ISSN:0884-0431    

DOI:10.1002/jbmr.5650050902

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

年代:1990

数据来源: WILEY

摘要:

AbstractAdjuvant‐induced arthritis in rats shares many of the features of humans with rheumatoid arthritis, including the development of osteopenia in areas distal to erosive joint disease. We established adjuvant arthritis in male and female Sherman strain rats and then studied external calcium balances and vitamin D metabolism during the period of acute active clinical, serologic, and pathologic arthritis and osteopenia and in the preclinical period. While ingesting a calcium‐sufficient vitamin D‐replete diet (0.6% calcium, 0.65% phosphorus, and 2.2 IU D3per g food), female rats with arthritis demonstrated reduced calcium balance (arthritic, 36 + 8 versus control, 169 + 13 mg per 6 days,p<0.02) because of inefficient gastrointestinal absorption of calcium (arthritic 9.7% versus control 37%). This was associated with calcitriol deficiency (arthritic 52 + 7 versus control 70 + 10 pg/ml) and reduced osteocalcin levels. Male rats with arthritis demonstrated an inability to raise serum calcitriol levels to the same degree as control rats (200 + 30 versus 440 + 70, respectively) while ingesting a calcium‐deficient diet (0.002% calcium, 0.34% phosphorus, and 2.2 IU D3per g food) and also had reduced balance (59 + 7 versus 85 + 10 mg per 6 days, respectively) due in part to decreased efficiency of absorption (55 versus 67%). No abnormalities in calcium balance or in serum calcitriol levels on the sufficient diet were present in the preclinical period. Physiologic calcitriol replacement to arthritic female rats increased osteoid available for mineralization and increased mineral apposition rates. Calcitriol deficiency in adjuvant‐induced arthritis is responsible, in part, for reduced calcium balance and likely contributes to the development of osteopenia during the acute stage of the systemic inflammator

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050903

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe human osteosarcoma cell line MG‐63 has been used to study the production of the bone‐specific protein, osteocalcin. In the absence of any stimuli, MG‐63 cells secreted very low levels of osteocalcin. The secretion of osteocalcin started after a lag time of 10‐12 h upon 1,25‐(OH)2D3treatment. Osteocalcin secretion was measured at doses as low as 0.03 nM (fourfold increase,p<0.05), and this activity increased further with higher doses of 1,25‐(OH)2D3to reach a plateau at 50 nM. The secretion increased transiently from very low levels in sparse cell cultures to peak values in subconfluent cultures (+ 40%), two‐ to threefold above values obtained for confluent cells. Values for confluent cells average 55.9 + 2.0 ng/ml protein per 48 h. A similar behavior is observed for 1,25‐(OH)2D3receptor concentration under similar experimental conditions.Bmaxincreased transiently from sparse to subconfluent cell cultures (40 ‐60% confluent) and reached values 50% lower in confluent cells. However, the receptor affinity was not affected by cell density. MG‐63 cells also possessed an alkaline phosphatase isoenzyme of the bone‐liver‐kidney type that was stimulated by 1,25‐(OH)2D3treatment (two‐ to threefold) and inhibited by parathyroid hormone (40 nM, ‐25%,p<0.025). PTH and PGE2increased cAMP production in a dose‐dependent manner, but the cells were irresponsive to salmon calcitonin. Basal and PTH‐responsive cyclic AMP production were also modulated by cell density. Dexamethasone pretreatment (100 nM, 48 h) stimulated the PTH‐dependent cAMP production but failed to influence the response to PGE2. Vitamin D3‐induced osteocalcin secretion was inhibited by 40 nM PTH (‐20%,p<0.01) and 5 nM PGE2(‐36%,p<0.005), a situation that could be related to the ability of these hormones to stimulate cAMP in these cells. These results show that the MG‐63 cell line is a good human osteoblastlike cell model in which bone‐specific protein synthesis (osteocalcin and alkaline phosphatase) is

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050904

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

年代:1990

数据来源: WILEY

摘要:

AbstractA technique has been established in which cancellous bone biopsies may be simultaneously perfused and subjected to mechanical load bearing. Assessments of cell viability over a period of 24 h were based on the cAMP response to parathyroid hormone, intracellular lactate dehydrogenase activity, and electron micrograph morphology. Two cellular responses to mechanical loading were demonstrated similar to those that follow “osteogenic” loading in vivo, as reported previously. These were (1) a rise in intracellular G6PD in lining cells immediately after loading, and (2) an increase in RNA synthesis measured in osteocytes 6 h after loading. In vivo the osteogenic response to loading was modulated by indomethacin. In these in vitro experiments, addition of indomethacin inhibited both the loading‐related G6PD and the RNA resp

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050905

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

年代:1990

数据来源: WILEY

摘要:

AbstractMatched samples of bone from the lumbar spine and tibia were obtained at autopsy from three adult males who had no known evidence of metabolic bone disease at the time of their demise. The soluble noncollagenous bone proteins were quantitatively extracted from these samples and assayed for the relative content of two bone‐associated proteins, osteocalcin and osteonectin. When compared to trabecular bone, cortical bone had higher levels of osteocalcin and much lower levels of osteonectin. When concentration is expressed per gram of dried bone, the osteocalcin excess in cortical bone ranged from 30‐ to 32‐fold, and the osteonectin excess in trabecular bone ranged from 21‐ to 47‐fold. These differences were significant (P<0.01) using analysis of variance. We conclude that the human skeleton is not homogeneous with regard to these biochemical markers and that cortical and trabecular bone are biochemically quite distinct. This implies that these two types of bone may be subject to distinct regulatory mechanisms and that global assessments of skeletal function and bone quality based upon soluble markers should be applied with caution. The data also imply that a differential assessment of skeletal performance may be possible using biochemical seru

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050906

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

年代:1990

数据来源: WILEY

摘要:

AbstractA group of 85 females aged 48‐77 years with postmenopausal crush fracture osteoporosis were investigated using a 7 day combined calcium balance and calcium47tracer kinetic turnover study to assess the influence of dietary calcium and net absorbed calcium on bone metabolism. During the study, patients were on their habitual diet, as determined by a prestudy registration. Dietary calcium was measured after double serving of all the meals. All urine and feces were collected and analyzed for calcium content. Bone mineralization rate and bone resorption rate were determined by applying the continuously expanding calcium pool model to the tracer kinetic data.Urine calcium excretion and net absorbed calcium were correlated (r= 0.64,p<0.0001) with the following equation: urinary excreted calcium (mmol/day) = 2.4 + 0.4 x net absorbed calcium (mmol/day). Dermal calcium loss was not correlated with net absorbed calcium or urinary calcium. The net amount of absorbed calcium necessary to balance urinary and dermal losses was calculated to be 4.2 mmol calcium per day. The daily calcium intake necessary for obtaining a net absorbed calcium in excess of the urinary and dermal calcium losses and thereby ensure skeletal integrity was estimated to be 34.2 mmol calcium per day compared to an average intake of 27.9 + 7.6 (mean + SD) mmol/day.Net absorbed calcium correlated negatively to bone resorption rate (r= ‐0.31,p<0.005) and positively to bone mineralization rate (r= 0.29,p<0.01) and to calcium balance (r= 0.66,p<0.0001). Dietary calcium intake and calcium balance correlated positively (r= 0.38,p<0.001). The minimum dietary calcium intake to ensure calcium balance was 34.5 mmol calcium per day when using this correlation.We conclude that excess net absorbed calcium in postmenopausal osteoporosis is not quantitatively excreted in the urine but seems to induce a more positive calcium balance by reducing bone resorption rate and increasing bone mineralization rate. The recommended calcium allowance in Western countries does not meet the minimum dietary calcium requirement to ensure calcium balance in patients with postmenopausal osteoporosis when dermal calcium loss is also taken into acc

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050907

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

年代:1990

数据来源: WILEY

摘要:

AbstractTo evaluate potential pharmacologic agents for the prevention or treatment of the bone loss associated with ovarian insufficiency, a predictable animal model is needed. To assess the potential utility of the ovariohysterectomized dog as a model of this condition, we characterized the sequential histomorphometric changes in canine cancellous bone in response to the loss of ovarian function. A group of 25 adult beagle dogs were ovariohysterectomized and terminated at 1, 3, 6, and 10 months following surgery. Iliac biopsies were performed following double‐fluorochrome labeling at the time of surgery and at termination. Static and dynamic histomorphometry was performed on undecalcified sections. By 3 months postovariohysterectomy, there was activation of cancellous bone remodeling as indicated by significant increases in mineralizing surface and bone formation rate. Increases in osteoid surface, mineralizing surface, and bone formation rate were also apparent at 1 month postovariohysterectomy, and although not statistically significant, these trends suggest the skeletal response to acute loss of ovarian function was rapid. This increase in bone remodeling was transient. By 6 months, mineralizing surface and bone formation rate were depressed below presurgical levels. In addition to a reduction in bone formation, a reduction in osteoblast function characterized by reduced labeling of osteoid and a disproportionate increase in eroded surface also occurred. By 10 months postovariohysterectomy, cancellous bone remodeling was not significantly different from presurgical levels. At no time was a significant reduction in bone volume detected. These data suggest that the changes in cancellous bone remodeling in the ovariohysterectomized dog are a series of transient phenomena. The duration and/or magnitude of these changes do not appear to be sufficient to effect a sizable or significant reduction in bone volume. The brief nature of the transients in bone remodeling and the lack of a sizable bone loss in the ovariohysterectomized dog limit the utility of this model for the routine assessment of agents for either the prevention or treatment of bone disease associated with ovarian insufficienc

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050908

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

年代:1990

数据来源: WILEY

摘要:

AbstractA group of 5‐day‐old mice were injected intraperitoneally with (3‐amino‐1‐hydroxypropylidine)‐1,1‐bisphosphonate (APD). Morphologic changes were observed in vitally stained osteoclasts on parietal bones 3 days later, and these were judged to be degenerative. At this time significantly increased numbers of nuclei per osteoclast and total numbers of osteoclast nuclei were observed. However, at 4 days after the injection of APD, the total numbers of osteoclasts were significantly reduced relative to controls. When parietal bones were maintained in culture, APD reduced osteoclast numbers and inhibited cell‐mediated45Ca2+release. Exposure of bones to parathyroid hormone increased the number of osteoclasts counted 1 day later. This effect was not blocked by APD. Calcitonin prevented the reduction in osteoclast numbers due to APD in vitro. We conclude that APD has a direct effect on resorbing m

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050909

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

年代:1990

数据来源: WILEY

摘要:

AbstractRecent studies have indicated that neutral collagenase can be produced in bones of rats. In addition, it has been demonstrated by in vitro studies that the enzyme is likely secreted by osteoblasts. Cells of the osteoblastic tumor cell line UMR‐106 can be stimulated to produce not only collagenase, but also collagenase inhibitor and plasminogen activator. However, it is conceivable that not all osteoblasts produce all of these proteins. In this study, in which UMR cells were maximally stimulated with PTH, only a subpopulation of cells was observed to produce enhanced levels of collagenase but all cells had the ability to synthesize plasminogen activator.Cells of the rat osteosarcoma line UMR‐106‐01 were stained for the presence of collagenase and tissue plasminogen activator using an immunohistochemical procedure. In many cases, the cells were exposed to monensin for the final 3 h of incubation as well as to the inducing agent PTH. Monensin prevented export of the enzymes, enabling them to be visualized within their cell of origin. Maximal stimulation of collagenase was demonstrated to occur 8 h after exposure to 10−8‐10−7M PTH. Under these conditions, 14‐17% of the cells appeared to synthesize elevated amounts of collagenase (as determined by intense staining). Without PTH stimulation, there was a low level of collagenase in all cells, but<1% of the cells stained heavily for the enzyme. In contrast, strong staining for plasminogen activator was observed in all cells with or without PTH treatment. This suggests that the regulation of collagenase production in osteoblasts occurs at the level of the individual cell such that there appear to be subpopulations of cells that respond differently to PT

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050910

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

年代:1990

数据来源: WILEY

摘要:

AbstractA group of 3‐month‐old Sprague‐Dawley rats were sham operated or ovariectomized and given daily injections of human PTH‐(1‐34) (8 or 16 μg per 100 g body weight) for 5 weeks. At the termination of the study histomorphometric techniques were used to examine changes in cortical and cancellous bone in the diaphysis and proximal metaphysis of the tibia. Ovariectomy resulted in a 50% decrease in cancellous bone that was accompanied by a 41 and 120% increase in osteoclasts and osteoblasts, respectively. In contrast, in the ovariectomized animals treated with PTH, the metaphyseal cancellous bone increased by over 300% to a level in excess of that present in the sham‐operated control animals. The increase in cancellous bone induced by PTH was associated with an over 70% increase in osteoblasts and tetracycline‐labeled area and an unexpected decrease in trabecular osteoclasts. In the tibial diaphysis PTH also decreased endosteal osteoclasts and at the same time increased osteoblast size and number as well as endosteal and periosteal bone formation; ovariectomy increased only periosteal bone formation. Our findings demonstrate that intermittent administration of PTH prevents ovariectomy‐induced bone loss and augments cancellous and cortical bone formation in sexually mature ovariectomized rats. Although the basis of the bone anabolic action of PTH remains elusive, our data indicate that it may involve the uncoupling of bone formation and resorption such that the latter is inhibited as bone formation is enhanced. Our findings are also compatible with the view that intermittent administration of PTH increases bone mass, in part by stimulating the proliferation and differentiation of osteoblast progenitors while inhibiting osteocla

ISSN:0884-0431    

DOI:10.1002/jbmr.5650050911

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

年代:1990

数据来源: WILEY