ISSN:0884-0431    

DOI:10.1002/jbmr.5650100702

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

年代:1995

数据来源: WILEY

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100703

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe enhanced precision of dual‐energy X‐ray absorptiometry (DXA) allows the detection of very small changes in bone mineral density (BMD). True clinical changes in BMD in patients must be evaluated with the appropriate error of variance. We evaluated the responsiveness of our measures to true bone loss using a statistical variance components model that characterizes the variability associated with error introduced by the machine, operator, and subjects. Our techniques were applied to data from a prospective study of BMD measurements on spine phantoms and on pre‐ and postmenopausal women performed on the same day or up to 4 weeks apart with DXA (QDR 1000W, Hologic). Our model determined that most of the error in measurements was introduced by operators' and subjects' variability rather than machine performance. The false‐positive rates for true bone change are significantly reduced when the appropriate CV% is used to estimate the significance of bone loss over time. Our study underscores the need to use the appropriate precision error to evaluate the clinical significance of changes in bone mass in individual subjects ov

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100704

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

年代:1995

数据来源: WILEY

摘要:

AbstractThis study was designed to assess the effects of 18 months of resistance exercise on regional and total bone mineral density (BMD) and soft tissue lean mass (STL) in premenopausal women aged 28–39 randomly assigned to an exercise or control group. Twenty‐two exercise and 34 control subjects completed the 18‐month training study. All subjects were previously inactive and untrained women. Initial, 5‐, 12‐ and 18‐month assessments were made of total and regional BMD and total and regional STL using dual energy X‐ray absorptiometry. All subjects consumed a 500 mg/day elemental calcium supplement throughout the study. Initial Ca intake without supplement averaged 1,023 mg/day in total sample. Serum levels of bone osteocalcin and dietary assessments using 12 randomly assigned days of diet records were also completed. Muscular strength was assessed from both 1 repetition maximum (RM) testing of 10 weightlifting exercises and by peak torque for hip abduction/adduction and knee extension/flexion. Training increased strength by 58.1% based on 1 RM testing and by 33.8% based on isokinetic testing at 18 months versus baseline. BMD increased significantly above baseline at the lumbar spine for the exercise group at 5 months (2.8%), 12 months (2.3%), and 18 months (1.9%) as compared with controls. Femur trochanter BMD increased significantly (p<0.05) in the exercise group at 12 months (1.8%) and 18 months (2.0%) but not at 5 months (0.7%) as compared with controls. No changes in total BMD, arm BMD, or leg BMD were found. There was a 20% increase in BGP in the exercise group as compared with controls at 5 months and this difference was maintained throughout the study. For STL, significant increases for total, arm, and leg were found at 5, 12, and 18 months for the exercise group versus control ranging from 1–6% over baseline. These results support the use of strength training for increasing STL and muscular strength with smaller but significant regional increases in BMD in the premenopa

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100705

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

年代:1995

数据来源: WILEY

摘要:

AbstractTo clarify events involved in 1,25(OH)2D3‐stimulated osteoclast‐like cell (OCLC) formation in primary murine marrow culture, we have characterized kinetics of precursor proliferation and fusion and their dependence on macrophage colony‐stimulating factor (MCSF).3H‐thymidine nuclear incorporation in tartrate‐resistant acid phosphatase positive multinucleated cells (TRAP+MNCs) was assessed:3H‐thymidine incorporation was greatest when tracer was added during day 4 or 5, with labeled nuclei in 81% (day 4) and 90% (day 5) of the TRAP+MNCs counted at the end of day 7. The percentage of total nuclei labeled was highest when3H‐thymidine was dosed on day 4 (58%), decreasing to 2% by day 7. Final TRAP+MNC numbers were depleted by 80% when treated for 24 h with hydroxyurea on either day 3 or 4; this inhibition dropped to 57% and 12% when hydroxyurea was pulsed during days 5 or 6, respectively. The absence of 1,25(OH)2D3during days 1–4 caused 70% attenuation of TRAP+MNC formation; however, exposure to3H‐thymidine during day 4 in this experiment resulted in subsequent labeling of 81% of the TRAP+MNCs formed, indicating that precursor proliferation occurred in the absence of 1,25(OH)2D3. To demonstrate that proliferation required MCSF, cultures were exposed to a monoclonal anti‐MCSF antibody during days 3, 4, 5, 6, or 7. Inhibition of TRAP+MNC formation was 85% when antibody was added during day 3. Antibody treatment after day 5 had little effect on the OCLC number. Fusion of precursors showed steady progression with OCLCs containing 4.8 ± 03 nuclei at the end of day 4, 8.3 ± 0.5 nuclei after day 5, 12.0 ± 1.3 after day 6, and 13.7 ± 1.5 at the end of day 7. This steady accretion of nuclei was unaffected by doses of MCSF antibody which blocked proliferation. In conclusion, we have shown that OCLCs arise from an MCSF‐dependent expansion of the precursor pool occurring during days 3 and 4. Fusion of these precursors, which begins as proliferation diminishes, is able to progress in the presence of anti‐MCSF antibody. These results should help refine the analysis of factors affecting proliferation and fusion of osteoclas

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100706

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

年代:1995

数据来源: WILEY

摘要:

AbstractMeasurements of lumbar spine (L1–L6) bone mineral density (BMD) and bone mineral content (BMC) of Wistar rats were obtained by dual energy X‐ray absorptiometry (DXA) (QDR‐1000W, Hologic Inc., Waltham, MA) to estimate reproducibility and investigate age‐related changes. In addition we evaluated the accuracy of the technique in female rats. The coefficients of variation (CV) for spine BMD measurements were found to range from 0.73–1.04 in vivo and from 0.36–1.56 in vitro. The in vitro measurements were performed in a 3 cm deep water bath to stimulate an equivalent tissue thickness. Spine BMC, measured in vivo and in vitro correlated closely with the subsequently determined ash weights (r2= 0.87 and 0.97, respectively). We examined age‐related spine BMD by DXA. A relatively constant increase in spine BMD was observed from 6 weeks to 22 weeks; spine BMD remained stable between 22 and 58 weeks. No peak was observed in spine BMD. To evaluate the effect of estrogen deficiency on animals of different ages, we measured spine BMD weekly in female rats subjected to ovariectomy (OVX) or sham operation at 8 and 23 weeks of age. The spine BMDs in each OVX rat were significantly lower than that of the controls. In the 23‐week‐old rats, bone loss was quite rapid for the first 3 weeks of observation and stable afterward. The BMD of 8‐week‐old OVX rats increased with body size. We conclude that DXA allows the observation of age‐related changes in the spine BMD of rats with great precision. The data we have gathered using this method should prove useful for the assessment of experimental models

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100707

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

年代:1995

数据来源: WILEY

摘要:

AbstractNitric oxide (NO) has been reported to inhibit osteoclastic bone resorption, yet potent stimulators of bone resorption, such as interleukin‐1 (IL‐1) and tumor necrosis factor (TNF), are known to stimulate NO production. This paradox prompted us to reinvestigate the relationship between NO production and bone resorption in mouse calvarial organ cultures. Control cultures and those stimulated with calciotropic hormones and individual cytokines produced little NO, and under these conditions the NO synthase inhibitor, L‐NG‐monomethyl arginine (LMMA), had no significant effect on bone resorption. Cytokine combinations were much more potent stimulators of NO production than individual cytokines. Dramatic stimulation of NO production and inhibition of bone resorption resulted when gamma‐interferon (IFN) was combined with IL‐1 or TNF and these effects were reversed by LMMA. IFN had no effect on bone resorption and little effect on NO production when used alone or in combination with calciotropic hormones, however, suggesting that IFN selectively inhibits cytokine‐induced bone resorption by generating large amounts of NO. IL‐1 and TNF acted together to stimulate NO production but to a lesser degree than when combined with IFN. LMMA inhibited bone resorption induced by IL‐1 and TNF, suggesting that lower concentrations of NO stimulate bone resorption. Experiments with the pharmacological NO donor S‐nitroso‐acetyl‐penicillamine (SNAP) supported this view in showing generalized suppression of bone resorption at high SNAP concentrations, but potentiation of IL‐1 induced bone resorption at lower SNAP concentrations. We conclude that cytokines are potent inducers of NO in bone and that cytokine‐induced NO production has biphasic effects on bone resorption. While the mechanisms of action of NO in bone will require further research, these data raise the possibility that local production of NO may be involved in the regulation of bone remodeling, especially in diseases of cytokine activation s

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100708

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

年代:1995

数据来源: WILEY

摘要:

AbstractImpaired bone formation due to defective osteoblast function, as reflected in a decreased serum osteocalcin (OC) concentration in the patients with diabetes, has been implicated in the development of diabetic osteopenia. The role of hyperglycemia in this decrease in serum OC concentration was investigated. 1,25‐dihydroxyvitamin D3(1,25[OH]2D3), an active form of vitamin D3, stimulated OC secretion from the human osteosarcoma cell line MG‐63 in a dose‐dependent manner. Exposure of the cells to high concentrations of glucose for 7 days significantly impaired 1,25(OH)2D3‐induced OC secretion as compared with that observed with cells maintained under normal glucose (5.5 mM) or high mannitol conditions. The inhibitory effect of glucose was in a dose‐dependent manner up to 55 mM. High glucose (55 mM) also attenuated the 1,25(OH)2D3‐induced increase in OC mRNA abundance in MG‐63 cells, suggesting that the inhibition of the 1,25(OH)2D3‐induced increase in OC secretion by exposure to a high concentration of glucose was, at least in part, mediated at the transcriptional level. High glucose significantly decreased the number of 1,25(OH)2D3receptors in MG‐63 cells, without any change in the dissociation constant for 1,25(OH)2D3; this effect was not mimicked by high mannitol, indicating specificity for glucose. These observations suggest that a high glucose concentration significantly impairs the ability of osteoblastic cells to synthesize OC in response to 1,25(OH)2D3by reducing 1,25(OH)2D3receptor number, and that impaired cell function caused by sustained exposure to high glucose contributes to the defect in bone formation observed in the patients with diab

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100709

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe influence of growth hormone on bone formation, mechanical strength, and composition has been investigated in femur middiaphyseal cortical bone from 2‐year‐old male rats. The rats were given biosynthetic human growth hormone (bhGH) at 2.7 mg/kg/day in two daily injections for 20, 40, or 80 days, and all animals were killed 80 days after the start of bhGH administration. Control animals were given saline. All animals were labeled with tetracycline on days 41 and 69. Only in the bhGH‐80‐day group was subperiosteal tetracycline double labeling seen all around the femur diaphysis, and this pattern was found in all animals of the group. Double labeling subperiosteally at the posteromedial aspect was found in all animals of the experiment, but compared with the control group, a 400% and an 800% increase in mineral apposition rate was seen in the bhGH‐40‐day and bhGH‐80‐day groups, respectively. Light microscopy and polarization microscopy showed that this newly deposited bone was organized in the same concentric lammellae and had the same direction of the collagen fibers when compared with the surrounding bone formed before the start of bhGH injections. The cortical bone cross‐sectional area was increased in the bhGH‐40‐day and bhGH‐80‐day groups. At the endosteum, scattered labeling was found in animals from all groups, and no differences in medullary cross‐sectional areas were seen. The mechanical analysis revealed an increased mechanical strength of the whole diaphyseal bone after bhGH administration. When the data were corrected for dimensions of the diaphyseal bone, no differences in intrinsic mechanical properties of the bone tissue were found. No differences in apparent density of dry defatted bone, ash, and collagen were seen, whereas apparent density of dry defatted bone minus ash was decreased in all groups given bhGH. Correspondingly, a slight increase in ash concentrations of the bhGH‐injected animals was seen. bhGH administration also increased the body weight, muscle mass, and total serum IGF‐I

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100710

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe etiology of age‐related bone loss is unclear but both lack of exercise and dietary calcium deficiency have been implicated in its causation. This 2‐year randomized placebo‐controlled study was designed to examine the effects of increased dietary calcium and exercise in 168 women who were more than 10 years postmenopausal. The subjects were randomized into one of 4 groups: placebo, milk powder containing 1 g of calcium, calcium tablets 1 g/night, and calcium tablets 1 g/night and an exercise regimen. The exercise group aimed to undertake 4 h of extra weight‐bearing exercise per week and were undertaking 10% more activity than other groups at 2 years. Bone mineral density at the lumbar spine, three hip sites, and two sites of the tibia close to the ankle joint were measured at 6 month intervals. Dietary intake was evaluated by a weighed food record, exercise was evaluated by an exercise diary, and blood and urine samples were obtained to examine effects on calcium homeostasis. Individual data points were compared using repeated measures ANOVA and least squares regression. Calcium supplementation by either the calcium tablets or the milk powder resulted in cessation of bone loss at the intertrochanteric hip site (placebo, calcium tablets, calcium and exercise, milk powder −0.81, +0.17, +0.23, and +0.07% per year, respectively;p<0.05 for all supplementation groups compared with placebo) with similar results at the trochanteric hip site. The calcium and exercise group had less bone loss at the femoral neck site when compared with calcium supplementation alone (placebo, calcium tablets, calcium and exercise, milk powder −0.67, −0.18, +0.28, and −0.18% per year, respectively;p<0.05 for calcium and exercise compared with calcium alone). There was a significant reduction in the rate of bone loss at the ultradistal site of the tibia (placebo, calcium tablets, calcium and exercise, milk powder −2.5, −1.6, −1.0, and −1.5% per year, respectively;p<0.05 for all supplementation groups compared with placebo). There was no significant bone loss at the spine site in any group. These data support the implementation of a simple public health regimen to prevent age‐related bone loss with calcium supplementation either by calcium tablet or by milk powder. The extra effect of exercise plus calcium at the femoral neck site suggests a site‐specific effect of physical activity on bone density in addition to its possible effect to prevent fracture by maintenance of muscle

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100711

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

年代:1995

数据来源: WILEY