. Frequently, bone aluminum accumulation is associated with normal or reduced amounts of unmineralized osteoid and low bone formation and is referred to as aplastic bone disease. In this study, we compared static and dynamic bone histomorphometric parameters and plasma PTH and aluminum levels in 12 patients with osteomalacia and 18 patients with aplastic bone disease who had been receiving dialysis for the same duration to determine if the difference in osteoid accumulation in these 2 lesions might be explained by differences in aluminum accumulation or PTH levels. The stainable bone surface aluminum level was significantly higher in the patients with osteomalacia compared to that in the group with aplastic bone [61 +/- 5% (+/- SEM) vs. 43 +/- 4%; P less than 0.02]. The rates of bone apposition and bone formation were lower in the group with osteomalacia (P less than 0.01). Plasma amino-terminal PTH was not significantly different in the 2 groups. The increment in plasma aluminum levels after a single infusion of deferoxamine was higher in the osteomalacic group than in the aplastic group, suggesting that the patients with osteomalacia accumulated more total body chelatable aluminum than did those with aplastic bone disease during a comparable length of time on dialysis. We conclude that the excess unmineralized osteoid in aluminum-related osteomalacia results from the high rate of total body aluminum accumulation, which directly causes uncoupling of matrix mineralization and matrix production, independent of PTH levels. Patients with aplastic bone disease who have accumulated lesser amounts of total body aluminum fail to develop excess unmineralized osteoid because production and mineralization of matrix are more closely coupled than in the osteomalacic lesion, despite a decline in osteoblast numbers.
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PMID:Osteomalacia and aplastic bone disease in aluminum-related osteodystrophy. 358 92

Serum osteocalcin (BGP), a vitamin K-dependent gamma-carboxyglutamic acid (GLA) containing bone protein, provides an index of bone turnover in patients with a variety of metabolic bone diseases. BGP increases with increasing age in both sexes, but more so in women. BGP rises above normal when the glomerular filtration rate falls below 30 ml/min. Because of its importance in bone disease, its low mol wt, and the effect of uremia, we measured BGP by RIA in serum and dialysate fluid in patients on hemodialysis (HD) or peritoneal dialysis (PD). In 32 HD patients (22 women and 10 men), serum BGP was not different pre- and postdialysis [67.5 +/- 4.4 (+/- SEM) ng/ml vs. 67.7 +/- 5.2), but was significantly elevated compared to the level in normal subjects (7.3 +/- 0.8 ng/ml). The sex difference previously reported in normal subjects was not found in patients with renal failure. The serum BGP level in 8 PD patients was 49.4 +/- 6.9 ng/ml, with a peritoneal fluid concentration of 27.6 +/- 9.3 ng/ml. The hemodialysate fluid concentration of BGP was 1.7 +/- 0.4 ng/ml, which was significantly lower than the serum BGP levels in the HD patients, the PD patients, and peritoneal fluid (P less than 0.01). A significant correlation existed among BGP, alkaline phosphatase, immunoreactive PTH, creatinine, and blood urea nitrogen. We conclude that BGP is markedly elevated in patients with renal failure, not altered in the serum by HD or PD, but very low in HD dialysate fluid. These findings may reflect a combination of impaired clearance and increased skeletal production. The difference in clearance between the peritoneal and hemodialysis fluid is compatible with the mol wt of BGP. In 15 patients who had successful kidney transplantation, serum BGP was normal despite an elevated serum PTH level.
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PMID:Serum and dialysate osteocalcin levels in hemodialysis and peritoneal dialysis patients and after renal transplantation. 388 31

Dispersed parathyroid cells were employed to study calcium-regulated parathyroid hormone (PTH) release in severe secondary hyperparathyroidism due to chronic renal insufficiency. Cell preparations were obtained from 16 parathyroid glands of 6 patients undergoing subtotal parathyroidectomy for parathyroid bone disease and/or hypercalcemia. The effects of increasing ambient calcium concentration on immunoreactive PTH release in vitro were assessed and compared with results observed in cells prepared from 7 adenomas and 6 normal parathyroid glands. There was no difference in maximal PTH release for the 3 types of tissue (mean +/- SEM, 8.48 +/- 1.9 , 8.1 +/- 3, and 10.1 +/- 0.78 ng/10(5) cells. h respectively). In 14 of 16 hyperplastic glands, 6 of 7 adenomas, and all of the normal glands, PTH release was inhibited more than 50% by 2-3 mM calcium (suppressible glands). Of the normal glands, half of the maximal inhibition of PTH release (the set-point) occurred at less than 1.03 mM calcium in 5 of 6 cases. In 12 of 14 suppressible hyperplastic glands and all of the 6 suppressible adenomas, on the other hand, the set-point was 1.03 mM or higher (p less than 0.01 and P less than 0.002, respectively). Thus, in severe secondary parathyroid hyperplasia due to chronic renal insufficiency, there is frequently an increase in the set-point for calcium without a change in the maximal secretory rate per cell. Abnormal calcium-regulated PTH release at the cellular level, therefore, is not limited to parathyroid neoplasia (i.e. adenoma or primary hyperplasia), but may occur in secondary hyperplasia as well.
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PMID:Abnormal regulation of parathyroid hormone release by calcium in secondary hyperparathyroidism due to chronic renal failure. 705 14

Type I collagen makes up more than 90% of bone matrix. Therefore, analysis of antigens related to collagen formation and degradation in bone should provide good and specific estimates of both bone resorption and bone formation rates. In this study we measured serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption and serum carboxy-terminal propeptide of type I procollagen (PICP) as a marker of bone formation. Serum levels of the two antigens were correlated to histomorphometric indices of bone resorption and bone formation calculated from iliac crest bone biopsies in a group of 18 individuals with high- and low-turnover bone disease (myxedema, primary hyperparathyroidism, and thyrotoxicosis). After logarithmic transformation the regression of S-ICTP on volume-referent resorption rate (BRs/R/BV) was significant (r = 0.61, p < 0.01, SEM/Y = 56%). S-ICTP also showed a significant regression on the volume-referent cancellous bone balance (r = -0.45, p < 0.05, SEM/Y = 412%). S-PICP was significantly correlated to the mineral appositional rate (r = 0.53, p < 0.05) and volume-referent bone formation rate (r = 0.61, p < 0.01, SEM/Y = 48%). The correlation to bone turnover as expressed in the activation frequency was also highly significant (r = 0.61, p < 0.01, SEM/Y = 51%). No significant correlation with wall thickness or bone balance was demonstrable per remodeling cycle. Thus, assays employing antigens that reflect collagen formation and degradation are useful instruments for the evaluation of rates of bone remodeling in metabolic bone disease.
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PMID:Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry. 844 31


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