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)

A prospective multicenter study was designed to determine the frequency and prognostic importance of hypercalciuria in children with hematuria. Urinary calcium excretion was examined in 215 patients with unexplained isolated hematuria (no proteinuria, urolithiasis, infection or systemic disorder). Hypercalciuria (urinary calcium excretion greater than 4 mg/kg/day) was identified in 76 patients (35%). Compared to patients with normal urinary calcium excretion, children with hematuria and hypercalciuria were characterized by male preponderance, white race, family history of urolithiasis, gross hematuria and calcium oxalate crystals. Renal biopsies were performed in 10 patients with urinary calcium excretion 0.4 to 2.5 mg/kg/day; three had IgA glomerulonephritis, three had glomerular basement membrane thinning, one had proliferative glomerulonephritis and three were normal. Renal biopsies in three patients with hypercalciuria showed focal segmental glomerulosclerosis, hereditary nephritis or no abnormalities. Oral calcium loading tests showed renal hypercalciuria in 26 patients, absorptive hypercalciuria in 15 patients and were not diagnostic in 35 patients. Serum parathyroid hormone, bicarbonate and phosphorus and urinary cyclic adenosine monophosphate concentrations were similar in the three groups of hypercalciuric patients. Urinary calcium excretion after one week of dietary calcium restriction was higher (5.8 mg/kg/day) in renal hypercalciuria than in other hypercalciuric patients (3.4 mg/kg/day), P less than 0.01. One to four years follow-up was available for 184 patients. Eight of 60 hypercalciuric patients developed urolithiasis or renal colic compared to 2 of 124 patients with normal urinary calcium excretion (P less than 0.001). Hypercalciuria is commonly associated with isolated hematuria and represents a risk factor for future urolithiasis in children with hematuria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Idiopathic hypercalciuria: association with isolated hematuria and risk for urolithiasis in children. The Southwest Pediatric Nephrology Study Group. 240 91

This study reports a 22% prevalence of significant cortical osteopenia in 206 patients, aged 7-20 years, with established insulin-dependent diabetes mellitus (IDDM). A parallel decrease in trabecular bone mass was also noted. Bone loss was more evident in males (16%) than in females (6%) and was rare before 10 years of age (3%). No relationship between bone loss and the duration of diabetes, degree of metabolic control or diabetic complications was apparent. Delayed skeletal maturation did not account for cortical thinning, and the mean bone age of osteopenic diabetics was similar to that of non-osteopenic diabetics. There was no significant correlation between HLA-antigen frequency and the predisposition to diabetic osteopenia. Metabolic alterations comparable with previous findings in the chronically diabetic rat were documented in IDDM. The data documented are consistent with the conclusion that IDDM results in intestinal hyperabsorption of calcium, absorptive hypercalciuria, phosphaturia, hypomagnesaemia, hyperphosphatasaemia, and decreased circulating parathyroid hormone levels. These alterations in mineral metabolism may relate to the decrease in cortical and trabecular bone mass observed in patients with IDDM.
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PMID:Alterations of bone and mineral metabolism in diabetes mellitus. Part II. Clinical studies in 206 patients with type I diabetes mellitus. 361 83

Bone thinning causing both fractures and severe pain not associated with fractures has been recognized in patients with chronic liver diseases. The patients most commonly affected are those with primary or secondary biliary cirrhosis, but those with alcoholic liver disease and cirrhosis after active chronic hepatitis may also be involved. Chronic liver disease has also been recognized as an important cause of osteoporosis in both sexes, with the mechanism thought to be a combination of calcium and/or vitamin D. The 9.1% patients with chronic active hepatitis accompanied with osteodystrophy. But 50% cirrhotic patients accompanied with osteodystrophy. Bone densitometry was determined by Digital Image Processing Method (Osteodystrophy < mean-2SD: age- and sex-matched normal value). Serum levels of osteocalcin (BGP) and parathyroid hormone (PTH) in patients of hepatic cirrhosis without osteodystrophy were lower than those with osteodystrophy. These results were suggested that hepatic osteodystrophy was rapidly turnover osteodystrophy. To function physiologically, vitamin D must be hydroxylation in liver to 25-(OH)-D and subsequently by the kidney to 1 alfa, 25-(OH)2-D. Osteodystrophy associated with hepatic cirrhosis is due to a defect in the 1 alfa-hydroxylation by the kidney rather than a hepatic hydroxylation defect. 1 alfa OH-D3 is very useful for treatment for hepatic osteodystrophy.
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PMID:[Hepatic osteodystrophy]. 964 89

Age-related changes in the microstructure of trabecular bone, such as decreases in trabecular number and trabecular thickness, lead to reductions in mechanical properties, such as Young's modulus and strength. Current drug therapy, such as bisphosphonate or parathyroid hormone, improves the mechanical properties of bone mainly by increasing the trabecular thickness, but not increasing the trabecular number. However, the mechanical efficacy of these treatments has not been fully quantified using trabecular bone models. In this study, we used an idealized three-dimensional (3D) microstructural model of trabecular bone to create bone loss either through trabeculae thinning or random removal of trabeculae, and simulated treatment by increasing the trabeculae thickness of the remaining trabeculae. The reduction in either the Young's modulus or the strength due to trabeculae loss was proportional to a much higher power of reduction in bone volume fraction than due to trabeculae thinning. This indicates that bone loss due to trabeculae loss is much more detrimental to Young's modulus and strength of trabecular bone than due to trabeculae thinning, indicating the importance of trabecular number and connectivity in the mechanical integrity of trabecular bone. In general, treatments by increasing the trabecular thickness of remaining trabeculae after trabeculae loss cannot fully recover the initial mechanical properties of intact bone, even if bone loss is fully recovered, whereas trabecular thickening can fully restore the mechanical properties after bone loss by trabeculae thinning. The results also show that the residual loss in mechanical properties is dependent on the extent of trabeculae loss.
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PMID:Mechanical consequence of trabecular bone loss and its treatment: a three-dimensional model simulation. 1185 49

Over the past 10 years, therapeutic optimism in osteoporosis has been fueled by the development of agents that inhibit the resorption of bone. An increase in bone density with the bisphosphonates alendronate and risedronate, for example, is associated with significant reductions in vertebral and hip fracture incidence. Although bone is clearly stronger when these agents are used, there is no conclusive evidence that they improve the microarchitectural defects that characterize the disorder. It has been known for years that parathyroid hormone (PTH) can be an anabolic agent in animals. Recently, it has been confirmed that low-dose, intermittent administration of PTH is associated with selective anabolic effects in human subjects, whereas higher doses administered continuously are associated with catabolic effects. This observation has led to an experimental design in which PTH is administered to human subjects once daily in doses that do not regularly lead to adverse events, such as hypercalcemia. Two-year studies using PTH alone have been directed at postmenopausal osteoporosis (PMO) in women and at men with idiopathic osteoporosis. In both women and men, PTH leads to marked increases in bone density at the lumbar spine and also, significantly, in the hip. In PMO, PTH is associated with significant reductions in vertebral and nonvertebral fractures. When PTH is used in combination with an anti-resorptive agent, like estrogen, the markedly positive effects on bone mass are also seen in PMO and in those with glucocorticoid-induced osteoporosis. After PTH is withdrawn, but estrogen therapy is continued, the gains in bone mass are maintained. It is not known whether gains in bone mass are maintained if PTH is withdrawn without continuing therapy with an anti-resorptive agent; however, preliminary data suggest that the gains in bone mass begin to be lost. Bone biopsy samples in PMO and in men with idiopathic osteoporosis, before and after therapy with PTH, when subjected to histomorphometric analysis show marked increases in cortical thickness and improvements in indices of trabecular connectivity, thus allaying concerns that PTH may cause cortical thinning. It would appear that the increase in cortical wall thickness is due, in part, to stimulation by PTH of periosteal apposition at a rate greater than its effect to cause endocortical resorption. In all studies reported to date, PTH appears to be well tolerated. The era of anabolic therapy for osteoporosis is at hand, with PTH being the first to be tested with sufficient rigor to demonstrate its efficacy.
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PMID:The potential of parathyroid hormone as a therapy for osteoporosis. 1208 Dec 55

The chronic excessive hypersecretion of parathyroid hormone (PTH) in primary hyperparathyroidism (PHPT) has significant impact on bone remodeling. Bone turnover increases by about 50%, leading to increased resorption at the endosteal envelope, increased cortical porosity, and thinning of cortical bone. In cancellous bone a different response is seen. Despite stimulation of bone resorption and formation at the tissue level, osteoclastic resorption and osteoblastic bone formation at individual bone multicellular units (BMUs) are reduced. This causes reduced erosion depth, reduced bone formation rate, and decreased thickness of bone structural units (BSUs), and bone balance at individual BMUs is preserved and may even improve. Thus, PHPT causes cortical bone loss. At the same time, however, cancellous bone structure remains unchanged or even improved, which may offset cortical bone loss. This probably explains the preservation of bone mass demonstrated in long-term follow-up studies of patients with mild PHPT (S-Ca2+ < 2.80 mM). In severe cases of PHPT (S-Ca2+ > 3.00 mM), the negative effects on cortical bone may override the positive impact on cancellous bone, and lead to bone loss and increased risk of fracture.
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PMID:Primary hyperparathyroidism: lessons from bone histomorphometry. 1241 84

My purpose in this article is to restore the histologic appraisal of renal bone disease to the mainstream of bone and mineral metabolism from which it has been separated for many years. Historically, both the two major components were found in varying degrees in most patients, although one or other of them often predominated. For more than 15 years bone biopsy has been used almost exclusively to classify individual patients into hyperparathyroid, osteomalacic, mixed and adynamic categories according to rigid non-overlapping criteria, and remarkably few histologic data have been reported. All metabolic bone diseases result from disordered bone remodeling, the physiologic mechanism for replacing bone that has become too old to carry out its mechanical or metabolic functions. Bone remodeling is not directly concerned with the regulation of plasma calcium, which reflects the level of equilibration at quiescent bone surfaces between systemic and bone extracellular fluid set by parathyroid hormone. The separation of remodeling from homeostasis explains the concurrence of increased turnover and decreased plasma calcium in chronic renal failure; it is the homeostatic system, rather than the remodeling system, which is resistant to parathyroid hormone. The effect of mild hyperparathyroidism is a nonspecific increase in bone turnover, of which the best index is the bone formation rate measured by double tetracycline labeling expressed per unit of bone surface. Increased turnover is always accompanied by increased reversible mineral deficit. In prolonged hyperparathyroidism there is also accelerated irreversible bone loss manifested mainly as thinning of cortical bone, detectable in chronic renal failure before any symptoms, due to increased resorption depth on the endocortical surface. In severe hyperparathyroidism resorbed bone is replaced, not by a lesser quantity of normal bone, but by a mixture of vascular fibrous tissue and woven bone, referred to as osteitis fibrosa. In osteomalacia there is increased accumulation of osteoid, due not to increased turnover, but to prolongation of mineralization lag time, which in conjunction with increased thickness, surface and volume of osteoid is diagnostic. Converting histomorphometric data into category assignment discards most of the useful information, which can be retained by two-dimensional representation of severity. For the hyperparathyroid dimension, bone formation rate measured by double tetracycline labeling expressed per unit of bone surface is the most useful although not ideal. For the osteomalacic dimension a mineralization index was constructed that is unaffected by age or race. In patients with osteitis fibrosa, bone formation rate per unit of bone surface and mineralization index were inversely correlated. For the third dimension a structure/formation index was constructed which increases with age in healthy women and shows weak inverse correlation with bone formation rate. The structure/formation index is lower than normal in patients with osteitis fibrosa, and should be useful in the study of osteopenia in chronic renal failure. Bone formation rate is low in osteomalacia, but some patients have subnormal rates through quite a different mechanism. The frequency of this finding has been overestimated for several reasons: failure to exclude atypical osteomalacia (increased surface and volume but not thickness of osteoid), use of inappropriate reference values, and failure to measure the bone formation rate on endocortical and intracortical surfaces. In healthy women bone formation rate can be zero on the cancellous surface alone. Low bone formation rate is sometimes due to diabetes but most often is the expected response to subnormal parathyroid hormone secretion accompanying an excess of calcium, a situation recognized only recently because of improvement in parathyroid hormone assay methodology. Low cancellous bone formation rate should not increase fracture risk because turnover is much lower in the peripheral than in the central skeleton, and all reports of increased fracture risk are flawed or open to different interpretation. Low bone formation rate is associated with reduced skeletal buffering of calcium and increased soft tissue calcification. This is not a new disease needing its own treatment, however, but represents the final stage of skeletal adaptation to a surfeit of calcium. The concept of adynamic bone disease has been harmful by directing attention away from the most important consequence of over-treatment of hyperparathyroidism.
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PMID:Renal bone disease: a new conceptual framework for the interpretation of bone histomorphometry. 1281 35

Characterization of trabecular bone structures requires necropsy of animals followed by a labor-intense histomorphometric or ex vivo micro-CT analysis. We tested the novel vivaCT40 from Scanco Medical AG (Bassersdorf, Switzerland), which allows monitoring such changes repeatedly in anesthetized rats and mice. Postmenopausal osteoporosis: in 8-month-old ovariectomized (OVX) rats, the vivaCT40 was capable of picking up the decrease in trabecular bone volume and trabecular thinning as well as the decrease in the number of trabecular elements as a function of time. The bone anabolic effects of parathyroid hormone [hPTH(1-34)], which resulted in an increase in trabecular thickness but not their number, as well as the bone protective effect of the two antiresorptive agents zoledronic acid (ZA) and 17-alpha ethinylestradiol (aEE), were detected correctly with the vivaCT40. Adjuvans arthritis: the vivaCT40 allowed measuring trabecular bone loss caused by periarticular inflammation in a rat model of adjuvans arthritis and demonstrated the bone protective effect of dexamethasone (DM). In addition, it was possible to image the subtle erosive lesions in subchondral bone caused by the inflammatory processes. Tumor osteolysis: the vivaCT40 allowed monitoring of the progressive osteolytic response following the local administration of 4T1luc2000 tumor cells into the tibia metaphysis of nude mice. The potent protective effect of ZA on tumor osteolysis was demonstrated. In summary, the new vivaCT40 can monitor the effects of known agents and diseases such as osteoporosis, inflammatory arthritis, and tumor invasion on 3-D trabecular microarchitecture accurately, repeatedly, reliably, and quickly in anesthetized rats and mice. The scanner represents a breakthrough for noninvasive imaging and structural measurements in small rodents.
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PMID:Noninvasive monitoring of changes in structural cancellous bone parameters with a novel prototype micro-CT. 1598 22

Vitamin D is synthesized in skin through a reaction mediated by sunlight, and it is metabolized to 25-hydroxyvitamin D, in liver, and in 1,25-dihydroxyvitamin D, in kidney. This last reaction has a tight feedback mechanism. 1,25-dihydroxyvitamin D is the active hormone, and its actions are mediated mainly by nuclear receptors. Its major functions are in calcium metabolism and bone mass maintenance. Hypovitaminosis D, as a disease in adult people, manifests itself with hypocalcemia and secondary hyperparathyroidism with subsequent loss of trabecular bone, thinning of cortical bone, and, eventually, a higher risk of fractures. Hypovitaminosis D is a very common condition in Europe, Africa, North America and some South American countries, such as Chile and Argentina. Measurement of serum total 25-hydroxyvitamin D concentration is the gold standard to diagnose vitamin D deficiency. Serum concentrations below 50 nmol/L are associated with an increase in parathyroid hormone concentration, and bone loss. Risk factors for vitamin D deficiency, like poor sunlight exposition, aging skin and factors that interfere with normal vitamin D metabolism, are well established. Oral vitamin D supplementation, an easy and inexpensive treatment, is needed to treat this illness.
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PMID:[Vitamin D deficiency in adults: to better understand a new presentation of an old disease]. 1662 72

Several studies have suggested an increased prevalence of osteopenia in dialysis. Peripheral quantitative computed tomography (pQCT) is a new technique that allows the noninvasive evaluation of trabecular and cortical bone separately. The aim of the study was: (1) to evaluate cortical bone by pQCT in continuous ambulatory peritoneal dialysis (CAPD) patients and compare the data with that obtained in healthy controls; and (2) to correlate cortical bone parameters with bone mineral density (BMD) of the lumbar spine and femoral neck and total bone mineral content (TBMC). Cortical bone parameters were obtained in 22 CAPD patients and 27 healthy individuals at the distal radius using a Stratec XCT 960 pQCT machine. In the dialysis patients, we also determined BMD and TBMC by bone densitometry. Dialysis patients, compared with controls, showed a significant reduction in volumetric cortical BMD (VcBMD) (p = 0.04) and cortical thickness (cThk) (p < 0.0001) with a significant increase in radial total cross-sectional area (TA) (p = 0.006), endosteal circumference (p < 0.0001), and buckling ratio (p < 0.0001). In CAPD patients, total time on dialysis correlated negatively with radial total BMD (p < 0.01) and VcBMD (p < 0.01). Age correlated positively with TA (p < 0.01), endosteal (p < 0.01), and periosteal circumferences (p < 0.01). Serum intact parathyroid hormone (PTH) levels correlated positively with endosteal (p = 0.04) and periosteal perimeter (p = 0.01). Total alkaline phosphatase correlated negatively with VcBMD (p < 0.01), and positively with endosteal perimeter (p = 0.02). Total bone mineral content correlated significantly with radial cortical content (p < 0.001), cross-sectional cortical area (cA; p < 0.001), and cThk (p < 0.01) but not with total radial BMD, VcBMD, or buckling ratio. No correlations were found between radial cortical parameters and BMD measured at the lumbar spine or femoral neck. We conclude that dialysis patients show cortical osteopenia with marked cortical thinning partially mediated by PTH action on bone. Total bone mineral content correlated with various radial cortical parameters (content, area, and thickness) but not with others. No correlations were found between cortical bone parameters measured at the peripheral skeleton with areal bone density measured at the axial skeleton. These findings suggest that pQCT may be a new tool in the assessment of bone fragility in dialysis patients.
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PMID:Evaluation of cortical bone by peripheral quantitative computed tomography in continuous ambulatory peritoneal dialysis patients. 1701 10


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