Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined renal handling of sulfate and phosphate anions in normal subjects, in patients with two Mendelian disorders of phosphate homeostasis [X-linked hypophosphatemia (XLH) and hypophosphatemic bone disease (HBD)], and in normal male mice (+/Y) and male littermates with murine X-linked hypophosphatemia (Hyp/Y). Serum sulfate was 0.30 +/- 0.04 mmol/l (mean and SD, n = 15) in control human subjects. The corresponding fractional excretion was 0.43 +/- 0.12, and absolute sulfate reabsorption, 15.1 +/- 5.0 mumol/100 ml GF. Patients with impaired phosphate homeostasis had normal renal handling of sulfate. Parathyroid hormone infusion inhibited phosphate reabsorption in normal subjects but did not change tubular reabsorption of sulfate. Serum sulfate was 1.24 +/- 0.20 mmol/l (mean and SD, n = 11) in +/Y mice; the corresponding fractional excretion was 0.38 +/- 0.13. Values in Hyp/Y littermates were not significantly different (1.21 +/- 0.16 mmol/l and 0.32 +/- 0.10, respectively). Brush-border membrane vesicles isolated from Hyp/Y renal cortex demonstrated impaired Na+-dependent phosphate uptake (45% of +/Y control) whereas Na+-dependent sulfate uptake was the same as control. These findings constitute further evidence that sulfate and phosphate anions are conserved from renal filtrate by independent processes in the brush-border membrane of mammalian kidney.
 ...
PMID:The effects of Mendelian mutation on renal sulfate and phosphate transport in man and mouse. 670 Oct 31

Secondary hyperparathyroidism is a universal complication of chronic renal failure. It has been proposed that the markedly elevated levels of immunoreactive parathyroid hormone (i-PTH) in uremia may represent a "uremic toxin" responsible for many of the abnormalities of the uremic state. Plasma i-PTH consists of a mixture of intact hormone, a single-chain polypeptide of 84 amino acids, and smaller molecular weight hormonal fragments from both the carboxy- and amino-terminal portion of the PTH molecule. The hormonal fragments arise from metabolism of intact PTH by peripheral organs as well as from secretion of fragments from the parathyroid glands. The structural requirements for the known biological actions of PTH reside in the amino-terminal portion of the PTH molecule. Carboxy-terminal fragments, biologically inactive at least in terms of adenylate cyclase activation, hypercalcemia, or phosphaturia, depend on the kidney for their removal from plasma, and thus accumulate in the circulation in chronic renal failure. It is unknown at the present time if other biological effects of these carboxy-terminal fragments may contribute to some of the biochemical alterations observed in uremia. The most significant consequence of increased PTH levels in uremia is the development of bone disease characterized by osteitis fibrosa. In addition, it would appear that PTH plays an important role in some of the abnormal electroencephalographic patterns observed in uremia. This may be due to a potential role of PTH in increasing calcium content of brain. Parathyroid hormone also has been implicated as a pathogenetic factor in many other alterations present in uremia, i.e., peripheral neuropathy, carbohydrate intolerance, hyperlipidemia, and other alterations. Unfortunately, outstanding clinical research is lacking in this field and conclusive experimental data are practically nonexistent. Further studies are necessary if one is to accept the concept of PTH being a significant "uremic toxin."
 ...
PMID:Parathyroid hormone metabolism and its potential as a uremic toxin. 699 9

Although the full mechanisms are not yet elucidated, research into the mechanism of toxicity of aluminum (Al) on bone formation and remodeling and on hematopoietic tissue is ongoing. In contrast little information exists on the interactive effects of systemic Al and the kidney. In bone, both clinically and experimentally, high doses of Al inhibit remodeling, slowing both osteoblast and osteoclast activities and producing osteomalacia and adynamic bone disease. In contrast, while very low levels of Al are mitogenic in bones of experimental animals, the effect of low levels of Al in humans is unknown. Aluminum has been shown to have its mitogenic action at the osteoblast, but whether the effect on resorption is viz osteoblast-directed changes in osteoclast activity has not yet been determined. Parathyroid hormone (PTH) levels are disrupted by Al in humans and animals. Whether altered PTH levels play a major or even a minor role in Al-dependent osteotoxicity requires clarification. In hematopoietic tissue, Al causes a microcytic anemia, not reversible by iron. Friend leukemia cells treated with Al have been reported to accumulate excess iron, without incorporating it into ferritin or heme. It is not yet known which steps in iron metabolism are disrupted by Al, if they involve a single mechanism of action, or even if this disruption in iron metabolism accounts for the anemia seen in Al toxicosis. In kidney, research is needed to evaluate Al nephrotoxicity; there are almost no studies in this area. Furthermore, research is needed to evaluate mechanisms of renal Al excretion, presently shown by one study to occur at the distal tubule. Such studies might well throw light on whether Al plays a role in aggravating renal insufficiency, or whether the role of the kidney in Al toxicosis is limited to the causative effect of renal compromise on Al accumulation. In summary, while a number of mechanisms have been proposed for the toxic action of Al, no single mechanism emerges to explain these diverse effects of systemic Al. Recommendations for future research are presented and summarized in Table 1.
 ...
PMID:Systemic aluminum toxicity: effects on bone, hematopoietic tissue, and kidney. 877 4

The measurement of calciotropic hormones may be useful in metabolic bone disease. Assays of intact parathyroid hormone are essential to differentiate between primary hyperparathyroidism and nonparathyroid-mediated hypercalcemia. Vitamin D status is best assessed by measuring serum 25(OH)D. Concentrations of calciotropic hormones should be measured in osteoporotic patients if the degree of osteopenia does not correlate with the risk factors. The decrease in circulating parathyroid hormone in osteoporotic patients treated with vitamin D reflects the success of the vitamin D treatment. Parathyroid hormone is also a potential anabolic agent.
 ...
PMID:Diagnostic and therapeutic aspects of calciotropic hormones. 922 85

African teenagers with slipped capital femoral epiphysis (SCFE) not infrequently also have genu valgum (knock-knee). Because we had previously demonstrated metabolic bone disease attributable to dietary calcium deficiency in black teenagers with genu valgum, we examined 29 black teenagers (15 male, 14 female) with SCFE for metabolic bone disease. Each patient had an iliac crest bone biopsy taken (after double tetracycline labeling) for routine histomorphometry, and blood and urine samples for bone biochemistry. Spinal bone mineral density was measured in 13 patients. Compared to reported data, we found our patients to be sexually more immature, older, at least as obese, and to have more severe and more frequently bilateral hip disease. Eighty percent of the children took dairy products only once or twice a week or less frequently, and 37.9% had genu valgum. Compared with race- and age-matched South Africans, bone biopsies in our patients showed lower bone volume (BV/TV, p = 0.0003), wall thickness (p = 0.0002), and trabecular thickness (Tb.Th, p = 0.0002), and a tendency to greater trabecular spacing (Tb.Sp, p = 0.053). Lower osteoid volume (OV/BV, p = 0.0001), osteoid surface (OS/BS, p = 0.0001), osteoid thickness (O.Th, p = 0.0002), double labeled surface (dLS/BS, p = 0.029), and bone formation rate (BFR/BS, p = 0.037) suggested poorer bone forming capacity in our patients. No evidence of hyperparathyroid bone disease or osteomalacia was found. BV/TV was below the reference range (14.2%) in 65.5% of cases; these patients had lower values for Tb.Th (p = 0.037) and Tb.N (p = 0.0003), greater Tb.Sp (p = 0.0002), a tendency to lower adjusted apposition rate (Aj.AR, p = 0.057), and had had less frequent intake of dairy products than those with normal BV/TV (p = 0.024). Furthermore, months since menarche correlated with histomorphometric variables BV/TV (r = 0.667, p = 0.009), Tb.Th (r = 0.745, p = 0.002), Tb.Sp (r = -0.549, p = 0.042), O.Th (r = 0.784, p = 0.0009), and Aj.AR (r = 0.549, p = 0.042). The correlation between Tb.Th and spinal bone mineral content (r = 0.656, p = 0.015) suggests that the reduced trabecular thickness reflected a generalized bone condition. A greater than normal proportion of patients had spinal bone mineral density values below -1 standard deviation (SD) of the mean (osteopenia) (p = 0.001). Patients tested for parathyroid hormone and 25-hydroxyvitamin D levels were found to have normal values. Parathyroid hormone correlated with Aj.AR (r = 0.661, p = 0.038) and serum phosphorus (r = -0.764, p = 0.010). We conclude that sexual immaturity and possibly past dietary calcium deficiency contributed to osteopenia, and that this, together with obesity, led to the development of more severe and more frequently bilateral SCFE in our patients than in reported series of black and white children.
 ...
PMID:Bone disease in African children with slipped capital femoral epiphysis: histomorphometry of iliac crest biopsies. 951 18

Cystic fibrosis (CF) patients often have low bone mineral density (BMD) and may suffer from fractures and kyphosis. The pathogenesis of low BMD in CF is multifactorial. To study bone metabolism, we collected fasting serum and urine from 50 clinically stable CF adults (mean age 28 years) and 53 matched controls to measure markers of bone formation and bone resorption. The CF subjects had moderate lung disease (FEV1: 46.1 +/- 18.6% predicted) and malnutrition (BMI: 20.0 +/- 3.3 kg/m2). Only 3 subjects had normal BMD. CF subjects had higher urinary N-telopeptides of type I collagen (81.0 +/- 60.0 vs 49.0 +/- 24.2 nm BCE/mmol creatinine, p = 0.0006) and free deoxypyridinoline (7.3 +/- 5.0 vs 5.3 +/- 1.9 nM/mM, p = 0.004) levels than controls. Serum osteocalcin levels were similar in the two groups, a result confirmed by two immunoassays that recognize different epitopes on osteocalcin. Serum bone-specific alkaline phosphatase levels were elevated in CF patients (32.0 +/- 11.3 vs 21.8 +/- 7.0 U/l, p < 0.0001), but were much more closely associated with serum total alkaline phosphatase levels (r = 0.51, p = 0.001) than with age or gender. Parathyroid hormone levels were elevated (p = 0.007) and 25-hydroxyvitamin D levels were depressed (p = 0.0002) in the CF patients in comparison with controls. These results indicate that adults with CF have increased bone resorption with little change in bone formation. Medications that decrease bone resorption or improve calcium homeostasis may be effective therapies for CF bone disease.
 ...
PMID:Abnormal bone turnover in cystic fibrosis adults. 1190 25

Kidney transplantation is the optimal form of renal replacement therapy for many with end-stage kidney disease. However, kidney transplantation comes with a unique set of medical complications, important among them is bone disease. Posttransplant bone disorders are manifestations of pathologic processes occurring posttransplant that are superimposed on preexisting disorders of bone and mineral metabolism secondary to kidney failure and/or diabetes mellitus. As a consequence of early rapid bone loss, which is seen commonly within the first 3 to 6 months of transplant, the fracture risk posttransplant increases and has been reported as high as 5% to 44%. Posttransplant fractures occur more commonly at peripheral than central sites. Patients with a history of diabetes mellitus are at particular risk for fracture. Parathyroid hormone (PTH) and osteocalcin levels generally decrease after transplantation. Alkaline phosphatase and urinary collagen cross-links are unpredictable. Bone histology varies. No single biomarker unequivocally distinguishes between the various bone disorders found on biopsy examination. Immunosuppression is a major cause of posttransplant bone disorders. Glucocorticoids lead to decreased bone formation whereas the calcineurin inhibitors appear to cause increased bone turnover. Evaluating and managing posttransplant bone disease is an integral part of posttransplant medical care.
 ...
PMID:Bone disease after kidney transplantation. 1473 May 14

Parathyroid hormone (PTH) levels have been used instead of bone histomorphometric analysis in renal failure, but the assessment of tetracycline-labeled bone biopsy remains the most reliable method to diagnose the different subtypes of renal osteodystrophy. The availability of the first-generation immunometric PTH assay (1(st) PTH-IMA) allowed the distinction between the different types of renal bone diseases. However, 1(st) PTH-IMA not only detects the intact hormone PTH(1-84), but also additional PTH truncated fragments. A second-generation immunometric PTH assay (2(nd) PTH-IMA) recognizes only PTH(1-84) and possible PTH fragments that are truncated at the carboxyl-terminus, but not PTH(7-84). In addition, whether assessment of the ratio PTH(1-84) and amino-terminally truncated PTH(1-84) fragments is a better predictor of bone turnover remains controversial. An initial study using the 2(nd) PTH-IMA suggested that the ratio between PTH(1-84) and amino-terminally truncated PTH(1-84) fragments more accurately predicts bone turnover in adult patients treated with hemodialysis. However, subsequent studies using the Scantibodies assay have failed to better predict the underlying bone disease in adults undergoing maintenance hemodialysis. Furthermore, a different 2(nd) PTH-IMA (Immutopics) with similar, but not identical, in vitro characteristics did not show a superior predictive value of the ratio in pediatric patients treated with peritoneal dialysis. Although the 2(nd) PTH-IMA may provide important new insights into the physiology of parathyroid gland function, at present, measurement of PTH using either 1(st) or 2(nd) PTH-IMAs provides similar accuracy for predicting bone turnover in patients treated with dialysis. Thus, the current data do not yet support the claim that 2(nd) PTH-IMAs provide an advantage over 1(st) PTH-IMAs for the diagnosis of the different subtypes of renal bone diseases.
 ...
PMID:New PTH assays and renal osteodystrophy. 1517 36

Renal osteodystrophy is a universal complication of uremia. Renal failure patients are at risk for low bone mineral density (BMD) and fractures. Parathyroid hormone (PTH) plays a pivotal role in the pathophysiology of uremic bone disease. Histomorphometric studies suggest that the maintenance of PTH levels between two and four times the upper limit of normal is associated with the lowest prevalence of two common forms of osteodystrophy: osteitis fibrosa cystica and adynamic bone disease. The purpose of this study was to investigate whether the above recommendation for PTH levels in dialysis patients corresponds to a more optimal BMD with a special emphasis on diabetic versus nondiabetic subjects. Twenty-eight patients with chronic renal failure on hemodialysis underwent measurement of PTH levels, as well as BMD at the lumbar spine, hip, and forearm. They were divided into three groups based on the mean PTH level over the 5 years prior to having BMD measured. Osteoporosis was diagnosed in 55% of men and 87% of women on dialysis. Predictors of BMD were gender, duration on hemodialysis, and diabetes. Our study supports the histomorphometry-based studies suggesting that the maintenance of intact PTH levels two to four times the upper limit of normal may be associated with better skeletal health in uremic patients on hemodialysis, and that the diabetic subgroup is at particular risk for low BMD.
 ...
PMID:Predictors of bone mineral density in patients on hemodialysis. 1525 16

Renal osteodystrophy (ROD), a metabolic bone disease accompanying chronic renal failure (CRF), is a major clinical problem in pediatric nephrology. Growing and rapidly remodeling skeletal systems are particularly susceptible to the metabolic and endocrine disturbances in CRF. The pathogenesis of ROD is complex and multifactorial. Hypocalcemia, phosphate retention, and low levels of 1,25 dihydroxyvitamin D(3) related to CRF result in disturbances of bone metabolism and ROD. Delayed diagnosis and treatment of bone lesions might result in severe disability. Based on microscopic findings, renal bone disease is classified into two main categories: high- and low-turnover bone disease. High-turnover bone disease is associated with moderate and severe hyperparathyroidism. Low-turnover bone disease includes osteomalacia and adynamic bone disease. The treatment of ROD involves controlling serum calcium and phosphate levels, and preventing parathyroid gland hyperplasia and extraskeletal calcifications. Serum calcium and phosphorus levels should be kept within the normal range. The calcium-phosphorus product has to be <5 mmol(2)/L(2) (60 mg(2)/dL(2)). Parathyroid hormone (PTH) levels in children with CRF should be within the normal range, but in children with end-stage renal disease PTH levels should be two to three times the upper limit of the normal range. Drug treatment includes intestinal phosphate binding agents and active vitamin D metabolites. Phosphate binders should be administered with each meal. Calcium carbonate is the most widely used intestinal phosphate binder. In children with hypercalcemic episodes, sevelamer, a synthetic phosphate binder, should be introduced. In children with CRF, ergocalciferol (vitamin D(2)), colecalciferol (vitamin D(3)), and calcifediol (25-hydroxyvitamin D(3)) should be used as vitamin D analogs. In children undergoing dialysis, active vitamin D metabolites alfacalcidol (1alpha-hydroxy-vitamin D(3)) and calcitriol (1,25 dihydroxyvitamin D(3)) are applied. In recent years, a number of new drugs have emerged that hold promise for a more effective treatment of bone lesions in CRF. This review describes the current approach to the diagnosis and treament of ROD.
 ...
PMID:Minimizing bone abnormalities in children with renal failure. 1689 52


<< Previous 1 2 3 4 Next >>