摘要:

AbstractExercise and muscle strength are important determinants of bone mass. Studies were carried out in normal young adult white males to determine the effects of exercise on vitamin D and mineral metabolism. Fourteen men who had engaged in regular muscle‐building exercises for at least 1 year and 14 age‐matched controls (age range, 19–36 year) were hospitalized on a metabolic ward and were given a constant daily diet estimated to contain 400 mg of calcium, 900 mg of phosphorus, 110 mEq of sodium, 65 mEq of potassium, and 18 mEq of magnesium. Body weight averaged 78 ± 3 kg in the exercisers and 72 ± 2 kg in the controls (NS). Serum calcium, ionized calcium, phosphate, magnesium, somatomedin‐C, and immunoreactive parathyroid hormone (PTH) were not different in the two groups, whereas serum Gla‐protein (39 ± 5 vs. 24 ± 2 ng/ml,p<0.01), 25‐hydroxyvitamin D (23 ± 2vs. 16 ± 2,p<0.05) and 1,25‐dihydroxyvitamin D [1,25(OH)2D] (40 ± 2vs. 29 ± 2 pg/ml,p<0.01) were higher in the exercisers than in the controls. Urinary calcium, phosphorus, sodium, potassium, creatinine clearance, and norepinephrine were not different in the two groups, whereas urinary magnesium (12.6 ± 1.0vs. 9.4 ± 0.5 mEq/d,p<0.01) and urinary cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) (2.52 ± 0.19vs. 1.72 ± 0.20 nM/dl glomerular filtrate,p<0.01) were higher in the exercisers than in the controls. There were positive correlations between serum 1,25(OH)2D and urinary calcium (r= 0.544,p<0.01) and between serum 1,25(OH)2D and urinary magnesium (r= 0.407,p<0.05) in all subjects. The results indicate that muscle‐building exercise is associated with increases in serum Gla‐protein, serum 1,25(OH)2D, and urinary cyclic AMP. The increase in serum Gla‐protein suggests that this for

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030402

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractAluminum accumulation by both dialysis patients and nonuremic patients, requiring chronic total parenteral nutrition, may be an etiological factor in the development of severe osteomalacia. To study the role of aluminum toxicity in bone, further experiments have been conducted in the nonuremic, vitamin D‐deficient rat. Weanling rats were raised on vitamin D‐deficient diets, and half received parenteral aluminum (5 mg/wk), for 30 days. In the first experiment low doses of 25‐OH cholecalciferol (500 ng/week) were given subcutaneously for a further 30 days. Control rats were maintained on a similar protocol, but were supplemented with cholecalciferol (5 μg/week) from the outset until sacrifice at 60 days. In the second experiment a single bolus of cholecalciferol (5 μ/g) was given to study short‐term changes in serum biochemistry and bone histology at 96 hr. Quantitative bone histomorphometric analyses of the proximal tibial metaphysis were made in all experimental groups. In the experimental vitamin D‐deficient group, with the highest bone aluminum content (as assessed by extraction of whole bone aluminum), X‐ray microanalysis was performed to determine the distribution of aluminum in bone tissue and bone cell organelles. The results showed that control rats treated with prolonged aluminum therapy (30 mg over 60 days) had evidence of both reduced osteoid matrix synthesis and mineralization. However, in vitamin D‐deficient rats, there was no evidence that aluminum exacerbated the osteomalacic lesion, even though there was histochemical evidence of aluminum deposition at the bone‐osteoid interface. X‐ray microanalysis confirmed the presence of aluminum at this site, but did not reveal significant peaks of aluminum either in mineralized bone or within osteoblasts. In both experiments, vitamin D‐induced osteomalacia was rapidly reversed by both low‐dose 25‐OH cholecalciferol and bolus cholecalciferol, suggesting that aluminum accumulation alone does not lead to impaired mineralization if other conditions favoring bone metabolism are present. In these experiments, secondary hyperparathyroidism may have been one such factor in explaining the failure of bone aluminum accumulation to impair bone mineralization in vitamin D‐deficient rats when compared to vitamin D‐replete controls. Although several animal models of aluminum toxicity have been explored, clearly the experimental conditions, dose, and duration of aluminum administration, and the degree of secondary hyperparathyroidism, are critical factors in determining whether aluminum accumulation in bone res

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030403

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractWe explored the effects of transfusion of carbonic anhydrase II (CA‐II)‐replete erythrocytes on systemic pH, serum electrolytes, and urinary acidification of a patient with CA‐II deficiency. Pretransfusion studies documented hyperchloremic acidosis, increased urinary pH with decreased titratable acidity, and profound CA‐II deficiency in erythrocytes. During transfusion, CA‐II in circulating erythrocytes increased to above the half‐normal levels seen in asymptomatic heterozygote carriers of CA‐II deficiency. However, no significant change occurred in venous, arterial or urinary pH, serum electrolytes, and urinary acid excretion during the transfusion or during the subsequent 60 hr of observation. These studies argue that the renal acidification defect in CA‐II deficiency results from deficiency of CA‐II in the renal parenchyma, and is not secondary to deficiency of CA‐II in erythrocytes. Bone marrow transplantation is not a promising approach to correct therenalmanifestations

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030404

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractThe ability of osteoclasts (OC) to migrate and resorb bone is thought to be dependent on cytoskeletal function and adhesion. Therefore, we investigated the cytoskeleton and the adhesion patterns of rabbit OC on glass and on devitalized bone slices, using specific antibodies to cytoskeletal elements and fluorescence and interference reflection microscopy. Microtubules (MT) were similar in OC on both substrata, and appeared in a pattern typical of that described for many cells. Multiple centriolar complexes were observed in most OC, either as one large aggregate in the center of the cell or dispersed singly or in small aggregates close to individual nuclei. Staining of microfilaments (MF) was similar on both substrata and appeared primarily as an F‐actin network. MF distribution was different in OC associated with resorption lacunae with intense staining over those regions. In the OC on glass, high F‐actin staining was detectable at the periphery in dots and rosette‐like structures, which also stained for vinculin. The adhesion patterns indicated that OC on glass do not make large focal contacts, but appear to make a few tiny focal contacts that are not associated with the rosette‐like structures. Most of the undersurface of the OC appeared either to be involved in close contacts or to be separated by distances of>100 nm from the substratum. These studies indicate that the MF distribution and the adhesion patterns of rabbit OC are typical of motile cells, that the distribution of the cytoskeleton of rabbit OC on glass and on bone slices is similar, and that MF may be involved in the morphological changes associated with res

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030405

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractPrimary bone cell cultures are used widely to examine the regulation of bone metabolism by growth factors and hormones. Characterization of this model system is now being conducted at the molecular level to define modulation of gene expression. Cells were obtained from rat parietal bone by sequential collagenase digestions. Cell populations were evaluated for bone‐related products, including collagen isoform expression and mRNA levels, alkaline phosphatase activity, and osteocalcin production. Serum‐deprived, confluent cultures of the first and second collagenase‐released populations produced a lower percentage of total protein as collagen than the third, fourth, and fifth populations, while co‐culturing the third through fifth populations resulted in the highest level. Collagen typing on SDS‐polyacrylamide gels revealed an abundance of mature type I collagen in all cell populations; type III collagen synthesis was undetectable by this method. This is in contrast to the presence of cytoplasmic mRNA for both type I and type III collagen in all cell populations, suggesting post‐transcriptional modulation of type III collagen synthesis. The expression of alkaline phosphatase and osteocalcin was highest in cultures of later released cells, indicating that these cell populations display phenotypic characteristics associated with cells of the osteobl

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030406

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractLoss of biomechanical function results in rapid bone loss. This study assesses the role of arachidonic acid metabolites in immobilization‐related osteopenia. A hind limb of the rat was immobilized by knee tenotomy and bone resorption and formation parameters were quantitated by histological methods in indomethacin‐treated (0.5 mg/kg per day) and vehicle‐treated animals. Control animals sacrificed 30, 72, and 240 hr post‐tenotomy revealed a significant increase in osteoclast number (30 hr) and resorption surfaces (72 hr) and a decrease in trabecular bone volume (240 hr) in the tenotomized tibiae. In the indomethacin‐treated tibial metaphysis, no significant differences were noted for these parameters by comparison to the nontenotomized leg. Bone formation parameters remained reduced in the tenotomized legs of both the indomethacin and vehicle‐treated groups compared to the control legs. Indomethacin inhibited bone resorption, but did not prevent the decrease in bone formation produced by immobilization over the 10 days of these

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030407

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractThe effects of Phenytoin (diphenylhydantoin, DPH) on calcium uptake in osteoblastic cells were studied to elucidate the potential mechanism of action of this antiepileptic drug on bone metabolism. Preincubation of the human osteoblastic osteosarcoma) cell line, SaOS‐2, and normal rat osteoblastic cells with DPH decreased basal calcium uptake. This inhibition occurred at DPH doses from 0.1 to 50 μg/ml. Parathyroid hormone (PTH) and prostaglandin E2(PGE2) increased calcium uptake in the SaOS‐2 cell line. Following preincubation with DPH, calcium uptake in cells treated with PTH or PGE2did not exceed control levels. However, significant increases in the PTH‐ or PGE2‐treated + DPH‐pretreated cells compared to DPH pretreatment alone were still observed. These studies indicate that DPH induces decreases in osteoblastic calcium influx and they add further information on the possible mode of action of this dr

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030408

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractThe influence of vitamin D metabolites (at 1 × 10−10M) on the calcification of cartilage matrix (measured by45Ca2+uptake) and the C‐propeptide of type II collagen (measured by radioimmunoassay) has been studied using organ cultures and chondrocytes isolated from growth plates of vitamin D‐deficient and ‐sufficient 11‐day‐old rats. Vitamin D‐deficient rats had reduced amounts of C‐propeptide in their serum and freshly isolated growth plate chondrocytes. In all chondrocytes cultured from vitamin D‐deficient animals, the C‐propeptide content was maximal at 24 hr whereas calcification continued to increase for up to 72 hr. In organ and chondrocyte cultures of tissue from vitamin D‐sufficient rats, both 1,25‐dihydroxycholecalciferol (1,25(OH)2D3) and 24,25‐dihydroxycholecalciferol (24,25(OH)2D3) were required for maximal stimulation of calcification and maximal increases in C‐propeptide content. In these D‐replete tissues, 24,25‐(OH)2D3had a less stimulatory effect on both calcification (organ and cell cultures) and C‐propeptide (organ cultures only), while 1,25(OH)2D3alone had no effect in cell cultures but an inhibitory effect in organ cultures.In all of these studies, maximal stimulation by vitamin D metabolites of45Ca2+incorporation was always accompanied by a maximal net increase in CPII content. Since increases were often quantitatively and temporally different, if would appear that the C‐propeptide does not simply accumulate by a process of passive binding to mineral but that its increased concentration is the result of an active process that may be causally related to calcification.These observations clearly demonstrate that 24,25(OH)2D3is alone required for maximal calcification of cartilage matrix in growth plate cartilages of vitamin D‐deficient rats and that this metabolite also produces maximal increases in the synthesis of the C‐propeptide. Moreover, 1,25(OH)2D3is required with 24,25(OH)2D3for the maximal calcification and maximal increases in the amount of C‐propeptide which ar

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030409

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractTo examine the role of lipid metabolism in the growth and function of osteoblast‐like cells, we studied ROS 17/2.8 osteosarcoma cells and primary cultures of rat calvarial osteoblasts during growth in a serum‐free medium supplemented by purified human lipoproteins or by liposomes. Increase in ROS cell number was measured in sparse (1–5 × 103/cm2) cultures over 6–8 days. Liposomes (0–300 μg/ml) and high (HDL), low (LDL), and very low density (VLDL) lipoprotein fractions (0–300 μg apoprotein) markedly stimulated cell growth. Cells plated at 5 × 103/cm2achieved growth rates in the presence of LDL or HDL comparable to 10% fetal bovine serum. Serum‐free culture with exogenous lipid maintained the response of cell cyclic AMP accumulation to parathyroid hormone. Cyclic AMP response to parathyroid hormone was enhanced by glucocorticosteroid, and was attenuated by 1,25‐dihydroxyvitamin D (1,25(OH)2D) with an EC50(10−10M) comparable to that previously observed in serum‐cultured cells (J. Biol. Chem. 258:736, 1985). 1,25(OH)2D also increased the alkaline phosphatase activity in ROS cells cultured in lipid‐supplemented serum‐free culture. Lipoproteins or liposomes also markedly enhanced the proliferative response of sparse cultures of normal rat osteobla

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030410

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractThe bone status of female rats, 6, 12, and 24 months of age was examined. Femur Ca, Pi, and osteocalcin contents, as well as biomechanical properties, were measured and correlated to physical indices and serum chemistry. Diaphyseal Ca, Pi, and osteocalcin did not change significantly with increasing age. Serum Ca and Piconcentrations were not altered in the aged rat. Immunoreactive parathyroid hormone (PTH) levels increased significantly with age, when analyzed by linear regression. Serum osteocalcin decreased progressively from 6 to 12 months (‐21%) and from 12 to 24 months (‐23%). Maximum breaking force required to fracture femurs at midshaft did not change with senescence. Hence, the strength of the femurs as an intact organ was not compromised in aging. However, ultimate stress, a parameter that normalizes for differences in bone geometry and size, decreased 14% from 12 to 24 months. Changes in other biomechanical parameters, including yield and ultimate deformation, strain, and modulus of elasticity, were relatively small, but statistically significant, or were negligible. Morphometric measurements indicated a progressive age‐related increase in second moment of area and cortical area. Medullary area did not change with age. Therefore, strength of the intact femur was maintained by architectural compensations, although normalized tissue strength decreased in senescence. The bone status and Ca/Pihomeostasis of the female rat were compared to similar findings, reported previously, for the male animal. The results suggest that bone status and mineral metabolism were compromised in the aged female rat, but the magnitude of change was less than that found for the senescent mal

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030411

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY