bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of hip fractures from pelvic radiographs: The study of osteoporotic fractures
Authors: Glüer Claus-C. , Cummings Steven R. , Pressman Alice , Li Jiao , Glüer Kathrin , Faulkner Kenneth G. , Grampp Stephan , Genant Harry K. 
Published: February 2010

Abstract
To determine whether simple measurements made on conventional radiographs of the hip could predict hip fractures, we obtained pelvic radiographs on 9704 white women age 65 or older. We analyzed the radiographs of all 162 women who subsequently suffered a hip fracture and 162 randomly selected women who did not. Adjusting for age, four measurements independently predicted hip fracture: reduced thickness of the femoral shaft cortex (odds ratio 1.7 per standard deviation; 95% confidence interval 1.2, 2.3) and of the femoral neck cortex (1.4 per standard deviation; 1.0, 1.9), reduction in an index of tensile trabeculae (2.0 per unit; 1.4, 2.9), and wider trochanteric region (1.4 per standard deviation; 1.0, 2.0). The combination of these four measurements predicted hip fracture at least as strongly as did measurement of bone density of the femoral neck (areas of the receiver-operating characteristic curve = 0.81 and 0.80, respectively). We conclude that simple measurements made on pelvic radiographs predict hip fractures as well as bone density of the hip.
Picomolar norethindrone in vitro stimulates the cell proliferation and activity of a human osteosarcoma cell line and increases bone collagen synthesis without an effect on bone resorption
Authors: Lau William K.-H. , Wang Shu Ping , Linkhart Thomas A. , Demarest Keith T. , Baylink David J. 
Published: February 2010

Abstract
To determine how progestins increase bone formation in vivo, the effects of the synthetic progestin norethindrone (NET), on aspects of bone formation in vitro were determined. NET at picomolar concentrations in vitro stimulated the proliferation of human TE85 osteosarcoma cells as assessed by the increase in [3H]thymidine incorporation into DNA and in cell number and also stimulated the release of osteocalcin in both the presence and absence of 10 nM 1,25-(OH)2D3. NET increased cellular alkaline phosphatase specific activity (an index of osteoblastic differentiation), but at much higher concentrations, that is, nanomolar. These findings suggest that low concentrations of NET act directly on human TE85 osteosarcoma cells to stimulate their proliferation, differentiation, and cell activity. Furthermore, mitogenic doses of NET stimulated bone collagen synthesis both in a chicken calvarial organ culture assay (assessed by the incorporation and hydroxylation of [3H]proline) and in a human TE85 osteosarcoma cell culture assay (determined by the incorporation of [3H]proline into collagenase-digestible proteins). In contrast, NET at 10−6-10−12 M had no apparent effect on the rate of basal or PTH-stimulated release of 45Ca from prelabeled mouse calvariae in vitro. In summary, this study has demonstrated for the first time that picomolar NET acted directly on human TE85 osteosarcoma cells to increase (1) cell proliferation and differentiation, (2) osteoblastic activity (i.e., osteocalcin synthesis), and (3) bone collagen synthesis in vitro. The same doses of NET in vitro did not reduce the bone resorption rate under our assay conditions. In conclusion, these in vitro osteogenic activities of NET suggest that it may be a useful therapeutic agent to increase bone formation in patients with low bone mass.
Calcium signaling in endothelin- and platelet-derived growth factor-stimulated chondrocytes
Authors: Dr. Stojilkovic Stanko S. , Vukicevic Slobodan , Luyten Frank P. 
Published: February 2010

AbstractIn bovine articular chondrocytes, endothelin (ET) and platelet-derived growth factor (PDGF) receptors mediate agonist-induced increases in inositol phosphate hydrolysis, cytoplasmic calcium concentration ([Ca2+]i), and mitogenesis. In most cells, ET stimulated nonoscillatory [Ca2+]i elevations with dose-dependent increases in both spike and plateau amplitudes. However, about 15% of cells showed oscillatory Ca2+ responses with a constant frequency and variable shape and duration of spiking. ET-1 and ET-2 were more potent than ET-3 in stimulating [Ca2+]i responses in inhibiting the specific binding of 125I-ET-1 and 125I-ET-3 and in promoting internalization of the receptor-ligand complex, consistent with actions through endothelin ETA receptors. Similar nonoscillatory and oscillatory patterns of Ca2+ responses were observed in PDGF-stimulated cells. In cells showing nonoscillatory Ca2+ responses to ET-1, subsequent stimulation with PDGF was frequently followed by the development of an oscillatory Ca2+ response. Nonoscillatory responses to both agonists were only slightly reduced in Ca2+-deficient medium, but the oscillatory responses were critically dependent on Ca2+ entry. Ca2+ spiking was not altered in the presence of the voltage-sensitive Ca2+ channel blocker, nifedipine; also, depolarization of chondrocytes by high K+ did not induce [Ca2+]i responses, confirming that voltagesensitive calcium channels are not expressed in these cells. At high agonist concentrations, ET- but not PDGF-stimulated cells underwent rapid desensitization. Activation of ETA and PDGF receptors was associated with differential stimulation of thymidine incorporation; ET-1 induced a low-amplitude bell-shaped doseresponse curve; PDGF induced a sustained sigmoidal and dose-dependent rise. These data indicate that two distinct types of Ca2+-mobilizing receptors initiate similar patterns of [Ca2+]i responses but have different capacities to maintain and reinitiate the Ca2+ signaling, as well as to promote mitogenesis.
Opposite effects of osteogenic protein and transforming growth factor β on chondrogenesis in cultured long bone rudiments
Authors: Dieudonné S.C. , Semeins C.M. , Goei S.W. , Vukicevic S. , Nulend Klein J. , Sampath T.K. , Helder M. , Burger E.H. 
Published: February 2010

Abstract
Osteogenic protein-1 (OP-1, also called BMP-7) is a bone morphogenetic member of the TGF-β superfamily. In the present study, we examined the effect of recombinant human OP-1 on cartilage and bone formation in organ cultures of metatarsal long bones of mouse embryos and compared the OP-1 effects with those of human TGF-β1 and porcine TGF-β1 and β2. Cartilage formation was determined by measurement of longitudinal growth of whole bone rudiments during culture and by the incorporation of 35SO4 into glycosaminoglycans. Mineralization was monitored by 45Ca incorporation in the acid-soluble fraction and by measuring the length of the calcifying center of the rudiment. Toluidine blue-stained histologic sections were used for quantitative histomorphometric analysis. We found that OP-1 stimulated cartilage growth as determined by sulfate incorporation and that it increased remarkably the width of the long bones ends compared with controls. This effect was partly caused by differentiation of perichondrial cells into chondrocytes, resulting in increased appositional growth. In contrast to OP-1, TGF-β1 and β2 inhibited cartilage growth and reduced the length of whole bone rudiments compared with controls. In the ossifying center of the bone rudiments, both OP-1 and TGF-β inhibited cartilage hypertrophy, growth of the bone collar, and matrix mineralization. These data demonstrate that OP-1 and TGF-β exhibit opposite effects on cartilage growth but similar effects on osteogenesis in embryonic mouse long bone cultures. Since both OP-1 and TGF-β have been demonstrated in embryonic cartilage and bone, these results suggest that they act as autocrine or paracrine regulators of embryonic bone development.
Effects of transforming growth factor β on bone nodule formation and expression of bone morphogenetic protein 2, osteocalcin, osteopontin, alkaline phosphatase, and type I collagen mRNA in long-term cultures of fetal rat calvarial osteoblasts
Authors: Harris S.E. , Bonewald L.F. , Harris M.A. , Sabatini M. , Dallas S. , Feng J.Q. , Ghosh-Choudhury N. , Wozney J. , Mundy G.R. 
Published: February 2010

Abstract
Transforming growth factor β (TGF-β) is one of the most abundant of the known growth regulatory factors stored within the bone matrix. When bone is resorbed, TGF-β is released in an active form and is a powerful bone growth stimulant. When injected into the subcutaneous tissue over the calvarial surface of rodents, it rapidly causes proliferation of the periosteal layer and accumulation of new woven bone. In this report, we describe the effects of TGF-β1 on first subcultures of fetal rat osteoblasts obtained from calvarial bones and cultured from confluence with ascorbic acid and β-glycerophosphate. Under these conditions, nodules with characteristics of normal bone appear by day 8. Similar to experiments described by Antosz et al., TGF-β added to confluent cultures inhibited the formation of bone nodules. Both the number and total area of the nodules were quantitated and shown to be completely inhibited by 2 ng/ml of TGF-β1. TGF-β also impaired the expression of genes associated with bone formation, including type I collagen, alkaline phosphatase, osteopontin, and osteocalcin. TGF-β also inhibited the expression of mRNA for the bone morphogenetic protein 2 (BMP-2). These results, showing suppression of markers representative of osteoblast differentiation, suggest that the effects of TGF-β to stimulate bone formation in vivo are not likely a result of effects on differentiated mineralizing osteoblasts but, as suggested by previous studies, more likely are caused by effects on osteoblast precursors. These results also suggest that endogenous BMP-2 expression in fetal rat calvaria cells is important for bone cell differentiation.
Anabolic effect of high doses of human parathyroid hormone (1–38) in mature intact female rats
Authors: Jerome C.P. 
Published: February 2010

Abstract
Adult female retired breeder Wistar rats were treated with placebo or with synthetic human parathyroid hormone (hPTH) fragment (1–38) by subcutaneous injection at doses ranging from 50 to 1000 μg/kg, 5 days per week, for 2–8 weeks. One group of rats received hPTH-(1–38), 400 μg/kg, 5 days per week for 4 weeks, followed by 4 weeks placebo. The effects on bone mass and structure were evaluated by histomorphometric analysis of cross sections of femoral metaphyses. The effects on bone formation were evaluated by measuring uptake of [H]tetracycline into femora and by qualitative evaluation of histologic sections after labeling with calcein and tetracycline. All doses of hPTH-(1–38) were anabolic. Lamellar bone formation was stimulated on all surfaces, and cancellous bone mass was increased as a result of trabecular thickening. Small quantities of woven bone were also formed in marrow cavities after treatment with 400 or 1000 μg/kg. Treatment with 1000 μg/kg had an effect on measured parameters similar to that with 400 μg/kg, and there was no evidence for a diminution of the anabolic effect at high doses. Animals treated with hPTH-(1–38) for 4 weeks followed by 4 weeks placebo tended to have less bone than those that received hPTH-(1–38) for 8 weeks but had significantly more bone than placebo-treated rats. In conclusion, daily injection of hPTH-(1–38) for 2–8 weeks at doses ranging from 50 to 1000 μg/kg had an anabolic effect on both cortical and trabecular bone in the femur of mature female intact rats. After withdrawal of treatment, the bone formation rate fell below levels in untreated animals, but bone mass remained higher.
New model for bone resorption study in vitro: Human osteoclast-like cells from giant cell tumors of bone
Authors: Grano Maria , Colucci Silvia , De Bellis Michele , Zigrino Paola , Argentino Luigi , Zambonin Giovanni , Serra Massimo , Scotlandi Katia , Teti Anna , Prof. Zallone Alberta Zambonin 
Published: February 2010

Abstract
Cells harvested from 12 human giant cell tumors of bone and kept in culture for several passages were characterized for bone-resorbing capability, total and tartrate-resistant acid phosphatase activity, response to the calciotropic hormone calcitonin, cell proliferation, multinucleation after passages, and presence of calcium sensing. Cells obtained from three tumors presented a complete panel of osteoclast characteristics and maintained their multinuclearity after several passages. Cells from four other tumors increased their cAMP levels after treatment with calcitonin, and the other five apparently consisted of cells of stromal origin. These human cell populations with osteoclast characteristics may provide valid in vitro models for the investigation of osteoclastic differentiation and activity.
Weight-bearing activity during youth is a more important factor for peak bone mass than calcium intake
Authors: Welten D.C. , Prof. Dr Kemper H. C. G. , Post G.B. , van Mechelen W. , Twisk J. , Lips P. , Teule G.J. 
Published: February 2010

Abstract
In a 15 year longitudinal study (Amsterdam Growth and Health Study) is evaluated the effect of daily calcium intake (CAI) during adolescence and young adulthood on the development of peak bone mass at age 27 when the influence of weight-bearing activity (WBA) and body weight was accounted for. A group of 84 males and 98 females were measured longitudinally from age 13 until age 28. Measurements were taken six times of anthropometric characteristics. Lifestyle was also evaluated six times by cross-check interviews of CAI and WBA. Bone mineral density (BMD) of the lumbar spine was determined at age 27 by dual x-ray absorption. Three periods were considered, that is, the adolescent period, the period 13–21 years, and the total period (13–27 years). In multiple linear regression analyses, only WBA and body weight were significant positive contributors to the final model of lumbar BMD at age 27. In all three periods WBA was the best predictor in males and body weight in females. ANOVA was performed on BMD and the highest and lowest quartiles of calcium intake with the significant predictor variables of the linear regression model as covariates. Again calcium intake appeared not a significant predictor of BMD in the three periods in both sexes. Regular weight-bearing exercise and at least a normal age-related body weight in adolescence and young adulthood are of key importance in reaching the highest lumbar peak bone mass at the age of 27 years.
Reference data for bone mass, calciotropic hormones, and biochemical markers of bone remodeling in older (55-75) postmenopausal white and black women
Authors: Kleerekoper Michael , Nelson Dorothy A. , Peterson Edward L. , Flynn Michael J. , Pawluszka Annie S. , Jacobsen Gordon , Wilson Paulette 
Published: February 2010

Abstract
From a random sample of our institution's health maintenance organization (HMO), we recruited 250 white women and 112 black women, aged 55-75, all of whom were 10 or more years postmenopause with minimal estrogen exposure and free of osteoporosis, other metabolic bone disease, and medical, surgical, or therapeutic situations that may influence bone loss. Bone mass was measured in the radius, spine, and femur by DXA and in L1 by QCT. Serum samples were analyzed for parathyroid hormone, calcidiol, calcitriol, osteocalcin, and bone alkaline phosphatase and urine samples analyzed for creatinine, calcium, and hydroxyproline. Mean Z score, based on published reference data for forearm and femoral neck BMD in the white women, was not significantly different from zero, but mean Z score at the lumbar spine was 0.6 (p &gt; 0.001), 17.2% of the individual values being &gt;2.0. In normal white women (BMI &gt; 27.3, n = 143), Z score was still &gt;2.0 in 10.3%, suggesting that the upper bound of the published reference interval may be too low. After adjustment for body mass index, BMD was greater in the forearm (9.8%), spine (8.7%), and femoral neck (14.7%) in black women (p &gt; 0.001 at all sites). At L1, adjusted BMC in the black women was 37.4% greater than in the white women (p &gt; 0.001). Serum calcidiol was significantly lower and serum PTH and calcitriol significantly higher in the black women. Despite this, biochemical markers of bone resorption and formation were significantly lower in the black women. We conclude that skeletally healthy older black women have a greater bone mass and lower rates of bone remodeling than a comparable group of white women. These data can serve as reference intervals for the variables measured.
Profile of ligand specificity of the vitamin D binding protein for 1α,25-dihydroxyvitamin d3 and its analogs
Authors: Bishop June E. , Collins Elaine D. , Okamura William H. , Professor Norman Anthony W. 
Published: February 2010

Abstract
The profile of structural preference for the ligand binding domain of the human vitamin D binding protein (DBP) was determined by steroid competition assay of 71 analogs of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3]. The following categories of structural modification were evaluated [values represent fold change; R = reduction, I = increase in binding to the DBP from the reference 1α,25(OH)2D3]: (1) deletion in the A ring of the 1α-hydroxyl (20-1600I); (2) conversion of the triene system to the previtamin form (6-40R); (3) addition of substituents to carbon 11 of the C ring (4-14R); (4) inversion of the C/D ring junction (8-20R); (5) unsaturation of the D ring (16-ene; 4-140R); (6) replacement of hydrogen with deuterium atoms (no effect); alteration of the side chain by (7) adding or deleting carbon atoms (5-12R); (8) addition of fluorines (0.2-10R); (9) presence of unsaturation (22-ene, 0-5R; 23-ene, 3R-10I; 23-yne, 5-20R); (10) addition of hydroxyls (2-100R); and (11) addition of an aromatic ring (0-20I). Thus the DBP ligand binding domain could tolerate only modest changes to the structure of 1α,25(OH)2D3 without a reduction in binding of the analog. The increases in binding seen in the aromatic side chain and with a triple bond at carbon-23 may be indicative of a preferred conformation of the flexible 1α,25(OH)2D3 side chain. In addition, a comparison was made of the DBP ligand binding domain with that of the human HL-60 cell 1α,25(OH)2D3 nuclear receptor. Both ligand binding domains could equivalently accommodate to the presence of (1) a side-chain cyclopropyl group, (2) 22-ene or 23-yne, (3) lengthening the side chain by two carbons, (4) presence of four to six fluorine atoms, (5) substitution of an oxygen for carbon 22, and (6) presence of a 22-[m-(dimethylhydroxymethyl)phenyl] aromatic group in the side chain. The DPB could tolerate better than the HL-60 cell receptor the presence of a 22-(p-hydroxyphenyl) aromatic group in the side chain and the absence of the 1α-hydroxyl. In contrast, the HL-60 cell receptor could tolerate better than the DBP the following structural modifications: presence of a 16-ene, or 16-ene plus 23-yne unsaturation, and presence of an 11β-hydroxyl.
Comparison of dosage-dependent effects of β-aminopropionitrile, sodium fluoride, and hydrocortisone on selected physical properties of cortical bone
Authors: DR. Lees Sidney , Hanson Douglas , Page Elizabeth , Mook Herbert A. 
Published: February 2010

Abstract
BAPN, sodium fluoride, and hydrocortisone are reported to induce altered mineralization states. Three separate sets of experiments, one set for each agent, were performed using male New Zealand white rabbits. In each experiment the rabbits were segregated into groups, each fed a specified weight-determined dose for 13 weeks and then sacrificed. Compact bone from the left femur and tibia were tested for density, composition, sonic velocity, longitudinal elastic modulus, equatorial diffraction spacing of mineralized collagen, diaphyseal cross-sectional area, and relative load stress. β-Aminopropionitrile (BAPN) induced monotonic degradation of all properties at all dose levels, corresponding to the decreasing density with dosage level. The elastic moduli show a decrease; the equatorial diffraction spacing of the collagen increases. The cross-sectioned diaphysis resembled woven bone. The variability in properties increased with dosage. The total cross-sectional area for a given weight increased, implying that the decreased elastic properties were compensated for by a larger area to support the weight. There was a slight increase in average density and other properties for fluoride-treated rabbits, peaking at 20 mg/kg BW/day. For higher dosages the properties are degraded and the values were much lower at high fluoride dosages than for BAPN. There was no peak for the equatorial diffraction spacing, which increased with dosage. It is inferred that the fluorosed apatite is denser than normal apatitic mineral and therefore has a smaller specific volume. A greater weight fraction of fluorosed mineral has a smaller volume fraction than the equivalent normal apatitic mineral. The bone sections look more normal, except for the porosis. The total cross-sectional area decreases when the bone density increases and then increases as the density falls, again implying that the area required to support body weight depends on the magnitude of the elastic moduli. There was a small change in some of the properties of the bones of the hydrocortisone-treated rabbits, but the effects on others were undetectable within the uncertainty of the procedures. There was no change in the cross-sectional areas of the diaphyses.
Does estimating volumetric bone density of the femoral neck improve the prediction of hip fracture? A prospective study
Authors: Cummings Steven R. , Marcus Robert , Palermo Lisa , Ensrud Kristine E. , Genant Harry K. 
Published: February 2010

AbstractStandard projectional bone density of the femoral neck (BMD), defined as bone mineral content divided by the projected area of the neck, predicts hip fractures but may not accurately estimate the true volumetric bone density of the femoral neck. To determine whether an estimate of the volumetric bone density of the neck, “bone mineral apparent density” (BMAD), would be a better predictor of hip fracture, we analyzed dual x-ray absorptiometry scans obtained prospectively from 7963 older white women, of whom 83 suffered a hip fracture during follow-up. Both BMD and BMAD were stronger predictors than bone mineral content (BMC) of the femoral neck. However, BMD and BMAD had very similar predictive values for hip fracture: each standard deviation decrease in either BMD or BMAD of the femoral neck increased the age-adjusted risk of hip fracture 2.6- to 2.7-fold. We conclude that BMD and BMAD of the femoral neck have a similarly strong predictive value for hip fracture.