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)

Phosphate (Pi) retention is a common problem in patients with chronic kidney disease, particularly in those who have reached end-stage renal disease (ESRD). In addition to causing secondary hyperparathyroidism and renal osteodystrophy, recent evidence suggests that, in ESRD patients, high serum phosphorus concentration and increased calcium and phosphorous (Ca x P) product are associated with vascular and cardiac calcifications and increased mortality. Dietary phosphorus restriction and Pi removal by dialysis are not sufficient to restore Pi homeostasis. Reduction of intestinal Pi absorption with the use of Pi binders is currently the primary treatment for Pi retention in patients with ESRD. The use of large doses of calcium-containing Pi binders along with calcitriol administration may contribute to over-suppression of parathyroid hormone secretion and adynamic bone disease as well as to a high incidence of vascular calcifications. When used in patients with impaired renal function, aluminium salts were found to accumulate in bone and other tissues, resulting in osteomalacia and encephalopathy.Sevelamer, an aluminium- and calcium-free Pi binder can reduce serum phosphorus concentration and is associated with a significantly lower incidence of hypercalcaemia, while maintaining the ability to suppress parathyroid hormone production. An additional benefit of sevelamer is its ability to lower low density lipoprotein-cholesterol and total cholesterol levels. Sevelamer attenuates the progression of vascular calcifications in haemodialysis patients, which may lead to lower mortality. The use of sevelamer in non-dialysed patients might aggravate metabolic acidosis, common in these patients. Several other calcium-free Pi binders are in development. Lanthanum carbonate has shown significant promise in clinical trials in ESRD patients. Magnesium salts do not offer a significant advantage over currently available Pi binders. Their use is restricted to patients receiving dialysis since excess magnesium must be removed by dialysis. Iron-based compounds have shown variable efficacy in short-term clinical trials in small numbers of haemodialysis patients. Mixed metal hydroxyl carbonate compounds have shown efficacy in animals but have not been studied in humans. Major safety issues include absorption of the metal component with possible tissue accumulation and toxicity.
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PMID:Safety of new phosphate binders for chronic renal failure. 1464 Jul 73

Lanthanum carbonate is a novel, non-aluminium, non-calcium phosphate binding agent that forms a water-insoluble compound, lanthanum phosphate, in the gut. Lanthanum carbonate (elemental lanthanum 375-3000 mg/day) reduced serum phosphorus levels compared with placebo in two randomised, double-blind, multicentre 4-week trials in patients with chronic renal failure receiving regular haemodialysis. In two large, randomised trials in patients with chronic renal failure requiring haemodialysis, lanthanum carbonate (elemental lanthanum 375-3000 mg/day) was as effective as calcium carbonate and/or other conventional phosphate binders in reducing and maintaining serum phosphorus levels (< or =5.6 mg/dL over 6 months and < or =5.9 mg/dL over 2 years). Lanthanum carbonate was generally well tolerated. Most adverse events were mild-to-moderate in severity, with gastrointestinal events being the most common. The tolerability profile of lanthanum carbonate was similar to those of conventional phosphate binders; however, hypercalcaemic episodes occurred significantly less frequently over 6 months with lanthanum carbonate than with calcium carbonate. In a randomised 1-year trial, numerically fewer lanthanum carbonate (elemental lanthanum < or =3750 mg/day) recipients had renal bone disease at study end than at baseline; however, in the calcium carbonate < or =9000 mg/day group, numerically more patients had renal bone disease at study end compared with baseline.
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PMID:Lanthanum carbonate. 1510 90

Preclinical studies have shown that lanthanum has a very high phosphate-binding capacity at gastrointestinal pH, while clinical trials have shown lanthanum carbonate to be an effective, well-tolerated phosphate binder for the treatment of hyperphosphataemia in patients with end-stage renal disease. Optimization of bone health is an important issue in these patients, and, based on theoretical grounds, there have been concerns that lanthanum will have toxic effects on bone similar to those of aluminium. However, compared with aluminium, absorption of lanthanum is extremely low and lanthanum treatment is not associated with systemic toxicity. In addition, unlike aluminium, elimination of lanthanum is not through the kidney, but mainly takes place via the biliary route and is, therefore, independent of renal function. This implies that patients with chronic renal failure are not at an increased risk for accumulation of the element, compared with patients with normal renal function. In animal studies, no adverse effects on bone were seen in healthy animals receiving lanthanum carbonate. In 5/6th nephrectomized rats, very high doses of lanthanum (1000-2000 mg/kg) affected bone mineralization. This was not due to a direct toxic effect on bone, but was secondary to phosphate depletion induced by lanthanum and, as with any gastro-intestinal phosphate-binding agent, can be reversed with a phosphate-supplemented diet. In a phase III clinical trial, bone biopsies were taken from dialysis patients at baseline and after 1 year of treatment with either lanthanum carbonate (median dose, 1250 mg/day) or calcium carbonate (median dose, 2000 mg/day). Patients treated with lanthanum carbonate for 1 year did not experience any of the aluminium-like toxic effects on bone expressed as either osteomalacia or adynamic bone disease.
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PMID:Improving outcomes in hyperphosphataemia. 1512 49

Our knowledge of the mineral metabolism disturbances and skeletal disorders in patients with chronic renal insufficiency has advanced significantly in the last years. Probably the most important what we have learned is, that apart of bone disease, hyperparathyroidism and its treatment can also lead to severe extra-skeletal complications, contributing to the progression of cardiovascular disease in this population. This fact has fundamentally changed our approach to the treatment, and - as a result - the new clinical practice guidelines on the management of mineral metabolism and bone disease in chronic renal failure have been developed. Mainstays of the new approach are lower recommended serum calcium and calcium-phosphate product. However, these targets are very difficult to achieve in clinical practice. During the last decade, some additional therapeutic agents have been welcomed. There are two effective calcium-free, aluminium-free phosphate binders, sevelamer hydrochloride, and lanthanum carbonate, four vitamin D analogues of newer generation, and--last but not least--modulators of calcium-sensing receptor, calcimimetics. Future studies will be needed to determine how these recent developments will be helpful. The optimal therapy for all end-stage renal failure complications is definitely renal transplantation.
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PMID:[New aspects in the management of renal osteodystrophy]. 1566 6

Aplastic bone disease (adynamic bone disease) has been attracted attention as the most frequent type of renal osteodystrophy in patients undergoing dialysis, and relatively low serum parathyroid hormone level is considered to be the major cause of aplastic bone disease. In aplastic bone disease, both the number of osteoblast and osteoclast are few and the speed of bone turnover is low, therefore, buffering action of bone for calcium and phosphorus is extremely disturbed. Hypercalcemia due to a prescription of large dose calcium carbonate and hyperphosphatemia derived by high protein diet in this occasion induce high serum calcium and phosphorus product level, and ectopic calcification is likely to occur. When ectopic calcification occur at artery it might develop ischemic change of visceral organ. Recently, the strong association between coronary arterial calcification and high serum calcium and phosphorus products is clarified by a method of electron-beam computed tomography. Based on these findings, high calcium and phosphorus product is now believed as a risk for poor patients' survival. Thus, we should pay attention to calcium and phosphorus product in patients suffering from aplastic bone disease.
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PMID:[Ectopic calcification in patients with aplastic bone disease undergoing dialysis]. 1577 11

Calcium (Ca) overload by Ca-containing phosphorus (P) binder has been suggested to be implicated in the pathogenesis of soft tissue and vascular calcification, which contribute to increased morbidity and mortality of cardiovascular disease in patients undergoing dialysis. Recently, a noncalcium P binder, sevelamer hydrochloride (sevelamer), has become available in Japan. However, Japanese patients undergoing dialysis might be less tolerant of sevelamer treatment, and it is likely to cause hypocalcemia because their dietary Ca intake is less than that in European and American patients. We evaluated the effects of combination therapy with sevelamer and calcium carbonate (CC) on mineral metabolism in Japanese hemodialysis patients, as an alternative form of P management. A total of 210 hemodialysis patients were enrolled, and were given a small dose of sevelamer (0.75-1.5 g/day) on CC treatment. Sevelamer dose was gradually increased, while CC decreased during 24 weeks. Five patients discontinued sevelamer treatment because of severe constipation, anorexia, and parathyroidectomy for severe secondary hyperparathyroidism. After 24 weeks, the dose of sevelamer was significantly increased to 3.29 g/day (initial dose: 1.47 g/day), while CC was decreased by 54%. Adjusted serum Ca significantly decreased (9.63 +/- 0.57-9.45 +/- 0.67 mg/dL; P = 0.0012), although serum P increased (5.89 +/- 1.32-6.25 +/- 1.32 mg/dL; P = 0.017). Serum intact PTH (iPTH) significantly increased in patients with a low or normal iPTH level (< or =300 pg/mL), while it did not change in patients with secondary hyperparathyroidism (>300 pg/mL). The results suggest that the therapeutic regimen is more tolerant and reduces Ca load in Japanese hemodialysis patients while avoiding hypocalcemia. In addition, the mitigated Ca overload could improve PTH hyposecretion in patients with adynamic bone disease, which is associated with soft tissue calcification and higher mortality in uremia.
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PMID:Combination therapy with sevelamer hydrochloride and calcium carbonate in Japanese patients with long-term hemodialysis: alternative approach for optimal mineral management. 1582

Fourier-transform infrared microspectroscopy (FTIRM) allows analysis of mineral content, mineral crystal maturity and mineral composition at approximately 10-micron spatial resolution. Previous FTIRM analyses comparing 4-micron thick sections from non-decalcified iliac crest biopsies from women with post-menopausal osteoporosis, as contrasted with iliac crest tissue from individuals without evidence of metabolic bone disease, demonstrated significant differences in average mineral content (decreased in osteoporosis) and mineral crystal size/perfection (increased in osteoporosis). More importantly, these parameters, which vary throughout the tissue in relation to the tissue age in healthy bone, showed no such variation in bone biopsies from patients with osteoporosis. The present study compares the spatial and temporal variation in mineral quantity and properties in trabecular bone in high- and low-turnover osteoporosis. Specifically, six biopsies from women (n=5) and one man with high-turnover osteoporosis (age range 39-77) and four women and two men with low turnover osteoporosis (age range 37-63) were compared to ten "normal" biopsies from three men and seven woman (age range: 27-69). "High turnover" was defined as the presence of increased resorptive surface, higher than normal numbers of osteoclasts and greater than or equal to normal osteoblastic activity. "Low turnover" was defined as lower than normal resorptive surface, decreased osteoclast number and less than normal osteoblastic activity. Comparing variations in FTIR-derived values for each of the parameters measured at the surfaces of the trabecular bone to the maximum value observed in multiple trabeculae from each person, the high-turnover samples showed little change in the mineral: matrix ratio, carbonate: amide I ratio, crystallinity and acid phosphate content. The low-turnover samples also showed little change in these parameters, but in contrast to the high-turnover samples, the low-turnover samples showed a slight increase in these parameters, indicative of retarded, but existent resorption and formation. These data indicate that FTIR microspectroscopy can provide quantitative information on mineral changes in osteoporosis that are consistent with proposed mechanisms of bone loss.
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PMID:Comparison of mineral quality and quantity in iliac crest biopsies from high- and low-turnover osteoporosis: an FT-IR microspectroscopic investigation. 1608 60

The aim of this study was to examine the therapeutic effect of hypocalcemic stimulation caused by sevelamer hydrochloride (SH) administration on adynamic bone disease (ABD). The subjects were 28 maintenance hemodialysis (HD) patients who had remained in ABD state in spite of no administration of vitamin D(3) since HD induction (15 males and 13 females;12 diabetic patients and 16 non-diabetic patients). The mean age was 61.8+/-9.5 years and the mean HD duration was 5.5+/-3.9 years. The calcium concentration in the dialysate was 3.0 mEq/L. We made the final daily dose of SH after two months the same as the first daily dose of calcium carbonate (CC) in the following manner. At first we administered only CC at breakfast and lunch and SH at supper. And for the next two weeks we administered CC at breakfast and SH at lunch and supper. And for the final two weeks we administered only SH. After that we increased the dose of SH as much as possible. We evaluated the therapeutic effect of the above treatment on ABD using intact-osteocalcin (iOC) [Teijin. Tokyo] as a marker before and 6, 12 months after the beginning of the replacement. If iOC Ievel of 30 to 70 ng/mL showed normal tumover bone (NTB), 5 cases (17.9%) changed into NTB in 6 months. 9 cases (32.1%) changed into NTB in 12 months and one case (3.6%) changed into ostitis fibrosa in 12 months. It is thought that SH is effective for the treatment of ABD but we have to be careful for ostitis fibrosa.
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PMID:[Treatment of adynamic bone disease with the complete replacement from calcium carbonate to sevelamer hydrochloride]. 1627 24

Secondary hyperparathyroidism is present in most patients with end-stage renal disease and has been linked to uremic bone disease, vascular calcification, and mortality. Current literature suggests an association between hypomagnesemia and cardiovascular disease in the general population. We reviewed all published studies on the relationship between serum magnesium and parathyroid hormone and the relationship between serum Mg and vascular calcification in dialysis patients. Of these, 10 of 12 studies of patients on hemodialysis and 4 of 5 studies of patients on peritoneal dialysis showed a significantinverse relationship between serum Mg and serum intact parathyroid hormone. Hyperparathyroidism develops in peritoneal dialysis patients dialyzed with a solution containing normal calcium (1.25 mmol/L) and low Mg (0.25 mmol/L), even though serum calcium is maintained at a normal level. Four of the hemodialysis studies and one of the peritoneal dialysis studies indicated that there is an inverse relationship between serum Mg and vascular calcification in these patients. Potential benefits have been attributed to magnesium carbonate as a phosphate binder and it may possibly be an effective, less toxic, less expensive phosphate binder. We believe that the role of Mg in secondary hyperparathyroidism and vascular calcification merits further investigation.
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PMID:Relationship between serum magnesium, parathyroid hormone, and vascular calcification in patients on dialysis: a literature review. 1672 31

A model of chronic kidney disease (CKD)-induced vascular calcification (VC) that complicates the metabolic syndrome was produced. In this model, the metabolic syndrome is characterized by severe atherosclerotic plaque formation, hypertension, type 2 diabetes, obesity, and hypercholesterolemia, and CKD stimulates calcification of the neointima and tunica media of the aorta. The CKD in this model is associated the adynamic bone disorder form of renal osteodystrophy. The VC of the model is associated with hyperphosphatemia, and control of the serum phosphorus both in this animal model and in humans has been preventive in the development of VC. This article reports studies that demonstrate reduction of established VC by the addition of sevelamer carbonate to the diets of this murine metabolic syndrome model with CKD. Sevelamer, besides normalizing the serum phosphorus, surprisingly, reversed the CKD-induced trabecular osteopenia. Sevelamer therapy increased osteoblast surfaces in the metaphyseal trabeculae of the tibia and femur. It also increased osteoid surfaces and, importantly, bone formation rates. In addition, sevelamer was found to be effective in decreasing serum cholesterol levels. These results suggest that sevelamer may have important actions in decreasing diabetic and uremic vasculopathy and that sevelamer carbonate may be capable of increasing bone formation rates that are suppressed by diabetic nephropathy.
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PMID:Reversal of the adynamic bone disorder and decreased vascular calcification in chronic kidney disease by sevelamer carbonate therapy. 1718 86


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