bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of Bone Degradation Products in Serum Using Antibodies Reactive with an Isomerized Form of an 8 Amino Acid Sequence of the C-Telopeptide of Type I Collagen
Authors: Bonde Martin , Garnero Patrick , Fledelius Christian , Qvist Per , Delmas Pierre D. , Christiansen Claus 
Published: April 2006

Abstract
An enzyme-linked immunosorbent assay for measuring type I collagen degradation products in serum (S-ELISA) was developed. The assay uses a high affinity polyclonal antibody which reacts with an isomerized form of an 8 amino acid sequence of the C-telopeptides of type I collagen (EKAHD-β-GGR). Cross-reactivity to a nonisomerized synthetic peptide form of the 8 amino acid sequence is less than 0.2%. Values obtained in a group of premenopausal women (age, 33.3 ± 3.11 years) were 69 ± 24 ng/ml (n = 22). In a group of early postmenopausal women (age, 51.8 ± 1.88 years) values obtained were 125 ± 43 ng/ml (n = 46), which represents an increase of 81% (p &lt; 0.001). Values found in untreated patients with Paget's disease were 234 ± 95 ng/ml (n = 15), and for primary hyperparathyroidism we found 335 ± 82 ng/ml (n = 10). Interveneous administration of a bisphosphonate (Pamidronate) to Paget's disease patients for 3 days was reflected in the S-ELISA by a decrease in the values of 55% when compared with values before treatment (n = 15). Following treatment with another bisphosphonate (Alendronate) for 6 months, values were decreased to 48 ± 19 ng/ml (n = 12), which corresponds to a 62% decrease. Clinical results presented in this context support that the assay is a sensitive and specific index of bone resorption. It may, therefore, prove useful in the follow up of treatment of patients with metabolic bone diseases and in the clinical investigation of osteoporosis.
Linkage Studies of a Missouri Kindred with Autosomal Dominant Spondyloepimetaphyseal Dysplasia (SEMD) Indicate Genetic Heterogeneity
Authors: Gertner Joseph M. , Whyte Michael P. , Dixon Peter H. , Pang Joanna T. , Trump Dorothy , Pearce Simon H. S. , Wooding Carol , Thakker Rajesh V. 
Published: April 2006

Abstract
A four-generation kindred (14 affected and 10 unaffected members) from Missouri, U.S.A. in which spondyloepimetaphyseal dysplasia (SEMD) had been inherited as an autosomal dominant disorder was investigated for linkage to 13 candidate loci: COL2AI, COL9AI, COL9A2, COL9A3, COL10A1, COL11A1, COL11A2, PSACH, FGFR3, decorin, CRTL1, COMP, and PTHRP. Mutations of COL2A1, COL9A2, COL10, and FGFR3 have been reported previously in the Strudwick type of SEMD, multiple epiphyseal dysplasia type 2 (EDM2), the Schmid type of metaphyseal dysplasia, and in achondroplasia, respectively, and the pseudoachondroplasia (PSACH) locus has been mapped to chromosome 19p12. In addition, mutations in COL9 and COL11A are associated with murine forms of degenerative joint disease and chondroplasia, respectively. The family proved informative for 12 of the 13 loci and was uninformative at the decorin locus. Linkage between this form of SEMD, designated the Missouri variant, SEMDMO, and the 12 informative candidate loci was excluded (LOD scores &lt;−2.00 at θ = 0.005 to 0.15), thereby indicating further genetic heterogeneity in these inherited disorders of bone and cartilage development.
Cortical Remodeling Following Suppression of Endogenous Estrogen with Analogs of Gonadotrophin Releasing Hormone
Authors: Bell Karen L. , Loveridge Nigel , Lindsay Peter C. , Lunt Mark , Garrahan Nigel , Compston Juliet E. , Reeve Jonathan 
Published: April 2006

Abstract
The effects of estrogen suppression on osteonal remodeling in young women was investigated using transiliac biopsies (eight paired biopsies + four single pre; three single post biopsies) taken before and after treatment for endometriosis (6 months) with analogs of gonadotrophin releasing hormone (GnRH). Estrogen withdrawal increased the proportion of Haversian canals with an eroded surface (106%, p = 0.047), a double label (238%, p = 0.004), osteoid (71%, p = 0.002), and alkaline phosphatase (ALP) (116%, p = 0.043) but not those showing tartrate-resistant acid phosphatase (TRAP) activity (p = 0.25) or a single label (p = 0.30). Estrogen withdrawal increased TRAP activity in individual osteoclasts in canals with diameters greater than 50 μm (p = 0.0089) and also the number of osteons with diameters over 250 μm (p = 0.049). ALP activity in individual osteoblasts was increased but not significantly following treatment (p = 0.051). Wall thickness was significantly correlated with osteon diameter (p &lt; 0.001). In a separate group of patients (four pairs + one post biopsy) on concurrent treatment with tibolone, there was no significant increase in the osteon density, cortical porosity, median canal diameter, or the markers of bone formation and resorption. Enzyme activities and numbers of active canals were also not increased with the concurrent treatment, but there was still an increase in the osteon diameter. As previously shown for cancellous bone, estrogen withdrawal increased cortical bone turnover. We have now shown that resorption depth within Haversian systems was also increased with treatment. The enhanced TRAP activity in individual osteoclasts supports the concept that osteoclasts are more active following estrogen withdrawal in agreement with theoretical arguments advanced previously. Understanding the cellular and biochemical mechanisms responsible for increased depth of osteoclast resorption when estrogen is withdrawn may allow the development of new strategies for preventing postmenopausal bone loss.
Serum Levels of Insulin-like Growth Factor (IGF) I, IGF-Binding Protein (IGFBP)-2, and IGFBP-3 in Osteoporotic Patients with and without Spinal Fractures
Authors: Sugimoto Toshitsugu , Nishiyama Katsuhito , Kuribayashi Fumihiko , Chihara Kazuo 
Published: April 2006

Abstract
The present study was performed to investigate the role of insulin-like growth factor I (IGF-I), IGF-binding protein-2 (IGFBP-2), and IGFBP-3 in age-dependent bone loss in postmenopausal Japanese women. One hundred and sixty-five Japanese women aged 43–88 years (mean age, 62) were enrolled in the cross-sectional study. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and midradius by dual-energy X-ray absorptiometry or single-photon absorptiometry. Serum levels of IGF-I, IGFBP-2, and IGFBP-3 were measured by radioimmunoassay. BMD at all sites as well as serum levels of IGF-I and IGFBP-3 declined with age, while the serum IGFBP-2 level increased with age. Serum IGFBP-3 and −2 levels were positively and negatively correlated with the serum IGF-I level, respectively. Serum IGF-I and IGFBP-3 levels showed positive correlationship with BMD at any site, particularly at the midradius, while the serum IGFBP-2 level showed negative correlation with BMD. Multiple regression analyses showed age-independent positive correlation between the serum IGF-I level and BMD at all sites as well as age-independent positive correlation between the serum IGFBP-3 level and midradius BMD. The relationship between susceptibility to osteoporotic spinal fracture and serum IGF-I, IGFBP-3, or −2 levels was examined by decade to exclude the influence of aging. Serum levels of IGF-I and IGFBP-3 were significantly lower in subjects with spinal fractures than those without fractures at any decade. No significant difference of serum IGFBP-2 level was observed between subjects with and without fractures. The present findings suggest that IGF-I and IGFBP-3 are important to maintaining bone mass quantitatively as well as qualitatively, and that the determination of serum IGF-I and IGFBP-3 levels could be clinically useful to predict the severity of osteoporosis, particularly the risk of bone fracture associated with osteoporosis.
Precision and Discriminatory Ability of Calcaneal Bone Assessment Technologies
Authors: Greenspan Susan L. , Bouxsein Mary L. , Melton Mary E. , Kolodny Andrea H. , Clair James H. , Delucca Paul T. , Stek Michael , Faulkner Kenneth G. , Orwoll Eric S. 
Published: April 2006

Abstract
To determine if measuring skeletal status at the calcaneus is a potentially valuable technique for diagnosing osteoporosis, we examined five calcaneal assessment techniques in 53 young normal women and 108 postmenopausal women with osteoporosis and compared these measurements to dual-energy X-ray absorptiometry (DEXA) at the calcaneus, hip, and spine. The five instruments, including single-energy X-ray absorptiometry (SEXA) and four quantitative ultrasound (QUS) instruments, were evaluated for precision, ability to discriminate osteoporotic from young normal subjects, and correlation to the other instruments. The coefficient of variation (%CV) for instrument, positioning, interobserver, and short-term precision of the five calcaneal instruments ranged from 1.34–7.76%, 1.63–7.00%, 1.84–9.44%, and 1.99–7.04%, respectively. The %CVs for positioning, interobserver, and short-term precision were similar for calcaneal DEXA, calcaneal SEXA, and stiffness (as measured by Achilles). The %CVs for instrument precision were similar between calcaneal DEXA and SEXA. The ability of the five calcaneal instruments to discriminate osteoporotic from young normal subjects was similar based on the analysis of area under the receiver operating characteristic curves (range 0.88–0.93) and equivalent to DEXA of the calcaneus and hip (0.88–0.93). The correlations between the measurements of five calcaneal instruments were strong (0.80 ≤ r ≤ 0.91, p &lt; 0.001). These data suggest that although the precision is variable, the calcaneal QUS and SEXA instruments can discriminate between osteoporotic patients and young normal controls and appear to be a useful technique for assessment of osteoporosis.
Reduced Bone Mass in Dutch Adolescents Fed a Macrobiotic Diet in Early Life
Authors: Parsons Tessa J. , van Dusseldorp Marijke , van Der Vliet Martine , van de Werken Karen , Schaafsma Gertjan , van Staveren Wija A. 
Published: April 2006

Abstract
This study investigated the effect of a macrobiotic (vegan-type) diet, low in calcium and vitamin D, consumed in early life, on bone mineral during adolescence. Bone mineral content (BMC) and bone area were measured in 195 adolescents (103 girls, 92 boys) aged 9–15 years, using dual-energy X-ray absorptiometry. Ninety-three adolescents (43 girls, 50 boys) had followed a macrobiotic diet in childhood, and 102 (60 girls, 42 boys) were control subjects. After adjustment for bone area, weight, height, percent body lean, age, and puberty, BMC was significantly lower in macrobiotic subjects, in boys and girls, respectively, at the whole body, −3.4% and −2.5%, spine, −8.5% and −5.0%, femoral neck, −8.0% and −8.2%, midshaft radius, −6.8% and −5.6%, and also in girls, at the trochanter, −5.8% (p &lt; 0.05). No group differences were observed at the wrist. Group differences were not explained by current calcium intake or physical activity. We conclude that the use of a macrobiotic diet in early childhood negatively influences adjusted bone mass at age 9–15 years, observations which may hold important implications for fracture risk in later life.
A Comparative Study of Trabecular Bone Properties in the Spine and Femur Using High Resolution MRI and CT
Authors: Link Thomas M. , Majumdar Sharmila , Lin John C. , Newitt David , Augat Peter , Ouyang Xiaolong , Mathur Ashwini , Genant Harry K. 
Published: April 2006

Abstract
The purpose of this study was to use high resolution (HR) magnetic resonance (MR) and computed tomography (CT) images combined with texture analysis to investigate the trabecular structure of human vertebral and femoral specimens and to compare these techniques with bone mineral density (BMD) in the prediction of bone strength. Twenty-nine bone cubes were harvested from 12 proximal femur cadaver specimens and 29 from 8 spines. HR MR and CT images were obtained, and texture analysis techniques were used to assess trabecular structure. Additionally, BMD, elastic modulus (EM), and maximum compressive strength were determined. R2 for EM versus texture measures computed in the MR images was higher (R2 = 0.27–0.64, p &lt; 0.01) in the spine than in the femur specimens (R2 = 0.12–0.22, p &lt; 0.05). R2 values were similar in the CT images. R2 for EM versus BMD was 0.66 (p &lt; 0.01) in the spine and 0.61 (p &lt; 0.01) in the femur specimens. In the MR images, texture measures combined with BMD in a multivariate-regression model significantly increased R2, while improvement was less significant in the CT images. Thus, texture analysis may provide additional information needed to analyze bone strength and quality.
Lack of Correlation Between Start Codon Polymorphism of the Vitamin D Receptor Gene and Bone Mineral Density in Premenopausal French Women: The OFELY Study
Authors: Eccleshall T. Ross , Garnero Patrick , Gross Coleman , Delmas Pierre D. , Feldman David 
Published: April 2006

Abstract
Previous studies have demonstrated an association between bone mineral density (BMD) and a start codon polymorphism (SCP) of the vitamin D receptor (VDR) gene in pre- and postmenopausal Caucasian and Japanese women. The SCP can be determined by a restriction fragment length polymorphism defined by the FokI restriction endonuclease. VDR alleles containing the FokI site are denoted by f and alleles lacking the site by F. In this study, the association between BMD and the SCP was examined in a group of 174 premenopausal French women who previously had been studied for a relationship between BMD and the VDR BsmI polymorphism. The SCP genotypes of the French women were FF 40%, Ff 44%, and ff 16% and they were independent of the BsmI genotype. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine, proximal femur, forearm, and total body. In contrast to previous reports, there was no association of BMD with SCP genotype in this group of Caucasian women at any site. We also measured several biochemical indices of calcium homeostasis and bone turnover. We found no statistically significant associations between SCP genotype and calcium, parathyroid hormone, or vitamin D levels. There was a 33.5% higher level of the skeletal resorption marker N-telopeptides of type I collagen in the women with the ff genotype when compared with women with the FF genotype (p = 0.004). Other bone turnover markers failed to show an association with SCP genotype. In summary, the SCP genotype may not be associated with reduced BMD in all geographical or ethnic populations.
Skeletal Effects of Low-Dose Cyclosporin A in Aged Male Rats: Lack of Relationship to Serum Testosterone Levels
Authors: Dr. Erben Reinhold G. , Stangassinger Manfred , Gärtner Roland 
Published: April 2006

Abstract
The aim of this study was to investigate the skeletal effects of cyclosporin A (CsA) in a dose range relevant to clinical medicine in lumbar vertebral cancellous bone of aged male rats and to correlate these effects with possible changes in serum testosterone levels. Thirty-one 18-month-old male Wistar rats were divided into four weight-matched groups and subcutaneously injected with either 0, 1, 3, or 5 mg of CsA/kg of body weight three times per week. After 4 weeks of treatment, all rats were killed after in vivo fluorochrome labeling and the first lumbar vertebrae analyzed by quantitative histomorphometry. Serum was analyzed for total calcium, creatinine, alkaline phosphatase, osteocalcin, parathyroid hormone, total testosterone, and CsA levels. CsA administration resulted in a dose-dependent increase in serum osteocalcin levels and in histomorphometric indices of cancellous bone turnover in the axial skeleton. Furthermore, CsA-treated rats showed a deterioration of vertebral cancellous bone structure with increased discontinuity of the trabecular bone network due to trabecular plate perforations. Serum testosterone levels were not significantly changed by CsA treatment and were uncorrelated to all biochemical or histomorphometric indices of bone turnover. We conclude that the 4-week administration of CsA at doses that are close to those used in transplantation patients induced high turnover osteopenia in the axial skeleton of aged, 18-month-old male rats, and that these effects were likely not mediated by changes in serum testosterone levels.
Leukemia Inhibitory Factor and Oncostatin M Influence the Mineral Phases Formed in a Murine Heterotopic Calcification Model: A Fourier Transform-Infrared Microspectroscopic Study
Authors: Bohic S. , Rohanizadeh R. , Touchais S. , Godard A. , Daculsi G. , Heymann D. 
Published: April 2006

Abstract
The study of bone mineralization processes is of considerable interest in understanding bone diseases and developing new therapies for skeletal disorders, particularly since bone homeostasis requires numerous cell types and a large cytokine network. Cell culture models of mineralization have often been used to study the cellular mechanisms of mineralization, but few data have been reported concerning the influence of extracellular matrix components and cytokines on the physicochemical properties of mineral. The purpose of this study was to analyze the effects of two cytokines, leukemia inhibitory factor (LIF) and oncostatin M (OSM), involved in bone metabolism on the physicochemical properties of bone mineral formed in a murine in vivo mineralization model. Murine bone marrow cells implanted under the kidney capsule in the presence or absence of cytokines led to heterotopic ossicle formation. A scanning electron microscopic microprobe revealed that heterotopic calcification had a lower (∼20%) Ca/P ratio after cytokine treatment as compared with the control without cytokine. Transmission electron microscopic analysis of cytokine-treated ossicles showed numerous areas with low mineral density, whereas electron diffraction pattern revealed an apatitic phase. These areas were not observed in the absence of cytokine. Moreover, Fourier transform-infrared microspectroscopy showed at the molecular level that the presence of either cytokine induced many microscopic areas in which short-range order organization, such as incorporation of carbonate and crystallinity/maturity of ossicle mineral, were modified. LIF and OSM influenced mineral phase formation in the present model and may thus be key protagonists in bone mineral development and skeletal diseases.
A New Method to Isolate Large Numbers of Rabbit Osteoclasts and Osteoclast-like Cells: Application to the Characterization of Serum Response Element Binding Proteins During Osteoclast Differentiation
Authors: David Jean-Pierre , Neff Lynn , Chen Yan , Rincon Mercedes , Horne William C. , Baron Roland 
Published: April 2006

Abstract
We have developed a new method that allows the purification of large numbers of both authentic osteoclasts (OCs) and in vitro differentiated osteoclast-like cells (OCLs) from rabbits. We characterized the OCLs in terms of the expression of different phenotypic markers of OC differentiation and their ability to resorb bone. The method provides a system for performing biochemical and molecular studies of OC differentiation and function in a single species. We used this system to characterize the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the expression of proteins that bind to the serum response element (SRE) of the c-fos promoter. We found that OCLs and OCs displayed similar SRE-binding activities, including the serum response factor (SRF). This pattern is established in a time-dependent and cell-specific manner in response to long-term treatment of rabbit bone marrow by 1,25(OH)2D3. Thus, 1,25(OH)2D3 can modulate SRF and/or SRF-related protein. This finding may contribute to understanding the role of c-Fos in the regulation of OC differentiation.
A New Perspective on the Causal Influence of Soft Tissue Composition on DXA-Measured In Vivo Bone Mineral Density
Authors: Bolotin H. H. 
Published: April 2006

Abstract
An extensive series of quantitative simulation studies replicating ideal dual-energy X-ray absorptiometric (DXA) bone mineral density (BMD) measurements of typical and realistic in vivo lumbar vertebral and proximal femoral sites has been carried out to quantitatively assess the extent of inherent systematic inaccuracies in such measurements. The results for these bone sites indicate that BMD inaccuracies as high as 20% or more can be anticipated clinically, particularly in cases of osteopenic, osteoporotic, and elderly patients. It is found that the most important soft-tissue anthropometric determinants of the extent of bone site-specific systematic in vivo BMD inaccuracies reflected in DXA measurements are the ratio of the areal density of extraosseous fat to that of lean muscle tissue immediately surrounding the interrogated bone site and the specific yellow/red marrow mix within the scanned bone. As such, the present findings focus directly on the question of whether or not the strong, positive correlations and associations between soft tissue compositional parameters and DXA-measured in vivo BMD determined in a large number of previous clinical investigations are, in toto or in part, biologically causal. The present results are seen to be quantitatively and qualitatively in conformity with the many clinical studies that have found marked general decreases (increases) in measured BMD as body weight and/or body fat mass decreases (increases). It is concluded that the clinically observed correlations between DXA-measured BMD and these anthropometric parameters are artefacts of the systematic errors (inaccuracies) inherent in planar DXA methodology and are unlikely to be of biological genesis.
Mechanism of Mechanically Induced Intercellular Calcium Waves in Rabbit Articular Chondrocytes and in HIG-82 Synovial Cells
Authors: Grandolfo Micaela , Calabrese Alessandra , D'andrea Paola 
Published: April 2006

Abstract
Intercellular communication through gap junctions allows tissue coordination of cell metabolism and sensitivity to extracellular stimuli. Intercellular Ca2+ signaling was investigated with digital fluorescence video imaging in primary cultures of articular chondrocytes and in HIG-82 synovial cells. In both cell types, mechanical stimulation of a single cell induced a wave of increased Ca2+ that was communicated to surrounding cells. Intercellular Ca2+ spreading was inhibited by 18α-glycyrrhetinic acid, demonstrating the involvement of gap junctions in signal propagation. In the absence of extracellular Ca2+, mechanical stimulation induced communicated Ca2+ waves similar to controls; however, the number of HIG-82 cells recruited decreased significantly. Mechanical stress induced Ca2+ influx both in the stimulated chondrocyte and HIG-82 cell, but not in the adjacent cells, as assessed by the Mn2+ quenching technique. Treatment of cells with thapsigargin and with the phospholipase C (PLC) inhibitor U73122 blocked mechanically induced signal propagation. These results provide evidence that in chondrocytes and in HIG-82 synovial cells, mechanical stimulation activates PLC, thus leading to an increase of intracellular inositol 1,4,5-trisphosphate. The second messenger, by permeating gap junctions, stimulates intracellular Ca2+ release in neighboring cells. It is concluded that intercellular Ca2+ waves may provide a mechanism to coordinate tissue responses in joint physiology.