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)

IGF-I is an anabolic hormone which has been reported to increase bone formation in several conditions of undernutrition. Advanced liver cirrhosis is associated with osteopenia and also with low serum levels of IGF-I. Previous results showed that low doses of IGF-I increase osteoblastic activity and decrease bone reabsorption in early liver cirrhosis. The aim of this study was to evaluate whether IGF-I-treatment also induces beneficial effect on osteopenia associated with advanced cirrhosis. Rats with ascitic cirrhosis were divided into two groups: group CI (n=10) which received saline and group CI+IGF (n=10) which were treated with IGF-I (2 microg/100 g bw x day, sc, during 21 days). Healthy controls which received saline were studied in parallel (CO n=10). On the 22nd day, the animals were sacrificed, and bone parameters were analyzed in femur. Posterior-anterior diameter was similar in all groups. No significant differences were observed in bone content of calcium, total proteins, collagen and hydroxyapatite in cirrhotic rats as compared with controls. However, CI rats showed significant reductions in total bone density (-13.5%, p<0.001) assessed by densitometry and radiological study. In CI+IGF rat bone density (assessed by densitometry) improved significantly as compared with CI animals. In summary, osteopenia characterized by loss of bone mass and preserved bone composition was found in rats with advanced cirrhosis induced by CCl4 and phenobarbital in drinking water. This bone disorder is partially restored by treatment with low doses of IGF-I during only three weeks. Thus, IGF-I could be considered as a possible therapy for osteopenia associated with advanced liver cirrhosis.
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PMID:Effects of IGF-I treatment on osteopenia in rats with advanced liver cirrhosis. 1101 14

The kidneys serve as both an endocrine organ and as a target of endocrine action, with the aim of controlling mineral and water balance. Hormones and other key metabolites regulate mineral homeostasis by altering gene function directly or by initiating a sequence of events, leading ultimately to a change in enzyme function. Two of these hormones, parathyroid hormone (PTH) and calcitriol (the active form of vitamin D), interact in multiple tissues in the body to regulate the flux of calcium and phosphorus between extra- and intracellular compartments. Changes in the concentration of PTH and vitamin D, or the interaction of these with other factors, lead to the aberrant regulation of calcium and phosphorus. Among other effects, this aberrant regulation leads to pathologic changes in bone metabolism. The pathology of renal bone disease varies along a spectrum from disorders of low turnover to those of high turnover. This spectrum reflects the results of therapeutic intervention, hormone balances, and other causes. Effective management of renal bone disease therefore requires thorough evaluation of relevant risk factors, measurement of biochemical markers of bone remodeling, and determination of the physical status of bone tissue either by bone mineral density or bone biopsy. Subsequent therapeutic intervention with newer vitamin D compounds, novel phosphate binders, calcimimetics, and the use of alternative dialysis modalities offer hope in normalizing bone remodeling and mineral balance. The human skeleton functions in two capacities: the storage of minerals and structural support of the body. It is the only tissue that behaves as both a major source and a sink of calcium (Ca) and phosphorus (P). Healthy bone is a composite of a collagenous matrix embedded with crystals of hydroxyapatite. On the surface of bone and within the calcified matrix are specialized cells that build and maintain the tissue, and facilitate the movement of Ca and P into and out of serum. Bone undergoes remodeling in response to either damage from mechanical strain or as part of the normal cycle of bone renewal. The process involves distinct steps of cellular activation, bone resorption, and subsequent bone formation. It is a relatively slow process that takes several months, and at any one time occurs at many different sites along the bone surface. Systemic factors, such as PTH and vitamin D, regulate the resorption and formation of bone, and thus the systemic movement of Ca and P. However, during conditions of stress and disease, other factors may also play a role. In patients with chronic renal disease, the balance of Ca and P is profoundly disturbed. This disruption and the compensatory changes that occur in response alter the normal processes of bone metabolism.
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PMID:Regulation of bone remodeling: impact of novel therapies. 1120 41

Congestive heart failure describes a syndrome with complex and variable symptoms and signs, including dyspnea, increased fatigability, tachypnea, tachycardia, pulmonary rales, and peripheral edema. Although this syndrome usually is associated with low cardiac output, it may occur in a number of so-called high output states, when the cardiac output is normal or greater than normal. A high output state may occur in chronic severe anemia, large arteriovenous fistula or multiple small arteriovenous shunts as in Paget's bone disease, some forms of severe hepatic or renal disorders, and acutely in septic shock. The syndrome of systemic congestion in a high output state is traditionally referred to as high output heart failure. However, the term is a misnomer because the heart in these conditions is normal, capable of generating very high cardiac output. The underlying problem in high output failure is a decrease in the systemic vascular resistance that threatens the arterial blood pressure and causes activation of neurohormones, resulting in an increase in salt and water retention by the kidney. Many of the high output states are curable conditions, and because they are associated with decreased peripheral vascular resistance, the use of vasodilator therapy for treatment of congestion may aggravate the problem. There are other clinically important issues in high output failure that have received little attention in the current medical literature. This article reviews the available data on high output cardiac failure with particular emphasis on the underlying mechanisms and treatment.
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PMID:High Output Cardiac Failure. 1124 61

Chronic aluminium exposure and toxicity related to aluminium absorption and contaminated dialysis fluid continue to be a problem for many patients with renal failure, particularly in South America and in some developing countries. The two most prevalent sources of aluminium in this population are water used to prepare dialysate and aluminium-containing phosphate binders. Of particular concern is the effect of aluminium at the level of the bone, the haematopoietic system and the brain. Here we focus mainly on the adverse effects of aluminium on bone, the preferred organ of aluminium accumulation in the body. Unfortunately, aluminium has a cumulative effect, thus even short-term exposure to aluminium in phosphate binders adds to the total load and may contribute to the risk of aluminium-related bone disease. Even a bone biopsy does not allow a precise determination of total bone aluminium content. We examine the mechanisms by which aluminium contributes to abnormal bone remodelling. Studies indicate that aluminium has a direct effect, inhibiting bone formation and resorption. There is also evidence for an indirect effect through the action of aluminium on parathyroid hormone synthesis and by its modulation of calcium activity. We discuss commonly used techniques for identifying aluminium load and review studies of chelation therapy as a method to lower aluminium load. It is apparent that aluminium overload has serious consequences for patients with chronic renal failure, yet this problem can be largely prevented by the use of aluminium-free phosphate binders. The deleterious effects on bone remodelling caused by chronic exposure to aluminium suggest that caution should be observed when using other metals as phosphate binders.
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PMID:The clinical impact of aluminium overload in renal failure. 1190 51

Several recent studies have revealed a wide role for nitric oxide (NO) in bone metabolism. Low doses of NO cause bone resorption, but higher doses of NO inhibit bone resorbing activity. Cytokines are potent stimulators of NO production. NO is a very short-lived molecules. It exists for only 6-10 s only before it is converted by oxygen and water into the end-products nitrates and nitrites. Osteoporosis is a metabolic bone disease, characterized by a decreased amount of bone and increased susceptibility to fracture. NO may be involved as a mediator of bone disease such as post-menopausal osteoporosis. Calcitonin is a peptide hormone that inhibits bone resorption. The function of calcitonin in some cells is often unclear. In this study 30 post-menopausal osteoporotic women of ages ranging between 55 and 59 years without systemic diseases and free of any drug therapy were included. Twenty of them, randomly chosen, were treated with calcium (500 mg day(-1))+calcitonin (nasal spray 100 U day(-1)) and the other 10 women (control group) were treated with calcium only. This treatment was applied for 6 months and NO values were measured in each of the two groups before and after treatment. Our findings demonstrate that NO regulates osteoclastic bone resorption activity in association with calcitonin.
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PMID:The effect of calcitonin treatment on plasma nitric oxide levels in post-menopausal osteoporotic patients. 1197 5

Subtotal parathyroidectomy or total parathyroidectomy (PTx) with autotransplantation are surgical procedures considered while the patient is included on the waiting list for renal transplantation. Total PTx alone is based in the possibility that a fragment of tissue (nodular hyperplasia in particular) left in the same pathophysiological environment of long term dialysis would show the same behavior and reproduce in time the same clinicopathological picture. The persistence of uremia induces a continued growth stimulus developing residual hyperplasia and consequently a very high risk of recurrence. We performed total PTx alone in 15 uremic patients excluded for renal transplantation 10 patients with undetectable iPTH serum concentration and were followed up for 37 to 144 months. There was no evidence of clinical bone disease (bone pain or fractures). Bone mineral lumbar spine and hip density was measured at the end of follow-up. The z score data showed that all patients had a bone mass similar than that expected for their age. Bone biopsies performed in four patients showed a uniform picture of low turnover without aluminium staining. Calcification of small arteries (digital and arcade vessels in hands and feet) were evaluated pre and post total PTx alone in nine out of the 10 patients with undetectable PTH levels. The small vessel calcification was present in five patients at the moment of PTx. At the end of the long term follow-up only one patient showed progression. In conclusion, total PTx without autotransplantation is a very effective and adequate treatment for refractory severe hyperparathyroidism in patients excluded for renal transplantation. Aluminium related osteopathy post PTx is a risk to be controlled with aluminium "free" dialysis water and avoiding aluminium containing phosphate binders.
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PMID:Parathyroidectomy in dialysis patients. 1198 31

Previously, we identified a parathyroid hormone-related high-turnover bone disease after gastrectomy in mini pigs. Dynamic [(18)F]fluoride ion positron emission tomography (PET) revealed that bone metabolism was significantly increased, but that bone blood flow derived from permeability-surface area product (PS product)-corrected K(1) values was not. Since bone blood flow and metabolism are coupled in normal bone tissues, we hypothesised that the capillary permeability and/or surface area might be altered in high-turnover bone disease. The "true" bone blood flow ( f(H2O)) was measured in vertebral bodies by dynamic [(15)O]H(2)O PET, followed by a 120-min dynamic [(18)F]fluoride ion PET study, 6 months after total gastrectomy (n=5) and compared with results in sham-operated animals (n=5). Estimates for bone blood flow based on PS-corrected K(1) values (f) and the net uptake of fluoride in bone tissue (K(i)), representing the bone metabolic activity, were calculated using standard compartmental modelling and non-linear fitting. Gastrectomy was followed by a significant elevation of K(i) and k(3) ( P<0.05), which was mainly caused by an increase of the fraction of bound tracer in tissue (P<0.01). In contrast, f(H2O), f, the single-pass extraction fraction of [(18)F]fluoride (E) and the volume of distribution (DV) of [(18)F]fluoride were not significantly different between groups. In both groups, a coupling of the mean f(H2O) and K(i) values was found, but the intercept with the y-axis was higher in high-turnover bone disease. It is concluded that in high-turnover bone disease following gastrectomy, the PS product for [(18)F]fluoride remains unchanged. Therefore, even in high-turnover bone diseases, [(18)F]fluoride ion PET can provide reliable blood flow estimates (f), as long as a proper PS product correction is applied. The increased bone metabolism in high-turnover bone disease after gastrectomy is mainly related to an up-regulation of the amount of ionic exchange of [(18)F]fluoride with the bone matrix, while tracer delivery remains unchanged.
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PMID:Coupling of porcine bone blood flow and metabolism in high-turnover bone disease measured by [(15)O]H(2)O and [(18)F]fluoride ion positron emission tomography. 1211 Nov 31

There are distinct differences between developing and developed countries regarding the pathogenesis and management of renal osteodystrophy. Such differences are due to ethnic factors, dialysis quality, types of membranes, dialysate water, lack of technical facilities to perform bone biopsies, beta2-microglobulin, aluminium and strontium toxicity, and iron overload as well as economic factors hampering the use of effective yet more expensive phosphate binders and active vitamin D. The prevalence of renal osteodystrophy in developing countries is higher than in developed countries. It ranges from 24.4% to 63%. Aluminium related bone disease is a common cause. High strontium levels and iron overload in developing countries play a major role in the development of renal bone disease among dialysis patients.
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PMID:Renal osteodystrophy in developing countries. 1219 31

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

Olpadronate is a nitrogenated bisphosphonate. Although it shares the therapeutic and pharmacological properties of pamidronate and alendronate, it has a greater dosage amplitude, more predictable effects and a greater digestive tolerability than other bisphosphates. Therefore, it may be more appropriate in the treatment of medical osteopathies, by both oral and parenteral routes of administration. According to various experimental and human models, the pharmacological potency of olpadronate is 5- to 10-times higher than that of pamidronate and close to that of alendronate. The two methyl groups bound to the nitrogen atom give the compound a high water solubility, which is about 8-times higher than that of the two other bisphosphonates. The lack of a terminal amino group in the side-chain of the molecule and the absence of crystallised forms of the compound in the digestive tract (due to its high water solubility) may avoid the potential for inducing oesophageal and gastrointestinal side-effects. These features may explain the high tolerability reported after the administration of doses of olpadronate (by the oral route) up to 5- to 10-times higher than the maximum tolerated dose of alendronate in Paget's bone disease and bone metastases, thus widening the possibilities for its clinical usage. In addition, initial pharmacokinetic studies suggest that olpadronate's oral bioavailability would fit into a confidence range of 2-4%, which contrasts with the erratic absorption shown by other highly potent bisphosphonates. The clinical efficacy demonstrated in preliminary studies in Paget's bone disease (including ultra-short treatments), and also in single-dose iv. therapy of hypercalcaemia of malignancies, renders olpadronate among the most promising bisphosphonate compounds, with potential use in the treatment of a variety of bone-involving diseases, such as osteoporosis, malignancies and rheumatoid arthritis.
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PMID:Olpadronate: a new amino-bisphosphonate for the treatment of medical osteopathies. 1599 50


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