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)

Mineral metabolism and bone histomorphometric status were evaluated in 31 hyperthyroid patients (HT) without clinical or radiological bone disease, both before and after treatment of hyperthyroidism. Blood and urine biochemical data were compared with those obtained in sex and age-matched controls. Iliac bone biopsies were available from 12 untreated HT and from 6 of them after treatment for analysis of trabecular bone. Mean plasma calcium was increased in HT but true hypercalcemia was seen in only one case and mean plasma immunoreactive parathormone (iPTH) was normal. Urine calcium excretion was markedly increased, especially in the fasting state. Biochemical parameters decreased after treatment, except for serum alkaline phosphatase and iPTH that, respectively, remained high and increased. Untreated state was characterized by an hyperremodelling state with enhanced activities of bone formation and bone resorption. Bone mineralization was normal. The mineral and bone changes were related to serum thyroid hormone levels. After treatment, the extent of formation surfaces still increased. The fact that, even though calcium metabolism abnormalities were corrected, active resorption surfaces did not change, suggests that trabecular osteoclastic resorption is not an important cause of mobilization of bone calcium to extracellular fluids in HT.
 ...
PMID:Effect of thyrotoxicosis and its treatment on mineral and bone metabolism. 357 53

Current thinking and available clinical data on the relationship between hyperthyroidism and bone disease are discussed. Data are also presented on TSH-suppressive and non-suppressive thyroid hormone therapy and its effect on bone. Although these data are clearly inconsistent, some risk factors for thyroid hormone induced osteopenia seem to be accepted: long standing, clinically manifest hyperthyroidism (a very rare disorder today because of early diagnosis and appropriate therapy), old age, menopause and total thyroidectomy. Thyroid hormone therapy (whether TSH-suppressive or not) has not been proven so far to lead to manifest osteoporosis.
 ...
PMID:Thyroid hormone excess and osteoporosis. 752 91

During the past several years, studies have suggested that exogenous thyroid hormone may adversely affect bone. In order to address this contention and to put the issue in perspective for clinicians who treat patients with thyroid hormone replacement, the available literature was reviewed, and the various study populations were characterized. Age, gender, and menopausal status of the patient are important factors, as are the indication for thyroid hormone replacement and the extent, duration, and severity of prior hyperthyroidism. Reliable measures of bone mineral density, particularly dual-energy x-ray, absorptiometry have become available, providing a more accurate reflection of this parameter in patients receiving thyroxine therapy in comparison with control subjects. The bulk of evidence indicates that long-term thyroxine therapy is safe if the dose is carefully monitored. Treatment with thyroxine does not produce clinically significant bone disease.
 ...
PMID:Thyroid hormone excess and bone--a clinical review. 1525 68

Hyperparathyroidism (HPT) is a significant clinical concern for patients with a variety of diseases, notably the secondary HPT associated with chronic kidney disease requiring dialysis. Secondary HPT is associated with elevated para-thyroid hormone (PTH) levels, decreased levels of 1,25 dihydroxyvitamin D, and disordered mineral levels (usually high calcium and phosphorus). If not controlled, secondary HPT can result in bone disease, vascular calcification, and ultimately, patient mortality. Established, conventional therapies, such as 1,25dihydroxyvitamin D analogues (vitamin D analogues) and phosphate binders, have proven to be inadequate in enabling patients to meet the National Kidney Foundation's-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) treatment goals for PTH, calcium and phosphorus levels. A novel therapeutic, cinacalcet HCl (formerly AMG 073; Sensipar in the US and Mimpara in Europe; Amgen, Inc.), binds directly to the calcium-sensing receptor (CaR) on the cells of the parathyroid gland, increasing the receptor's sensitivity to calcium and reducing PTH, serum calcium and phosphorus levels. Treatment with cinacalcet in clinical trials has safely and effectively improved achievement of the NKF-K/DOQI goals. Cinacalcet has also reduced serum calcium levels in patients with primary HPT, including parathyroid carcinoma, in the clinical trial setting. Evidence suggesting the utility of cinacalcet in these diseases and the potential for additional therapeutic applications will be discussed.
 ...
PMID:Cinacalcet HCl: a novel therapeutic for hyperparathyroidism. 1579 35

Metabolic acidosis is noted in the majority of patients with chronic kidney disease (CKD) when glomerular filtration rate (GFR) decreases to less than 20% to 25% of normal, although as many as 20% of individuals can have acid-base parameters close to or within the normal range. Acidosis generally is mild to moderate in degree, with plasma bicarbonate concentrations ranging from 12 to 22 mEq/L (mmol/L), and it is rare to see values less than 12 mEq/L (mmol/L) in the absence of an increased acid load. Degree of acidosis approximately correlates with severity of renal failure and usually is more severe at a lower GFR. The metabolic acidosis can be of the high-anion-gap variety, although anion gap can be normal or only moderately increased even with stage 4 to 5 CKD. Several adverse consequences have been associated with metabolic acidosis, including muscle wasting, bone disease, impaired growth, abnormalities in growth hormone and thyroid hormone secretion, impaired insulin sensitivity, progression of renal failure, and exacerbation of beta 2 -microglobulin accumulation. Administration of base aimed at normalization of plasma bicarbonate concentration might be associated with certain complications, such as volume overload, exacerbation of hypertension, and facilitation of vascular calcifications. Whether normalization of plasma bicarbonate concentrations in all patients is desirable therefore requires additional study. In the present review, we describe clinical and laboratory characteristics of metabolic acidosis, discuss potential adverse effects, and address benefits and complications of therapy.
 ...
PMID:Metabolic acidosis of CKD: diagnosis, clinical characteristics, and treatment. 1595 26

The story of thyroid calcitonin is an illuminating example of the voyage of hormone from a therapeutic tool for bone disease to a tumour marker to screen for subclinical forms of cancer. Identified as a new thyroid hormone implicated in calcium metabolism, its pharmacological action offered a new therapeutic tool for the management of bone disease. By measuring the circulating calcitonin, a range of values was obtained for oncologists because the evolution of a newly identified form of thyroid cancer--medullary (MTC)--was poorly understood. Researchers' interest shifted from calcitonin physiological action to its use as tumour marker able to diagnose MTC, especially in genetically predisposed families. Then, oncologists and geneticists combined their efforts to identify genetic mutation(s) implicated in MTC, an example of the decoding that is demanded of contemporary laboratory-based medicine to recognise a pathological entity.
 ...
PMID:Calcitonin's fantastic voyage: from hormone to marker of a genetic disorder. 1798 60

Parathyroid gland carcinoma is a rare malignancy. The tumor is mostly functioning, causing severe hyperparathyroidism, with high serum calcium level and severe bone disease. Non-functioning parathyroid carcinomas are extremely rare. We report on a 60-year-old male patient admitted to ENT Department due to a large neck tumor mass compressing the thyroid and trachea. Preoperatively, thyroid hormone, parathyroid hormone (PTH) and calcium serum levels were normal. The following immunohistochemical markers (DAKO, Denmark) were used: bcl-2; CD-10; Chromogranin-A; Cyclin-D1; EMA; Ki-67; Mdm-2; p-53; PGP-9,5; RCC; Synaptophysin; Thyroglobulin; and TTF-1. Immunohistochemical analysis indicated the diagnosis of a primary parathyroid gland carcinoma. Tumor cells showed diffusely positive immunohistochemical staining with chromogranin-A and PGP-9,5, positive staining of variable intensity with synaptophysin, and weakly positive reaction with EMA. Also, the cytoplasm of tumor cells was diffusely positively stained with bcl-2, while the nuclei showed positive reaction with p-53 oncogene and TTF-1. The remaining markers (CD-10, cyclin-D1, Ki-67, Mdm-2, RCC and thyroglobulin) were negative. Four years after the surgery, the patient died from renal carcinoma pulmonary metastases and liver cirrhosis complications. In conclusion, non-functioning parathyroid gland carcinoma is a very rare disease. Detailed immunohistochemical analysis is needed to distinguish it from other thyroid and parathyroid neoplasms and metastatic carcinoma. Surgical treatment is presently the best mode of therapy.
 ...
PMID:Non-functioning parathyroid gland carcinoma: case report. 2226 88

In 1891, Von Recklinghausen first established the association between the development of osteoporosis in the presence of overt hyperthyroidism. Subsequent reports have demonstrated that BMD loss is common in frank hyperthyroidism, and, to a lesser extent, in subclinical presentations. With the introduction of antithyroid medication in the 1940s to control biochemical hyperthyroidism, the accompanying bone disease became less clinically apparent as hyperthyroidism was more successfully treated medically. Consequently, the impact of the above normal thyroid hormones in the pathogenesis of osteoporosis may be presently underrecognized due to the widespread effective treatments. This review aims to present the current knowledge of the consequences of hyperthyroidism on bone metabolism. The vast number of recent papers touching on this topic highlights the recognized impact of this common medical condition on bone health. Our focus in this review was to search for answers to the following questions. What is the mechanisms of action of thyroid hormones on bone metabolism? What are the clinical consequences of hyperthyroidism on BMD and fracture risk? What differences are there between men and women with thyroid disease and how does menopause change the clinical outcomes? Lastly, we report how different treatments for hyperthyroidism benefit thyroid hormone-induced osteoporosis.
...
PMID:Metabolic and clinical consequences of hyperthyroidism on bone density. 2397 Aug 97

This review presents the views of an expert group of nephrologists from the Middle East along with an international expert on adaptation and implementation of the 2009 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for evaluation and manage-ment of mineral and bone disorders in chronic kidney disease (CKD-MBD) for practice in the Middle East countries. The members of the panel examined the KDIGO guidelines and formulated recommendations that can be implemented practically for the management of CKD-MBD in the Middle East. There was a broad agreement on most of the recommendations made by the KDIGO work-group. However, the panelists commented on specific areas and amplified certain concepts that might help the nephrologists in the Middle East. The final document was reviewed by all participants as well as by members of the Middle East task force implementation group for KDIGO guidelines. Their comments were incorporated. The guideline statements are presented along with detailed rationale and relevant discussion as well as limitations of the evidence. The panel recognized the need to upgrade the suggestion of KDIGO related to lateral abdominal radiograph and echocardiogram in patients with CKD stages 3-5D into a stronger recommendation. The panel underlined the risk of hyper-phosphatemia to CKD-MBD and the importance of prompt initiation or modification of therapy according to rising trends in para-thyroid hormone level. They recommended the use of non-calcium-based phosphate binders as the first-line therapy in CKD patients with signs of vascular calcification. The panel agreed that all aspects of the KDIGO recommendations concerning bone biopsy, evaluation and treatment of bone disease after kidney trans-plantation should be implemented as such.
...
PMID:Adaptation and implementation of the "Kidney Disease: Improving Global Outcomes (KDIGO)" guidelines for evaluation and management of mineral and bone disorders in chronic kidney disease for practice in the Middle East countries. 2443 98

Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has been implicated in thyroid hormone-associated bone loss. Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed decreased trabecular (-54%, P < .001) and cortical bone density (-5%, P < .05) and reduced cortical thickness (-15%, P < .001), whereas hypothyroid mice showed a higher trabecular bone density (+26%, P < .001) with unchanged cortical bone parameters. Histomorphometry and biochemical markers of bone remodeling indicated high bone turnover in hyperthyroid mice and low bone turnover in hypothyroid mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (-24%, P < .001) and increased in hypothyroid mice (+18%, P < .01). The increase of the number of DKK1-positive cells in hypothyroid mice was confirmed at the tissue level. Interestingly, sclerostin was increased in both disease models, although to a higher extent in hyperthyroid mice (+50%, P < .001, and +24%, P < .05). Serum sclerostin concentrations adjusted for bone mass were increased by 3.3-fold in hyperthyroid (P < .001) but not in hypothyroid mice. Consistently, sclerostin mRNA expression and the number of sclerostin-positive cells were increased in hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone-induced changes in bone remodeling are associated with a divergent regulation of DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones may contribute to thyroid hormone-associated bone disease and altered expression of Wnt inhibitors may emerge as potential therapeutic targets.
...
PMID:Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1. 2621 91


1 2 Next >>