bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of Trabecular Bone Structure with Age, Bone Mineral Density, and Osteoporotic Status: In Vivo Studies in the Distal Radius Using High Resolution Magnetic Resonance Imaging
Authors: Majumdar S. , Genant H. K. , Grampp S. , Newitt D. C. , Truong V.-H. , Lin J. C. , Mathur A. 
Published: April 2006

Abstract
High resolution magnetic resonance (MR) images of the distal radius were obtained at 1.5 Tesla in premenopausal normal, postmenopausal normal, and postmenopausal osteoporotic women. The image resolution was 156 μm in plane and 700 μm in the slice direction; the total imaging time was ∼16 minutes. An intensity-based thresholding technique was used to segment the images into trabecular bone and marrow, respectively. Extensions of standard stereological techniques were used to derive measures of trabecular bone structure from these segmented images. The parameters calculated included apparent measures of trabecular bone volume fraction, trabecular thickness, trabecular spacing, and trabecular number. Fractal-based texture parameters, such as the box-counting dimension, were also derived. Trabecular bone mineral density (BMD) and cortical bone mineral content (BMC) were measured in the distal radius using peripheral quantitative computed tomography (pQCT). In a subset of patients, spinal trabecular BMD was measured using quantitative computed tomography (QCT). Correlations between the indices of trabecular bone structure measured from these high-resolution MR images, age, BMD, and osteoporotic fracture status were examined. Cortical BMC and trabecular BMD at the distal radius, spinal BMD, trabecular bone volume fraction, trabecular thickness, trabecular number, and fractal dimension all decreased with age. Trabecular spacing showed the greatest percentage change and increased with age. In addition, significant differences were evident in spinal BMD, radial trabecular BMD, trabecular bone volume fraction, trabecular spacing, and trabecular number between the postmenopausal nonfracture and the postmenopausal osteoporotic subjects. Trabecular spacing and trabecular number showed moderate correlation with radial trabecular BMD but correlated poorly with radial cortical BMC. High resolution MR imaging, a potentially useful tool for quantifying trabecular structure in vivo, may have applications for understanding and evaluating skeletal changes related to age and osteoporosis.
A Preliminary Evaluation of the Lunar Expert-XL for Bone Densitometry and Vertebral Morphometry
Authors: Lang Thomas , Takada Masahiko , Gee Richard , Wu Chun , Li Jiao , Hayashi-Clark Cynthia , Schoen Susan , March Vesta , Genant Harry K. 
Published: April 2006

Abstract
We have evaluated the Lunar Expert-XL for standard bone mineral densitometry (BMD) and for morphometric imaging of the spine in the lateral projection. The short-term precision in vitro of the Expert-XL for BMD measurements was 0.7% for the Hologic and European spine phantoms, and the long-term stability (15-month) measurements had a 1.1% coefficient of variation. The precision in vivo for three operators examining a group of 10 premenopausal women was 0.9–1.5% for lumbar spine (L2–L4), 1.7–2.2% for the femoral neck, and 0.9% for the total hip region of interest. For a group of nine postmenopausal women, the lumbar spine, femoral neck, and total femur precision ranges were 2.0–2.4, 1.2–2.9, and 1.6–1.7% respectively. For L2–L4, BMD comparison between the Expert-XL and DPX-L yielded a correlation coefficient of r = 0.98, a slope of 0.86, and an intercept of 0.139 g/cm2. The femoral neck results were r = 0.92, slope = 1.00, and intercept = 0.03 g/cm2. In an evaluation of the Expert-XL for lateral morphometry, we employed a group of 16 postmenopausal women. Comparison of vertebral dimensions between the Expert-XL and radiographic morphometry showed strong agreement (r = 0.97), but the interobserver variability for vertebral height was higher for the Expert-XL than for radiographs (3–5% vs. 1–2%). In a subset of four women who had repeat scans, the interscan precision for measuring vertebral dimensions was 1.9, 4.1, and 4.3% for the L1–L4, T12–T8, and T7–T5 levels respectively. In the Expert-XL images, it was possible to identify clearly L4–T4 in 10 of 16 patients and L4–T6 in 15 of 16, indicating potential utility for vertebral fracture prescreening.
Pulsating Fluid Flow Stimulates Prostaglandin Release and Inducible Prostaglandin G/H Synthase mRNA Expression in Primary Mouse Bone Cells
Authors: Klein-Nulend Jenneke , Burger Elisabeth H. , Semeins Cornelis M. , Raisz Lawrence G. , Pilbeam Carol C. 
Published: April 2006

Abstract
Bone tissue responds to mechanical stress with adaptive changes in mass and structure. Mechanical stress produces flow of fluid in the osteocyte lacunar-canalicular network, which is likely the physiological signal for bone cell adaptive responses. We examined the effects of 1 h pulsating fluid flow (PFF; 0.7 ± 0.02 Pa, 5 Hz) on prostaglandin (PG) E2, PGI2, and PGF2α production and on the expression of the constitutive and inducible prostaglandin G/H synthases, PGHS-1, and PGHS-2, the major enzymes in the conversion of arachidonic acid to prostaglandins, using mouse calvarial bone cell cultures. PFF treatment stimulated the release of all three prostaglandins under 2% serum conditions, but with a different time course and to a different extent. PGF2α was rapidly increased 5–10 minutes after the onset of PFF. PGE2 release increased somewhat more slowly (significant after 10 minutes), but continued throughout 60 minutes of treatment. The response of PGI2 was the slowest, and only significant after 30 and 60 minutes of treatment. In addition, PFF induced the expression of PGHS-2 but not PGHS-1. One hour of PFF treatment increased PGHS-2 mRNA expression about 2-fold relative to the induction by 2% fresh serum given at the start of PFF. When the addition of fresh serum was reduced to 0.1%, the induction of PGHS-2 was 8- to 9-fold in PFF-treated cells relative to controls. This up-regulation continued for at least 1 h after PFF removal. PFF also markedly increased PGHS activity, measured as the conversion of arachidonic acid into PGE2. One hour after PFF removal, the production of all three prostaglandins was still enhanced. These results suggest that prostaglandins are important early mediators of the response of bone cells to mechanical stress. Prostaglandin up-regulation is associated with an induction of PGHS-2 enzyme mRNA, which may subsequently provide a means for amplifying the cellular response to mechanical stress.
Strain Gradients Correlate with Sites of Exercise-Induced Bone-Forming Surfaces in the Adult Skeleton
Authors: Judex Stefan , Gross Ted S. , Zernicke Ronald F. 
Published: April 2006

Abstract
Physical activity is capable of increasing adult bone mass. The specific osteogenic component of the mechanical stimulus is, however, unknown. Using an exogenous loading model, it was recently reported that circumferential gradients of longitudinal normal strain are strongly associated with the specific sites of periosteal bone formation. Here, we used high-speed running to test this proposed relation in an exercise model of bone adaptation. The strain environment generated during running in a mid-diaphyseal tarsometatarsal section was determined from triple-rosette strain gages in six adult roosters (&gt;1 year). A second group of roosters was run at a high speed (1500 loading cycles/day) on a treadmill for 3 weeks. Periosteal surfaces were activated in five out of eight animals. Mechanical parameters as well as periosteal activation (as measured by incorporated fluorescent labels) were quantified site-specifically in 12 30° sectors subdividing a mid-diaphyseal section. The amount of periosteal mineralizing surface per sector correlated strongly (R2 = 0.63) with the induced peak circumferential strain gradients. Conversely, peak strain magnitude and peak strain rate were only weakly associated with the sites of periosteal activation. The unique feature of this study is that a specific mechanical stimulus (peak circumferential strain gradients) was successfully correlated with specific sites of periosteal bone activation induced in a noninvasive bone adaptation model. The knowledge of this mechanical parameter may help to design exercise regimens that are able to deposit bone at sites where increased structural strength is most needed.
Mechanism of the Mitogenic Effect of Fluoride on Osteoblast-like Cells: Evidences for a G Protein–Dependent Tyrosine Phosphorylation Process
Authors: Caverzasio Joseph , Palmer Gaby , Suzuki Atsushi , Bonjour Jean-Philippe 
Published: April 2006

Abstract
Recent results indicate that a fluoroalumino complex (AlFx) is probably the molecule responsible for the mitogenic effect of fluoride in MC3T3-E1 osteoblast-like cells. Initial analysis suggested that a tyrosine phosphorylation (tyr phos) process similar to that induced by thrombin and activation of the p42 MAP kinase (ERK 2) mediate this cellular response. In the present study, the signaling mechanism activated by AlFx was further investigated. The results indicated that AlFx dose-dependently enhanced the tyr phos of the cell adhesion proteins FAK and paxillin, as well as of the adaptor molecules p46shc, p52shc, and p66shc and their association with GRB2. Pretreatment of MC3T3-E1 cells with cytochalasin D completely prevented FAK and paxillin tyr phos without any alteration in the tyr phos of Shc proteins and activation of ERK2 induced by AlFx. This observation suggests that in confluent MC3T3-E1 cells, there is no link between the activation of FAK induced by AlFx and the stimulation of ERK2. Pretreatment of the cells with pertussis toxin inhibited Shc phosphorylation, activation of ERK2, and markedly reduced cell replication induced by AlFx. This toxin also significantly reduced the stimulation of Pi transport activity induced by AlFx in these cells. Alteration in tyr phos induced by AlFx was not associated with any detectable inhibition of tyrosine phosphatase activity in MC3T3-E1 cell homogenates, suggesting that enhanced tyr phos induced by AlFx probably resulted from activation of a tyrosine kinase. In conclusion, the results of this study suggest that the mitogenic effect of fluoride in MC3T3-E1 osteoblast-like cells is mediated by the activation of a pertussis toxin–sensitive Gi/o protein and suggest an important role for these heterotrimeric G proteins in controlling the growth and differentiation of bone-forming cells.
Parathyroid Hormone Up-Regulation of Connexin 43 Gene Expression in Osteoblasts Depends on Cell Phenotype
Authors: Schiller Paul C. , Roos Bernard A. , Howard Guy A. 
Published: April 2006

Abstract
Accumulating evidence indicates that gap junctions, primarily composed of connexin 43 (Cx43), are distributed extensively throughout bone. We have previously reported that in osteoblastic cells parathyroid hormone (PTH) increases both the steady-state levels of transcripts for Cx43 and gap-junctional intercellular communication in a process involving cyclic adenosine monophosphate (cAMP). We now present data showing that the mechanism of stimulation of Cx43 gene expression by PTH involves an increased rate of Cx43 gene transcription without affecting Cx43 transcript stability in UMR 106 osteoblastic cells. Activation of the protein kinase C pathway is not involved in this process. Inhibiting translation consistently decreases the PTH-mediated stimulation of Cx43 gene expression at all the times we tested (1–3 h). However, this effect is only partial, demonstrating that de novo protein synthesis is required for full stimulation. PTH increases the steady-state levels of Cx43 mRNA in several osteoblastic cell lines, albeit to different levels. We were unable to detect PTH stimulation in ROS 17/2.8 osteoblastic cells, suggesting that the effect of PTH on Cx43 gene expression may depend on the developmental state of the cell along the osteoblastic differentiation pathway. In the MC3T3-E1 preosteoblastic cell line, we find that PTH increases Cx43 gene expression in proliferating and maturing osteoblastic cells, but not in nondividing, differentiated osteoblasts, where the basal level of Cx43 gene expression is elevated. Unlike PTH, the osteotropic hormones 1,25-dihydroxyvitamin D3 and 17β-estradiol do not appear to affect Cx43 gene expression in UMR 106 osteoblastic cells.
Establishment of an Osteocyte-like Cell Line, MLO-Y4
Authors: Kato Yoichi , Windle Jolene J. , Koop Barbara A. , Mundy Gregory R. , Bonewald Lynda F. 
Published: April 2006

Abstract
Although osteocytes are the most abundant cells in bone, their functional role remains unclear. In part, this is due to lack of availability of osteocyte cell lines which can be studied in vitro. Since others have shown that cell lines can be readily developed from transgenic mice in which the SV40 large T-antigen oncogene is expressed under the control of a promoter which targets the cells of interest, we used this approach to develop an osteocyte cell line. We chose as a promoter osteocalcin, whose expression is essentially limited to bone cells and which is expressed more abundantly in osteocytes than in osteoblasts. From these transgenic mice, we isolated cells from the long bones using sequential collagenase digestion and maintained these cells on collagen-coated surfaces which are optimal for osteocyte maintenance and growth. We describe here the properties of a cell line cloned from these cultures, called MLO-Y4 (for murine long bone osteocyte Y4). The properties of MLO-Y4 cells are very similar to primary osteocytes. Like primary osteocytes and unlike primary osteoblasts, the cell line produces large amounts of osteocalcin but low amounts of alkaline-phosphatase. The cells produce extensive, complex dendritic processes and are positive for T-antigen, for osteopontin, for the neural antigen CD44, and for connexin 43, a protein found in gap junctions. This cell line also produces very small amounts of type I collagen mRNA compared with primary osteoblasts. MLO-Y4 cells lack detectable mRNA for osteoblast-specific factor 2, which appears to be a positive marker for osteoblasts but may be a negative marker for osteocytes. This newly established cell line should prove useful for studying the effects of mechanical stress on osteocyte function and for determining the means whereby osteocytes communicate with other bone cells such as osteoblasts and osteoclasts.
Unweighting Accelerates Tidemark Advancement in Articular Cartilage at the Knee Joint of Rats
Authors: Dr. O'Connor Kim M. 
Published: April 2006

Abstract
Morphologic development of articular cartilage is influenced by biologic adaptation to functional demands. It has been theorized that intermittent stresses generated by load bearing and motion determine cartilage thickness by controlling advancement of the subchondral mineralization front. The mineralization front is comprised of two interfaces, the tidemark and chondroosseus junction, each of which advances through a different biologic process. This study was designed to evaluate the influence of one month of hind limb unweighting, with and without concurrent restriction of joint motion, on mineral apposition at the tidemark and vascular invasion at the chondroosseus junction in the knee joints of young adult rats. In mobile joints, hind limb unweighting induced a 2-fold increase in the tidemark mineral apposition rate (p = 0.0001) at the primary weight bearing region, resulting in a thinning of the uncalcified cartilage layer and a concurrent thickening of the calcified layer. Cast immobilization negated the effect of unweighting at the tidemark while it activated subchondral vascular encroachment into the calcified cartilage (p = 0.001). These findings suggest that cartilage thinning associated with the elimination of weight bearing is mediated through a different biological mechanism than cartilage loss associated with restriction of joint motion.
The Usefulness of Bone Turnover in Predicting the Response to Transdermal Estrogen Therapy in Postmenopausal Osteoporosis
Authors: Dr. Gonnelli S. , Cepollaro C. , Pondrelli C. , Martini S. , Monaco R. , Gennari C. 
Published: April 2006

Abstract
Transdermal estrogen therapy is now an accepted form of treatment for postmenopausal osteoporosis. Ninety postmenopausal osteoporotic women were randomized to receive either transdermal estrogen (0.05 mg/day 17β-estradiol) and calcium (n = 45) or calcium alone (n = 45). The study period was 2 years. Bone mineral density (BMD) at the lumbar spine (by dual-energy X-ray absorptiometry [DXA]) and markers of bone turnover (alkaline phosphatase, osteocalcin, hydroxyproline, pyridinoline cross-links) were assessed at baseline and after 1 and 2 years. In the estrogen-treated group, BMD showed a significant increase (p &lt; 0.001) both after 1 and 2 years, with a reduction in biochemical markers. To investigate the effectiveness of estrogen treatment of postmenopausal osteoporosis in relation to bone turnover, we also divided the patients on the basis of bone turnover, as assessed by measurement of whole body retention (WBR) of99mTc-methylene diphosphonate. WBR revealed that 26 patients had high bone turnover (HT) and 55 had low bone turnover (LT). The response to estrogen was greater in the HT patients than in the LT patients; in fact BMD increased by 5.7 and 6.6% in HT patients and by 2.6 and 2.7% in LT patients after 1 and 2 years, respectively. In conclusion, the present study demonstrates that, while the BMD decreases in the patients treated with calcium alone, 2-year treatment with transdermal estrogen increases axial BMD and that the response to estrogen treatment is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful to identify those postmenopausal osteoporotic women who may especially benefit from treatment with estrogen.
New Aspects of Endochondral Ossification in the Chick: Chondrocyte Apoptosis, Bone Formation by Former Chondrocytes, and Acid Phosphatase Activity in the Endochondral Bone Matrix
Authors: Roach Helmtrud I. 
Published: April 2006

Abstract
A detailed histological study of the growth plates from 9− to 20-day-old embryonic chick long bones was carried out with the aim of clarifying the long-debated question of the fate of the hypertrophic chondrocytes. Since resorption in chick bones does not occur synchronously across the plate as it does in mammals, specialized regions develop and the fate of the chondrocyte depends on its location within the growth plate. Where resorption took place, as at the sites of primary vascular invasion or at the main cartilage/marrow interface, chondrocytes underwent apoptosis before the lacunae were opened. In addition, spontaneous apoptosis of chondrocytes occurred at apparently random sites throughout all stages of chondrocyte differentiation. In older chick bones, a thick layer of endochondral bone matrix covered the cartilage edge. This consisted of type I collagen and the typical noncollagenous bone proteins but, in addition, contained tartrate-resistant acid phosphatase in the mineralized matrix. Where such matrix temporarily protected the subjacent cartilage from resorption, chondrocytes differentiated to bone-forming cells and deposited bone matrix inside their lacunae. At sites of first endochondral bone formation, some chondrocytes underwent an asymmetric cell division resulting in one daughter cell which underwent apoptosis, while the other cell remained viable and re-entered the cell cycle. This provided further support for the notion that chondrocytes as well as marrow stromal cells give rise to endochondral osteoblasts.
Influence of Physical Activity on Vertebral Deformity in Men and Women: Results from the European Vertebral Osteoporosis Study
Authors: Silman A. J. , O'Neill T. W. , Cooper C. , Kanis J. , Felsenberg D. 
Published: April 2006

Abstract
Physical activity is associated with an increased bone mass and a reduced risk of hip fracture. There are, however, no data from population samples of men and women concerning the effect of regular levels of physical activity on the risk of vertebral deformity. The aim of this study was to determine the relationship between regular physical activity and vertebral deformity in European men and women. A population survey method was used. Thirty-six centers from 19 European countries participated. Each center recruited a population sample of men and women aged 50 years and over. Those who took part received an interviewer-administered questionnaire and lateral thoracolumbar radiographs. Subjects were asked about two dimensions of physical activity: (1) the level of physical activity undertaken either at work or at home on a daily basis at three different age periods: 15–25 years, 25–50 years, and 50+ years; and (2) the amount of time spent walking or cycling out of doors each day. Spinal radiographs were evaluated morphometrically and the presence of vertebral deformity was defined according to the McCloskey method. In total, 14,261 subjects, aged 50–79 years, from 30 centers were studied, of whom 809 (12.0%) men and 884 (11.7%) women had one or more deformities. After adjusting for age, center, smoking, and body mass index, very heavy levels of activity in all three age groups were associated with an increased risk of vertebral deformity in men (odds ratios, age adjusted [OR], 1.5–1.7; with all 95% confidence intervals [CI] excluding unity). No increased risk was observed in women. Current walking or cycling more than ½ h/day was associated with a reduced risk of vertebral deformity in women (OR 0.8; 95% CI 0.7–1.0). We conclude that regular walking in middle-aged and elderly women is associated with a reduced risk of vertebral deformity. By contrast, heavy levels of physical activity in early and middle adult life are associated with an increased risk in men. These differences are of relevance in understanding the epidemiology of vertebral deformity and planning programs of prevention.