ISSN:0884-0431    

DOI:10.1002/jbmr.5650090302

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe consistency of bone mass measurements across bone sites was examined in a cohort of elderly Japanese‐American women. The study included 744 women of mean age 66.6 years (age range 47–82 years) who had bone densitometry measurements at the spine, calcaneus, and distal and proximal radius. The women were classified at the four bone sites as in the lower, middle, or upper bone mass tertile for their age. Slightly more than half (56%) of the women were in the lower tertile at one or more of the bone sites, and such women were usually in the lower category at more than one site. Of the women, 24% were classified in the lower tertile at all four sites. Furthermore, as a group, women classified as in the low bone mass category at any one site had a low average bone mass at all four sites. Prospectively, the number of low bone mass sites predicted the risk of new spine fractures after adjusting for age and the number of spine and nonspine prevalent fractures. The risk increased approximately 1.3‐fold for each additional low bone mass site. A subgroup (15%) of the population had marked heterogeneity in bone mass between sites. These women had one or more lower tertile bone mass site(s) and one or more upper tertile bone mass site(s). The results suggest that osteoporosis may occur as either a generalized or as a regional dis

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090303

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

年代:1994

数据来源: WILEY

摘要:

AbstractMenopause leads to rapid bone loss, mainly as a result of estrogen deficiency superimposed on the age‐related linear bone loss. The influence of age at menopause on bone loss is unclear, although early menopause is widely considered a risk factor for osteoporosis. Vertebral bone mineral density (BMD) was measured in 1667 women divided into five groups according to hormonal status and age at menopause. Menopausal status was an independent predictor of BMD in a multiregression analysis, along with current age, years since menopause (YSM), weight, and height. For the same chronologic age (55 years), women with early menopause had a 15% lower BMD and a higher YSM than women whose menopause occurred later (“normal” menopause). After adjusting for the interval since menopause, postmenopausal women with early menopause were found to have lower vertebral BMD than postmenopausal women with normal menopause. Finally, after the age of 60,66% of the women with early menopause had a BMD that was below the fracture threshold compared to 18% of the women with normal menopause. The results of this cross‐sectional study suggest that early menopause is associated with a quantitatively higher bone loss than in women with menopause of later onset and thus constitutes a risk factor for osteo

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090304

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

年代:1994

数据来源: WILEY

摘要:

AbstractBone mineral density (BMD) measurements by dual‐energy x‐ray absorptiometry (DXA) are planar measurements. By measuring planar BMD in anteroposterior (AP) and lateral projections, it is possible to estimate the volumetric BMD by assuming that the vertebral body is an ellipsoid cylinder. Correction for the third dimension could improve the diagnostic accuracy of spinal BMD measurement in osteoporosis. The aims of this study were (1) to determine the effect of aging on volumetric BMD compared to planar measurements; and (2) to evaluate the diagnostic accuracy of volumetric BMD in comparison to planar measurements. We studied 26 postmenopausal women with osteoporotic vertebral fractures and 114 age‐ and sex‐matched controls without vertebral fractures from a population‐based group. AP and lateral decubitus BMD of the lumbar spine were measured by DXA using a Lunar DPX (precision error for AP measurement, 0.8%; for lateral measurement of vertebra L3, 6.4%). Between the ages of 51 and 85 years the decreases in volumetric BMD of L3 (vol L3), lateral BMD of L3 (lat L3), AP BMD of L3 (AP L3), and AP BMD of L2–4 (AP L2–4) were 31, 28, 17, and 17%, respectively. The decrease in BMD compared to controls in the osteoporotics for vol L3, lat L3, AP L3, and AP L2–4 were 31, 34, 23, and 23%; expressed as Z scores, the decreases were −1.36, −1.33, −1.46, and −1.47 standard deviation units. The areas under ROC analysis curves for vol L3, lat L3, AP L3, and AP L2–4 were 85, 86, 87, and 87%, respectively. We conclude that there is a greater decrease in volumetric and lateral BMD of vertebra L3 than the AP measurements, both with age and in postmenopausal osteoporosis compared to age‐matched controls. However, the diagnostic accuracy was not improved by correcting BMC for vertebral volume. The greater decreases observed with aging may result from the high proportion of cancellous bone in the vertebral body. The lack of improvement in diagnostic accuracy may be because of the large precision error in lateral decubitus (and hence volumetric) BMD measurements. It is possible that the diagnostic accuracy of estimated volumetric BMD may improve with the use of lateral supine DXA, a measurement

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090305

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

年代:1994

数据来源: WILEY

摘要:

AbstractBone formation during mechanical unloading is reduced, mainly as a result of osteoblastic hypofunction. At the same time, the total number of osteoblasts per long bone is also markedly reduced. We tested the hypothesis that the number of osteogenic precursors present in the bone marrow stroma was concomitantly diminished by using an in vitro cell culture system in which femoral adherent bone marrow cells differentiate into active osteoblasts and produce bone‐like nodules. Hindlimbs of 32‐day‐old male rats were either immobilized (unloaded) by sciatic neurectomy (immo) or sham operated (sham) and animals were killed after 11 days. Femora were either ashed to determine bone mass or used to generate bone marrow cultures. Adherent marrow cells were cultured in the presence of ascorbic acid, β‐glycerophosphate, and dexamethasone. Bone mass was significantly reduced in unloaded femora (by 16%) and tibiae (by 18%). The number of adherent cells (determined on day 6) was reduced by 50% in the immo group. Reduced cell number did not result from slower proliferation in culture since [3H]thymidine incorporation on days 4 and 6 was similar in the two groups. The osteogenic potential in vitro of marrow from unloaded bones was diminished compared with that from loaded ones as evidenced by (1) lower alkaline phosphatase (ALP) activity per mg protein (by 25–40%, examined on days 6 and 12), and (2) reduced nodule formation (by 70%, expressed as percentage of the dish area stained with Alizarin Red S on day 21). None of these changes occurred in the contralateral limb of operated (immobilized) animals. In an additional experiment, adherent cells from both groups were subcultured on day 6 and seeded at an equal density of 40,000 cells per 35 mm dish. The osteogenic potential in cultures from unloaded bones was reduced as evidenced by lower ALP activity (by 25–40%) and fewer nodules formed (by 40%). These experiments show that unloading for 11 days causes a deficit in bone mass and reduces the number of femoral adherent marrow stromal cells and their osteogenic potential in vitro in subsequent (ex vivo) cultures. They also suggest that unloading specifically reduces the number of osteogenic precursors present within the m

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090306

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

年代:1994

数据来源: WILEY

摘要:

AbstractIt is now widely accepted that insulin‐like growth factor‐I (IGF‐I) has a local regulatory role in bone remodeling. IGF‐I has also been demonstrated to regulate proliferation of bone‐derived endothelial cells. Such studies suggest a role of IGF‐I in skeletal angiogenesis. Using BBE cells, a bovine bone endothelial cell line, we characterized the kinetics and chemical properties of IGF‐I receptors and examined the effect of IGF‐I on bone endothelium migration. Two classes of binding sites with high affinity for IGF‐I were detected by binding experiments on bone endothelial cells. Both competition analyses and cross‐linking studies revealed the presence of type I IGF receptor in bone endothelial cells. Moreover, these cells produced and released authentic IGF‐I into the medium, as evidenced by radioimmunoassay analyses of gel‐filtered conditioned media. Both IGF‐I binding capacity and release decreased either with increases in cell number or after treatment with 17β‐estradiol (17βE2) and parathyroid hormone (PTH). Both hormones also inhibited chemotactic responses of bone endothelial cells to IGF‐I. Taken together, these results strongly suggest that IGF‐I, a growth factor that promotes the proliferation of various bone cell types, also induces growth and chemotactic responses in bone endothelium acting through the type I IGF receptor. This may be part of a generalized response of bone cells to IGF

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090307

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

年代:1994

数据来源: WILEY

摘要:

AbstractIntestinal calcium absorption declines with aging as a result of decreased renal 1,25‐dihydroxyvitamin D3[1,25‐(OH)2D3] biosynthesis. At least part of the decline in 1,25‐(OH)2D3may be due to acquired resistance to parathyroid hormone (PTH) stimulation of renal 25‐hydroxyvitamin D1‐hydroxylase (1‐OHase) activity. To test whether aging rats can increase 1,25‐(OH)2D3production in response to PTH, male rats of the same litter were fed a normal Ca diet and were sacrificed at 175–225 g (young rats) or 3 months later at 350–425 g (aging rats). At sacrifice, basal serum 1,25‐(OH)2D3levels (88 ± 16 versus 49 ± 8 pg/ml,P<0.05) and in vitro renal proximal tubule 1‐OHase activity (178 ± 15 versus 77 ± 5 pmol/mg protein/5 minutes,n= 6,P<0.001) were lower in aging animals. rPTH‐(1–34) (10−11or 10−11M) increased in vitro 1,25‐(OH)2D3secretion by perifused renal proximal tubules from young but not aging rats. For young and aging rats, rPTH‐(1–34) (10−7M) increased proximal tubule cAMP‐dependent protein kinase (PKA) activity, and lower concentrations (10−11M) stimulated translocation of protein kinase C (PKC) activity from cytosolic to soluble membrane proximal tubule cell fractions. The results of this study show that PTH activation of 1,25‐(OH)2D3production may involve both signaling pathways, with the PKC pathway responsive to lower concentrations of the hormone. The acquired resistance to PTH stimulation of 1,25‐(OH)2D3production in aging appears not

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090308

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe developed a sensitive two‐site sandwich ELISA for quantitative analysis of human osteocalcin in serum or plasma. Our method is based on two different highly specific antibodies recognizing epitopes at different ends of the protein so that only intact osteocalcin is detected. The method is fast (total analysis time less than 6 h/96 wells), precise (intraassay variation less than 2.3% at four different levels;n= 10, and interassay variation less than 2.5%,n= 5, respectively), and accurate, with a mean recovery of 105%. The detection limit in serum is approximately 0.1 μg/liter. The mean concentration of osteocalcin in normal serum with this assay is 3.3 μg/liter (SD 3.7 μg/liter; range 0.1–13.1 μg/liter;n= 41), and the reference range is 0.28–10.1 μg/liter (10 and 90% confidence limits). The method shows a reasonable positive linear correlation with other osteocalcin assays (Incstar,r= 0.55,p<0.05,n= 13; Henning Oscatest,r= 0.52,p<0.005,n= 34). A good correlation (r= 0.70,p<0.001) between individual osteocalcin and bone‐specific alkaline phosphatase serum concentrations was observed in normal subjects. We found a low or undetectable concentration of intact osteocalcin in serum of all four of our patients with acute primary hyperparathyroidism, and in all five patients with hypocalcemic secondary hyperparathyroidism, which suggests that PTH effectively inhibited the synthesis of osteocalcin in osteoblasts. The serum concentration of intact osteocalcin was elevated in two of three patients with chronic primary hyperparathyroidism. In five patients with normocalcemic secondary hyperparathyroidism, the serum concentration of intact osteocalcin was low: three had a normal and two had an elevated value. An age‐related decrease in intact osteocalcin in serum of females younger than 50 years and an increase in older women

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090309

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

年代:1994

数据来源: WILEY

摘要:

AbstractBone is subject to continuous remodeling throughout life. The age‐related loss of (trabecular) bone, leading to senile osteopenia, is mainly due to impaired bone formation. Osteoblasts (OB) and osteoclasts (OC) have been identified as playing a crucial role in the process of bone turnover, but the contribution made by their precursors is not well documented. We analyzed the cells of the osteoblast and osteoclast cell lineage along the trabecular bone of tibiae and the stromal cells in the marrow of aging BN/Bi Rij rats using electron microscopy. It appeared possible to distinguish preosteoblasts (pre‐OB), OB, preosteoclasts (pre‐OC), OC, and inactive bone‐lining cells. Periods of increase, the maximal peak, and the decrease in trabecular bone volume were defined by means of morphometric measurements of trabecular bone volume. We found a decrease of more than 10‐fold in the number of OB with age, but the numbers of pre‐OB, pre‐OC, and OC expressed per unit bone length, although variable, were age independent. The relative bone resorption and formation surface, expressed as a percentage of the total bone surface, decreased 2‐ and 15‐fold, respectively. In 2‐year‐old animals the total volume of stromal cells, part of which constitutes the stem cell compartment of the osteogenic lineage, was a quarter of that found in 1‐month‐old animals and a third of that found in 6‐month‐old animals. The loss of trabecular bone is concomitant with a sharp increase in the ratio of pre‐OB/OB, the ratio of OC/OB, and in the ratio of resorption to formation surfaces. There was no relation between the ratio of pre‐OC/OC with age. These data lead to the conclusion that the main factor causing bone loss with age is a dimini

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090310

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

年代:1994

数据来源: WILEY

摘要:

AbstractFemora from young adult Wistar rats were prepared for both light and electron microscopy. Routinely processed wax sections showed the appearance of cement lines immediately proximal to the resorption surface formed by active osteoclasts and distal to the onset of lamella formation in femoral bone tissue. This early stage of extracellular matrix elaboration at reversal lines was then studied by scanning electron microscopy (SEM) of actively remodeling sites, mainly on trabecular and endosteal surfaces. The resorption surface was shown to comprise a decalcified collagenous mat with individual fibers running either parallel or perpendicular to the surface plane. By examining different, neighboring, areas of resorption lacunae, a temporal sequence of new extracellular matrix production could be established. Before the deposition of new collagen, globular accretions were deposited onto the resorption surface. In areas where individual collagen fibers were oriented perpendicular to the surface plane, this globular matrix was initially deposited on the exposed fiber tips. The globules increased in size and fused laterally to form a continuous cement layer, which not only interdigitated with the collagen mesh of the resorption surface but also provided anchorage for new collagen fibers, which themselves became mineralized. These morphologic results provide a mechanistic explanation of coupling at reversal lines.

ISSN:0884-0431    

DOI:10.1002/jbmr.5650090311

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

年代:1994

数据来源: WILEY