ISSN:0884-0431    

DOI:10.1002/jbmr.5650040202

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

年代:1989

数据来源: WILEY

摘要:

AbstractWe have designed a cyclic regimen for the treatment of osteoporosis based on the activate, depress, free, and repeat (ADFR) concept. Osteoclastic bone resorption is activated by 7 days of oral neutral phosphate and inhibited with a brief pulse (5 days) of etidronate disodium at a high dose (20 mg/kg body weight). Patients next take calcium supplements for 48 days before resuming phosphate to enter the next cycle. Osteoporotic women increased the bone mineral density of the lumbar spine at 6 months by 7.2 ± 5.2% (mean ± SD,N= 14) and at 12 months by 8.2 ± 4.0% (N= 8). Control observations in regularly exercising postmenopausal women (N= 30) showed no significant change in spine mineral density after 20 months (0.5 ± 3.2%), confirming the stability of the measurement technique. The two patients who responded poorly to the cyclic regimen each showed a blunted rise in serum PTH during oral phosphate administration, suggesting that the rise in PTH induced by oral phosphate may be an important component of this cyclic regimen. This preliminary study does not identify which component or components of the regimen are responsible for the increase in bone mass but provides positive encouragement for randomized studies designed to determine the optimum dosage, duration, and timing of each component of the regi

ISSN:0884-0431    

DOI:10.1002/jbmr.5650040203

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

年代:1989

数据来源: WILEY

摘要:

AbstractForearm bone mineral density (BMD) was measured by single‐energy photon absorptiometry in 360 healthy females without known axial fractures, 202 of whom were postmenopausal. The three sites addressed included an ultradistal (U) region containing approximately 60% trabecular bone. The other sites, distal (D) and shaft (S), were progressively more cortical. Reproducibility was 1.7–1.9% CV. The earliest evidence of a significant correlation between BMD and years since menopause was seen in trabecular bone in subjects aged 45–55 years. Fractional decrease in BMD, relative to the premenopausal value, was significantly larger at U than at S for the decades 55–65 years and above. Fractional rates of bone loss at all sites were a maximum in the first postmenopausal decade, the rate at U being 0.035, approximately 1.5 times that at D or S. A total of 33 subjects reported 54 previous minimally traumatic nonaxial (MTNA) fractures. When BMD measurements of the entire study were divided into quintiles, the prevalence of MTNA fracture cases in the lowest quintile was eight times that of each of the upper three quintiles. Prevalence of fracture cases ranked by quintiles of BMD were not different for the three scan sites. Therefore, ultradistal measurements confer no advantages over distal or shaft BMD for discriminating past MTNA fracture cases but do show larger fractional rates of loss during the first postmenopausal decade. When early postmenopausal women (with years since menopause ≤ 10) having BMD at U below the 15th age‐corrected percentile, and their high BMD peers above the 75th percentile, were studied prospectively over 9–24 months there were no differences in their mean fractional rates of bone loss. These rates confirmed cross‐sectional measurements based on years since menopause ≤ 10 but without

ISSN:0884-0431    

DOI:10.1002/jbmr.5650040204

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

年代:1989

数据来源: WILEY

摘要:

AbstractTo examine the effects of 24,25‐(OH)2D3and 1,25‐(OH)2D3on fetal long bone modeling the radii and ulnae of 16 day fetal mice were grown in vitro for 2 days. Their growth, mineralization, and resorption were assessed by measuring diaphyseal length, calcium and phosphorus content, hydroxyproline‐protein ratios, and the release of incorporated45Ca. The results showed that 24,25‐(OH)2D3at concentrations of 10−10‐10−8M stimulated the growth of the bones as indicated by their increased diaphyseal length, periosteal bone area, and hydroxyproline content. Calcium and phosphorus content was significantly increased;45Ca release was unaltered. Bones incubated in media containing 10−6M 24,25‐(OH)2D3responded in a similar fashion to bones incubated in media containing 10−10‐10−8M 1,25‐(OH)2D3, with inhibition of bone growth as indicated by reduced diaphyseal length, periosteal bone area, hydroxyproline‐protein ratios, and calcium and phosphorus content;45Ca release was significantly increased. Neither metabolite affected total bone length. The results suggest a role for 24,25‐(OH)2D3in the growth of fetal mice bones in vitro and also confirm the findings from previous studies that 1,25‐(OH)2D3and high concentrations of 24,25

ISSN:0884-0431    

DOI:10.1002/jbmr.5650040205

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe effect of transforming growth factor β (TGF‐β) on cellular proliferation of osteoblastic MC3T3‐E1 cells was studied with particular emphasis on its effect on modulation of epidermal growth factor (EGF) receptors. In other cells, TGF‐β has been reported to augment EGF receptors. Exposure of MC3T3‐E1 cells to TGF‐β initially increased cell surface EGF receptor levels and decreased the rate of DNA synthesis. The initial elevation of EGF receptor levels was due to increased receptor number per cell, not to changes in binding affinity. On the contrary, prolonged exposure (longer than 40 h) resulted in a decrease in EGF receptor and an increase in the rate of DNA synthesis. Thus, the effects of TGF‐β on these cells appears to be biphasic, reflecting complex mechanisms of action; the early effects of TGF‐β may be consistent with cellular differentiation to the osteoblastic phenotype with decreased cellular proliferation, whereas chronic exposure of these cells to TGF‐β stimulated cellular proliferation and inhibited osteoblastic phenotype expression. It is not likely that stimulation of cellular proliferation was through elevation of EGF receptor levels, because TGF‐β did not enhance the stimulatory effect of EGF on cellular proliferation. Thus, we conclude that TGF‐β possesses a stimulatory effect on the cellular proliferation of osteoblastic MC3T3‐E1 cells independent of its modulativ

ISSN:0884-0431    

DOI:10.1002/jbmr.5650040206

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe hyperthyroid state in vivo is associated with an increase in osteoblast number and activity, suggesting that thyroid hormone may stimulate osteoblast replication and function. We therefore examined the effects of T3(16–1170 pM) on replication rate as assessed by cell counts in UMR‐106 osteoblastic osteosarcoma cells cultured for 5–10 days in medium supplemented with 10% hormone‐stripped fetal calf serum (FCS). Despite the virtual absence of thyroid hormone in the control medium (total T3concentration, 0.02 ng/ml), the addition of T3in concentrations to 1000 pM did not increase the cell replication rate. At higher T3concentrations, a slight decrease in growth rate was observed. No significant 5′‐monodeiodinase activity was detected in UMR‐106 cell homogenates. However, nuclear binding of T3was demonstrated in intact cells. A high‐affinity nuclear binding component was identified with aKaof 2.6 × 1010M−1and a maximum binding capacity of 7.7 pg T3per mg DNA, equivalent to 51 binding sites per cell nucleus. A lower affinity nuclear T3binding component with aKaof 1.8 × 109M−1was also identified. Thus, despite the presence of nuclear T3receptors, UMR‐106 cells do not exhibit a m

ISSN:0884-0431    

DOI:10.1002/jbmr.5650040207

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

年代:1989

数据来源: WILEY

摘要:

AbstractCells showing osteoclastic characteristics have not been identified outside bone. Because osteoclasts originate from an extraosseous source, this suggests that identifiable osteoclastic features do not develop until the precursors enter bone, where the local microenvironment may signal osteoclastic differentiation or maturation. We assessed the influence of bone matrix on osteoclastic differentiation by incubating bone marrow cells, after removal of pre‐existing osteoclasts, on plastic coverslips or slices of devitalized cortical bone. We found that there was a threefold increase in the number of osteoclast‐specific MAb‐positive cells on the bone matrix compared with plastic coverslips. The number of MAb‐positive cells correlated with the extent of excavation of the surface of the bone slices. Multinuclearity correlated with MAb‐positive cell density, and for any given density the proportion of MAb‐positive cells that were multinucleate was similar on plastic and bone. We conclude that, in the presence of 1,25‐(OH)2vitamin D3, bone matrix stimulates the generation of osteoclasts but has no demonstrable influence on the fusion of mononuclear osteoclast

ISSN:0884-0431    

DOI:10.1002/jbmr.5650040208

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

年代:1989

数据来源: WILEY

摘要:

AbstractWe studied the binding and degradation of125I‐labeled epidermal growth factor (EGF) by UMR‐106 osteosarcoma cells and the regulation of EGF receptor affinity for EGF by the phorbol ester 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) and by treatments that raise intracellular levels of cyclic AMP. Cell surface binding of [125I]EGF to A431 cells reached a plateau after a 30 minute incubation at 37°C but was undetectable in UMR‐106 cells. Degradation of [125I]EGF proceeded at a 50‐fold higher rate in A431 cells on a per cell basis, but receptor‐bound [125I]EGF was internalized and degraded at a 3.5‐fold higher rate by UMR‐106 cells on a per receptor basis. At 4°C, [125I]EGF labeled a single class of surface binding sites in the UMR‐106 cell. Treatment with TPA at 37°C reduced subsequent cell surface binding of [125I]EGF at 4°C a maximum of 80% with an IC50of 1.25 ng/ml. Maximal TPA reduction of [125I]EGF binding was observed within 5–15 minutes and was due to a reduction in the affinity of cell surface receptors of [125I]EGF without a change in receptor density. Pretreatment of the cells for 4 h with 30 μM forskolin, 1 mM isobutylmethylxanthine (IBMX) plus 30 μM forskolin, or 1 mM IBMX plus 100 ng/ml parathyroid hormone (PTH) attenuated the loss in [125I]EGF binding caused by a subsequent dose of 10 ng/ml of TPA by 17% (p<0.0005), 39% (p<0.0002), and 35% (p<0.002), respectively. We concluded that activation of protein kinase C decreases the affinity of UMR‐106 EGF receptors and that this action may be opposed by the activation of

ISSN:0884-0431    

DOI:10.1002/jbmr.5650040209

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe study centered on a controversy about whether long‐term estrogen replacement therapy may ameliorate the osteoporosis seen in patients with Turner's syndrome. This study comprised 26 adult patients with Turner's syndrome (9 treated and 17 untreated or insufficiently treated) and 12 adult women with pure gonadal dysgenesis (8 untreated and 4 treated). A low bone density below ‐2 standard deviations from the age‐ and sex‐matched predicted normal mean was documented by dual‐photon absorptiometry of the lumbar spine in all the untreated and insufficiently treated patients, but only in 6 treated patients. The biochemical indices of bone resorption (urinary hydroxyproline excretion and plasma tartrate‐resistant acid phosphatase activity), as well as osteoblastic function (serum osteocalcin and bone alkaline phosphatase isoenzyme), were significantly increased in untreated and insufficiently treated patients compared with treated patients. A significant negative correlation was found between biochemically documented osteoresorption and spinal bone mineral density corrected for age of the patients. Significant positive correlations were found between serum osteocalcin and bone alkaline phosphatase isoenzyme and between biochemical indices of bone resorption and formation. Although in the patients there was an evidence of a high bone remodeling rate, the rate of bone mass loss seemed to be low, comparable with that seen in oophorectomized women who had already passed their accelerated phase of bone loss. The results indicate that long‐term hormonal replacement therapy is justified in gonadal dysgenesis, regardless of the karyotype of the patient, to prevent further b

ISSN:0884-0431    

DOI:10.1002/jbmr.5650040210

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

年代:1989

数据来源: WILEY

摘要:

AbstractPrevious studies have suggested that vitamin D metabolites directly influence the differentiation and maturation of chondrocytes in calcifying cartilage. Recently, this laboratory has shown that the response of chondrocyte plasma membrane and matrix vesicle enzymes to 1,25‐(OH)2D3and 24,25‐(OH)2D3is both cell and membrane specific. The current study demonstrates that cell replication and matrix protein synthesis are also modulated by vitamin D. Confluent, third‐passage growth zone (GC) and resting zone (RC) costochondral chondrocytes were incubated in medium containing 10−13‐10−7M 1,25‐(OH)2D3or 10−12‐10−6M 24,25‐(OH)2D3. The amount of collagenase‐digestible protein (CDP) secreted into the media was inversely proportional to the concentration of fetal bovine serum (FBS). At 10% FBS, greater than 80% of the CDP was incorporated into the matrix. 1,25‐(OH)2D3stimulated CDP and percentage collagen synthesis by GC cells but had no effect on the synthesis of noncollagenous protein (NCP). 1,25‐(OH)2D3inhibited CDP and percentage collagen synthesis by RC cells but did not alter NCP synthesis. [3H]thymidine incorporation was inhibited in both cell types, whether confluent or subconfluent cultures were examined. At 10−6and 10−7M 24,25‐(OH)2D3, there was a significant decrease in CDP production and percentage collagen synthesis by RC cells but no effect on NCP. However, at 10−9and 10−10M hormone there was an increase in NCP production but no effect on CDP, resulting in a decrease in percentage collagen synthesis. CDP and NCP production were unaffected by 24,25‐(OH)2D3in GC cells. High concentrations of hormone inhibited [3H]thymidine incorporation in both cell types. 24,25‐(OH)2D3also stimulated [3H]uridine incorporation at 10−8and 10−9M in RC cells. These data support the hypothesis that vitamin D metabolites influence the development and maturation of calcifying cartilage and that the response of cells to hormone i

ISSN:0884-0431    

DOI:10.1002/jbmr.5650040211

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

年代:1989

数据来源: WILEY