bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Vertebral Strength In Vitro by Spinal Bone Densitometry and Calcaneal Ultrasound
Authors: Cheng Xiao G. , Nicholson Patrick H. F. , Boonen Steven , Lowet Geert , Brys Peter , Aerssens Jeroen , van der Perre Georges , Dequeker Jan 
Published: April 2006

Abstract
Spinal bone mineral density (BMD) measurements and calcaneal ultrasound were compared in terms of their ability to predict the strength of the third lumbar vertebral body using specimens from 62 adult cadavers (28 females, 34 males). BMD was measured using dual X-ray absorptiometry (DXA) in both vertebra and calcaneus. Quantitative computed tomography (QCT) was used to determine trabecular BMD, cortical BMD, cortical area, and total cross-sectional area (CSA) of the vertebral body. Bone velocity (BV) and broadband ultrasonic attenuation (BUA) were measured in the right calcaneus. Vertebral strength was determined by uniaxial compressive testing. Vertebral ultimate load was best correlated with DXA-determined vertebral BMD (r2 = 0.64). Of the QCT parameters, the best correlation with strength was obtained using the product of trabecular BMD and CSA (r2 = 0.61). For vertebral ultimate stress, however, the best correlation was observed with QCT-measured trabecular BMD (r2 = 0.51); the correlation with DXA-determined BMD was slightly poorer (r2 = 0.44). Calcaneal ultrasound correlated only weakly with both ultimate load and stress with correlation coefficients (r2) of 0.10–0.17, as did calcaneal BMD (r2 = 0.18). Both spinal DXA and spinal QCT were significantly (p &lt; 0.001) better predictors of L3 ultimate load and stress than were either calcaneal ultrasound or calcaneal DXA. Multiple regression analysis revealed that calcaneal ultrasound did not significantly improve the predictive ability of either DXA or QCT for L3 ultimate load or stress. Calcaneal DXA BMD, bone velocity, and BUA correlated well with each other (r2 = 0.67–0.76), but were only modestly correlated with the DXA and QCT measurements of the vertebra. These data indicate that spinal DXA and spinal QCT provide comparable prediction of vertebral strength, but that a substantial proportion (typically 40%) of the variability in vertebral strength is unaccounted for by BMD measurements. Ultrasonic measurements at the calcaneus are poor predictors of vertebral strength in vitro, and ultrasound does not add predictive information independently of BMD. These findings contrast with emerging clinical data, suggesting that calcaneal ultrasound may be a valuable predictor of vertebral fracture risk in vivo. A possible explanation for this apparent discrepancy between in vivo and in vitro findings could be that current clinical ultrasound measurements at the calcaneus reflect factors that are related to fracture risk but not associated with bone fragility.
Prevalence of Low Femoral Bone Density in Older U.S. Adults from NHANES III
Authors: Looker Anne C. , Orwoll Eric S. , Johnston C. Conrad , Lindsay Robert L. , Wahner Heinz W. , Dunn William L. , Calvo Mona S. , Harris Tamara B. , Heyse Stephen P. 
Published: April 2006

Abstract
Most estimates of osteoporosis in older U.S. adults have been based on its occurrence in white women, even though it is known to affect men and minority women. In the present study, we used dual-energy X-ray absorptiometry measurements of femoral bone mineral density (BMD) from the third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) to estimate the overall scope of the disease in the older U.S. population. Specifically, we estimate prevalences of low femoral BMD in women 50 years and older and explore different approaches for defining low BMD in older men in that age range. Low BMD levels were defined in accordance with an approach proposed by an expert panel of the World Health Organization and used BMD data from 382 non-Hispanic white (NHW) men or 409 NHW women ages 20–29 years from the NHANES III dataset. For women, estimates indicate 13–18%, or 4–6 million, have osteoporosis (i.e., BMD &gt;2.5 standard deviations [SD] below the mean of young NHW women) and 37–50%, or 13–17 million, have osteopenia (BMD between 1 and 2.5 SD below the mean of young NHW women). For men, these numbers depend on the gender of the reference group used to define cutoff values. When based on male cutoffs, 3–6% (1–2 million) of men have osteoporosis and 28–47% (8–13 million) have osteopenia; when based on female cutoffs, 1–4% (280,000–1 million) have osteoporosis and 15–33% (4–9 million) have osteopenia. Most of the older U.S. adults with low femur BMD are women, but, regardless of which cutoffs are used, the number of men is substantial.
Expression of the CT/CGRP Gene and Its Regulation by Dibutyryl Cyclic Adenosine Monophosphate in Human Osteoblastic Cells
Authors: Drissi H. , Hott M. , Marie P. J. , Lasmoles F. 
Published: April 2006

Abstract
There is general agreement that calcitonin (CT) inhibits bone resorption by its effects on osteoclast function. CT was also found to have direct effects on osteoblast-like cells. In this study, we investigated the expression of CT and calcitonin gene-related peptide (CGRP), the two peptides encoded by the CT/CGRP gene, in human osteosarcoma cell lines and in normal human trabecular osteoblastic cells (HOB), and we studied the modulation of CT/CGRP gene expression by dibutyryl cyclic adenosine monophosphate ((Bu)2 cAMP), a cAMP analog. We first detected by Northern blot hybridization the presence of CT and CGRP mRNAs in different osteosarcoma cell lines (OHS-4, MG-63, Saos-2, HOS-TE85) and HOB cells. In the steady state, OHS-4 cells express slightly more CT and CGRP mRNAs than other cell lines or normal human osteoblasts, in parallel with messengers of differentiated osteoblasts, such as osteocalcin (OC) and alkaline phosphatase (ALP). OHS-4 cells also express CT and CGRP proteins, as demonstrated by immunocytochemistry. Stimulation of OHS-4 cells with 1 mM (Bu)2 cAMP induced a significant increase in mRNA levels for CT (×2.5) and CGRP (×3), as determined by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) procedure. The involvement of a transcriptional mechanism in this effect was evidenced by nuclear run-off transcription assay. In addition, (Bu)2 cAMP increased OC (×4) and ALP (×3) mRNA levels in OHS-4 cells. These effects were observed at 24 h and were maximal at 48 h, indicating that (Bu)2 cAMP induced cell differentiation and increased the transcription of the CT/CGRP gene in OHS-4 osteoblast-like cells. The results indicate that human osteosarcoma cells and primary human osteoblastic cells express CT and CGRP mRNA and proteins, and that (Bu)2 cAMP, an activator of protein kinase A, induces up-regulation of osteoblastic phenotypic genes and enhances CT and CGRP gene transcription, indicating that induction of osteoblastic differentiation by (Bu)2 cAMP is associated with enhanced expression of CT and CGRP in human osteoblastic cells.
Premenopausal Ovariectomy-Related Bone Loss: A Randomized, Double-Blind, One-Year Trial of Conjugated Estrogen or Medroxyprogesterone Acetate
Authors: Prior Jerilynn C. , Vigna Yvette M. , Wark John D. , Eyre David R. , Lentle Brian C. , Li David K. B. , Ebeling Peter R. , Atley Lynne 
Published: April 2006

Abstract
The purpose of this study was to contrast the effects of conventional estrogen treatment with medroxyprogesterone on cancellous and cortical bone change in the first year following premenopausal ovariectomy. This 1-year double-blind randomized therapy trial was stratified by osteoporosis family history and performed in an academic medical center and community hospitals. Premenopausal women 45 ± 5 years old, postovariectomy for benign diseases were provided 600 mg/day of calcium and randomized to daily therapy with conjugated equine estrogen (CEE, 0.6 mg) or medroxyprogesterone (MPA, 10 mg). The primary outcome variable was spinal quantitative computed tomography (QCT) bone density change over 1 year with additional outcomes of dual-energy X-ray absorptiometry (DXA) of proximal femur (FN), whole body (WB), and spine segment (WBS) and N-telopeptide, bone-specific alkaline phosphatase, and other bone marker, hormonal, and weight changes. Results in the 33 women completing the study, whose initial bone densities were normal (QCT 133 mg/cm3, femoral neck 0.94 g/cm2, whole body DXA 1.13 g/cm2), showed annual QCT loss during CEE therapy of −11.5 mg/cm3 (p &lt; 0.0007) and MPA bone loss of −19.7 mg/cm3 (p &lt; 0.0001). Losses were marginally greater on MPA than CEE (p = 0.04). Extremely high postovariectomy (5 days) and pretreatment resorption markers (&gt;3 SD above premenopausal normal levels) were significantly related to bone loss. Across the year, resorption decreased during CEE but increased on MPA treatment. Significant DXA bone losses were prevented by CEE treatment (−1.4% FN, −.4% WB, and −1.5% WBS, all NS). However, DXA bone loss was not prevented by MPA treatment (−5% FN, −2.8% WB, and −6.1% WBS, all p &lt; 0.03). Average weight gain was significant (+3.2 ± 4.0 kg) and greater on CEE than MPA (+4.7 vs. +2.0 kg, p = 0.049). In conclusion, CEE therapy did not prevent significant 8% cancellous spinal bone loss in the first year following premenopausal ovariectomy, despite supplementation with 600 mg/day of calcium, good control of vasomotor symptoms, and nearly 5 kg of gain in weight. Significant DXA bone loss, however, was prevented by CEE, but not by MPA therapy. These unexpected results were statistically related to high bone resorption following ovariectomy, which CEE suppressed but MPA did not. Bone formation markers increased during MPA therapy but were unchanged during CEE therapy.
Parathyroid Hormone Enhances Early and Suppresses Late Stages of Osteogenic and Chondrogenic Development in a BMP-Dependent Mesenchymal Differentiation System (C3H10T½)
Authors: Hollnagel Angela , Ahrens Marion , Gross Gerhard 
Published: April 2006

Abstract
The role of parathyroid hormone (PTH) upon osteo-/chondrogenic development was investigated in a bone morphogenetic protein (BMP)-dependent differentiation system involving the recombinant expression of BMPs in mesenchymal progenitor cells (C3H10T½). The constitutive expression of the PTH/PTH related protein receptor in this system led to a marked stimulation of chondrogenic and osteogenic development, while the permanent application of the ligand PTH(1–34) resulted in opposite responses by stimulating the early and suppressing the late stages of osteo-/chondrogenic development. These contrasting effects of PTH(1–34) on osteogenic and chondrocytic development seem, therefore, to depend on the cellular state of differentiation. The osteogenic and chondrocytic differentiation potential was substantiated histologically and by genetic analyses of marker genes like c-fos, alkaline phosphatase, osteocalcin, collagen α1(I), and collagen α1(II). The capacity to regulate osteogenic and chondrogenic development is located in the amino-terminal (1–34) region of the PTH molecule and seems to be mediated by the cyclic adenosine monophosphate signaling cascade. The application of other PTH domains like PTH(28–48) and PTH(53–84) did not exhibit significant responses. PTH acts as an essential factor in mesenchymal development controlling rates of differentiation into the osteogenic or chondrogenic lineage. The analysis of PTH effects in this system demonstrates the value of recombinant mesenchymal progenitor cells in the in vitro analysis of osteo-/chondrogenic development.
Developmental Restriction of Embryonic Calvarial Cell Populations as Characterized by Their In Vitro Potential for Chondrogenic Differentiation
Authors: Toma Cyril D. , Schaffer Jonathan L. , Meazzini M. Costanza , Zurakowski David , Nah Hyun-Duck , Gerstenfeld Louis C. 
Published: April 2006

Abstract
The mechanism(s) by which the cells within the calvaria tissue are restricted into the osteogenic versus the chondrogenic lineage during intramembranous bone formation were examined. Cells were obtained from 12-day chicken embryo calvariae after tissue condensation, but before extensive osteogenic differentiation, and from 17-day embryo calvariae when osteogenesis is well progressed. Only cell populations from the younger embryos showed chondrogenic differentiation as characterized by the expression of collagen type II. The chondrocytes underwent a temporal progression of maturation and endochondral development, demonstrated by the expression of collagen type II B transcript and expression of collagen type X mRNA. Cell populations from both ages of embryos showed progressive osteogenic differentiation, based on the expression of osteopontin, bone sialoprotein, and osteocalcin mRNAs. Analysis using lineage markers for either chondrocytes or osteoblasts demonstrated that when the younger embryonic cultures were grown in conditions that were permissive for chondrogenesis, the number of chondrogenic cells increased from ∼15 to ∼50% of the population, while the number of osteogenic cells remained almost constant at ∼35–40%. Pulse labeling of the cultures with BrdU showed selective labeling of the chondrogenic cells in comparison with the osteogenic cells. These data indicate that the developmental restriction of skeletal cells of the calvaria is not a result of positive selection for osteogenic differentiation but a negative selection against the progressive growth of chondrogenic cells in the absence of a permissive or inductive environment. These results further demonstrate that while extrinsic environmental factors can modulate the lineage progression of skeletal cells within the calvariae, there is a progressive restriction during embryogenesis in the number of cells within the calvaria with a chondrogenic potential. Finally, these data suggest that the loss of cells with chondrogenic potential from the calvaria may be related to the progressive limitation of the reparative capacity of the cranial bones.
Regulation of Interleukin-6 Secretion from Mononuclear Blood Cells by Extracellular Calcium
Authors: Bornefalk Eva , Ljunghall Sverker , Lindh Erik , Bengtson Olof , Johansson Anna G. , Ljunggren Östen 
Published: April 2006

Abstract
Interleukin-6 (IL-6) is known to enhance osteoclast recruitment, and thereby bone resorption. Thus, IL-6 has been proposed to mediate hypercalcemia in multiple myeloma and the enhanced osteoclastic activity seen in postmenopausal osteoporosis. We recently reported that the calcium concentration in plasma affects IL-6 secretion from mononuclear blood cells. To investigate the underlying mechanism, we have studied the effect of calcium on IL-6 formation in mononuclear blood cells ex vivo and in vitro. Thirteen healthy volunteers were given 1 g of calcium orally after overnight fasting. Plasma levels of ionized calcium (pCa2+) and serum levels of parathyroid hormone (sPTH) were measured after 2 and 4 h, with all subjects still fasting. After 2 h, pCa2+ was increased and sPTH decreased in all 13 persons. IL-6 secretion ex vivo from mononuclear blood cells drawn 4 h after calcium intake was increased 185% as compared with IL-6 secretion from cells drawn just before calcium intake. In control experiments without calcium intake, there was no alteration in pCa2+ and no effect on IL-6 secretion from mononuclear blood cells. In vitro studies revealed that stimulation of isolated mononuclear blood cells with physiological concentrations of calcium dose-dependently increased IL-6 secretion with an estimated EC50 at 1.2 mM Ca2+. No effect on the IL-6 secretion was seen following treatment of the isolated mononuclear blood cells with PTH or calcitonin. These observations demonstrate that the plasma calcium concentration affects IL-6 secretion from mononuclear blood cells. The in vitro data indicate the involvement of a direct calcium sensing mechanism. These findings might have implications in hypercalcemia and should also be borne in mind when considering the role of cytokines in osteoporosis.
Reduced Rates of Skeletal Remodeling Are Associated with Increased Bone Mineral Density During the Development of Peak Skeletal Mass
Authors: Slemenda Charles W. , Peacock Munro , Hui Siu , Zhou Lifen , Johnston C. Conrad 
Published: April 2006

Abstract
Two related studies were conducted to assess the associations between markers of skeletal modeling and remodeling in healthy children. Members of monozygotic twin pairs, aged 6–14, enrolled in a clinical trial of calcium supplementation, were studied at the end of the period of supplementation and for 3 years thereafter. Supplemented children had significantly higher rates of gain in bone mineral density (BMD) (+3% on average) during the period of supplementation accompanied by significantly lower concentrations of serum osteocalcin (OC, −15%). During postsupplement follow-up, both differences in BMD and OC disappeared. Black females, age matched to the baseline ages of the white children, had significantly lower serum concentrations of both OC and tartrate-resistant acid phosphatase (TRAP) at all ages and higher BMDs. When stratified on serum TRAP concentrations, regardless of race, children with lower concentrations had significantly higher BMDs, and no racial differences were apparent. In regression models accounting for 70–80% of the variability in BMD in children, body size and TRAP, but not race, remained significantly associated with BMD. The skeletal advantages seen with calcium supplementation and black race appear to be associated with reduced rates of skeletal turnover. Given that markers of turnover during growth reflect both skeletal modeling and remodeling, and there is no apparent advantage to reduced skeletal modeling, it seems probable that reduced remodeling is the factor that accounts for the increases in bone mass.
The Ca2+-Sensing Receptor (CaR) Activates Phospholipases C, A2, and D in Bovine Parathyroid and CaR-Transfected, Human Embryonic Kidney (HEK293) Cells
Authors: Kifor Olga , Diaz Ruben , Butters Robert , Brown Edward M. 
Published: April 2006

Abstract
The extracellular Ca2+ (Cao2+)-sensing receptor (CaR) is a G protein–coupled receptor that activates phospholipase C (PLC). In the present studies, we assessed Cao2+-dependent changes in the generation of inositol phosphates (IP), free arachidonic acid (AA), and phosphatidylbutanol (PtdBtOH) by PLC, phospholipase A2 (PLA2), and phospholipase D (PLD), respectively, in bovine parathyroid cells as well as in wild-type or CaR-transfected human embryonic kidney (HEK293) cells (HEK-WT and HEK-CaR, respectively). Elevated Cao2+ increased the formation of IPs in parathyroid cells as well in HEK-CaR but not in HEK-WT cells. High Cao2+ also elicited time- and dose-dependent increases in PtdBtOH in parathyroid cells and HEK-CaR but not in HEK-WT cells. Brief treatment of parathyroid and HEK-CaR cells with an activator of protein kinase C (PKC), phorbol 12-myristate,13-acetate (PMA), stimulated PLD activity at both low and high Cao2+. Moreover, high Cao2+-stimulated PLD activity was abolished following down-regulation of PKC by overnight phorbol myristate acetate (PMA) pretreatment, suggesting that CaR-mediated activation of PLD depends largely upon stimulation of PKC. High Cao2+ likewise increased the release of free AA in parathyroid and HEK-CaR but not in HEK-WT cells. Mepacrine, a general PLA2 inhibitor, and AACOCF3, an inhibitor of cytosolic PLA2, reduced AA release in parathyroid cells at high Cao2+, suggesting a major role for PLA2 in high Cao2+-elicited AA release. Pretreatment of parathyroid cells with PMA stimulated release of AA at low and high Cao2+, while a PKC inhibitor, chelerythrine, reduced AA release at high Cao2+ to the level observed with low Cao2+ alone. Thus, PKC contributes importantly to the high Cao2+-evoked, CaR-mediated activation of not only PLD but also PLA2. Finally, high Cao2+-stimulated production of IP, PtdBtOH, and AA all decreased substantially in parathyroid cells cultured for 4 days, in which expression of the CaR decreases by 80% or more, consistent with mediation of these effects by the receptor. Thus, the CaR activates, directly or indirectly, at least three phospholipases in bovine parathyroid and CaR-transfected HEK293 cells, providing for coordinate, receptor-mediated regulation of multiple signal transduction pathways in parathyroid and presumably other CaR-expressing cells.
Evidence of a Correlation of Estrogen Receptor Level and Avian Osteoclast Estrogen Responsiveness
Authors: Pederson Larry , Kremer Matthew , Foged Niels Tækker , Winding Bent , Ritchie Candace , Fitzpatrick Lorraine A. , Oursler Merry Jo 
Published: April 2006

Abstract
Isolated osteoclasts from 5-week-old chickens respond to estradiol treatment in vitro with decreased resorption activity, increased nuclear proto-oncogene expression, and decreased lysosomal enzyme secretion. This study examines osteoclasts from embryonic chickens and egg-laying hens for evidence of estrogen responsiveness. Although osteoclasts from both of these sources express estrogen receptor mRNA and protein, estradiol treatment had no effect on resorption activity. In contrast to the lack of effect on resorption, estradiol treatment for 30 minutes resulted in steady-state mRNA levels of c-fos and c-jun increasing in osteoclasts from embryonic chickens and decreasing in osteoclasts from egg-laying hens. These data suggest that a nuclear proto-oncogene response may not be involved in estradiol-mediated decreased osteoclast resorption activity. To examine the influence of circulating estrogen on osteoclast estrogen responsiveness, 5-week-old chickens were injected with estrogen for 4 days prior to sacrifice. Estradiol treatment of osteoclasts from these chickens did not decrease resorption activity in vitro. Transfection of an estrogen receptor expression vector into osteoclasts from the estradiol-injected chickens and egg-laying hens restored estrogen responsiveness. Osteoclasts from 5-week-old chickens and estradiol treated 5-week-old chickens transfected with the estrogen receptor expression vector contained significantly higher levels of estrogen receptor protein and responded to estradiol treatment by decreasing secretion of cathepsins B and L and tartrate-resistant acid phosphatase. In contrast, osteoclasts from embryonic chickens, egg-laying hens, and estradiol-treated 5-week-old chickens either untransfected or transfected with an empty expression vector did not respond similarly. These data suggest that modulation of osteoclast estrogen responsiveness may be controlled by changes in the osteoclast estrogen receptor levels.
Modulation of the Effects of Glucocorticoids on Collagen Synthesis in Fetal Rat Calvariae by Insulin-like Growth Factor Binding Protein-2
Authors: Kream Barbara E. , Tetradis Sotirios , Lafrancis Denise , Fall Pamela M. , Feyen Jean H. M. , Raisz Lawrence G. 
Published: April 2006

Abstract
To test the hypothesis that insulin-like growth factors (IGFs) play a role in the response of bone to glucocorticoids, we determined the effects of cortisol on the incorporation of [3H]proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP), the percent collagen synthesis, and the incorporation of [3H]thymidine into DNA of 21-day fetal rat calvariae cultured in the presence and absence of recombinant human insulin-like growth factor binding protein-2 (IGFBP-2). At 24 h, cortisol (100 nM) increased CDP labeling and the percent collagen synthesis, and these effects were blocked by IGFBP-2 (1000 nM). At 24 h, cortisol decreased the incorporation of [3H]thymidine into bone, which was not affected by the addition of IGFBP-2. At 48 h, cortisol (1000 nM) decreased CDP labeling, which was maintained in the presence of IGFBP-2. At 48 h, IGFBP-2 alone decreased basal levels of CDP and NCP labeling and the percent collagen synthesis. Our data suggest that endogenous IGFs maintain basal levels of collagen synthesis and mediate the early stimulatory effect of glucocorticoids on collagen synthesis in fetal rat calvariae. However, blocking endogenous IGFs does not abrogate the inhibitory effect of glucocorticoids on DNA synthesis and the later inhibition of collagen synthesis in calvariae.