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

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 patient with secondary hyperparathyroidism (2 degrees HPT) underwent a total parathyroidectomy (PTx) without autotransplantation and showed interesting changes in the morphology of his iliac bone before and after the surgery. A 70-year-old man had been on hemodialysis for chronic glomerulonephritis since 1987. He had been administered calcium carbonate 6.0 g daily to prevent reabsorption of phosphorus and alfacalcidol 1.0 microg three times weekly at the end of hemodialysis. In September 2000, his intact parathyroid hormone (iPTH; 1-84 PTH) was 610 pg/mL; therefore, from 2.5 microg to 10 microg 22-oxacalcitriol (maxacalcitol, a derivative of active vitamin D) was administered intravenously three times weekly at the end of hemodialysis. This compound is used in Japan for 2 degrees HPT. However, the iPTH progressed, and hypercalcemia and hyperphosphatemia were observed. Ultrasonography of the neck illustrated three enlarged parathyroid glands that were each over 1.0 cm in diameter. On 14 July 2004, a PTx without autotransplantation (PTx alone) and an iliac crest bone biopsy were performed. Bone specimens showed mild lesions of hyperparathyroidism, but did not meet the criteria for osteitis fibrosa. One year after the procedure, a second biopsy was obtained to investigate the bone turnover in response to a lack of parathyroid hormone. The bone specimen showed tetracycline labeling at the time of PTx alone, and new bone apposition on the surface without tetracycline labeling. This adynamic bone disease (ABD) suggested that new bone apposition in the absence of tetracycline labeling had occurred after the PTx alone, and it had likely occurred over the course of one year.
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PMID:A case report of a bone histomorphometrical analysis after a total parathyroidectomy. 1937 76

Chronic kidney disease (CKD) is commonly, if not universally, associated with derangements in bone and mineral metabolism, characterized by hyperphosphatemia, low calcitriol levels, and secondary hyperparathyroidism. The spectrum of these disorders is termed renal osteodystrophy or chronic kidney disease-mineral bone disease complex. Aggressive phosphorus control is the cornerstone of management to prevent debilitating complications. Dietary control, phosphate binders, and administration of active vitamin D analogues is the most common initial therapy. Frequently parathyroidectomy is required to reverse or slow the pathological changes when medical management fails. The most common adverse effect of parathyroidectomy is hypocalcemia. We describe a case report of severe hypocalcemia (secondary to surgical hypoparathyroidism) and "hungry bone syndrome," treated successfully with teriparatide (Forteo) in a patient who underwent renal transplantation following subtotal parathyroidectomy.
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PMID:Hypoparathyroidism associated with severe mineral bone disease postrenal transplantation, treated successfully with recombinant PTH. 1949 22

The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the management of chronic kidney disease-mineral and bone disorder (CKD-MBD) is intended to assist the practitioner caring for adults and children with CKD stages 3-5, on chronic dialysis therapy, or with a kidney transplant. The guideline contains recommendations on evaluation and treatment for abnormalities of CKD-MBD. This disease concept of CKD-MBD is based on a prior KDIGO consensus conference. Tests considered are those that relate to the detection and monitoring of laboratory, bone, and cardiovascular abnormalities. Treatments considered are interventions to treat hyperphosphatemia, hyperparathyroidism, and bone disease in patients with CKD stages 3-5D and 1-5T. The guideline development process followed an evidence based approach and treatment recommendations are based on systematic reviews of relevant treatment trials. Recommendations for testing used evidence based on diagnostic accuracy or risk prediction and linked it indirectly with how this would be expected to achieve better outcomes for patients through better detection, evaluation or treatment of disease. Critical appraisal of the quality of the evidence and the strength of recommendations followed the GRADE approach. An ungraded statement was provided when a question did not lend itself to systematic literature review. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.
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PMID:KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). 2894 64

Hyperphosphatemia is considered as an independent risk factor for surrogate clinical endpoints like vascular calcification (VC) and bone disease, or hard clinical outcomes like cardiovascular events. To date, various treatment options for phosphate removal or reduction are available. The great expectations put into calcium-based phosphate binders were mitigated because of their possible contribution to progressive VC, particularly in patients treated simultaneously with active vitamin D derivatives. Thus, a paradigm change occurred whereby the main clinical concern shifted from the avoidance of hypocalcemia to that of the consequences of inducting a positive calcium balance. Sevelamer-HCl treatment allowed a comparable control of hyperphosphatemia with a lower risk of hypercalcemia than calcium-based phosphate binders, and a slower progression of VC; however, convincing evidence of improved clinical outcomes in dialysis patients is lacking. Although data on the safety and efficacy of lanthanum carbonate in the treatment of hyperphosphatemia have been provided in long-term clinical studies, there is still an ongoing scientific debate about its possible long-term toxicity. Moreover, there are no data from randomized clinical trials demonstrating beneficial effects of La carbonate treatment on VC or cardiovascular outcomes. In the absence of convincing clinical trials testing the effects of non-metal-based phosphate binders on cardiovascular and global outcomes it appears reasonable to maintain bone health and mineral homeostasis by mainly relying on adaptations of standard therapies. Noncalcium, non-aluminum-based binders might be reserved for patients with major mineral metabolism abnormalities and a high risk of VC.
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PMID:Phosphate metabolism in chronic kidney disease: from pathophysiology to clinical management. 1970 81

Recent advances in our understanding of the excess mortality of chronic kidney disease (CKD) due to cardiovascular complications, obtained through observational studies, demonstrate that vascular calcification and hyperphosphatemia are major cardiovascular risk factors. Mechanistic studies demonstrate that these two risk factors are related and that hyperphosphatemia directly stimulates vascular calcification. The role of hyperphosphatemia in stimulating vascular calcification in CKD is associated with a block to the skeletal reservoir function in phosphate balance due to excess bone resorption. This has led to the realization that renal osteodystrophy is linked to vascular calcification by disordered mineral homeostasis (phosphate) and that a multiorgan system fails in CKD, leading to cardiovascular mortality. In children with renal disease, the multiorgan system fails, just as in adults, but the outcomes have been less well studied, and perceptions of differences from adults are possibly incorrect. Vascular calcification and cardiovascular mortality are less prevalent among pediatric patients, but they are present. However, CKD-induced vascular disease causes stiffness of the arterial tree causing, in turn, systolic hypertension and left ventricular hypertrophy as early manifestations of the same pathology in the adult. Because of the role of the skeleton in these outcomes, renal osteodystrophy has been renamed as the CKD mineral bone disorder (CKD-MBD). This review, which focuses on the pediatric patient population, describes our current state of knowledge with regards to the pathophysiology of the CKD-MBD, including the new discoveries related to early stages of CKD. As a new necessity, cardiovascular function issues are incorporated into the CKD-MBD, and new advances in our knowledge of this critical component of the disorder will lead to improved outcomes in CKD.
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PMID:Cardiovascular risk in chronic kidney disease (CKD): the CKD-mineral bone disorder (CKD-MBD). 1989 75

Hyperphosphatemia is a central characteristic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Phosphorus excess is an independent cardiovascular risk factor for morbidity and mortality in patients with advanced CKD. Over the past 40 years, hyperphosphatemia has been a central therapeutic issue in advanced CKD. Mainstays of hyperphosphatemia treatment are reduction of dietary phosphorus, use of phosphate binders, and optimized phosphorus removal via dialysis. Currently, several phosphate binders are approved for use (aluminum, calcium, lanthanum, sevelamer); all share a common functionality in that they bind phosphorus and reduce the amount absorbed in the gastrointestinal lumen. Over the last decade, nephrologists have debated the relative tolerability and efficacy of these agents, especially the potential for vascular calcification and cardiovascular risk reduction. Recent research has focused on the question of whether a metal-free, calcium-free, and non-absorbed binder, such as sevelamer, offers advantages over other binder types. Most notable may be the potential benefit of reducing calcium load. In addition, sevelamer has several additional pleiotropic effects that may extend its basic indication, some of which may help attenuate vascular calcification. These include effects on bone turnover and the link between abnormal vascular processes and bone metabolism (the so-called 'bone-vascular axis'), as well as lipid metabolism, and systemic inflammatory mediators such as fetuin-A. We review the evidence for these pleiotropic effects, and suggest these may help in some way to improve the substantial disease burden in the CKD-MBD population.
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PMID:Sevelamer and the bone-vascular axis in chronic kidney disease: bone turnover, inflammation, and calcification regulation. 1994 24

This commentary provides a US perspective on the 2009 KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). KDIGO is an independent international organization with the primary mission of the promotion, coordination, collaboration, and integration of initiatives to develop and implement clinical practice guidelines for the care of patients with kidney disease. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI), recognizing that international guidelines need to be adapted for each country, convened a group of experts to comment on the application and implementation of the KDIGO guideline for patients with CKD in the United States. This commentary puts the KDIGO guideline into the context of the supporting evidence and the setting of care delivered in the United States and summarizes important differences between prior KDOQI guidelines and the newer KDIGO guideline. It also considers the potential impact of a new bundled payment system for dialysis clinics. The KDIGO guideline addresses the evaluation and treatment of abnormalities of CKD-MBD in adults and children with CKD stages 3-5 on long-term dialysis therapy or with a kidney transplant. Tests considered are those that relate to laboratory, bone, and cardiovascular abnormality detection and monitoring. Treatments considered are interventions to treat hyperphosphatemia, hyperparathyroidism, and bone disease in patients with CKD stages 3-5D and 1-5T. Limitations of the evidence are discussed. The lack of definitive clinical outcome trials explains why most recommendations are not of level 1 but of level 2 strength, which means weak or discretionary recommendations. Suggestions for future research highlight priority areas.
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PMID:KDOQI US commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD-Mineral and Bone Disorder (CKD-MBD). 2036 41

Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.
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PMID:The bone histology spectrum in experimental renal failure: adverse effects of phosphate and parathyroid hormone disturbances. 2042 57

FGF23 is a novel bone-derived hormone that plays an important role in the regulation of phosphate and 1,25-dihydroxy vitamin D metabolism. FGF23 binds to FGF receptor1 (FGFR1) -Klotho complex in the kidney and thereby induces phosphaturia and suppresses 1,25-dihydroxyvitamin D synthesis. In patients with chronic kidney disease (CKD) , circulating FGF23 levels are progressively increased to compensate for persistent phosphate retention, but this results in reduced renal production of 1,25-dihydroxyvitamin D and leads to secondary hyperparathyroidism. In patients undergoing dialysis, FGF23 levels are markedly elevated in response to hyperphosphatemia and active vitamin D therapy, which in turn cause hypophosphatemia and reduced 1,25-dihydroxyvitamin D after kidney transplantation. FGF23 also acts directly on the parathyroid to decrease parathyroid hormone synthesis and secretion; however, in end-stage CKD patients, markedly elevated FGF23 fails to suppress the secretion of parathyroid hormone. Recent data suggest that this parathyroid resistance to FGF23 may be caused by decreased expression of FGFR1-Klotho complex in hyperplastic parathyroid glands. Further elucidation of FGF23-Klotho axis will help us to improve the understanding of the pathogenesis of CKD-mineral and bone disorder.
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PMID:[CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Role of FGF23-Klotho axis in CKD-MBD]. 2058 81


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