UMLS:C0005940 - FACTA Search

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Query: UMLS:C0005940 (bone disease)
7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than 60% of patients on chronic haemodialysis (HD) have a serum phosphate level above 5.5 mg/dl (1.75 mmol/l), which recently has been recommended as an appropriate target in patients with end-stage renal disease (ESRD). Preventing hyperphosphataemia and elevated Ca x P product not only ameliorates the progression of secondary hyperparathyroidism and bone disease, but also appears to reduce cardio-vascular morbidity and mortality from vascular calcifications. Dietary phosphate restriction and the administration of aluminium and calcium salts have been the principal means of phosphate control over the last decade. Unfortunately, the protean disturbances of toxic aluminium accumulation in the body virtually eliminated aluminium from clinical practice. Calcium-based therapy, although well tolerated, results in frequent hypercalcaemia when administered concurrently with vitamin D analogues, despite a decrease in the concentration of dialysate calcium. Sevelamer (Renagel((R))) has been a novel, non-absorbable calcium- and aluminium-free synthetic polymer. In initial studies, sevelamer reduced serum phosphate, Ca x P product and parathyroid hormone (PTH) in a manner comparable with calcium acetate therapy. However, the effect on PTH levels may prove to be inconsistent. It seems somewhat less effective in binding phosphate than aluminium, although no direct comparisons have been made. In a recent study, it attenuated the progression of vascular calcification in HD patients. It also binds bile acids, resulting in substantially lower low-density lipo-protein cholesterol levels. The major obstacle to its current use is a substantial increase in the cost associated with sevelamer therapy.
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PMID:Hyperphosphataemia and treatment with sevelamer in haemodialysis patients. 1281 70

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

Phosphorus control remains a relevant clinical problem in dialysis patients. With age, however, serum phosphorus level decreases significantly because of a spontaneous decrease in protein intake. Older patients usually need lower doses of phosphorus binders. Nevertheless, hyperphosphataemia is observed in a quarter of patients aged >65 years. Phosphorus retention is related to an imbalance between phosphorus intake and removal by dialysis, and is usually aggravated when vitamin D analogues are employed. Hyperphosphataemia induces secondary hyperparathyroidism and the development of osteitis fibrosa. Recent publications describe an association between phosphorus retention and increased calcium and phosphorus product (Ca2+ x P), with significant progression of tissue calcification and higher mortality risk. Dietary intervention, phosphorus removal during dialysis and phosphorus binders are current methods for the management of hyperphosphataemia. However, the phosphorus removed by standard haemodialysis is insufficient to achieve a neutral phosphorus balance when protein intake is >50 g/day. Additional protein restriction may impose the risk of a negative protein balance. More frequent dialysis may help to control resistant hyperphosphataemia. Phosphorus binders constitute the mainstay of serum phosphorus level control in end-stage renal disease patients. Aluminium-based phosphorus binders, associated with toxic effects, have largely been substituted by calcium-based phosphorus binders. However, widespread use of calcium-based phosphorus binders has evidenced the frequent appearance of hypercalcaemia and long-term progressive cardiovascular calcification. Sevelamer, a relatively new phosphorus binder, has proved efficacious in lowering serum phosphorus and parathyroid hormone (PTH) levels without inducing hypercalcaemia. Furthermore, several investigators have reported that sevelamer may prevent progression of coronary calcification. However, its efficacy in severe cases of hyperphosphataemia remains to be confirmed in large series. There are no specific guidelines for phosphorus control in the elderly. Until more information is available, levels of mineral metabolites should be targeted in the same range as those recommended for the general population on dialysis (calcium 8.7-10.2 mg/dL, phosphorus 3.5-5.5 mg/dL and Ca2+ x P 50-55 mg2/dL2). PTH values over 120 ng/L help to avoid adynamic bone disease. Since elderly patients have a higher incidence of adynamic bone (which buffers less calcium) and vascular calcification, sevelamer should be the phosphorus binder of choice in this population; but sevelamer is costly and its long-term efficacy has not been definitively validated. Patients with low normal levels of calcium may receive calcium-based phosphorus binders with little risk. Patients with low values of PTH and high normal calcium should receive sevelamer. Tailored combinations of calcium-based phosphorus binders and sevelamer should be considered, and calcium dialysate concentration adjusted accordingly.
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PMID:Management of hyperphosphataemia in dialysis patients: role of phosphate binders in the elderly. 1497 34

Hyperphosphatemia is associated with soft-tissue calcification and bone disease. Nephrologists prescribe phosphate binders to decrease dietary phosphate absorption, reduce serum phosphorus concentrations, and minimize the risk for soft-tissue calcification and bone disease. Recent data suggest that the dose of calcium used as a phosphate binder may contribute to the risk for cardiovascular calcification. Chronic positive calcium balance from diet, dialysis, and calcium-based phosphate binders or intermittent hypercalcemia may favor precipitation of calcium and phosphate into tissues. Calcium suppresses parathyroid hormone (PTH) secretion and bone turnover, limiting the ability of bone to incorporate calcium and phosphorus. Sevelamer, a non-absorbed polymer, allows physicians to bind dietary phosphate and decrease serum phosphorus without unwanted absorption of metals or calcium or over-suppression of PTH. In a comparative trial, calcium-based phosphate binders were associated with progressive coronary artery and aortic calcification that was attenuated by sevelamer. The optimal phosphate binder is one that controls hyperphosphatemia prevents soft-tissue calcification and preserves bone health.
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PMID:Arterial calcification in chronic kidney disease. 1549 Mar 99

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

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

In June 2003, sevelamer hydrochloride became widely available in Japan and was expected to control hyperphosphatemia in hemodialysis patients without inducing hypercalcemia. To evaluate the impact of sevelamer therapy on mineral metabolism, we recruited 954 hemodialysis patients from 21 renal units just before the general release of sevelamer in Japan. The serum calcium, phosphate, and parathyroid hormone levels determined on enrollment were compared with those later measured in June 2004. Sevelamer was prescribed for 169 of the 859 patients for whom data were available in 2004. The mean calcium level, phosphate level, and calcium x phosphate product were all significantly reduced during the 12-month study period, but the intact parathyroid hormone (iPTH) level did not change. As a result, the percentage of patients who achieved a calcium x phosphate product of <55 mg(2)/dL(2) was significantly increased, but there were no changes in that of patients who achieved the target ranges for phosphate (3.5-5.5 mg/dL) or iPTH (150-300 pg/mL). Among sevelamer-treated patients, iPTH significantly increased, and this change was more marked in the patients with an initial iPTH level <150 pg/mL. Sevelamer was useful for reducing the serum calcium level and calcium x phosphate product, but hyperphosphatemia and hyperparathyroidism were not improved in our study population at 12 months after the release of sevelamer. A decrease in the calcium load might result in the exacerbation of hyperparathyroidism. However, among patients with relative hypoparathyroidism, sevelamer therapy may be beneficial for the prevention of adynamic bone disease.
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PMID:Influence of sevelamer on mineral metabolism and hyperparathyroidism in Japanese hemodialysis patients. 1749 3

In chronic kidney disease patients, bone and mineral abnormalities have a major impact on morbidity and mortality. Hyperphosphatemia has been associated with increased mortality and with the development of cardiovascular calcification, an independent predictor of mortality. Vascular calcifications have been associated with low bone turnover, low bone volume and lower activation frequency. In dialysis patients, the treatment of hyperphospathemia with calcium based compounds, when compared with sevelamer, is associated with more frequent episodes of hypercalcemia, suppression of intact parathyroid hormone and with progression of coronary calcifications. In the presence of adynamic bone disease, calcium load has a significantly higher impact on aortic calcifications and stiffening. A randomized, prospective, open label study, evaluated patients with bone biopsies at the beginning and after 1 year treatment period with sevelamer hydrochloride or calcium carbonate. Sevelamer treatment resulted in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate, but bone formation rate increased and trabecular architecture improved only with sevelamer. In incident dialysis patients, treatment with sevelamer has been associated with better survival, while in prevalent patients a clear benefit could only be demonstrated in older patients and in patients treated for more than 2 years.In conclusion, the treatment of hyperphosphatemia with sevelamer hydrochloride, a non-calcium and non-metal containing phosphate binder, is associated with a beneficial effect on vascular calcification progression, bone disease and most likely with a survival benefit in some hemodialysis patients populations.
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PMID:Treatment of hyperphosphatemia with sevelamer hydrochloride in dialysis patients: effects on vascular calcification, bone and a close look into the survival data. 1903 24

Hyperphosphatemia in dialysis patients is known to cause secondary hyperparathyroidism and high-turnover bone disease. Sevelamer hydrochloride (sevelamer) is a nonabsorbed, calcium-free phosphate-binder. We determined the effect of sevelamer on parathyroid hormone (PTH)-induced high bone turnover. Rats were sham-operated or 5/6-nephrectomized (Nx) and fed a phosphate loading diet for 16 weeks or 5/6-nephrectomized and fed a phosphate loading diet for 8 weeks and then fed the same diet containing 3% sevelamer for the subsequent 8 weeks (Nx-S). Sevelamer significantly reduced serum PTH. The relative osteoid volume (OV/BV), osteoid surface (OS/BS), eroded surface (ES/BS), mineral appositional rate (MAR), volume-referent bone formation rate (BFR/TV), and bone-referent bone formation rate (BFR/BV) were measured for vertebral bone histomorphometric analysis. All parameters were statistically higher in the Nx rats than in the sham-operated control rats. The administration of sevelamer attenuated increases in OV/BV, ES/BS, BFR/TV, and BFR/BV. For femur histomorphometric analysis, the porosity area (%) (PoAr/CtAr), osteoid surface on the periosteal surface, osteoid surface on the endocortical surface (OS/Es), mineral appositional rate on the periosteal surface, mineral appositional rate on the endocortical surface, bone formation rate on the periosteal surface, and bone formation rate on the endocortical surface (Es BFR) were calculated. All parameters were higher in the Nx group than in the control group. Sevelamer inhibited the elevation of PoAr/CtAr, OS/Es, and Es BFR. Our findings suggest that the decrease in PTH by sevelamer may be beneficial in the treatment of high PTH-induced bone disease.
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PMID:Effect of sevelamer hydrochloride on bone in experimental uremic rats. 1937 69

A change in paradigm occurred lately whereby not hypocalcemia but hypercalcemia and positive calcium balance were considered negative factors. Namely, the use of calcium- based binders in combination with vitamin D analogues, has been shown to lead to an over-suppression of parathyroid hormone (PTH) and development of low-bone turnover adynamic bone disease (ABD). The changing prevalence of various types of bone diseases from a high to low-bone turnover goes in line with the presence of increased risk for vascular calcification (VC), morbidity and mortality in the dialysis population. The attenuation of the previous great expectations in calcium-based phosphate binders and vitamin D-analogues entailed a new treatment strategy to preserve bone and vascular health. Hence, a new evidence for treatment of ABD with various types of non calcium based binders and low calcium dialysate is presented. Sevelamer treatment has reduced calcium concentration and increased PTH levels, resulting in the improvement of markers of bone turnover, increased bone formation and improved trabecular architecture, providing a slower progression of VC. Data on lanthanum beneficial effect on ABD histology have been demonstrated in long-term clinical studies. Although there is a slow release of lanthanum from its bone deposits after discontinuation of the treatment and no association with aluminium- like bone toxicity, there is still an ongoing scientific debate about its long-term toxic potential. Finally, reducing the number of calcium based binders and low calcium dialysate (1.25 mmol/l) has been reported to have an impact on the evolution towards markers reflecting higher bone turnover. Then, adoption of the non calcium-based binders should be reserved to high risk patients with ABD and progression of vascular calcifications associated with increased morbidity and mortality.
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PMID:Strategies to manage low-bone turnover. 1966 99

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