Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The RecQ family of DNA helicases have potential roles in DNA repair, replication and/or recombination pathways. In humans, a defect in the RecQ family helicases encoded by the BLM, WRN and RECQ4 genes gives rise to Bloom's (BS), Werner's (WS) and Rothmund-Thomson (RTS) syndromes, respectively. These disorders are associated with cancer predisposition and/or premature aging. In Bloom's syndrome, affected individuals are predisposed to many types of cancer at an early age. Werner's syndrome is a premature aging disorder with a complex phenotype, which includes many age-related disorders that develop from puberty, including greying and thinning of the hair, bilateral cataract formation, type II diabetes mellitus, osteoporosis and atherosclerosis. The phenotype of Rothmund-Thomson syndrome patients also consists of some features associated with premature aging, as well as predispositon to certain cancers. Here, we discuss the molecular basis of these RecQ helicase-deficient disorders.
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PMID:Premature aging in RecQ helicase-deficient human syndromes. 1220 42

Bone loss and long-term persistence of osteoporosis with increased fracture risk are common after liver transplantation. It is unknown whether transplantation-induced disruption of hepatic nerves, serving numerous regulatory metabolic and sensory functions, is herein involved. To test this possibility, we measured bone mineral density (BMD) by peripheral quantitative computed tomography (pQCT) and studied dynamic histomorphometry, radiocalcium kinetics, and biochemical parameters in 7 liver-transplanted and 7 sham-operated inbred rats. Although liver function was normal in TX rats, trabecular BMD of the first lumbar vertebra and total BMD of the femoral diaphysis were decreased by 13% and 6%, respectively, 9 months postsurgery. The breaking force of the femur was significantly lower by 21%. However, bone mass in the femoral and tibial metaphysis was preserved as evidenced by pQCT measurements and histomorphometry. Trabecular width and wall thickness were significantly decreased in vertebral cancellous bone, whereas indices of bone formation and resorption were normal or slightly reduced. Serum minerals, mineral balance, fractional and net absorption of Ca and Mg, serum calciotropic hormones, IGF-I, leptin, specific activity of 45Ca in bone, 45Ca excretion, and biochemical indices of bone formation and bone resorption remained unchanged. We conclude that liver transplantation-related denervation causes cancellous and cortical bone loss in well-innervated bone sites such as the lumbar spine and the long bone diaphysis. Cancellous bone loss in TX rats is due to an impairment of osteoblast team performance and subsequent trabecular thinning. The mechanism uncovered by our study may contribute to long-term bone loss after liver transplantation.
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PMID:Regional bone loss after orthotopic liver transplantation in inbred rats: the role of hepatic denervation. 1220 Jun 52

The bone fragility of osteoporosis is not fully explained by a deficit in bone mass. Histomorphometric examination of transilial bone biopsies has identified microstructural defects that-in light of what is known about the mechanical properties of structural materials-further compromise bone strength. Histomorphometric measures describe the biopsy specimen, the configuration of its trabeculae in space, and the extent to which its trabecular lattice is intact. In postmenopausal women with established osteoporosis, a deficit of both cortical and cancellous bone is typical, i.e., both cortical thickness and cancellous bone volume tend to be substantially reduced. Much of the cancellous bone deficit can be attributed to loss of entire trabecular elements rather than to generalized thinning of trabeculae. Direct measures of trabecular connectivity confirm this impression: women with established osteoporosis have fewer trabecular nodes and more termini than healthy women, even at the same cancellous bone volume. Evidence for accumulated microdamage in transilial biopsies is circumstantial, and the phenomenon itself may well be localized to fracture sites. Histomorphometric data from transilial biopsies comprise a large body of information about the structural and functional character of osteoporosis and provide valuable information about the effects of new treatments on bone microstructure.
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PMID:Bone microstructure in osteoporosis: transilial biopsy and histomorphometry. 1246 43

Metabolic bone diseases such as osteoporosis usually cause a decrease in bone mass and a deterioration of bone microarchitecture leading to a decline in bone strength. Methods to predict bone strength in patients are currently based on bone mass only. It has been suggested that an improved prediction of bone strength might be possible if structural changes are taken into account as well. In this study we evaluated which structural parameters (other than bone mass) are the best predictors for changes in bone mechanical properties of the human radius after different bone atrophy scenarios and whether the original strength of the affected bone can be recovered if bone loss is restored by thickening of the remaining structures. To answer these questions, a human radius was measured with a microcomputer tomography scanner to extract the full three-dimensional architecture of the distal radius at an isotropic resolution of 80 microm. Eight models with modified bone architecture were created and the mechanical variations due to these modifications were studied using microfinite element (micro-FE) simulations. In four models mass was lowered by 20%, either by reducing cortical thickness, trabecular thickness, or number of trabeculae or by overall thinning of structures. In the other four models bone mass was restored to the original value using a trabecular bone thickening procedure. The micro-FE analyses revealed that most load was carried by the cortical bone. For this reason, bone strength was affected most in the reduced cortical thickness model. For the same reason, the trabecular bone atrophy scenarios, all of which affected bone strength in a very similar way, resulted in less dramatic bone strength reduction. The restoration of bone mass did not recover the original bone strength. These findings demonstrate that the importance of different parameters for the prediction of bone strength also depends on the mechanical loading. This could explain why results of earlier studies on the importance of structural parameters can be inconsistent and site-dependent.
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PMID:Mechanical consequences of different scenarios for simulated bone atrophy and recovery in the distal radius. 1467 53

Trabecular or cancellous bone, the type of bone found in the vertebrae and near the joints of long bones, consists of a network of plates and struts. Accurate measurement of trabecular thickness is of significant interest, for example, to assess the effectiveness of anabolic (bone forming) agents of patients with osteoporosis. Here, we introduce a new fuzzy distance transform (FDT)-based thickness computation method that obviates binary segmentation and that can effectively deal with images acquired at a voxel size comparable to the typical trabecular bone thickness. The method's robustness is shown on the basis of micro-CT images of human trabecular bone, resampled at progressively coarser resolution and after application of rotation and addition of noise as a means to simulate the in vivo situation. Reproducibility of the method is demonstrated with micro-CT images by comparing histograms of thickness within and between data sets and with micro-MRI volume data sets of human volunteers imaged repeatedly. Finally, with in vivo micro-MR images from a prior study in rabbits subjected to corticosteroid exposure, it is demonstrated that short-term treatment resulting in trabecular thinning can be quantified with the new method.
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PMID:Measurement of trabecular bone thickness in the limited resolution regime of in vivo MRI by fuzzy distance transform. 1471 87

Bone mineral density (BMD) is the principal diagnostic tool used in clinical settings to diagnose and monitor osteoporosis. Experimental studies on ex vivo bone samples from multiple skeletal locations have been used to propose that their breaking stress bears a power-law relationship to volumetric BMD, with a location-dependent index. We argue that a power-law cannot represent effects of trabecular removal, which is one of the leading causes of reduction in bone strength. A new expression, proposed on the basis of theoretical and numerical analysis of a mathematical model, is tested using previously published data on bone samples from iliac crest and vertebral body. It represents the experimental biomechanical data at least as well as the power-law, and provides means for extrapolating results from small biopsy samples to an entire bone. In addition, changes caused by trabecular thinning and anisotropy can be modeled by the expression.
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PMID:An expression relating breaking stress and density of trabecular bone. 1521 30

Osteoporosis is associated with thinning of cortical and trabecular bone, which reduces bone strength and predisposes individuals to fracture development. Femoral neck fractures in patients with osteoporosis may not be apparent on radiographs. Magnetic resonance imaging is useful at detecting these radiographically occult fractures; yet, the practice has not been widely adopted in Hong Kong. In this article, we review our experience of early magnetic resonance imaging in this clinical context--that is, imaging performed within 48 hours of presentation to hospital. Twenty-eight patients (age range, 69-93 years) over a 3-year period were studied. Magnetic resonance imaging revealed radiographically occult neck fractures in 14 (50%) cases (equivalent to 4% of all femoral neck fractures). These fractures were treated surgically (64%) or conservatively (36%) with good bone healing and clinical outcome. When no femoral neck fracture was present, magnetic resonance imaging revealed an alternative cause for symptoms in all 14 cases. We strongly endorse the use of early magnetic resonance imaging for patients with osteoporosis who have a clinically suspected femoral neck fracture that is not visible radiographically.
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PMID:Early magnetic resonance imaging of radiographically occult osteoporotic fractures of the femoral neck. 1529 73

Osteoporosis-related bone damage causes major socioeconomic problems. For efficient use of therapeutic agents, it is necessary to be able to reliably identify patients with high propensity for nontraumatic fracture. Age-related bone loss imposes several architectural changes in bone; one of the few ways to estimate damage due to individual changes, and hence determine the most serious types of damage, is via the analysis of suitable mathematical models. Anatomical sites such as the vertebral body, proximal femur, and distal radius are locations where most age-related fractures occur. The inner porous (or trabecular) bone from these sites, which resemble disordered cubic networks, play a significant role in load transmission at these sites. Analysis of a mathematical model of porous bone is used to show that perforation of elements of the network is the most damaging architectural change to a bone. We also show that an expression for bone strength, derived on this basis, can capture changes in strength caused by the inclusion of other features like thinning of trabecular bone and the anisotropy of the network. We finally argue that bone density, which is currently the most routinely used diagnostic, cannot be a reliable surrogate for bone strength.
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PMID:A study of age-related architectural changes that are most damaging to bones. 1537 23

Glucocorticoids are important drugs in the treatment of variety diseases, but long-term period use can lead to various adverse effects, including osteoporosis. Glucocorticoid-induced osteoporosis is mainly caused by inhibition of osteoblastic bone formation, which results not only in decreased bone mineral density, but reduction of bone strength by trabecular thinning in bone microstructures. The evidence suggests that daily oral glucocorticoid doses higher than 5 mg prednisolone or equivalent increase the risk of fracture within 3-6 months after the start of therapy. High-dose inhaled glucocorticoids may also increase fracture risk. The diagnostic procedures are similar to those for primary osteoporosis, but the diagnostic threshold for bone mineral density needs to be higher than that for primary osteoporosis. Treatment with vitamin D, calcitonin, sex hormone replacement, and bisphosphonates has been shown to be effective, and bisphosphonates have been demonstrated to be the most valuable drugs for glucocorticoid-induced osteoporosis. There are several lines of evidence indicating that they are effective in preventing and treating low bone mineral density and in reducing fracture risk.
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PMID:Glucocorticoid-induced osteoporosis. 1551 6

The administration of oral glucocorticoids is associated with a significant decrease in bone formation (low turnover) and with generalized thinning of bone trabecula. These condition will be worse of bone quality and bone strength than high turnover state that indicate partial breakage of bone trabecula. Because the cut-off value of bone mineral density induced fracture is higher in glucocorticoid-induced osteoporosis than in postmenopausal osteoporosis.
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PMID:[Bone quality in glucocorticoid induced osteoporosis]. 1557 12


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