bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of aerobic training on bone mineral density of postmenopausal women
Authors: Martin Daniel , Notelovitz Morris 
Published: February 2010

Abstract
A total of 76 women were enrolled and 55 naturally postmenopausal women completed a 12 month study investigating the effects of aerobic training plus calcium supplementation on lumbar (L2–4) bone mineral density (BMD) and forearm BMD. Training was conducted on treadmills at 70–85% of maximal heart rate for 30 or 45 minutes, three times per week for 12 months. Lumbar BMD was measured with dual-photon absorptiometry and forearm BMD with single-photon absorptiometry. Groups were similar with respect to age, weight, months since menopuase, height, maximal oxygen uptake (Vo2max), and lumbar and forearm BMD upon entering the study. Following training, percentage changes in Vo2max were significantly different between the control and exercise groups but not between exercise groups. ANOVA evaluating lumbar BMD revealed a nonsignificant interaction effect and no significant changes (p &gt; 0.05) between groups or times. The control (N = 19), 30 minute (N = 20), and 45 minute (N = 16) groups percentage lumbar BMD changes (X ± SD) over 12 months were -0.61 ± 3.40, -0.48 ± 3.63, and 0.81 ± 4.53%, respectively. The 95% confidence limits for percentage changes in lumbar BMD for the control, 30 minute, and 45 minute groups were -2.25 to 1.02, -2.18 to 1.22, and -1.16 to 3.22%, respectively. Forearm BMD changes were also not significant. Improvement in lumbar BMD was weakly but positively correlated with improvements in VO2max, r = 0.28, p &lt; 0.05. Women ≤ 6 years of the onset of menopause had an accelerated lumbar BMD loss compared to subjects who were &gt;6 years postmenopausal, and this subset's BMD changes were examined. The recently postmenopausal control subjects' (N = 7) lumbar BMD mean percentage change was -3.36 ± 1.53 versus -1.67 ± 1.75% for the 11 recently postmenopausal exercise (30 + 45 minute groups) subjects, p &lt; 0.05. None of the forearm BMD changes in the recently menopausal subset were significant. Thus, although 12 months of aerobic exercise training did not result in significant increases in forearm or lumbar BMD, training attenuated lumbar BMD loss in women who were ≤ 6 years of the onset of the menopause.
Effects of endurance exercise on bone mass and mechanical properties in intact and ovariectomized rats
Authors: Barengolts E.I. , Curry D.J. , Bapna M.S. , Kukreja S.C. 
Published: February 2010

Abstract
Exercise may play a role in the prevention of bone fractures in postmenopausal osteoporosis. The effects of endurance exercise on bone properties were assessed in 9-month-old sham-operated (SH) and ovariectomized (OVX) rats. The rats were either kept sedentary (SED) or were exercised (EX) on a rodent treadmill at 21 m/minute, 7% grade, 40 minutes/day, 4 days/week for 3 months. Bone mineral (by ash weight), morphometry, and biomechanical properties (by three-point bending) were evaluated after excision of bones at sacrifice. Ovariectomy resulted in a loss of bone mineral in femur, tibia, and fourth lumbar vertebra (L4), but biomechanical (force, deformation, stress, strain, and modulus of elasticity) and morphometric (length, cortial and medullary area, and moment of inertia) properties of femur were maintained. The ash weight of femur and tibia, but not L4, as well as femur yield and maximum force and moment of inertia, were improved in OVX-EX rats compared to OVX-SED animals. In SH rats exercise had no influence on ash weight of any of the three bones or femur morphometric properties, yet femur maximum force and plastic deformation were significantly enhanced compared to SH-SED rats. The results of the present study suggest that endurance exercise has beneficial effects on the bone mineral as well as biomechanical properties (femur yield and maximum force) during early stages after ovariectomy and improves the bending strength of the intact femur without an effect on bone mineral in sham-operated rats.
Endothelin-1 modulates calcium signaling by epidermal growth factor, α-thrombin, and prostaglandin E1 in UMR-106 osteoblastic cells
Authors: Tatrai Agnes , Stern Paula H. 
Published: February 2010

AbstractLocal factors play an important role in the regulation of bone metabolism. The homologous and heterologous desensitization of responses to these factors may be crucial in the modulation of bone cell signaling. In this study, the effects and interactions of endothelin-1 (25 nM), α-thrombin (0.9 μM), epidermal growth factor (40 nM), prostaglandin E1 (5 μM), and prostaglandin F1α (5 μM) were examined on calcium signaling in UMR-106 rat osteoblastic osteosarcoma cells. Intracellular calcium was measured using fluo-3 fluorescent dye. All agents elicited calcium transients at these concentrations and showed homologous desensitization to their repeated administration. Preincubation for 60 minutes with 500 μM monodansylcadaverine and 30 minutes or 24 h preincubation with 0.5 μM indomethacin did not affect homologous desensitization, suggesting that neither the internalization of receptors nor prostaglandins are involved in this event. Pretreatment for 3 minutes with 2 μM 4β-phorbol-12β,13α-dibutyrate significantly reduced the calcium elevations elicited by the first application of these compounds, whereas an inactive phorbol, 12,13-didecanoate, had no effect. Pretreatment for 4 minutes with 0.5 μM forskolin decreased the calcium signal response to PGE, only. Pretreatment with endothelin-1 for 3 minutes significantly decreased the calcium signals elicited by epidermal growth factor and α-thrombin. Prior administration of endothelin-1 significantly increased prostaglandin E1-stimulated calcium transients, whereas prostaglandin F1α responses were not affected. Preincubation with indomethacin did not alter any of the interactions. Responses to endothelin-1 were not significantly altered by 2–3 minutes pretreatment with the other factors, nor was there cross-desensitization among the other factors. The results could indicate that endothelin-1 has a unique and specific role in the modulation of bone cell signaling.
Role of the negative glucocorticoid regulatory element in glucocorticoid repression of the human osteocalcin promoter
Authors: Morrison Nigel , Eisman John 
Published: February 2010

Abstract
In osteoblast-like cells in culture, the human osteocalcin gene promoter basal activity is repressed by glucocorticoids, reflecting the repression of serum osteocalcin concentrations noted in syndromes of glucocorticoid excess. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the active hormonal form of vitamin D, induces the osteocalcin promoter through a vitamin D response element (VDRE), and glucocorticoids also repress the vitamin D-induced promoter. This study addresses the role of a glucocorticoid receptor (GR) binding site overlapping the TATA box of the osteocalcin promoter, which had been proposed as a negative glucocorticoid response element (nGRE), invoking a steric interference mechanism of glucocorticoid repression. Confirmation of the role of the nGRE in regulating basal activity was obtained using promoter constructs containing a TATA box swap. However, a minor component of repression of 1,25-(OH)2D3 induced activity remained in the absence of the nGRE. In addition, glucocorticoid repression of the human osteocalcin promoter was shown to be cell line specific. This result is not compatible with a simple model of repression and suggests the existence of unidentified cell-specific factors that are involved in the repression event. Repression of the osteocalcin promoter was compatible with a composite model involving both the nGRE site and glucocorticoid regulation of factors that bind the vitamin D response element.
Detection and measurement of vitamins K1 and K2 in human cortical and trabecular bone
Authors: Hodges S.J. , Bejui J. , Leclercq M. , Delmas P.D. 
Published: February 2010

Abstract
Vitamin K plays an essential role in the gamma carboxylation of the gla-containing proteins of bone matrix, such as osteocalcin. We have measured the concentration of vitamin K1 (VK) and of the menaquinones MK-6, MK-7, and MK-8, the three major vitamin K2 moieties, in trabecular and cortical bone taken from the femoral neck of patients undergoing hip replacement. Both bone compartments were found to contain large amounts of VK, MK-6, MK-7, and MK-8. Concentrations were as high as those reported for the liver, the major storage organ for vitamin K. Further research is required to examine the association between vitamin K in bone and the gamma carboxylation of vitamin K-dependent bone proteins.
Oscillations in inositol 1,4,5-trisphosphate and diacyglycerol induced by vitamin D3 metabolites in confluent mouse osteoblasts
Authors: Grosse Brigitte , Bourdeau Agnès , Dr. Lieberherr Michèle 
Published: February 2010

Abstract
For the last 5 years, attention has focused on the nongenomic effects of 1,25-(OH)2D3, but considerably less is known about the mechanisms of the nonnuclear actions of 24,25-(OH)2D3. The present study examines and compares the rapid (5–90 s) effects of 100 pM to 10 nM 24,25-(OH)2D3, 10 pM to 1 nM 1,25-(OH)2D3, and 1–100 nM 25-OHD3 on the formation of inositol phosphates and lipids in confluent mouse osteoblasts. 24,25-(OH)2D3 and 25-OHD3 effects were dose dependent; those of 1,25-(OH)2D3, were dose dependent in a bell-shaped manner. The two dihydroxylated metabolites induced a multiphasic response in inositol 1,4,5-trisphosphate (IP3) formation with three stimulation peaks; the IP3 response to 25-OHD3 was monophasic. The amplitude of the IP3 response to 24,25-(OH)2D3 was greater and its oscillation period was slower than that induced by 1,25-(OH)2D3. The diacylglycerol (DAG) responses to secosteroids showed two stimulation peaks that appeared at different times depending on the secosteroid used. Pretreatment with neomycin totally inhibited the first DAG response; neomycin had no effect on the second peak of DAG induced by 25-OHD3, whereas it partially blocked the second response of DAG to 24,25-(OH)2D3 and 1,25-(OH)2D3. These data show for the first time that 24,25-(OH)2D3 can modulate phospholipid metabolism in confluent mouse osteoblasts as early as 5–10 s. The first pathway used by all three secosteroids is that of the hydrolysis of phosphatidylinositol 4,5-bisphosphate via phospholipase C activation, leading to the formation of the two second messengers, IP3 and DAG, since neomycin totally blocked the response. Thus, the action of these secosteroids on the osteoblast membrane may also implicate several steps of the phosphatidylcholine cycle, according to the metabolite tested. Finally, these data point to a direct interaction of vitamin D metabolites with specific membrane recognition moieties.
Human parathyroid hormone (1–34) and (1–84) increase the mechanical strength and thickness of cortical bone in rats
Authors: Dr. Ejersted Charlotte , Andreassen T.T. , Oxlund H. , Jørgensen P.H. , Bak B. , Häggblad J. , Tørring O. , Nilsson M.H.L. 
Published: February 2010

Abstract
An anabolic effect on bone of intermittent parathyroid hormone (PTH) treatment has been found in patients with osteoporosis and also in experimental animals. Controversies exist, however, about whether the positive effect on the trabecular bone balance occurs at the expense of the cortical bone. We examined the biomechanical quality of cortical bone after intermittent treatment with different doses of PTH and, furthermore, compared the effects of PTH-(1–34) and PTH-(1–84). Groups of rats were treated with biosynthetic human PTH-(1–34) or PTH-(1–84), 1.1, 3.3, 10, or 30 nmol/kg/day for 30 days. No changes in the body weights and no changes in the lengths of the femora were observed after the PTH treatments. The bio-mechanical properties were analyzed by means of a materials-testing machine. A dose-related increase in the bending strength and stiffness of the femora was found, and this increase in mechanical strength corresponds with a 9–12% increase in the cross-sectional area of the femoral diaphyses. The deflection capability and energy absorption were not influenced by any of the PTH treatments. No differences were found between the effects of PTH-(1–34) or PTH-(1–84) on the biomechanical properties of the femora. Consequently, intermittent treatment with biosynthetic PTH-(1–34) or PTH-(1–84) increased the formation of cortical bone, and the biomechanical competence of the femora was found to be preserved.
Influence of exercise on cancellous bone of the aged female rat
Authors: Yeh James K. , Aloia John F. , Chen Meng M. , Tierney Joan M. , Sprintz Sharon 
Published: February 2010

Abstract
Dual-energy x-ray absorptiometry and dynamic histomorphometry were used to examine the effect of treadmill exercise on the bone density and cancellous bone formation and resorption in the proximal tibia and fifth lumbar vertebra (L5) of the aged female rat. Female rats aged 14 months were divided into four groups: 8 controls and 10 exercised for a 9 week study and 8 controls and 9 exercised for a 16 week study. Exercise consisted of running on a flat-bed treadmill, 17 m/minute, 1 h/day, 5 days/week. Tibial metaphysis and L5 vertebral density of each rat were measured in the 16 week study by DXA at weeks 0, 9, and 16. Compared to the control group, a significant increase in bone density in both metaphyseal tibia and L5 vertebra was apparent at 16 weeks after exercise training (P = 0.046 and 0.025, respectively, by two-way ANOVA). Histomorphometric analysis showed that the trabecular bone eroded surface and the ratio of eroded to mineralizing surface in tibial metaphysis were significantly lower in the exercised than in the respective control group in both the 9 and 16 week studies. In L5 vertebra, these decreases by exercise were apparent only in the 16 week study. A significant increase in the bone formation rate was apparent in the cancellous bone of the tibia but not of the vertebra after 16 weeks of exercise (P &lt; 0.05). The trabecular architecture (bone number and separation) of the L5 vertebra in the exercised rats did not differ from that of the controls in either study. The trabecular bone volume and trabecular number of the tibial metaphysis were higher and the separation was less in the exercised rats but not significantly different from the control at each time point. In conclusion, it was demonstrated that the tibial metaphyseal and L5 vertebral bone density were higher in the treadmill-exercised than in the nonexercised adult rat. Increased bone formation and suppressed resorption could account for the beneficial effect of exercise on cancellous weight-bearing bone. In cancellous non-weight-bearing bone, it could be primarily in suppressing bone resorption and inhibiting age-related loss.
Vertebral fracture assessment using a semiquantitative technique
Authors: Genant Harry K. , Wu Chun Y. , van Kuijk Cornelis , Nevitt Michael C. 
Published: February 2010

Abstract
The assessment of vertebral fracture by conventional radiography has been refined and improved using either semiquantitative or quantitative criteria. The inter- and intraobserver variability was determined for a semiquantitative visual approach that we routinely use in clinical studies for assessing prevalent and incident vertebral fractures. In addition, the semiquantitative approach was compared with a quantitative morpho-metric approach. The incidence and prevalence of vertebral fractures were determined in 57 postmenopausal women (age 65–75 years) by three independent observers. The radiographic basis for fracture definitions and the source of interpretative errors are illustrated. The results show excellent intraobserver agreement and good interobserver agreement for the semiquantitative technique. We conclude that the semiquantitative approach can be applied reliably in vertebral fracture assessment when performed using well-defined criteria.
Rapid publication: Flanking markers define the X-linked hypophosphatemic rickets gene locus
Authors: Econs Michael J. , Fain Pamela R. , Norman Michael , Speer Marcy C. , Pericak-Vance Margaret A. , Becker Peggy A. , Barker David F. , Taylor Arlene , Drezner Marc K. 
Published: February 2010

Abstract
X-linked hypophosphatemic rickets (HYP) is an X-linked dominant disorder characterized by decreased renal tubular phosphate reabsorption and consequent hypophosphatemia. The defect in tubular phosphate reabsorption is probably secondary to an unidentified humoral factor. Identification of the humoral factor and a full understanding of the pathophysiology of the disease await the identification of the HYP gene. Previously we demonstrated that DXS257 and DXS41 are flanking markers for the HYP gene. Two markers, DXS365 and DXS274, are tightly linked to the HYP gene, but investigators have been unable to determine whether they are centromeric or telomeric to the disease gene. Since tightly linked flanking markers are necessary prerequisites to obtain the gene by positional cloning techniques, we sought to determine the relative positions of these markers to the HYP gene by expanding our data base for linkage studies. We also investigated a new polymorphic probe for linkage to HYP to construct a more detailed genetic map around the HYP locus. Our data indicate that the markers DXS365, DXS274, and DXS92 are tightly linked to the HYP locus and suggest a locus order of Xtel-(DXS444/DXS315)-DXS43-(DXS257/DXS365)-HYP-(DXS274/DXS41/DXS92)-DXS451-DXS319-Xcen. These results will facilitate attempts further to localize and clone the HYP gene.
PCR detection of cytokines in normal human and pagetic osteoblast-like cells
Authors: Birch M.A. , Ginty A.F. , Walsh C.A. , Fraser W.D. , Gallagher J.A. , Bilbe G. 
Published: February 2010

Abstract
We investigated the expression of cytokine transcripts in osteoblast-like cells derived from explants of pagetic and normal bone. A reverse transcription-linked PCR was used that allowed the simultaneous analysis of a range of cytokines. Normal osteoblast-like cells were found to contain the transcripts for IL-1β, IL-6, and TGF-β1. For the first time we detected in bone cells the two other mammalian isoforms of TGF-β, β2, and β3. Furthermore, we have also identified mRNA for IL-3 and the novel chemotactic factor, IL-8. Using this sensitive technique it was not possible to detect mRNA for IL-1α, IL-2, IL-4, IL-5, IL-7, TNF-α, or interferon-γ. The human osteosarcoma cell line Saos-2 also showed a similar pattern of expression of these cytokines to primary osteoblast-like cells, with the exception that TNF-α was also identified. Cells isolated from pagetic bone showed essentially the same profile of cytokine expression as normal bone except that TNF-α was also detected in two of four samples. The cytokine profile of successive populations of cells harvested from one explant culture at 9, 22, and 57 days showed a consistent pattern of cytokine expression, demonstrating the phenotypic stability of the osteoblast-like cells in long-term cultures.
Preliminary characterization of porcine bone marrow stromal cells: Skeletogenic potential, colony-forming activity, and response to dexamethasone, transforming growth factor β, and basic fibroblast growth factor
Authors: Dr. Thomson B.M. , Bennett J. , Dean V. , Triffitt J. , Meikle M.C. , Loveridge N. 
Published: February 2010

AbstractNeonatal pig bone marrow stromal cells (PBMSC) were tested in vivo and in vitro to establish their use as a large-animal model for the study of skeletogenesis. When implanted in diffusion chambers in athymic mice for 6–8 weeks, both freshly isolated pig bone marrow and passage 2 PBMSC formed partially mineralized cartilage, bone-like material, and fibrous tissue. The cartilage showed metachromatic, perilacunar staining with toluidine blue and safronin O, alcian blue staining for chondroitin and keratan sulfate, and intense immunostaining for type II collagen. Osteocalcin was immunolocalized to the mineralized regions, consistent with the formation of bone. Alkaline phosphatase was primarily observed in cell layers at boundaries between tissue types. Unstimulated monolayer cultures of PBMSC produced type I but not type II collagen, responded to dexamethasone (10−8 M) with a 1.7-fold increase in alkaline phosphatase activity, and were stimulated to divide by basic fibroblast growth factor (1.5-fold; EC50 1 ng/ml). Transforming growth factor β (TGF-β) blocked both dexamethasone-induced alkaline phosphatase expression (EC50, 1 ng/ml of TGF-β) and the mitogenic effects of bFGF (EC50 0.06 ng/ml of TGF-β). When incubated for 10–14 days in medium containing dexamethasone, β-glycerophosphate and ascorbate PBMSC formed mineralized nodules. Calcification occurred in the middle of the aggregates and was associated with intensely alkaline phosphatase positive cells and a dense type I collagen-rich matrix. PBMSC also displayed colony-forming unit-fibroblastic activity, with approximately 1 in 80 of the plated cells formed colonies &gt; 128 cells over 14–21 days. PBMSC therefore mimic the known activities of stromal cells from other species, including the human, suggesting that they are a valid model for skeletal research.
Tumor necrosis factor α modulates parathyroid hormone action in UMR-106–01 osteoblastic cells
Authors: Hanevold C.D. , Yamaguchi D.T. , Jordan S.C. 
Published: February 2010

Abstract
Tumor necrosis factor (TNF-α) has been shown to play an important role in local control of bone remodeling. The interaction of TNF-α and PTH was evaluated in UMR-106–01 cells, a phenotypic osteoblastic osteosarcoma cell line. We examined the influence of TNF-α on the two signal transduction systems triggered by PTH in UMR-106–01 cells, adenylate cyclase and free cytosolic calcium ([Ca2+]i). cAMP generation was inhibited in TNF-α-pretreated cells by 69, 61, 34, and 21% at PTH concentrations of 0.1, 1, 10, and 100 nM, respectively. Inhibition was seen at TNF-α doses of 100–1500 units/ml after a minimum incubation time of 12 h. TNF-α inhibition of the PTH-stimulated increase in [Ca2+], was even more pronounced: treated cells showed no change in baseline [Ca2+]i, after stimulation with 40 nM PTH. Treatment with TNF-α was also found to inhibit both arms of the PTH response in the nontransformed osteoblastic cell line, MC3T3-El. TNF-α treatment did not alter cAMP generation in response to PGE2. TNF-α inhibition of the PTH-stimulated cAMP response was reversed completely by addition of cholera toxin (5 μg/ml) and partially by forskolin (10 μM) but not pertussis toxin (100 and 500 ng/ml). Scatchard analysis using PTHrP revealed that TNF-α treatment reduced the number of receptors but had no effect on KD. These findings suggest that TNF-α inhibits the osteoblastic response to PTH at least in part because of a reduction in receptor number. Further investigation is indicated to provide insight into the interaction of calciotropic hormones and cytokines in vivo.
Long-term fracture prediction by bone mineral assessed at different skeletal sites
Authors: Dr. Melton L. Joseph , Atkinson Elizabeth J. , O'Fallon W. Michael , Wahner Heinz W. , Riggs B. Lawrence 
Published: February 2010

AbstractBone mineral density (BMD) was measured at the lumbar spine and cervical and intertrochanteric regions of the proximal femur by dual-photon absorptiometry and bone mineral content was assessed at the distal and midradius by single-photon absorptiometry in an age-stratified random sample of 304 Rochester, Minnesota women aged 30–94 years. Over follow-up extending to 10 years (median 8.3 years), 93 women experienced 163 new fractures. After adjusting for age, these bone mineral measurements predicted the likelihood of any incident fracture due to moderate trauma, with relative hazards varying from 1.4 to 1.6 per SD decrease in baseline bone mineral. A 1 SD decrease in lumbar spine BMD increased the risk of a new vertebral fracture comparably to a 17 year increase in age; a 1 SD decrease in femoral BMD was comparable to a 13–14 year increase in age on the risk of a hip fracture. We conclude that bone mineral measurements made at a variety of skeletal sites can predict the occurrence for at least 8–10 years of moderate trauma fractures of the sort that might be related to osteoporosis.