Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal osteodystrophy presents with a spectrum of histologic abnormalities. A new entity characterized by a marked decrease in bone turnover without osteoid accumulation, that is, adynamic bone disease, has recently emerged. This new form was thought to be primarily related to aluminum accumulation. Since aluminum-containing phosphate binders have been widely replaced by calcium salts, adynamic bone disease would be expected to disappear over time. However, not only is adynamic bone disease observed in the absence of aluminum intoxication, its incidence does not seem to have decreased. We conducted a retrospective study in 1,803 patients on chronic maintenance dialysis who were biopsied during the last 10 years and assessed the incidence of adynamic bone disease over time in an effort to elucidate the factors associated with its occurrence. Adynamic bone disease was first seen in 1984 in the laboratory. Its incidence increased gradually over the years and, in 1991, still affected approximately 20% of the patients. The primary factors associated with the occurrence of adynamic bone disease include: (a) aluminum accumulation which is currently found in 60% of the patients on chronic maintenance dialysis undergoing biopsies, (b) increasing age of the patients on dialysis, (c) diabetes, and, possibly, (d) chronic ambulatory peritoneal dialysis. The clinical relevance of adynamic bone disease deserves further study. At present, this entity is associated with a tendency towards hypercalcemia, aging of bone due to stunted bone remodeling, a condition which might be associated with impaired repair of physiologic microdamages, and accumulation of microfractures leading to mechanical incompetence and ultimately to higher risk of fractures.
 ...
PMID:Risk of adynamic bone disease in dialyzed patients. 140 83

Adynamic bone disease unrelated to aluminum deposition, with low parathyroid hormone (PTH) levels, has increased in patients with end-stage renal failure. Some patients present with severe secondary hyperparathyroidism despite calcitriol administration and phosphate restriction. Because therapeutic and environmental factors are now similar among hemodialyzed patients, the variable incidence of secondary hyperparathyroidism may be caused by genetic heterogeneity. To examine this possibility, we analyzed restriction fragment length polymorphisms of the vitamin D receptor (VDR) gene in 877 Japanese hemodialysis patients. VDR allelic polymorphism was determined by the method of Morrison et al. Polymerase chain reaction (PCR) amplification and a BsmI endonuclease restriction site at the 5' end of the VDR gene defined BB (absence of restriction site on both alleles), Bb (heterozygous), or bb (restriction site on both alleles). The mean serum PTH level was lower in BB patients (86 +/- 102 pg/mL) than in bb patients (148 +/- 217 pg/mL; P < 0.05). The serum osteocalcin level was also lower in BB than in bb patients (P < 0.05). If results were re-analyzed excluding patients with a history of dialysis exceeding 10 years or those with non-insulin-dependent diabetes mellitus (NIDDM) or who had undergone parathyroidectomy, the differences in serum PTH levels were greater. However, there was no significant difference in serum PTH levels among the VDR genotypes, only for patients with NIDDM. The present study shows that patients with the b allele for the VDR gene have more severe secondary hyperparathyroidism than patients without the b allele. However, NIDDM or a long history of hemodialysis has a stronger power to influence PTH secretion.
 ...
PMID:Vitamin D receptor gene polymorphisms affect secondary hyperparathyroidism in hemodialyzed patients. 974 Jan 63

In the early stages of renal failure, hyperparathyroidism develops as a compensatory mechanism to control serum levels of calcium, phosphorus and calcitriol. As kidney disease progresses, this ability to maintain mineral homeostasis is lost, leading to the development of renal osteodystrophy (ROD). Over the past decade, the pattern of ROD seen in patients with chronic kidney disease (CKD) has changed. Previously, the majority of patients had mixed uraemic osteodystrophy or aluminium-related osteomalacia. The decreased use of aluminium-based phosphate binders, coupled with improvements in the management of hyperphosphataemia, led to a reduction in the prevalence of these types of ROD. Since the mid-1990s, there has been an increase in the prevalence of adynamic bone disease as a result of increased suppression of parathyroid hormone through the use of calcium-based phosphate binders and calcitriol therapy. Adynamic bone disease is also associated with several clinical factors, such as older age, use of continuous ambulatory peritoneal dialysis and the presence of diabetes mellitus, as well as the use of calcitriol therapy. Studies of calcium metabolism in patients with CKD have shown that adynamic bone disease is a distinct clinical condition that leads to hypercalcaemia via mechanisms different from that seen in high-turnover bone disease. As high calcium x phosphorus product has been associated with soft tissue and vascular calcifications, and increased mortality, optimizing bone health may be an important way of reducing cardiovascular risk in patients with CKD. To do this, novel, effective, non-calcium, non-aluminium phosphate binders will be necessary.
 ...
PMID:The importance of bone health in end-stage renal disease: out of the frying pan, into the fire? 1512 48

Adynamic bone disease (ABD) is a well-recognized clinical entity in the complex chronic kidney disease (CKD)-mineral and bone disorder. Although the combination of low intact parathyroid hormone (PTH) and low bone alkaline phosphatase levels may be suggestive of ABD, the gold standard for precise diagnosis is histomorphometric analysis of tetracycline double-labeled bone biopsies. ABD essentially is characterized by low bone turnover, low bone volume, normal mineralization, and markedly decreased cellularity with minimal or no fibrosis. ABD is increasing in prevalence relative to other forms of renal osteodystrophy, and is becoming the most frequent type of bone lesion in some series. ABD develops in situations with reduced osteoanabolic stimulation caused by oversuppression of PTH, multifactorial skeletal resistance to PTH actions in uremia, and/or dysregulation of Wnt signaling. All may contribute not only to bone disease but also to the early vascular calcification processes observed in CKD. Various risk factors have been linked to ABD, including calcium loading, ageing, diabetes, hypogonadism, parathyroidectomy, peritoneal dialysis, and antiresorptive therapies, among others. The relationship between low PTH level, ABD, increased risk fracture, and vascular calcifications may at least partially explain the association of ABD with increased mortality rates. To achieve optimal bone and cardiovascular health, attention should be focused not only on classic control of secondary hyperparathyroidism but also on prevention of ABD, especially in the steadily growing proportions of diabetic, white, and elderly patients. Overcoming the insufficient osteoanabolic stimulation in ABD is the ultimate treatment goal.
...
PMID:Adynamic bone disease: from bone to vessels in chronic kidney disease. 2549 81