bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change in bone mass immediately before menopause
Authors: Recker Robert R. , Lappe Joan M. , Davies K. Michael , Kimmel Donald B. 
Published: February 2010

Abstract
A group of 75 healthy women nearing menopause were entered into a longitudinal study of bone mass and bone cell function. All were at least 46 years, were still menstruating, and had premenopausal levels of follicle stimulating hormone (FSH) and estradiol (E2). Bone density measurements of the spine (dual-photon absorptiometry, DPA) and total-body (DPA) and forearm (single-photon absorptiometry, SPA) were made at 6 month intervals along with measurements of FSH and E2 over an average of 2.04 + 0.45 years. The annual rate of change in bone mass was determined for each individual by regressing the bone mass measurement at each site at the time of observation. The slopes were pooled, and the percentage annual change was calculated as the mean slope divided by the initial mean bone mass value. The mean rates of change in bone mass were calculated with and without weighting by length of observation. No meaningful differences in the results were seen in the weighted values compared to the unweighted values, and none of the sites showed a slope significantly different from zero. Demonstrated reproducibility and sample size provided sufficient power to detect annual weighted rates of change of 0.81% for spine BMC, 0.69% for spine BMD, 1.31% for forearm BMC, 1.55% for forearm BMC/BW, and 1.09% for total body bone mineral. We conclude that if changes in bone mineral are occurring in women at this age, they are substantially less than 1%/ year for spine and not much more for the forearm or total skeleton.
Advantages of peripheral radiogrametry over dual-photon absorptiometry of the spine in the assessment of prevalence of osteoporotic vertebral fractures in women
Authors: Meema Erik H. , Meindok Harry 
Published: February 2010

Abstract
Since osteoporosis develops in most postmenopausal women and is probably the most important single factor in the pathogenesis of osteoporotic fractures of the spine, hip, and wrist (and at other sites), methods suitable for mass screening should be developed. In this study of 97 women aged 24–79, measurements of the lumbar spine mineral content by dual-photon absorptiometry (DPA) were compared with the summed combined cortical thickness measurements from radiographs of the radius and metacarpal II (MR). There was good correlation between the two methods (r = 0.90). The correlation of age with MR was higher than with DPA. The correlation of years postmenopause was significant with MR but not with DPA. Taking the -2 SD level of the premenopausal means to be previously established vertebral fracture thresholds, 24% of the DPA measurements, but no MR measurements in patients with vertebral compressions, were above the fracture threshold. Since MR measurement requires taking only two small plain radiographs using ordinary x-ray equipment, it is concluded that this less expensive method is better suited to screening for osteoporotic vertebral fracture risk in postmenopausal women than DPA.
Relationship between the location of osteoblastic alkaline phosphatase activity and bone formation in human iliac crest bone
Authors: Bradbeer Jeremy N. , Zanelli Joan M. , Lindsay Peter C. , Pearson Josephine , Reeve Jonathan 
Published: February 2010

Abstract
It is not feasible to use in vivo tetracycline double labeling to study bone formation in biopsies taken during the emergency fixation of fractures. We therefore compared the trabecular localization and extent of osteoblastic alkaline phosphatase (AP) perimeters with tetracycline and osteoid perimeters in iliac crest biopsies from 7 women with postmenopausal osteoporosis and 13 women without metabolic bone disease. Fresh biopsies were chilled to -70°C, and triplicate serial unfixed undecalcified cryostat sections were cut and reacted for AP, stained for osteoid, or mounted unstained. At individual remodeling sites, the mineralizing perimeter (M.Pm) was measured as the extent of a double or single label accompanied by ≥ 1 lamella of osteoid and ≥ 1 lamella of mineralized matrix between the mineralization front and the adjacent label. Osteoid perimeters (O.Pm) and AP perimeters (AP.Pm) were also measured. In each biopsy there was good agreement between the location of AP and bone formation (x statistic, range 0.71–1.0). The overall sensitivity and specificity of AP as an indicator of the location of bone formation were 0.963 and 0.902, respectively. At the level of the basic multicellular unit, in those samples in which &gt;3 active BMUs were found, there was (1) significant positive correlation between the M.Pm and both AP.Pm and AP-positive O.Pm (except 1 patient) and (2) no significant difference between the M.Pm and AP-positive O.Pm (17 of 18 patients and 18 of 18 patients at the tissue level). At the tissue level, the line of regression of AP-positive O.Pm on M.Pm (calculated either as label 2 extent or conventionally as dL + 1/2sL extent) was not significantly different from the line of identity. The presence of osteoblastic AP activity in biopsies from normal and osteoporotic patients distinguishes osteoid currently contributing to bone formation and should be useful for the study of bone formation in unlabeled bone samples from such individuals. Further studies are necessary to establish the broader applicability of this technique, particularly when a mineralization defect is involved, as in osteomalacia.
Extracellular matrix formation by osteoblasts from patients with osteogenesis imperfecta
Authors: Fedarko Neal S. , Moerike Martin , Brenner Rolf , Robey Pamela Gehron , Vetter Ulrich 
Published: February 2010

Abstract
Extracellular matrix proteins synthesized by bone cells isolated from 16 patients with different forms of osteogenesis imperfecta (OI) were analyzed in vitro. Specific components of the extracellular matrix by OI and age-matched cultures were investigated by steady-state radiolabeling followed by quantitation of label into specific proteins and comparison of OI cultures to those of age-matched controls. The in vitro proliferation of OI bone cells was found to be lower than that of control cells. In seven patients, abnormalities of the α1(I) and/or α2(I) chains of type I collagen were detected by gel electrophoresis. In two of these patients, the mutations in the COLIA1 and COLIA2 genes have been previously identified. Although the amount of total protein synthesized by the cells in culture was the same for OI bone cells and age-matched control cells, OI bone cells showed a significantly reduced synthesis of not only collagen but also other bone matrix glycoproteins. The synthesis of osteonectin (SPARC/BM40) and three proteoglycans [a large chondroitin sulfate proteoglycan, biglycan (PGI), and decorin (PGII)] was found to be decreased in OI cells. The reduction was most pronounced at the developmental age at which these macromolecules reach maximal levels during normal development.
Effect of fluoride on bone and bone cells in ovariectomized rats
Authors: Modrowski Dominique , Miravet Livia , Feuga Michel , Bannié Florence , Marie Pierre J. 
Published: February 2010

Abstract
To evaluate whether treatment with a mitogenic agent may increase bone formation and bone mass in osteopenia induced by estrogen deficiency, we determined the effect of oral fluoride treatment on bone and bone cells in ovariectomized rats. Sodium fluoride (NaF) was administered to 3-month-old ovariectomized rats 1 day after ovariectomy (OVX) for 1, 3, and 6 months. NaF was given in drinking water at the dose of 1 mg/kg body weight per day. Fluoride administration led to a partial prevention of the bone loss induced by OVX as shown by histologic analysis of tibial metaphysis and by evaluation of femoral calcium content. These beneficial effects of fluoride were more striking at early time points (1 and 3 months postovariectomy) than after 6 months of treatment. The increase in trabecular bone volume in OVX rats treated with fluoride was associated with a rise in the osteoblast surface, which was increased by 60, 72, and 235% at 1, 3, and 6 months postovariectomy compared to untreated OVX rats. In OVX rats and in sham-operated rats plasma osteocalcin was increased in correlation with the osteoblast surface. However, these two parameters were not correlated in OVX rats treated with fluoride. The heat-labile bone-specific alkaline phosphatase in plasma was decreased in OVX rats treated with fluoride compared to OVX rats, suggesting that both the number and the activity of osteoblasts were affected by NaF treatment. To examine the effect of fluoride on the osteocalcin production and the proliferative capacity of bone cells, osteoblastic cells were isolated by collagenase digestion from the bone surface of tibia in treated and untreated OVX rats. In OVX rats DNA synthesis by cultured bone cells was markedly increased compared to sham rats. In OVX rats treated with fluoride DNA synthesis tended to be further increased compared to untreated OVX rats as evaluated by thymidine incorporation into DNA. Osteocalcin production by osteoblastic cells in vitro was comparable in the different groups. The results of this study show that oral treatment with fluoride partially prevents the bone loss induced by estrogen deficiency in OVX rats. This beneficial effect of fluoride results from a further stimulation of bone formation as shown in vivo by an increased extent of bone-forming cells and in vitro by an enhancement of the proliferative capacity of osteoblastic cells isolated from the bone surface.
The calcium oxalate crystal growth inhibitor protein produced by mouse kidney cortical cells in culture is osteopontin
Authors: Worcester Elaine M. , Blumenthal Samuel S. , Beshensky Ann M. , Lewand Donna L. 
Published: February 2010

Abstract
Urine 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 × 10−8 M. 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 inhibitory protein in urine.
Genetic expression of extracellular matrix proteins correlates with histologic changes during fracture repair
Authors: Jingushi Seiya , Joyce Michael E. , Bolander Mark E. 
Published: February 2010

Abstract
We 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 synthesis.
Estrogen and progesterone replacement therapy reduces glucocorticoid-induced bone loss
Authors: Lukert Barbara P. , Johnson Bruce E. , Robinson Ralph G. 
Published: February 2010

Abstract
This 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 doses of 5–15 mg/day.
Biochemical parameters associated with low bone density in healthy men and women
Authors: Dr. Sherman Sheryl S. , Tobin Jordan D. , Hollis Bruce W. , Gundberg Caren M. , Roy Tracey A. , Plato Chris C. 
Published: February 2010

Abstract
A causal role in age-related bone loss has been attributed to alterations in vitamin D status, the bone mineral regulating hormones, and/or renal function. We assessed biochemical parameters of bone metabolism and renal function in healthy subsets of young and old men (n = 191) and women (n = 120) and evaluated the relationships between these parameters and bone mineral density (BMD) in the radius, spine, and femur. There were no significant associations between BMD at any site and serum 25-OHD, 1,25-(OH)2D, PTH, or creatinine clearance in either young men or in young or old women, after controlling for age. In old men, however, lower radius BMD was significantly related to higher PTH and higher 1,25-(OH)2D and marginally related to lower 25-OHD values. In young men, there were unexpected but significant associations between lower femoral neck BMD and higher serum osteocalcin and urinary calcium/creatinine excretion after age adjustment. In old women, lower spine and radius BMD was also significantly correlated with higher serum osteocalcin. In this healthy, vitamin D-replete population, there were significant cross-sectional declines in BMD in the femur in young and old men and at all sites in old women. Elevated remodeling may be an important feature that contributes to reduced femoral BMD in young men and reduced spine and radius BMD in old women. However, compromised renal function or levels of 1,25-(OH)2D or elevated PTH appear to be neither necessary nor relevant as determinants of osteopenia in the spine or femur in these normal, healthy men and women.
Transcriptional activation of c-fos and c-jun protooncogenes by serum growth factors in osteoblast-like MC3T3-E1 cells
Authors: Okazaki Ryo , Ikeda Kyoji , Sakamoto Akemi , Nakano Toshiaki , Morimoto Kyoko , Kikuchi Tomoko , Urakawa Kazumi , Ogata Etsuro , Matsumoto Toshio 
Published: February 2010

Abstract
The present study was undertaken to clarify the relationship between c-fos and c-jun protooncogene expression and the differentiation and/or proliferation of osteoblasts, using osteoblast-like MC3T3-E1 (E1) cells. c-fos mRNA was barely detectable, whereas c-jun mRNA was constitutively expressed in E1 cells after serum deprivation for 24–72 h. When serum was added, a rapid and transient induction of c-fos and c-jun mRNAs was observed. The c-fos and c-jun mRNAs reached peak levels at 30 minutes, with a rapid disappearance of c-fos mRNA within 3 h and a much slower decrease in c-jun mRNA. The addition of serum together with cycloheximide, an inhibitor of protein synthesis, resulted in the superinduction of both c-fos and c-jun mRNAs. Among various growth factors, PDGF, EGF, and bFGF mimicked the serum effect, whereas IGF-I and TGF-β failed to induce c-fos and c-jun mRNA. The effects of PDGF, EGF, and bFGF were completely abolished by pretreatment with actinomycin D, an inhibitor of RNA synthesis, suggesting a transcriptional mechanism. Nuclear runoff experiments showed that the transcription rate of c-fos and c-jun protooncogenes was increased by serum and growth factors. The effects of PDGF, EGF, and bFGF were inhibited by H-7 or staurosporine, inhibitors of protein kinase C (PKC), but not by HA1004 with a much weaker inhibitory activity, suggesting the involvement of PKC for the activation of the protooncogenes. PDGF, EGF, and bFGF, which induced the expression of c-fos and c-jun protooncogenes, stimulated the proliferation of E1 cells, whereas IGF-I and TGF-β, which failed to induce the expression of the protooncogenes, had no effect or an inhibitory effect on the proliferation of E1 cells, respectively. In addition, when the protooncogene induction was inhibited by H-7, but not by HA1004, the proliferative responses to the growth factors were also completely abolished. Although E1 cells are known to develop osteoblastic phenotypes during prolonged culture period, the expression of c-fos and c-jun mRNAs was not altered during 2–28 days of culture at various stages of differentiation. These results suggest that the expression of c-fos and c-jun protooncogenes may play a role as an immediate early event in the proliferative responses of osteoblasts to various growth factors.
Mechanical properties of trabecular bone within and adjacent to osseous metastases
Authors: Hipp John A. , Rosenberg Andrew E. , Hayes Wilson C. 
Published: February 2010

Abstract
Despite radiographic and histologic evidence of trabecular bone density changes within and adjacent to osseous metastases, there currently exist no data to demonstrate whether these changes are important in predicting the risk of fracture. To determine if these density changes result in significant reductions in mechanical properties, trabecular bone specimens were prepared from lower thoracic and lumbar vertebrae from two cadavers with radiographic, gross, and histologic evidence of lytic and/or blastic osseous metastases. Each specimen was classified as normal, lytic, or blastic based on appearance in fine-grain radiographs of 8–9 mm thick coronal plane sections. Specimens were tested to failure in uniaxial compression, and tissue and apparent densities were measured. Mean tissue densities were within normal ranges. The mean apparent density for all specimens combined was within the normal range for human vertebrae, and the mean apparent density for radiographically normal (0.131 g/ml) and lytic (0.111 g/ml) specimens was less than the mean apparent density of blastic (0.182 g/ml) specimens (p &lt; 0.02). The moduli of lytic and blastic specimens were less than for normal specimens (p &lt; 0.025). The strength of lytic specimens was less than normal (p = 0.057), but the strength of blastic specimens was not (p &gt; 0.1). Apparent density explained significant fractions of the variations in both modulus (p &lt; 0.001) and strength (p &lt; 0.001). The data suggest that blastic changes associated with osseous metastases to trabecular bone disrupt the normal dependence of trabecular mechanical properties on apparent density, but lytic changes do not. These data also suggest that fracture risk predictors that utilize bone density to estimate stiffness or strength should adjust for the effects of metastases.
Effects of endothelin-1 on signal transduction in UMR-106 osteoblastic cells
Authors: Tatrai Agnes , Lakatos Peter , Thompson Sharron , Stern Paula H. 
Published: February 2010

AbstractEndothelin-1 is now recognized to affect the functions of a number of tissues and to activate calcium/phospholipid second messenger pathways in target cells. In the present study, we characterized its effects on signal transduction in UMR-106 cells. To study calcium transients elicited by endothelin-1, cells were loaded either with fluo-3 (for the measurement of cytosolic free calcium) or chlortetracycline (for the measurement of intracellularly stored calcium) as fluorescent probes. Intracellular production of inositol phosphates and cyclic AMP was also measured. Endothelin-1 elicited dose-dependent cytosolic calcium transients with an ED50 of 20 nM. This effect was also seen in EGTA-containing or calcium-free medium; however, the signals were reduced in magnitude. The dihydropyridine calcium channel antagonist nifedipine did not affect the response. Repeated administration of endothelin-1 resulted in homologous desensitization of the response. A 4 minute pretreatment with phorbol ester reduced the initial response to endothelin-1 in both calcium-containing and calcium-free media. A 24 h pretreatment with indomethacin had no effect on response. Using chlortetracycline as an indicator, a significant reduction in intracellularly stored calcium by endothelin-1 was observed. This was prevented by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate, a blocker of calcium release from internal stores. Endothelin-1 also stimulated the dose-dependent production of inositol phosphates by UMR-106 cells. Indomethacin was also without effect on this process. The increase in inositol trisphosphates was seen within the same time frame as the increase in cytosolic calcium. Endothelin-1 did not influence cyclic AMP production over 5 minutes in these cells. In conclusion, endothelin-1 has a significant effect on UMR-106 osteoblastic cells to activate the calcium and inositol phosphate second messenger systems. Our findings raise the intriguing question of the physiologic role of endothelin-1 in bone metabolism.