bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Vertebral and Femoral Strength In Vitro by Bone Mineral Density Measured at Different Skeletal Sites
Authors: Cheng Xiao G. , Lowet Geert , Boonen Steven , Nicholson Patrick H. F. , Van Der Perre Georges , Dequeker Jan 
Published: April 2006

Abstract
The aim of the present study was to investigate the prediction of vertebral and femoral strength in vitro by bone mineral density (BMD) measured at different skeletal sites. The third lumbar vertebral body, the right proximal femur, and the right calcaneus were removed from 38 male and 32 female cadavers (mean age 69 years, range 23–92 years). Areal BMD of all bone specimens was determined by dual-energy X-ray absorptiometry (DXA). The failure load of the vertebral body and the femur was determined by mechanical testing. Vertebral and femoral strength were both greater in males than females (p &lt; 0.01), as was BMD at all sites (p &lt; 0.01). Vertebral strength correlated well with vertebral BMD (r2 = 0.64) but was only moderately correlated with BMD measured at the femur (r2 = 0.36) or the calcaneus (r2 = 0.18). Femoral strength showed the highest correlations with femoral BMD (r2 = 0.88) and somewhat weaker relationships with BMD at the vertebra (r2 = 0.50) and the calcaneus (r2 = 0.54). BMD values at the vertebra, femur, and calcaneus were only moderately interrelated (r2 = 0.31–0.65), and vertebral strength correlated only modestly with the strength of the femur (r2 = 0.36). These in vitro results support the concept that optimal prediction of vertebral or femoral strength by DXA requires site-specific assessments.
The Diuretic Indapamide Increases Bone Mass and Decreases Bone Resorption in Spontaneously Hypertensive Rats Supplemented with Sodium
Authors: Lalande Agnès , Roux Christian , Graulet Anne-Marie , Schiavi Pierre , De Vernejoul Marie-Christine 
Published: April 2006

Abstract
Clinical and epidemiological studies suggest that thiazide diuretics can prevent bone loss and decrease the incidence of hip fractures. However, the mechanism of the effect of diuretics on bone is not clearly established. Indapamide (IDP), a sulfonamide diuretic related to thiazides, is used to treat hypertension. Sixty spontaneously hypertensive rats (SHRs) were divided into four groups and treated with or without IDP (1.5 mg/kg/day) during 8 weeks in the presence or absence of a high sodium load (8% NaCl supplementation in the diet). Sodium and calcium excretions were increased in the rats receiving the high sodium load (SHR + 8% NaCl) comparatively with control rats (SHR). IDP decreased and increased, respectively, calcium and sodium excretions. Serum parathyroid hormone (PTH) was unchanged in any group. Bone density was measured at the femur, tibia, and vertebrae, and bone morphometry was performed at the metaphysis of the femur to evaluate bone architecture. Rats fed a high sodium diet had an average 5.5% decreased bone density at every site except the femoral diaphysis. The trabecular bone volume was also decreased (SHR + 8% NaCl vs. SHR, 11.99 ± 0.78 vs. 17.51 ± 1.5%, p &lt; 0.05). An increase in trabecular separation suggested that these changes were due to increased bone resorption. In the SHR + 8% NaCl + IDP group, IDP increased bone density and trabecular bone volume (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 16.52 ± 1.04 vs. 11.99 ± 0.78%, p &lt; 0.05). Trabecular separation and pyridinoline/creatinine excretion (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 136.39 ± 9.62 vs. 195.18 ± 22.34 nmol/mmol, p &lt; 0.05) were also decreased by IDP. These results show that in rats receiving a high sodium diet, IDP can reverse sodium-induced bone loss and increased bone resorption independently of changes in serum PTH.
Familial Resemblance of Bone Mineral Density (BMD) and Calcaneal Ultrasound Attenuation: The BMD in Mothers and Daughters Study
Authors: Danielson Michelle E. , Cauley Jane A. , Baker Carol E. , Newman Anne B. , Dorman Janice S. , Towers Jeffrey D. , Kuller Lewis H. 
Published: April 2006

Abstract
The familial resemblance in bone mineral density (BMD) and calcaneal broadband ultrasound attenuation (BUA) was examined in 207 mother-daughter pairs. Mothers were participants in the Study of Osteoporotic Fractures. Three groups of daughters were recruited based on their maternal history of “fracture,” “low BMD” without fracture (&lt; 0.58 g/cm2, t-score &lt; −2.5), and “normal BMD” without fracture (&gt; 0.67 g/cm2, t-score &gt; −1.6). Data on other potentially heritable factors known to influence BMD and BUA were also collected. BMD was measured at the hip, spine, whole body, and calcaneus. Calcaneal BUA was assessed using the Walker-Sonix UBA 575. Total hip and femoral neck BMD were significantly lower (5.0–8.0%, p &lt; 0.017) among daughters, in particular premenopausal daughters, of mothers with established osteoporosis (“fracture” or “low BMD”) compared with daughters of mothers at lower risk of osteoporosis (“normal BMD”). BUA did not differ across daughter groups. Lifestyle characteristics (dietary calcium, smoking, physical activity) were not highly correlated in mothers and daughters. Height, weight, and body composition were significantly correlated within mother-daughter pairs and could be a potential mechanism by which BMD is inherited. Among pre- and postmenopausal daughters, heritability estimates ranged from 50–63% and 34–48%, respectively. Heritability for calcaneal BUA (53%) was evident among postmenopausal daughters only. In conclusion, familial association in BMD was strongest among premenopausal daughters. Estimates of heritability suggest that maternal BMD and BUA are important independent predictors of BMD and BUA among daughters, reinforcing the importance of prevention and early intervention among women with a positive family history of osteoporosis. (J Bone Miner Res 1999;14: 102–110)
Structure of the Femoral Neck in Hip Fracture: Cortical Bone Loss in the Inferoanterior to Superoposterior Axis
Authors: Dr. Bell K. L. , Loveridge N. , Power J. , Garrahan N. , Stanton M. , Lunt M. , Meggitt B. F. , Reeve J. 
Published: April 2006

Abstract
Although bone mass is a contributory risk factor for hip fracture, its distribution about the femoral neck is also important. Femoral neck biopsies were obtained from 13 females with intracapsular hip fracture (fracture: mean age 74.3 ± 2.3 years [SEM]) and 19 cadaveric samples (control: 9 males and 10 females 79.4 ± 1.7 years) and the areas of cortical and cancellous bone were quantitated in octants. In the control group, although males had larger bones than females, the proportions of cortical and cancellous bone were not different (p &gt; 0.05) between the genders. The total amount of bone, as a proportion of bone + marrow, was significantly reduced in the fractures compared with the female controls (%Tt.Ar: fracture 27.83 ± 1.18, female control 33.62 ± 1.47; p = 0.0054). Reductions in cortical bone area occurred in all regions but particularly in the inferior, inferoanterior, and anterior octants (p &lt; 0.05). There were no differences between cases and controls in the regional amount of cancellous bone (all regions, p &gt; 0.178). Marked reductions in mean cortical bone width between the fracture and female control group occurred in the anterior, inferoanterior (31%), and superoposterior (25%) regions. Representing cortical widths as simple Fourier functions of the angle about the center of area (R2adj = 0.79) showed in the cases that there was preservation of the cortical bone in the inferior region, with the proportional loss of cortical bone being greatest in the inferoanterior and superoposterior regions. It is concluded that loss of cortical, rather than cancellous, bone predominates in cases of femoral neck fracture. This loss occurs primarily along the inferoanterior to superoposterior axis. As this axis bears the greatest strain during a fall, it is hypothesized that specific thinning of the cortex in these regions leads to an exaggerated propensity to fracture in those so affected, above that resulting from an equivalent general decrease in bone mass.
Good Maintenance of High-Impact Activity-Induced Bone Gain by Voluntary, Unsupervised Exercises: An 8-Month Follow-up of a Randomized Controlled Trial
Authors: Heinonen Ari , Kannus Pekka , Sievänen Harri , Pasanen Matti , Oja Pekka , Vuori Ilkka 
Published: April 2006

Abstract
The purpose of this study was to evaluate whether premenopausal women's voluntary unsupervised aerobic and step training could maintain the skeletal benefits obtained by an 18-month supervised high-impact training, and if so, to what extent. Thirty women of the original 39 study subjects (i. e., persons who completed the preceding 18-month randomized training intervention and who volunteered to continue the training on their own for a further 8 months) and 19 women of the 45 original control subjects (i.e., persons who volunteered to continue as controls) were included. The study group trained an average of twice per week and the training consisted of regular aerobic and step classes provided by local fitness centers. Areal bone mineral density (BMD, g/cm2) was measured from the lumbar spine, femoral neck, trochanter area of the femur, distal femur, patella, proximal tibia, calcaneus, and dominant distal radius at baseline and after 18 and 26 months. During the extended 8-month follow-up, the BMD of the study group increased more at the femoral neck (the intergroup change was +0.9% at 18 months and +2.8% at 26 months, p = 0.004 for the change between 18 and 26 months) and remained at the 18-month level at the distal femur, patella, proximal tibia, and calcaneus. In these sites, the statistically significant changes during the entire 26 months of training were 1.7–4.0% in the training group as compared with the changes of −0.9–1.5% in the control group. In the lumbar spine, BMD decreased from the 18-month level in both groups. In conclusion, the significant BMD increases that were obtained by supervised 18-month high-impact training were effectively maintained with subsequent unsupervised regular aerobic and step classes (twice per week). The finding emphasizes the effectiveness and feasibility of self-controlled aerobic and step exercises in the primary prevention of osteoporosis among healthy premenopausal women.
Smoking, Antioxidant Vitamins, and the Risk of Hip Fracture
Authors: Melhus Håkan , Michaëlsson Karl , Holmberg Lars , Wolk Alicja , Ljunghall Sverker 
Published: April 2006

Abstract
Smoking increases the concentrations of free radicals, which have been suggested to be involved in bone resorption. We examined whether the dietary intake of antioxidant vitamins may modify the increased hip fracture risk associated with smoking. We prospectively studied 66,651 women who were 40–76 years of age. Forty-four of the cohort members who sustained a first hip fracture within 2–64 months of follow-up (n = 247) and 93 out of 873 age-matched controls were current smokers. Information on diet was obtained by a validated food-frequency questionnaire. The relative risk of hip fracture for current versus never smokers was analyzed in relation to the dietary intake of antioxidant vitamins stratified into two categories (low/high), where median intakes among the controls were used as cut-off points. After adjustment for major osteoporosis risk factors, the odds ratio (OR) for hip fracture among current smokers with a low intake of vitamin E was 3.0 (95% confidence interval 1.6–5.4) and of vitamin C 3.0 (1.6–5.6). In contrast, the OR decreased to 1.1 (0.5–2.4) and 1.4 (0.7–3.0) with high intakes of vitamin E and C, respectively. This effect was not seen for beta-carotene, selenium, calcium, or vitamin B6. In current smokers with a low intake of both vitamins E and C, the OR increased to 4.9 (2.2–11.0). The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers. Our results suggest a role for oxidant stress in the adverse effects on the skeleton of smoking, and that an insufficient dietary intake of vitamin E and C may substantially increase the risk of hip fracture in current smokers, whereas a more adequeate intake seems to be protective.
Osteoclast Formation in Bone Marrow Cultures from Two Inbred Strains of Mice with Different Bone Densities
Authors: Linkhart Thomas A. , Linkhart Susan G. , Kodama Yoshiaki , Farley John R. , Dimai H. Peter , Wright Kenneth R. , Wergedal Jon E. , Sheng Matilda , Beamer Wesley G. , Donahue Leah Rae , Rosen Clifford J. , Baylink David J. 
Published: April 2006

Abstract
For the purpose of identifying genes that affect bone volume, we previously identified two inbred mouse strains (C57BL/6J and C3H/HeJ) with large differences in femoral bone density and medullary cavity volume. The lower density and larger medullary cavity volume in C57BL/6J mice could result from either decreased formation or increased resorption or both. We recently reported evidence suggesting that bone formation was increased in vivo and that osteoblast progenitor cells are more numerous in the bone marrow of C3H/HeJ compared with C57BL/6J mice. In the present study, we determined whether osteoclast numbers in vivo and osteoclast formation from bone marrow cells in vitro might also differ between the two mouse strains. We have found that the number of osteoclasts on bone surfaces of distal humerus secondary spongiosa was 2-fold higher in 5.5-week-old C57BL/6J mice than in C3H/HeJ mice of the same age (p &lt; 0.001). Bone marrow cells of C57BL/6J mice cocultured with Swiss/Webster mouse osteoblasts consistently produced more osteoclasts than did C3H/HeJ bone marrow cells at all ages tested from 3.5–14 weeks of age (p &lt; 0.001). Osteoclast formation was also greater from spleen cells of 3.5-week-old C57BL/6J mice than C3H/HeJ mice. The distribution of nuclei per osteoclast and the 1,25-dihydroxyvitamin D3 dose dependence of osteoclast production from bone marrow cells were similar. Osteoclasts that developed from both C57BL/6J and C3H/HeJ marrow cells formed pits in dentin slices. Cultures from C57BL/6J marrow cells formed 2.5-fold more pits than cultures from C3H/HeJ marrow cells (p &lt; 0.02). We compared the abilities of C57BL/6J and C3H/HeJ osteoblasts to support osteoclast formation. When bone marrow cells from either C57BL/6J or C3H/HeJ mice were cocultured with osteoblasts from either C57BL/6J or C3H/HeJ newborn calvaria, the strain from which osteoblasts were derived did not affect the number of osteoclasts formed from marrow cells of either strain. Together, these observations suggest that genes affecting the bone marrow osteoclast precursor population may contribute to the relative differences in bone density that occur between C3H/HeJ and C57BL/6J mouse strains.
Differential Cell Surface Expression of the STRO-1 and Alkaline Phosphatase Antigens on Discrete Developmental Stages in Primary Cultures of Human Bone Cells
Authors: Gronthos Stan , Zannettino Andrew C. W. , Graves Stephen E. , Ohta Shuichi , Hay Shelley J. , Simmons Paul J. 
Published: April 2006

Abstract
Human osteoblast-like cells can be readily cultured from explants of trabecular bone, reproducibly expressing the characteristics of cells belonging to the osteoblastic lineage. Dual-color fluorescence-activated cell sorting was employed to develop a model of bone cell development in primary cultures of normal human bone cells (NHBCs) based on the cell surface expression of the stromal precursor cell marker STRO-1 and the osteoblastic marker alkaline phosphatase (ALP). Cells expressing the STRO-1 antigen exclusively (STRO-1+/ALP−), were found to exhibit qualities preosteoblastic in nature both functionally by their reduced ability to form a mineralized bone matrix over time, as measured by calcium release assay, and in the lack of their expression of various bone-related markers including bone sialoprotein, osteopontin, and parathyroid hormone receptor based on reverse trancriptase polymerase chain reaction (PCR) analysis. The majority of the NHBCs which expressed the STRO-1−/ALP+ and STRO-1−/ALP− phenotypes appeared to represent fully differentiated osteoblasts, while the STRO-1+/ALP+ subset represented an intermediate preosteoblastic stage of development. All STRO-1/ALP NHBC subsets were also found to express the DNA-binding transcription factor CBFA-1, confirming that these cultures represent committed osteogenic cells. In addition, our primer sets yielded four distinct alternative splice variants of the expected PCR product for CBFA-1 in each of the STRO-1/ALP subsets, with the exception of the proposed preosteoblastic STRO-1+/ALP− subpopulation. Furthermore, upon re-culture of the four different STRO-1/ALP subsets only the STRO-1+/ALP− subpopulation was able to give rise to all of the four subsets yielding the same proportions of STRO-1/ALP expression as in the original primary cultures. The data presented in this study demonstrate a hierarchy of bone cell development in vitro and facilitate the study of bone cell differentiation and function.
Signaling Reactions Induced in Human Fibroblasts During Adhesion to Cementum-Derived Attachment Protein
Authors: Saito Masahiro , Narayanan Sampath 
Published: April 2006

Abstract
Cementum-derived attachment protein (CAP) is a Mr 56,000 collagenous protein which promotes the adhesion and spreading of mesenchymal cell types. The CAP promotes the adhesion of osteoblasts and periodontal ligament cells better than gingival fibroblasts, while epithelial cells do not adhere to CAP-coated surfaces. To understand the mechanisms involved in CAP action, we have studied the signal transduction events induced by the CAP in human fibroblasts during cell adhesion. Human gingival fibroblasts were serum starved for 48 h, trypsinized, and added to non–tissue culture plastic plates previously coated with CAP. At various time points, attached cells were examined for induction of signaling reactions. Adherence of cells to plates coated with CAP caused tyrosine phosphorylation of proteins migrating on PAGE with molecular mass of 125–130, 85, 70, and 42–44 kDa. We identified focal adhesion kinase p125fak and p130Cas as components of the 125–130 kDa protein band; however, p125fak was the major phosphorylated component. ERK-1 and ERK-2 were detected in the 42–44 kDa protein band, but only the ERK-2, not ERK-1, was phosphorylated. Adhesion to CAP-stimulated mitogen-activated protein kinase (MAPK) activity and induced the expression of c-fos mRNA. Protein-tyrosine phosphorylation and c-fos mRNA expression were not induced in unattached cells, and adhesion was not abolished by the protein tyrosine kinase inhibitor, genestein. MAPK activity and c-fos mRNA expression were not induced in monolayer cultures, indicating that these reactions are induced by adhesion and not necessary for cell adhesion. The kinetics of MAPK activation were different from cells attaching on fibronectin (FN) or polylysine, and c-fos mRNA levels increased only half as much on FN and very little on polylysine. These data demonstrated that CAP and other adhesion molecules present in mineralized tissue matrices induce characteristic signaling events during adhesion, which may play a role in recruitment of specific cell types during wound healing and in mediating their specific biological functions.
Defining Incident Vertebral Deformity: A Prospective Comparison of Several Approaches
Authors: Black Dennis M. , Palermo Lisa , Nevitt Michael C. , Genant Harry K. , Christensen Lisa , Cummings Steven R. ,   for the Study of Osteoporotic Fractures Research Group
Published: April 2006

Abstract
Vertebral deformities are common and important outcomes in clinical trials and epidemiologic studies of osteoporosis. While several different methods for defining new deformities have been proposed, it is not clear which is best. We used data from serial spine radiographs obtained an average of 3.7 years apart in 7238 women age ≥65 years from the Study of Osteoporotic Fractures to compare several approaches to defining new deformities by morphometry including a fixed percentage reduction in any vertebral height (FIXED%), a change in a summary spinal deformity index, a change in a vertebra from no prevalent deformity at baseline to a deformity at follow-up, as well as several variations of these methods. We compared results of each definition with several clinical correlates, including height loss, back pain, age, baseline bone mineral density, and the presence of a baseline deformity. We also estimated the sample size required for a clinical trial using various cut points. At a given level of incidence, all methods had similar relationships with each of the correlates. Given that similarity, the FIXED% method was simplest and needed no reference data. Using the FIXED% method, a 20–25% vertebral height reduction criterion for deformity maximized the power for a clinical trial. We conclude that all of the morphometric approaches to defining incident deformities have similar relationships to clinical correlates of vertebral deformity, but that use of a fixed percentage reduction in vertebral height is the simplest and most practical. For the FIXED% method, a 20–25% reduction in vertebral height minimizes the sample size required for clinical trials and epidemiologic studies.
On the Trabecular “Thickness”-Number Problem
Authors: Frost Harold M. 
Published: April 2006

Abstract
The decrease in trabecular number with aging and in osteoporosis seems to be naturally irreversible. In one view the resulting loss of bone strength would be irreversible too, but in another view the remaining trabeculae could increase their strength, chiefly by thickening. Whether that can occur has become important for osteoporosis research and management as well as for some biomechanical issues. This article reviews evidence and ideas that concern that matter. It suggests why the second view could be correct although previous studies did not detect it. However, that view still needs the kind of proof the general skeletal science community could accept.
Vitamin D Receptor Interactions with the Rat Parathyroid Hormone Gene: Synergistic Effects Between Two Negative Vitamin D Response Elements
Authors: Russell John , Ashok Sheela , Koszewski Nicholas J. 
Published: April 2006

Abstract
Vitamin D response elements (VDREs) that are required for negative regulation of rat parathyroid hormone (rPTH) gene expression have been characterized. Gel mobility shift assays using DNA restriction enzyme fragments and recombinant proteins for vitamin D and retinoic acid X receptors (VDR/RXR) revealed a sequence between −793 and −779 that bound a VDR/RXR heterodimer with high affinity (VDRE1). Furthermore, a lower affinity site (VDRE2) was detected that acted in combination with VDRE1 to bind a second VDR/RXR complex. As determined by ethylation interference analysis, the nucleotide sequence of VDRE1 consisted of GGTTCA GTG AGGTAC, which is remarkably similar to the sequence of the negative VDRE found in the chicken PTH (cPTH) gene. Using the same technique, VDRE2 was identified between positions −760 and −746 and contained the sequence AGGCTA GCC AGTTCA. Functional analysis was determined by transfection studies with plasmid constructs that expressed the gene for chloramphenicol acetyl transferase (CAT). The ability of the VDREs to regulate gene expression was tested in their native context with the rPTH promoter as well as when positioned immediately upstream from the cPTH promoter. With either plasmid construct, exposure to 10−8 M 1,25(OH)2D3 resulted in a 60–70% decrease in CAT gene expression when both VDRE1 and VDRE2 were present. Examination of the individual VDREs showed that inhibition by 10−8 M 1,25(OH)2D3 was only 35–40% when just VDRE1 was present. By itself, VDRE2 was even less effective, as significant inhibition of CAT activity (20%) was observed only in the presence of higher concentrations of 1,25(OH)2D3 (10−7 M) or when a plasmid vector that overexpressed the VDR protein was cotransfected. In conclusion, the rPTH gene contains two negative VDREs that act in concert to bind two RXR/VDR heterodimer complexes and that both VDREs are required for maximal inhibition by 1,25(OH)2D3.