Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of insulin on plasma and bone mineral homeostasis was studied in the BB rat model, which develops an autoimmune form of diabetes at the age of about 100 days. Untreated diabetes of short duration resulted in hypercalciuria and intestinal calcium malabsorption despite increased free concentrations of serum 1,25-dihydroxyvitamin D. The concentrations of two vitamin D-dependent calcium-binding proteins were also decreased: a low duodenal calbindin-D 9K concentration corresponding to the low intestinal active calcium absorption and a low serum osteocalcin concentration, corresponding to a low bone formation and highly correlated with serum IGF-I concentration. Indeed, on bone histology a very low number of osteoblasts and low osteoblast activity (osteoid formation and mineral apposition rate) were observed. Similar abnormalities persisted in rats with long-standing diabetes resulting in markedly decreased bone mass and increased brittleness of bone. Diabetes therefore resulted in low-turnover osteoporosis. Several hormones (testosterone, growth hormone and 1,25-dihydroxyvitamin D) and growth factors (IGF-I and its binding proteins) with known effects on bone were markedly decreased in diabetic rats. A continuous infusion of testosterone, GH or 1,25-(OH)2D3 for 14 d by miniosmotic pumps could not improve the biochemical or histomorphometric abnormalities. Insulin infusion for 2 weeks, however, rapidly increased and overcorrected the number of osteoblasts, normalized serum osteocalcin and IGF-I concentrations but could not yet normalize bone mineralization. Continuous infusion of IGF-I alone did not improve the osteoblast number of osteocalcin but markedly stimulated bone mineralization. From these data we can conclude that both insulin and IGF-I are potent bone growth factors but with different mode of action. In human type 1 diabetes, a similar decrease in serum osteocalcin and IGF-I was observed. A reduction of regional bone mass, both in long and trabecular bones, is frequently observed in human diabetes. Cumulative data from case control studies indicate that the life-time fracture risk is increased in diabetes.
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PMID:Diabetic bone disease. Low turnover osteoporosis related to decreased IGF-I production. 146 60

The synthesis of osteocalcin or bone gla protein by osteoblasts is markedly stimulated by 1,25-(OH)2D, a key hormone in the regulation of bone mineralization. The circulating levels of osteocalcin have been shown to reflect both the osteoid matrix production and the formation rate of mineralized bone in several metabolic bone diseases (osteoporosis, thyrotoxicosis, primary hyperparathyroidism) in which both mechanisms are tightly coupled because of the absence of mineralization defect. In this study, we measured in 12 patients (7 women, 5 men, 56 +/- 15 yr old) with untreated osteomalacia serum osteocalcin and vitamin D metabolites (25OHD and 1,25-(OH)2D). The results were correlated with biochemical and histomorphometric assessment of bone remodeling. Osteomalacia was due to vitamin D deficiency (5 cases), to vitamin D malabsorption (6 cases), and to hypophosphataemia in 1 case. When compared to control values, serum osteocalcin was increased in patients with osteomalacia (7.4 +/- 4 vs. 3.7 +/- 1.3 ng/mL; P less than 0.001) and was positively correlated with serum alkaline phosphatase (r = 0.65; P = 0.03) and negatively with 25 OHD (r = -0.61; P = 0.04). Serum osteocalcin was not correlated with 1,25-(OH)2D [r = -0.45; not significant (NS)] even after exclusion of the patient with hypophosphataemia. Serum osteocalcin was positively correlated with the osteoid volume and osteoid perimeter (r = 0.71 and 0.69 respectively; P less than 0.01) but not with any of the tetracycline-based parameter of bone mineralization at the tissue level (r ranging from -0.41 to +0.42, NS). Serum 25 OHD, but not 1,25-(OH)2D, was positively correlated with the mineralization rate (r = 0.59; P less than 0.05 and r = 0.54; NS). We conclude that in patients with osteomalacia, a condition which is characterized by an increased osteoid accumulation due to a decreased mineralization rate, the increased level of serum osteocalcin reflects the increased osteoid synthesis but not the mineralization defect. In this disease, serum osteocalcin is inversely correlated to the severity of vitamin D deficiency reflected by serum 25 OHD, but not to the serum levels of 1,25-(OH)2D.
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PMID:Serum osteocalcin is increased in patients with osteomalacia: correlations with biochemical and histomorphometric findings. 156 62

Intestinal disease might contribute to osteopenia. Measurements of IgA antibodies to gliadin have been established as an accepted screening procedure for detection of coeliac disease. When we applied these measurements to 92 patients with verified osteoporosis, 11 subjects (12%) were found to have elevated levels. This is markedly higher than the incidence in healthy subjects (3%). However, the patients with raised levels of IgA antibodies displayed no clinical symptoms and no laboratory evidence of calcium malabsorption. Thus their values for serum calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase and osteocalcin, as well as the fasting urinary excretion of hydroxyproline and calcium, were similar to those found in other patients with osteoporosis. Intestinal biopsy verified coeliac disease in three patients and was normal in another three. This gives an incidence of verified coeliac disease in this patient group that is approximately tenfold higher than that in the healthy population. Subclinical coeliac disease appears to be unusually over-represented among patients with idiopathic osteoporosis, and screening for gliadin antibodies might therefore be a valuable addition to the routine assessment of the osteopenic patient. The mechanisms underlying the relationship are not clear, but calcium malabsorption is not evident.
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PMID:Screening for antibodies against gliadin in patients with osteoporosis. 158 66

Osteomalacia is characterized by large osteoid seams and a preserved volume of bone trabeculae. The mineralization of newly formed bone requires adequate concentrations of calcium and phosphate: the Ca.P product has been regarded as a useful, empirical diagnostic test of osteomalacia. It decreases in patients with osteomalacia mainly because they have very low plasma phosphate levels. At present total body bone mineral and total body bone density can be directly measured by whole body absorptiometry, which indicates the lowest total mineral content of the skeleton which can increase quickly after adequate treatment. The main symptoms of osteomalacia are: bone pain; muscular weakness (commonly as pelvic girdle myopathy); Looser-Milkman pseudofractures or more often a pattern of generalized demineralization at X-ray. The main biochemical parameters in osteomalacia include: defective calcium absorption with hypocalcemia and hypocalciuria; defective intestinal phosphate absorption with hypophosphatemia; there is often increased renal phosphate clearance due to hypocalcemia and secondary hyperparathyroidism; elevated alkaline phosphatase and osteocalcin levels; high bone turnover confirmed by kinetic studies carried out with radiocalcium or 99mTc-MDP. An etiological classification of the osteomalacias includes: 1) nutritional osteomalacia: a) inadequate exposure to sunlight and/or insufficient vitamin D intake; b) defective intestinal absorption of vitamin D because of malabsorption syndromes (e.g. jejuno-ileal bypass for obesity).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The osteomalacias. 166 41

Abuse of alcohol is considered to be an important risk factor for fractures and osteoporosis. Alcohol abuse is associated with deleterious changes in bone structure detected by histomorphometry, and with a decrease in bone mineral density. These changes may also be produced by factors commonly associated with alcohol abuse, e.g., nutritional deficiencies, liver damage, and hypogonadism. Thus the etiology of alcohol-associated bone disease is multifactorial. Alcohol has, however, clear-cut direct effects on bone and mineral metabolism. Acute alcohol intoxication causes transitory hypoparathyroidism with resultant hypocalcemia and hypercalciuria. Prolonged moderate drinking elevates serum parathyroid hormone (PTH) levels, whereas chronic alcoholics are characterized by low serum levels of vitamin D metabolites with resultant malabsorption of calcium, hypocalcemia, and hypocalciuria. Independently of whether alcohol consumption is of short duration, social, or heavy and chronic, it seems to suppress the function of osteoblasts, as evidenced by low serum levels of osteocalcin. It has recently been reported, however, that alcohol can also have a beneficial effect on bone. Among postmenopausal women, moderate alcohol consumption correlates positively with central and peripheral bone mineral density, and with serum estradiol levels.
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PMID:Alcohol and bone. 193 4

Osteoporosis is more common in chronic alcoholics than in age-matched controls. Possible aetiological factors are: malabsorption of calcium and vitamin D; liver disease and abnormal parathyroid function. The possibility that alcohol may directly affect osteoblastic function has, however, received little attention. We measured plasma osteocalcin, a protein synthesised specifically by osteoblasts, in chronic alcoholics. Our data show that these have low plasma osteocalcin but normal calcium, magnesium and parathormone, which suggest that alcohol may be directly toxic to osteoblasts.
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PMID:Bone disease in chronic alcoholism: the value of plasma osteocalcin measurement. 278 3

Inflammatory bowel disease (Crohn's disease and ulcerative colitis) is associated with decreased bone mineral density and increased risk of osteoporosis. However, the pathogenesis of this bone loss is not yet fully understood. In the present study we measured lumbar bone mineral density (by dual photon absorptiometry), serum levels of parathyroid hormone (PTH) and vitamin D metabolites, and serum markers of bone turnover (alkaline phosphatase and osteocalcin) in 15 patients with Crohn's disease and in 4 patients with ulcerative colitis. The median duration of the disease was 4 years and the median lifetime steroid dose was 10g of prednisone. We compared our results to a control group of 19 normal persons, who were matched for age and sex to the patients. We found that lumbar bone density was reduced by 11% in patients compared with control persons (Z-score -0.6 +/- 0.6 versus -0.1 +/- 0.8; p < 0.05). In patients, the serum levels of PTH, 25-hydroxyvitamin D3, and calcitriol (1,25(OH)2D3) were significantly reduced compared with control persons. Serum alkaline phosphatase activity (AP) was significantly higher in the patients and was inversely related to lumbar bone density. Osteocalcin values were not different between patients and control persons. There was also no difference in serum levels of calcium between the two groups, whereas phosphorus levels were higher in patients. We conclude that malabsorption of calcium was not a primary cause of bone loss in our patients, because we did not find secondary hyperparathyroidism. Accordingly, we did not find a severe vitamin D deficiency, since 25-hydroxyvitamin D3 levels were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone mineral density and calcium regulating hormones in patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis). 800 8

Severe osteoporosis represents a major complication of corticosteroid (CST) excess. Steroid-induced osteoporosis is characterized by both increased bone resorption and inhibition of bone formation. Excessive bone resorption is attributed to hyperparathyroidism which is secondary to calcium malabsorption. Calcium and vitamin D supplementation or treatment with inhibitors of bone resorption are of benefit but they usually lead to further inhibition of bone formation. The inhibition of bone formation in CST treated patients is due in part to suppression of adrenal androgen secretion. Thus the suppressed circulating levels of osteocalcin, a biochemical marker of osteoblast activity, in patients on CST can be reverted to normal by administration of anabolic steroids. In a prospective controlled trial in patients on long-term CST therapy we have observed that nandrolone decanoate therapy, 50 mg intramuscularly every 3 weeks for 18 months, induces a transient increase in bone mass within the first 6 months of treatment and prevent further losses thereafter. The sequential biochemical changes indicate that nandrolone decanoate in patients on CST inhibits bone resorption without affecting or even increasing bone formation. Furthermore in patients on CST treatment the virilizing activity of nandrolone decanoate was virtually negligible at least within the 18 months of treatment. These results indicate that anabolic steroid administration may represent a rational and convenient strategy for preventing and treating CST-induced osteoporosis.
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PMID:Anabolic steroids in corticosteroid-induced osteoporosis. 825 56

The elderly subject is prone to both vitamin B insufficiency and calcium insufficiency due to a low calcium intake and calcium malabsorption. These two alterations may lead to secondary hyperparathyroidism, and thus to increased bone loss. We investigated 72 elderly subjects (16 men and 56 women) with vitamin D insufficiency and 25 healthy elderly women with normal vitamin D status, with respect to their indices of calcium metabolism and of bone remodeling: serum total alkaline phosphates (phosphatases), bone AP (BAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), urine hydroxyproline (HYP), and the 3-OH-pyridinium derivatives pyridinoline (PYD) and deoxypyridinoline (DPD), which are new markers of bone resorption. We then studied the modifications of these markers in the patients with vitamin D insufficiency at 3 months and 6 months after onset of a daily vitamin D and calcium supplementation. When compared with elderly subjects with normal vitamin D status, patients with vitamin D insufficiency had increased intact parathyroid hormone (iPTH) levels (60.1 +/- 10.2 vs 30.2 +/- 4.5, p < 0.001) and a high bone turnover as reflected by increased values of most serum and urine markers of bone remodeling. PYD and DPD levels were significantly correlated with all indices of bone turnover, unlike HYP, which showed no correlation with bone formation markers (AP, BAP, and BGP). A daily supplement of 800 IU vitamin D3 and 1 g of elemental calcium increased 25(OH)D levels and induced a dramatic decrease of iPTH levels; at 3 and 6 months, the mean iPTH level decreased by 50% (p < 0.0001), reaching the mean value of healthy vitamin D sufficient elderly women. All markers of bone turnover, except TRAP, decreased significantly at 3 and 6 months. The PYD/DPD ratio increased significantly at 3 and 6 months. The decrease of bone markers was more marked in patients with more severe hyperparathyroidism, the greatest variations being obtained with BAP (45%, p = 0.006) and DPD (43%, p = 0.036) levels. Most markers of bone remodeling are increased in elderly subjects with vitamin D insufficiently and vary with its correction. However, BAP and DPD are the most sensitive indicators of increased bone turnover due to secondary hyperparathyroidism.
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PMID:Markers of bone remodeling in the elderly subject: effects of vitamin D insufficiency and its correction. 859 53

Osteoporosis and magnesium (Mg) deficiency often occur in malabsorption syndromes such as gluten-sensitive enteropathy (GSE). Mg deficiency is known to impair parathyroid hormone (PTH) secretion and action in humans and will result in osteopenia and increased skeletal fragility in animal models. We hypothesize that Mg depletion may contribute to the osteoporosis associated with malabsorption. It was our objective to determine Mg status and bone mass in GSE patients who were clinically asymptomatic and on a stable gluten-free diet, as well as their response to Mg therapy. Twenty-three patients with biopsy-proven GSE on a gluten-free diet were assessed for Mg deficiency by determination of the serum Mg, red blood cell (RBC) and lymphocyte free Mg2+, and total lymphocyte Mg. Fourteen subjects completed a 3-month treatment period in which they were given 504-576 mg MgCl2 or Mg lactate daily. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and osteocalcin were measured at baseline and monthly thereafter. Eight patients who had documented Mg depletion (RBC Mg2+ < 150 microM) underwent bone density measurements of the lumbar spine and proximal femur, and 5 of these patients were followed for 2 years on Mg therapy. The mean serum Mg, calcium, phosphorus and alkaline phosphatase concentrations were in the normal range. Most serum calcium values fell below mean normal and the baseline serum PTH was high normal or slightly elevated in 7 of the 14 subjects who completed the 3-month treatment period. No correlation with the serum calcium was noted, however. Mean serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and osteocalcin concentrations were also normal. Despite only 1 patient having hypomagnesemia, the RBC Mg2+ (153 +/- 6.2 microM; mean +/- SEM) and lymphocyte Mg2+ (182 +/- 5.5 microM) were significantly lower than normal (202 +/- 6.0 microM, p < 0.001, and 198 +/- 6.8 microM, p < 0.05, respectively). Bone densitometry revealed that 4 of 8 patients had osteoporosis of the lumbar spine and 5 of 8 had osteoporosis of the proximal femur (T-scores < or = -2.5). Mg therapy resulted in a significant rise in the mean serum PTH concentration from 44.6 +/- 3.6 pg/ml to 55.9 +/- 5.6 pg/ml (p < 0.05). In the 5 patients given Mg supplements for 2 years, a significant increased in bone mineral density was observed in the femoral neck and total proximal femur. This increase in bone mineral density correlated positively with a rise in RBC Mg2+. This study demonstrates that GSE patients have reduction in intracellular free Mg2+, despite being clinically asymptomatic on a gluten-free diet. Bone mass also appears to be reduced. Mg therapy resulted in a rise in PTH, suggesting that the intracellular Mg deficit was impairing PTH secretion in these patients. The increase in bone density in response to Mg therapy suggests that Mg depletion may be one factor contributing to osteoporosis in GSE.
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PMID:Magnesium deficiency: possible role in osteoporosis associated with gluten-sensitive enteropathy. 911 91


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