摘要:

AbstractOsteoporosis is widely viewed as a major public health concern, but the exact magnitude of the problem is uncertain and likely to depend on how the condition is defined. Noninvasive bone mineral measurements can be used to define a state of heightened fracture risk (osteopenia), or the ultimate clinical manifestation of fracture can be assessed (established osteoporosis). If bone mineral measurements more than 2 standard deviations below the mean of young normal women represent osteopenia, then 45% of white women aged 50 years and over have the condition at one or more sites in the hip, spine, or forearm on the basis of population‐based data from Rochester, Minnesota. A smaller proportion is affected at each specific skeletal site: 32% have bone mineral values this low in the lumbar spine, 29% in either of two regions in the proximal femur, and 26% in the midradius. Although this overall estimate is substantial, some other serious chronic diseases are almost as common. More importantly, low bone mass is associated with adverse health outcomes, especially fractures. The lifetime risk of any fracture of the hip, spine, or distal forearm is almost 40% in white women and 13% in white men from age 50 years onward. If the enormous costs associated with these fractures are to be reduced, increased attention must be given to the design and implementation of control programs directed at this major health proble

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070902

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe effect of four different neuropeptides and norepinephrine (NE) on cyclic AMP formation in four different osteoblastic cell lines and in isolated neonatal mouse calvarial bone cells has been examined. In the rat osteosarcoma cell line UMR‐106–01, vasoactive intestinal polypeptide (VIP, 0.001–1 μM), calcitonin gene‐related peptide (CGRP, 0.3–30 nM), and NE (0.1–300 μM), but not neuropeptide Y (NPY, 0.001–1 μM) or substance P (SP, 0.1–10 μM), caused a dose‐dependent stimulation of cyclic AMP formation. The stimulatory effects were synergistically potentiated by forskolin (0.1–3 μM). The effects of NE and VIP were time dependent, with an optimal effect seen at 5 minutes. The amount of cyclic AMP accumulated in cells stimulated with NE and VIP was in the same range. The amplitude of the cyclic AMP response induced by CGRP was smaller than that caused by VIP and NE. In the human osteosarcoma cell line Saos‐2, NE (0.1 μM) and VIP (0.3 μM) stimulated cyclic AMP formation, and the effect was synergistically potentiated by forskolin. In the absence of forskolin, no effect of CGRP (30 nM) could be seen in the Saos‐2 cells, but in the presence of forskolin (3 μM) a stimulatory effect was observed. SP and NPY did not change basal cyclic AMP levels in Saos‐2 cells. In the osteoblastic osteosarcoma cell line of rat, ROS 17/2.8, NE (0.1 μM) caused a significant stimulatory action on cyclic AMP formation that was synergistically potentiated by forskolin (3 μM), VIP, CGRP, and SP did not affect the cellular content of cyclic AMP in ROS 17/2.8. In the mouse calvarial cell line MC3T3‐E1 and in enzymatically isolated mouse calvarial bone cells, NE (0.1 μM), VIP (0.3 μM), and CGRP (30 nM), but not SP (10 μM) or NPY (1 μM), stimulated cyclic AMP formation. In UMR‐106–01 cells and in isolated bone cells, but not in Saos‐2 and ROS 17/2.8 cells, NPY (1 μM) inhibited the stimulatory effect of NE (0.3 μM) on cyclic AMP formation. These data show that osteoblastic cell lines are equipped with receptors for neuropeptides and NE. Since VIP, CGRP, NPY, and NE have been shown to occur in nerves of the skeleton, the observations in the present paper suggest the possibility that neurohormones may have

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070903

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe development of secondary hyperparathyroidism was studied in relation to changes in serum ionized Ca (Ca2+), 25‐OHD, and 1,25‐(OH)2D concentrations in six dogs maintained on a low‐Ca (0.05%), high‐Na (1.6%), and vitamin D‐deficient diet for 91 weeks. Blood samples and evaluations of the parathyroid function were obtained before and after 3, 12, 24, 36, and 91 weeks of diet. Serum iPTH was measured by an intact hormone (I) and a carboxy‐terminal (C) assay. The sigmoidal relationship between ionized Ca and iPTH values was evaluated mathematically. Results are means ± SD. Statistically significant changes over a time period were evaluated by an ANOVA for repeated measurements. Over the first 3 weeks, serum Ca2+, 25‐OHD, and 1,25‐(OH)2D did not change but stimulated I‐iPTH increased 84.3 ± 39.9% (p<0.005) and C‐iPTH only 25.3 ± 12.2% (p<0.01), a significant difference (p<0.02). The increase in stimulated I‐iPTH reached 487.4 ± 139.6% (p<0.0001) and 418.4 ± 76.9% (p<0.0001) for C‐iPTH by the end of the study. Similar significant increases were seen in basal and nonsuppressible iPTH at or after week 12. Serum 25‐OHD concentration had decreased significantly at 12 weeks (0 = 99.9 ± 28.3 to 12 = 40 ± 6.8 nM,p<0.005) and even more so at 91 weeks (4.1 ± 0.3 nM,p<0.0005); this could be related to stimulated I‐iPTH at 12 weeks (r= −0.5472,p<0.02) and thereafter, even though 25‐OHD does not have a direct effect on the parathyroid glands. Even if serum Ca2+had only decreased at week 36 (0 = 1.36 ± 0.02 to 36 = 1.32 ± 0.02 mM,p<0.05), it could be inversely related to stimulated I‐iPTH from week 24 (r= −0.4290,p<0.05). Serum 1,25‐(OH)2D increased up to 24 weeks (0 = 109.7 ± 20.7 to 24 = 173.4 ± 28.7 pM,p<0.0005) at which time it was positively related to stimulated I‐iPTH (r= 0.506,p<0.02); it then decreased to slightly below basal level by week 91 (82.7 ± 8.6 pM). Despite these two added stimuli, progression of the parathyroid function did not accelerate after week 24. In conclusion, dietary changes appear to be the main factor stimulating secondary hyperparathyroidism in this model. The addition of a low serum Ca2+and a relatively low level o

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070904

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

年代:1992

数据来源: WILEY

摘要:

AbstractUrine contains proteins that inhibit the growth of calcium oxalate (CaOx) crystals and may prevent the formation of kidney stones. We have identified a potent crystal growth inhibitor in the conditioned media from primary cultures of mouse kidney cortical cells. Conditioned media, incubated with the kidney cells for 6–72 h, was assayed for crystal growth inhibition; inhibitory activity increased 15‐fold by 24 h. Inhibitory activity was purified from serum‐free media containing proteinase inhibitors using anion‐exchange and gel‐filtration chromatography. A single band of molecular weight 80,000 daltons was seen after SDS‐polyacrylamide gel electrophoresis. The sequence of the N‐terminal 21 amino acids of this protein matched that of osteopontin (OP), a phosphoprotein initially isolated from bone matrix. Antisera raised to fusion proteins produced by plasmids containing the N‐terminal or C‐terminal portions of OP cDNA also cross‐reacted with the protein purified from cell culture media on western blots. The effect of the purified protein on the growth of CaOx crystals was measured using a constant composition assay. A 50% inhibition of growth occurred at a protein concentration of 0.85 μg/ml, and the dissociation constant of the protein with respect to CaOx crystal was 3.7 × 10−8M. The concentration of OP in mouse urine, measured using antibodies raised to the purified protein, was approximately 8 μg/ml. We conclude that OP is synthesized by kidney cortical tubule cells and functions as a crystal growth inh

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070905

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe investigated heritability as a risk factor for the development of osteoporosis in two randomly selected populations of postmenopausal women and their premenopausal daughters. We determined the familial resemblance in bone mass at three sites; the distal forearm, lumbar spine, and proximal femur, premenopausally and with increasing maternal postmenopausal age. We also examined the bone mass of daughters in relation to mothers with and without osteoporotic fractures. Peak bone mass among premenopausal siblings was significantly correlated at all sites (r= 0.30–0.42,p<0.001). The same levels of resemblance were found between early postmenopausal mothers and premenopausal daughters. There was no significant difference in bone mass at any skeletal site between daughters of women with either peripheral or spinal fractures and daughters of women without fractures. We also examined familial resemblance with four biochemical markers of bone turnover (fasting urinary calcium and hydroxyproline, both corrected for creatinine, serum alkaline phosphatase, and plasma bone Gla protein). A generally significant resemblance were seen in premenopausal siblings (r= 0.25–0.39, hydroxyproline NS), but not between premenopausal daughters and postmenopausal mothers. We conclude that peak bone mass is hereditary in the distal forearm, lumbar spine, and proximal femur, but the mother‐daughter resemblance explains only about 16% of the variability in daughters' bone mass. Furthermore, daughters of women with a moderate state of osteoporotic fractures are not substantially at an increased risk of having a low peak bone mass compared to the daughters of women without frac

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070906

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe characterized gene expression in the reparative callus that formed after fracture of the rat femur. The callus was divided into regions of bone formation (hard callus) and cartilage formation (soft callus), and gene expression was examined separately in each region. Expression of extracellular matrix protein genes varied with the progression of repair and differed between hard and soft calluses. Messenger ribonucleic acids (mRNAs) for osteonectin, alkaline phosphatase, and type I procollagen were detected in the hard callus at maximal levels during endochondral ossification and bone remodeling (day 15) and at 50% maximal levels during intramembranous bone formation (day 7). Messenger RNAs for these proteins in the soft callus were detected at low levels during chondrogenesis (day 9) but increased to 80% of maximal levels with chondrocyte hypertrophy and mineralization of the cartilage matrix (day 13). Messenger RNAs for type II procollagen and proteoglycan core protein were detected at maximal levels in the soft callus during chondrogenesis (day 9). Osteocalcin gene expression was detected in the hard callus during endochondral ossification and remodeling but not during intramembranous bone formation or at any time in the soft callus. Osteonectin mRNA was detected in both the hard and soft callus throughout the entire course of fracture repair. Expression of cartilage and bone‐related genes correlated with the temporal sequence of histologic changes, suggesting transcriptional regulation of gene expression during repair. Differences in gene expression between hard and soft callus and in each of these regions as repair progressed suggest local regulation of gene expression during cell differentiation and matrix synthesi

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070907

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe purpose of this work was to test the hypothesis that reduced responsiveness of target organs to 1,25‐dihydroxyvitamin D3[1,25‐(OH)2D3] is associated with osteoporosis. Peripheral blood mononuclear (PBM) cells have been previously shown to be a valid model for the action of 1,25‐(OH)2D3on its classic target organs in various pathologic and physiologic situations. The responsiveness of lymphocytes to the hormone can be assessed by the extent of inhibition it exerts on the proliferative response to mitogenic lectins. A group of 39 postmenopausal women, at least 10 years after the menopause, participated in the study. Osteoporosis, defined as the presence of at least one nontraumatic vertebral crush fracture, was diagnosed in 19 subjects. Mitogenesis of PBM cells stimulated by phytohemagglutinin and cultured for 72 h in the presence or absence of 1,25‐(OH)2D3(0.03–1 nmol/liter) was assessed by [3H]thymidine incorporation during a 4 h pulse. The maximal inhibitory effect of 1,25‐(OH)2D3at saturating concentration (1 nM/liter) was 74.6 ± 2.8% (mean ± SEM) for normal compared to 65.3 ± 2.9% for osteoporotic women (P= 0.015). The geometric mean of the ED50values of 1,25‐(OH)2D3was 60% higher in the osteoporotic than in the normal group (P= 0.035). Our data are consistent with the notion that reduced responsiveness of target organs to 1,25‐(OH)2D3is associated

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070908

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

年代:1992

数据来源: WILEY

摘要:

AbstractThis is a retrospective study of 15 postmenopausal or amenorrheic women aged 34–78 years who had taken prednisone for 6–108 months and were followed for 1 year while continuing to take doses of 5–15 mg/day. A total of 8 patients were treated with 0.6256 mg Premarin daily for 25 days and 5 mg/day of medroxyprogesterone on days 15–25 (ERT, group 2); 7 were followed without ERT (group 1). A group of 17 women, matched for age, were randomly selected from our computerized data base to serve as a control group (group 3), and 10 women of similar age who were taking ERT only (group 4) were selected to compare the response to ERT to that of group 2. Bone density (BD) was measured in the lumbar spine baseline and at 1 year using dual‐photon or dual‐energy x‐ray absorptiometry. Spine density did not change significantly during the year of observation in group 1. Although BD decreased in 5 of 7 patients, the change was not significant (‐0.034 ± 0.018 g/cm2,p= 0.10). In group 2 BD increased significantly, with 7 of 8 patients showing an increase (0.037 ± 0.011 g/cm2,p= 0.008). BD did not change significantly in the control group (0.013 ± 0.008 g/cm2,p= 0.16). Loss of bone from the spine was significantly greater in group 1 than in controls (p= 0.02), but changes in group 2 were similar to those in the control group (p= 0.66). Changes in BD in group 2 were similar to those in group 4; that is, the response to ERT of patients taking prednisone was comparable to that of women taking ERT only. The change in spine density correlated with the cumulative dose of prednisone taken during the year of observation in the group not taking ERT (r= 0.759,p= 0.05) but not in the group taking ERT (r= 0.134,p= 0.73). This suggests that ERT protects against bone loss for at least 1 year throughout the dosage range studied. We concluded that ERT prevents vertebral bone loss for at least 1 year in the majority of women taking prednisone chronically in do

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070909

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

年代:1992

数据来源: WILEY

摘要:

AbstractBecause of the differences in the interactions of ultrasound and x‐ray waves with bone, quantitative ultrasound (QUS) techniques may yield information about skeletal status not accessible by regular bone densitometry (BD) techniques. However, relatively strong correlations have been reported between broad‐band ultrasound attenuation (BUA) and several x‐ray‐based BD methods. We assessed the precision and association of single x‐ray absorptiometry (SXA) and BUA of the calcaneus. We examined both BUA and SXA at the calcaneus using special software for matching the regions of interest. An algorithm was derived and applied to correct the observed correlation coefficients for the attenuation effect caused by the precision errors for BUA and SXA. In a group of 33 volunteers covering a wide range of age and calcaneal bone mineral densities, the site‐matched and precision‐adjusted correlation coefficient between BUA and SXA wasr= 0.58, with a standard error of the estimate (SEE) of 14.41 dB/MHz, or 17.08%. For the subgroup of 25 women the correlation was stronger, withr= 0.72 and SEE = 11.53 dB/MHz, or 14.33%. SXA precision was 0.79% for the regular region of interest (ROI) and 1.22% for the site‐matched ROI. BUA precision was 2.76% for the entire subject group and 1.63% for women of age 40 or older. The observed correlation coefficient between ultrasound and x‐ray based techniques of the order of 0.7 is significant, but it leaves about 50% of the variability unexplained. It remains to be investigated to what extent the unexplained 50% is related to bone strength or structure or whether it reflects a variability unrelated to os

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070910

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

年代:1992

数据来源: WILEY

摘要:

AbstractClinical application of techniques for assessing bone mineral density (BMD) requires accurate and precise measurements that can be related to clearly defined normal ranges. In this study we investigated the clinical interpretation of BMD values in a group of individuals measured on the same day with two different dual‐energy x‐ray densitometers (Lunar DPX and Hologic QDR 1000). The BMD results were analyzed as absolute values in g/cm2and with respect to young and age‐specific normals as defined by each manufacturer. Absolute BMD values measured by the two instruments were highly correlated (lumbar spiner= 0.98, femoral neckr= 0.95;p<0.0001). In the lumbar spine, the two instruments assigned almost identical values when expressed as a percentage of age‐matched values and as a percentage of young normals, despite a small but systematic difference between the values assigned for the latter index. In the femoral neck, however, there were significant differences in assignments between instruments, expressed both as a percentage of young normal (mean difference 6.2%) and with respect to age‐matched values (mean difference 3.3%). In particular, in premenopausal subjects femoral neck values with the Hologic instrument were assigned significantly lower values. This study shows effective comnparability between these two instruments for absolute and relative values for the lumbar spine, as well as for absolute values at the femoral neck, but important differences for normality assignments at the femoral neck. These latter differences may produce bias in the “diagnosis” of femoral neck osteoporosis and may have important implications for clinical decision making. Until these differences are resolved, clinicians should not rely solely on femoral neck BMD measurements in clinical de

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070911

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

年代:1992

数据来源: WILEY