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Query: UMLS:C0205700 (ash)
 15,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anabolic effect of intermittent treatment with parathyroid hormone (PTH) on cortical bone was investigated. Groups of rats were injected with human PTH (1-34) or PTH (1-84), 1.1, 3.3, 10, and 30 nmol/kg/day for 30 days. A dose-related increase in bone formation rate at the femoral middiaphysis was found at both the periosteum and the endosteum and also an increase in bone mass, with no change in the bone lengths or body weight gain of the rats. The highest mineral apposition rate, as analyzed by tetracycline labeling, was found at the periosteal postero-medial aspect and at the endosteal anterior aspect. This pattern of bone modeling was also found in the PTH-treated animals, although more and more areas were included in bone mineral apposition. The PTH treatments did not change the porosity of the cortical bone nor the concentration and biochemical stability of the collagen. The highest doses of PTH resulted in a slight reduction in the ash concentration of cortical bone. No differences were found between the effects of PTH (1-34) and PTH (1-84) on bone formation rate, bone mass, porosity, and biochemical parameters. Consequently, intermittent treatment with PTH increased the formation of cortical bone dose dependently, at both the periosteum and the endosteum and increased the bone mass of these growing rats, with no change in the body weight gain or femoral growth rate compared with the control animals. The responses of the cortical bone modeling were increased by the PTH treatments without changing its direction or pattern.
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PMID:Parathyroid hormone (1-34) and (1-84) stimulate cortical bone formation both from periosteum and endosteum. 829 53

The objective of this study was to evaluate the effects of a long-term, low-calcium diet on fetal calcium metabolism and fetal skeleton development in ewes. Eleven pregnant sheep were assigned to two groups, fed either a diet low in calcium (0.26% total dry matter) or normal in calcium (0.8% total dry matter) for 2 months, starting at 60 days gestational age. The ewes fed the low calcium diet showed lower plasma levels of calcium and higher plasma levels of hydroxyproline, parathyroid hormone, and 1,25(OH)2D compared with the ewes fed the normal calcium diet. There were no differences in these variables between the two groups of fetuses. These observations suggest that the plasma components of calcium homeostasis measured in the fetal lamb in the present study are independent of the ewe and are not significantly affected by the presence of lowered maternal calcium for many weeks during pregnancy. Despite the ability of the fetus of the ewe on the low calcium diet to maintain relatively normal circulating plasma components of calcium homeostasis, long-term maternal hypocalcemia delayed fetal skeletal ossification as shown by histological examination of the fetal humerus. The fetal humerus from low calcium-fed ewes showed a lower proportion of bone versus cartilage (45.6 +/- 5.9 versus 57.4 +/- 4.6%, mean +/- SD) lower ash content (15.4 +/- 1.5 versus 17.4 +/- 1.0%), and lower specific gravity (1.19 +/- 0.2 versus 1.22 +/- 0.02) (P < 0.05) than the humerus from fetuses of normal calcium-fed ewes. This study shows that the long-term calcium intake of the ewe does affect fetal skeletal development, despite a lack of observable effects on fetal plasma concentrations of calcium or known calcium regulating hormones such as 1,25(OH)2D or parathyroid hormone.
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PMID:Humeral skeletal development and plasma constituent changes in fetuses of ewes maintained on a low calcium diet from 60 days of gestation. 846 9

The aim of this investigation was to compare the effects of sodium fluoride (NaF) and parathyroid hormone (PTH) on ash density and strength in an osteopenic rat model. The study comprised 66 female virgin rats divided into the following 11 groups, each comprising six animals: baseline controls; baseline ovariectomized (ovx); intact controls (5 and 16 weeks), ovx controls (5 and 16 weeks); ovx-treated with PTH (0.02 mg/kg per day, 5 and 16 weeks); ovx treated with NaF (10 mg/kg per day, 5 and 16 weeks); ovx-treated with NaF (1.0 mg/kg per day, 16 weeks). Ovariectomy was performed at 12 weeks of age, 14 weeks prior to start of treatment. Ash density, bone fluoride content, and biomechanical analyses were performed on femoral cortical bone, the right femoral neck, and the sixth lumbar vertebral body. ovx had no effect on cortical bone, whereas the femoral neck displayed a significantly lower bone strength in ovx baseline animals compared with intact baseline rats (p < 0.05). Vertebral ash density was found to be significantly decreased in ovx rats after 5 and 16 weeks (p < 0.05). Treatment with fluoride had little effect on the osteopenic rat skeleton. Cortical ash density was significantly lower than ovx and intact groups in the high-dose-treated rats after 5 (p < 0.01) but not after 16 weeks. High doses of fluoride for 16 weeks induced a significant increase in maximum load and normalized strength in cortical bone when compared with intact animals (p < 0.05), but not at the other bone sites. Cortical bone strength was not different from the ovx animals at either timepoint. In fluoride-treated animals, femoral neck bone strength, vertebral body bone strength, bone quality, and ash density were found to be at about ovx levels and, in the vertebral body, significantly lower than intact animals (p < 0.05, p < 0.01). In contrast, treatment with PTH increased ash density, bone strength, and bone quality to above ovx levels (p < 0.01), and above the level of the intact animals also, although significant values were reached for cortical bone strength only (p < 0.01). Additionally, biomechanical competence and ash density measurements were significantly higher in PTH-treated rats compared with fluoride-treated rats. In conclusion, this study has shown that PTH has a highly anabolic effect and is capable of effectively restoring ovx-induced loss of bone mass and biomechanical competence. In addition, in this osteopenic rat model, PTH proved much more advantageous than treatment with fluoride, which failed to restore the ovx-induced loss of bone strength.
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PMID:A comparison of the effects of two anabolic agents (fluoride and PTH) on ash density and bone strength assessed in an osteopenic rat model. 914 41

The effect of dietary citric acid supplementation on calcium (Ca) and phosphorus (P) bioavailability was studied in rats fed 3 different diets containing 0.1, 0.5 or 1.0 g/100g Ca during 7 weeks. Citric acid supplementation increased intestinal Ca and P absorption and the Ca and P retention/intake ratio only in rats fed the 1% Ca diet. It also increased the P concentration of bone ashes in rats fed the 0.5% Ca diet (18.9 +/- 0.2 vs 17.5 +/- 0.5%) and the 1% Ca diet (20 +/- 0.1 vs. 19 +/- 0.3%), and the Ca bone ash concentration in rats fed the 1% Ca diet (36.7 +/- 0.4 vs. 35.7 +/- 0.5%). In rats fed the 1% Ca diet, plasma P concentration was decreased by citric acid supplementation (2.09 +/- 0.10 vs. 2.45 +/- 0.08 mmol/l) while urinary P excretion was increased (18.2 +/- 2.3 vs. 2.0 +/- 0.3 mmol/4 days), together with a decrease in plasma calcitriol concentration (54.4 +/- 2.6 vs. 79.6 +/- 2.5 ng/l), but no change of the circulating parathyroid hormone level. This study indicates that citric acid supplementation together with a Ca-rich diet allows to obtain an increased retention of Ca and P in bone. The prolonged administration of Ca citrate supplements may therefore help to increase bone mineral concentration.
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PMID:Stimulation by citric acid of calcium and phosphorus bioavailability in rats fed a calcium-rich diet. 925 73

Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hypergastrinemia. In chickens, omeprazole induces growth not only of the acid-producing mucosa (probably reflecting the trophic action of gastrin), but also of the parathyroid glands (hypertrophy + hyperplasia), while suppressing bone density and body weight gain without affecting blood calcium. The first part of the present study was concerned with the effect of omeprazole, ergocalciferol (vitamin D2), and restricted food intake on the gene expression of parathyroid hormone (PTH) in the parathyroid glands of the chicken. Chickens were treated with omeprazole (400 micromol/kg/day, I.M.), food restriction, omeprazole + food restriction, ergocalciferol (250 000 IU/kg/day, S.C.), or ergocalciferol + omeprazole for 5 weeks. The weight gain of the chickens was monitored, and the weights of the parathyroid glands and femurs were determined at sacrifice. PTH mRNA in the parathyroid glands was analyzed by Northern blot. The second part of the study examined the effect of 3 weeks of continuous gastrin infusion (chicken gastrin 20-36, 5 nmol/kg/hour, S.C.) on the expression of PTH mRNA in the parathyroid glands. Omeprazole reduced the body weight and femur density (ash weight per volume) while greatly increasing the weight of the parathyroid glands and the PTH gene expression. Food restriction alone and ergocalciferol alone (at a dose that raised blood Ca2+) were without effect, but food restriction greatly enhanced the omeprazole-evoked increase in parathyroid gland weight and PTH gene expression. Gastrin increased the weight of the parathyroid glands and reproduced the effect of omeprazole on PTH gene expression. Hence, it seems likely that the effect of omeprazole reflects the ensuing hypergastrinemia.
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PMID:Chicken parathyroid hormone gene expression in response to gastrin, omeprazole, ergocalciferol, and restricted food intake. 926 12

This study was designed to determine the fate of new parathyroid hormone (PTH)-induced cortical bone after withdrawal of PTH treatment, and to evaluate whether subsequent treatment with a bisphosphonate would influence this. Six groups of 21-month-old rats were used: a baseline group killed at the beginning of the experiment, three groups injected with human PTH (1-34) (62 mug/kg) daily for 8 weeks (day 1-56), then one group was killed and the other two groups were injected for another 8 weeks (day 57-112) with either saline or bisphosphonate (risedronate 5 mug/kg twice a week). Two control groups were injected with vehicle for the first 8 weeks, then one group was killed and the other group injected with saline the next 8 weeks. All animals were labeled with tetracycline and calcein on day 35 and day 49 of the experiment, respectively. PTH increased periosteal (35%) and in particular endosteal mineralizing surfaces (188%), mineral appositional rates, and bone formation rates at the femur diaphysis, leading to an increase in cortical cross-sectional area of 31%. Withdrawal of PTH induced a fast and pronounced endosteal bone resorption whereas risedronate prevented this resorption. No differences were seen in apparent density of dry defatted bone and ash among the groups. PTH increased the mechanical strength of the femur diaphysis; ultimate load increased by 64% and ultimate stress by 25%. A pronounced decrease in mechanical strength and competence was found after withdrawal of PTH: ultimate load decreased by 31% and ultimate stress by 21%. Risedronate, however, prevented this decrease in mechanical strength and competence in these 2-year-old rats.
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PMID:Bisphosphonate maintains parathyroid hormone (1-34)-induced cortical bone mass and mechanical strength in old rats. 950 56

The present study was designed to examine the metabolic changes and early effects of short-term parathyroid hormone (PTH) treatment on bone mass, mineral content, and strength. Forty-eight 10-week-old intact female rats were randomized into six groups. The three PTH-treated groups were subcutaneously given PTH 50 microg/kg body weight daily for 5 (PTH5), 10 (PTH10), or 15 (PTH15) days. The three respective time control groups (C5, C10, and C15) were injected with saline solution. In serum, total calcium, alkaline phosphatase, and insulin-like growth factor-I (IGF-I) were analyzed. Bone mass was estimated with wet and dry weights of the femora and hydroxyproline content of the tibiae. Ash weight and calcium, magnesium, and phosphorus contents (determined by AAS) were used to measure femoral mineral content. Bone mineral density (BMD) of the femora was measured using dual-energy X-ray absorptiometry (DXA) and the biomechanical properties of the femoral neck were tested. After 5 days of PTH treatment, some trends of the anabolic actions of PTH could be observed, but there was no significant effect on relevant parameters of bone formation. After 10 days, bone mass, mineral content (assessed by ash weight), and BMD of the PTH-treated rats were significantly increased compared with those of controls. The relative femoral magnesium content of the PTH-treated animals was significantly higher than that of controls. After 15 days, the length of the femora, bone mass, mineral content, BMD, and the width of the femoral neck were increased, and its biomechanical properties were significantly improved in PTH-treated rats compared with the respective time control group. PTH treatment significantly increased circulating alkaline phosphatase and decreased systemic IGF-I concentrations throughout the study. In conclusion, intermittent PTH administration to still growing female rats is anabolic in bone with significant effects already taking place after 10 days of treatment. The effects of PTH consisted of: (1) an increase in bone mass and mineral content with a transient augmentation of relative magnesium content; and (2) improved width and mechanical properties of the femoral neck after 15 days of treatment. These effects are accompanied by an increase in longitudinal bone growth. They are unlikely related to any changes in systemic IGF-I concentrations.
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PMID:Early effects of short-term parathyroid hormone administration on bone mass, mineral content, and strength in female rats. 951 14

When administered intermittently, parathyroid hormone (PTH) is a strong anabolic agent, increasing both bone mass and bone mechanical strength and competence. This study evaluates the fate of PTH-induced bone in vertebral bodies after withdrawal of PTH treatment in normal old rats. Sixty-seven 21-month-old male rats were treated with 62 microg/kg/day PTH(1-34) for 8 weeks, followed by saline or bisphosphonate (risedronate, 5 microg/kg twice a week) for another 8 weeks. The rats were scanned by dual-energy X-ray absorptiometry at intervals. The bone mineral content (BMC) of L2-5 increased by 33% during the PTH treatment. The BMC started decreasing shortly after withdrawal of PTH and continued to decline during the 8 weeks after withdrawal of PTH. Risedronate, however, prevented this decrease in BMC. All rats were labeled with tetracycline and calcein 3 weeks and 1 week before the cessation of PTH therapy. In the cancellous bone, PTH increased the mineralized surface: 32.9% +/- 2.8% (mean +/- standard error of the mean) vs. controls 12.0% +/- 1.5%, the mineral appositional rate (0.65 +/- 0.02 to 0.88 +/- 0.06 microm/day), and the cancellous bone volume (BV/TV: 14.5% +/- 0.7% to 27.5% +/- 1.7%). Withdrawal of PTH induced a fast and pronounced bone resorption, decreasing both the extent of the fluorochrome labels and the cancellous bone volume to control values. Risedronate prevented this resorption. In the cortical bone of the vertebral shell, PTH induced large increases in the endocortical mineralized surface, mineral appositional rate, and cortical area. The endocortical fluorochrome labels were, however, resorbed after withdrawal of PTH. Risedronate maintained both the fluorochrome labels and the cortical area. At the periosteum, the response to PTH was less evident, however, and hardly any labeling was seen at the periosteum facing the vertebral canal either in the controls or in the PTH-treated rats. The compressive strength of the vertebral body specimens increased with PTH treatment whether measured in newtons (317 +/- 23 to 623 +/- 54 N), normalized to cross-sectional area (23.0 +/- 1.4 to 44.7 +/- 2.5 N/mm2), or to ash content per millimeter height (58 +/- 2 to 76 +/- 2 N x mm/mg). Withdrawal of PTH decreased the compressive strength and competence to control values. Risedronate, however, maintained the PTH-induced mechanical strength and competence. The study discloses that even in very old rats withdrawal of PTH treatment causes a rapid and pronounced decline in the bone mass deposited during PTH treatment; treatment with risedronate can, however, maintain the PTH-induced bone properties in the axial skeleton of old rats.
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PMID:Withdrawal of parathyroid hormone treatment causes rapid resorption of newly formed vertebral cancellous and endocortical bone in old rats. 966 29

Disorders in which magnesium (Mg) depletion is common have an associated high incidence of osteoporosis. Mg depletion in humans results in hypocalcemia, low serum parathyroid hormone (PTH) and 1, 25(OH)2-vitamin D levels, as well as PTH and vitamin D resistance which may serve as mechanisms for the development of osteoporosis. In order to determine if isolated Mg depletion will result in bone loss, we have induced dietary Mg deficiency in the rat. Adult (290 g) female rats were given either a low-Mg diet (2 mg/100 g chow; n = 6) or a normal control Mg diet (63 mg/100 g chow; n = 6). Dietary calcium (Ca) was normal in both groups (592 mg/100 g chow). At 12 weeks, blood was obtained for serum Mg, Ca, PTH, 1,25(OH)2-vitamin D, and osteocalcin determinations. The rats were then euthanized and the femurs obtained for mineral analysis and histomorphometry. Serum Mg in the low-Mg group was less than control (0.4 +/- 0.2 vs. 1.9 +/- 0.2 mg/dl, p < 0.001; mean +/- SD) while serum Ca was higher (11. 7 +/- 0.5 vs. 9.3 +/- 0.4 mg/dl, p < 0.001). PTH was suppressed in the Mg-deficient group (36 +/- 16 vs. 109 +/- 30 pg/ml in controls, p < 0.002). Serum 1,25(OH)2-vitamin D was also suppressed in the Mg-deficient animals (7.1 +/- 4.8 vs. 28.5 +/- 8.2 pg/ml in controls, p < 0.002). Serum osteocalcin levels were not different (19.8 +/- 2.5 ng/ml in Mg-deficient rats vs. 15.3 +/- 3.4 ng/ml in controls). While the ash weight of Ca and phosphorus in the femur did not change, the ash weight of Mg fell (low-Mg group 0.55 +/- 0.01%, controls 0.65 +/- 0.02%, p < 0.001). Histomorphometry demonstrated reduction in bone mass; the trabecular bone volume in the femur of the low-Mg group was reduced from control (7.7 +/- 0.2 vs. 13.7 +/- 1.9%, p < 0.002). A surprising new observation was an increase in osteoclast (OC) bone resorption with Mg depletion. The number of OC per millimeter bone surface was 16.9 +/- 1.3 in the low-Mg group versus 7.8 +/- 1.5 in controls (p < 0.001). The percentage of bone surface occupied by OC was 38.3 +/- 3.7 in the low-Mg group versus 17.7 +/- 2.4 in controls (p < 0.001). This increased resorption occurred with an inappropriate non-altered bone-forming surface relative to control (% osteoid surface: low-Mg group 2.4 +/- 0.7 vs. controls 2.6 +/- 0.4; % osteoid volume: low-Mg group 0.25 +/- 0.09 vs. controls 0.38 +/- 0.06; number of osteoblasts per millimeter bone surface: low-Mg group 0.9 +/- 0.3 vs controls 1.3 +/- 0.3). No increase in bone-forming surface or osteoblast number despite an increase in OC-resorbing surface and OC number strongly suggests impaired activation of osteoblasts and an uncoupling of bone formation and bone resorption. Our data demonstrate that Mg depletion in the rat alters bone and mineral metabolism which results in bone loss.
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PMID:Magnesium deficiency induces bone loss in the rat. 970 67

In humans, gastric surgery results in in osteopenia via mechanisms that are insufficiently understood; surgery-induced changes in the hormonal axes involving the stomach, thyroid, and the parathyroids may play a role. To study this in more detail, we evaluated calcium (Ca), magnesium (Mg), and phosphorus (P) metabolism as well as physical, chemical, and histomorphometric bone parameters in rats rendered hypergastrinemic by fundectomy (FX). In independent experiments, the response to an oral Ca challenge was investigated in intact rats versus FX, and in thyroidectomized versus thyroid-intact FX rats. Sixteen weeks following FX, body weight was approximately 80% that of sham-operated controls. In urine, P excretion was elevated fivefold, the pH was significantly decreased, and cAMP excretion was elevated as compared with controls; serum parathyroid hormone (PTH), calcitonin, 25OHD, Ca, Mg, and P were normal; gastrin and 1,25(OH)2D were elevated. On the basis of bone ash mineral content, FX rats developed significant osteopenia, and histomorphometry indicated only slightly elevated bone turnover and mineralization. Following oral Ca, thyroid-intact FX rats developed hypercalcemia, serum gastrin decreased, and calcitonin increased significantly; in thyroidectomized FX rats, calcitonin remained at baseline levels although there was a similar degree of hypercalcemia; PTH decreased during the hypercalcemic period in both groups. Serum gastrin did not correlate with calcitonin or PTH, and in multivariate regression analysis the only predictor of serum 1, 25(OH)2D was urinary phosphorus. It was concluded that in the FX rat (1) osteopenia is not caused by intestinal Ca malabsorption, vitamin D, Ca deficiency, or secondary hyperparathyroidism; (2) osteopenia may be related to PTH-independent urinary hyperexcretion of P, followed by a rise of serum 1,25(OH)2D; (3) the existence of endocrine axes among gastrin, calcitonin, and PTH cannot be substantiated. FX osteopenia appears to be related to gastric acid abolition, and the reactive hypergastrinemia probably stabilizes the mass and turnover of bone.
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PMID:Gastric fundectomy in the rat: effects on mineral and bone metabolism, with emphasis on the gastrin-calcitonin-parathyroid hormone-vitamin D axis. 979 30


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