bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Trends in the Aging Femoral Neck and Proximal Shaft: Analysis of the Third National Health and Nutrition Examination Survey Dual-Energy X-Ray Absorptiometry Data
Authors: Beck Thomas J. , Looker Anne C. , Ruff Christopher B. , Sievanen Harri , Wahner Heinz W. 
Published: April 2006

Abstract
Hip scans of U.S. adults aged 20–99 years acquired in the Third National Health and Nutrition Examination Survey (NHANES III) using dual-energy X-ray absorptiometry (DXA) were analyzed with a structural analysis program. The program analyzes narrow (3 mm wide) regions at specific locations across the proximal femur to measure bone mineral density (BMD) as well as cross-sectional areas (CSAs), cross-sectional moments of inertia (CSMI), section moduli, subperiosteal widths, and estimated mean cortical thickness. Measurements are reported here on a non-Hispanic white subgroup of 2719 men and 2904 women for a cortical region across the proximal shaft 2 cm distal to the lesser trochanter and a mixed cortical/trabecular region across the narrowest point of the femoral neck. Apparent age trends in BMD and section modulus were studied for both regions by sex after correction for body weight. The BMD decline with age in the narrow neck was similar to that seen in the Hologic neck region; BMD in the shaft also declined, although at a slower rate. A different pattern was seen for section modulus; furthermore, this pattern depended on sex. Specifically, the section modulus at both the narrow neck and the shaft regions remains nearly constant until the fifth decade in females and then declined at a slower rate than BMD. In males, the narrow neck section modulus declined modestly until the fifth decade and then remained nearly constant whereas the shaft section modulus was static until the fifth decade and then increased steadily. The apparent mechanism for the discord between BMD and section modulus is a linear expansion in subperiosteal diameter in both sexes and in both regions, which tends to mechanically offset net loss of medullary bone mass. These results suggest that aging loss of bone mass in the hip does not necessarily mean reduced mechanical strength. Femoral neck section moduli in the elderly are on the average within 14% of young values in females and within 6% in males.
Role of Activator Protein 1 Transcriptional Activity in the Regulation of Gene Expression by Transforming Growth Factor β1 and Bone Morphogenetic Protein 2 in ROS 17/2.8 Osteoblast-like Cells
Authors: Palcy Sandrine , Bolivar Isabel , Goltzman David 
Published: April 2006

Abstract
In osteoblastic cells, transforming growth factor β1 (TGF-β1) has been found to regulate the expression of a variety of proto-oncogenes including c-fos, c-jun, and junB. The c-fos in particular has been implicated in the mitogenic effect of TGF-β1. Here, we examined the role of these early response genes in the regulation of osteoblast (OB) gene expression by two members of the TGF-β superfamily, TGF-β1 and bone morphogenetic protein 2 (BMP-2). In ROS 17/2.8 cells, TGF-β1 as well as BMP-2 up-regulated the expression of junB and c-fos messenger RNAs (mRNAs), and this increase was correlated in both cases with an increase in activator protein 1 (AP-1) DNA-binding activity involving JunB and c-Fos proteins. Protein kinase C (PKC)- and protein tyrosine kinase (PTK)-dependent pathways have been implicated in both TGF-β1 signaling and AP-1 gene regulation. Therefore, using the kinase inhibitors chelerythrine chloride and genistein, we showed that PKC and PTK activities, respectively, participated in TGF-β1- and BMP-2-induced increases in junB mRNA levels. Similarly, these kinase activities were involved in the stimulatory effect of BMP-2 on c-fos mRNA expression. Using a natural dominant negative for AP-1 transcriptional activity in ROS 17/2.8 cells, we then showed that AP-1 transcription factors mediated TGF-β1- and BMP-2-regulated expression of the (α1) collagen I gene as well as TGF-β1-regulated expression of the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor. Our data emphasize the role of the AP-1 transcription factor in TGF-β1 and BMP-2 signaling and highlight the importance of this transcription factor family in the expression of OB genes.
Influence of Bone Tissue Density and Elasticity on Ultrasound Propagation: An In Vitro Study
Authors: de Terlizzi Francesca , Battista Stefano , Cavani Francesco , Canè Valerio , Cadossi Ruggero 
Published: April 2006

Abstract
Ultrasound (US) waves are mechanical vibrations that are applied to a material—bone tissue—in order to study its properties, that is, density, elasticity, and structure. In this study we evaluated in which way density and elasticity of the spongy bone influenced the transmission of 1.25 MHz US pulses. Twelve cylindrical specimens (diameter, 8 mm; height, 5 mm) excised from phalanxes of pig were decalcified with 0.5 M EDTA for different times (0, 2, and 5 days). During these periods, the samples underwent the following investigations: US transmission, density, and elasticity measurements. To assess the homogeneity of decalcification, the cross-sections of some samples were microradiographed. A detailed analysis of the US signal received was performed using velocity, Fourier analysis, and some parameters typical of signal processing technique. A good correlation was found between US velocity and density (r2 = 0.70); a lower correlation was found between velocity and elasticity (r2 = 0.59). If density and elasticity are considered simultaneously, the correlation with the US velocity improves significantly (r2 = 0.84). Fourier analysis enabled us to observe a shift of the main frequency toward lower values as the decalcification process advanced. We also observed that in the regressions weighted for density, US velocity correlated poorly with elasticity (r2 = 0.16), whereas signal processing parameters maintain a good correlation with elasticity (ultrasound peak amplitude [UPA], r2 = 0.48; slope, r2 = 0.62). In this study, it has been observed that when using a signal processing technique to analyze US pulses, it is possible to identify some parameters that are related in different ways to density and to elastic properties of bone. Our results show the potentiality of US technique to separate information on bone density and elasticity that X-ray-based densitometric methods do not provide.
Quantitative Ultrasound Does Not Reflect Mechanically Induced Damage in Human Cancellous Bone
Authors: Nicholson P. H. F. , Bouxsein M. L. 
Published: April 2006

Abstract
This study investigated the ability of quantitative ultrasound (QUS) to detect reductions in the elastic modulus of cancellous bone caused by mechanical damage. Ultrasonic velocity and attenuation were measured using an in-house parametric imaging system in 46 cancellous bone cores from the human calcaneus. Each core was subjected to a mechanical testing regime to (a) determine the predamage elastic modulus, (b) induce damage by applying specified strains in excess of the yield strain, and (c) measure the postdamage elastic modulus. The specimens were divided into four groups: a control group subjected to a nominally nondestructive 0.7% maximum strain (ϵm) and three damage groups subjected to increasing strain levels (ϵm = 1.5, 3.0, and 4.5%). QUS measurements before and after the mechanical testing showed no significant differences between the control group and damage groups, despite highly significant (p &lt; 0.001) reductions in the elastic modulus of up to 72%. These results indicate that current QUS techniques do not intrinsically reflect the elastic properties of cancellous bone. This is consistent with ultrasonic properties being determined by other factors (apparent density and/or architecture), which normally are associated strongly with elastic properties, but only when bone is mechanically intact. Clinically, this implies that ultrasound cannot be expected to detect bone fragility in the absence of major changes in bone density and/or trabecular architecture.
Strong Prediction of Fractures Among Older Adults by the Ratio of Carboxylated to Total Serum Osteocalcin
Authors: Luukinen H. , Käkönen S.-M. , Pettersson K. , Koski K. , Laippala P. , Lövgren T. , Kivelä S.-L. , Väänänen H. K. 
Published: April 2006

Abstract
We examined serum total osteocalcin (TOC), carboxylated osteocalcin (COC), and their ratio (COC/TOC) by one-step two-site immunofluorescent assays in 87% (n = 792) of all home-dwelling persons of 70 years or older living in a defined area in northern Finland. Other baseline subject-related risk factors of fractures were assessed by postal questionnaires, interviews, clinical examinations, and tests. During a 5-year follow-up period, all falls and fractures (n = 106) were recorded by regular phone calls and by examining all the medical records yearly. Serum TOC and COC concentrations increased with advancing age and were higher in women than in men, but corresponding differences were not found in the case of COC/TOC. The adjusted relative risk of fracture was elevated in association with low (≤−1 SD from the mean) COC; hazard ratio (HR, 95% CI) 2.00 (1.20-3.36) and low COC/TOC; HR 5.32 (3.26-8.68), the relative risk being highest in the population older than 80 years; and HR 7.02 (2.42-20.39). The predictive value of low COC/TOC lasted 3 years. The multivariable-adjusted relative risk of hip fracture (n = 26) in regard to low COC/TOC ratio was 3.49 (1.12-10.86), as compared with the persons who did not suffer hip fractures. Our results suggest that serum COC concentrations and, more strongly, COC/TOC, predict the occurrence of fractures in older community-dwelling adults. The risk of fracture associated with low COC/TOC equals the hip fracture risk previously verified for concomitant high serum undercarboxylated OC concentrations and low bone mineral density.
“Café-Au-Lait Spots” Caused by Vitiligo in McCune-Albright Syndrome
Authors: Whyte Michael P. , Podgornik Michelle N. , Zerega Jan , Reinus William R. 
Published: April 2006

Abstract
Café-au-lait spots, fibrous dysplasia of bone, and endocrine gland hyperactivity are the principal features of McCune-Albright syndrome (MAS). Café-au-lait spots appear at, or soon after, birth. We illustrate “café-au-lait spots” acquired during middle age in a patient with MAS that are an illusion caused by vitiligo. This 64-year-old woman is the oldest patient reported with this disorder.
The Mechanical Properties of Cancellous Bone in the Proximal Tibia of Ovariectomized Rats
Authors: Hogan Harry A. , Ruhmann Sean P. , Sampson H. Wayne 
Published: April 2006

Abstract
The “mature rat model” is an effective and often-used surrogate for studying mechanisms and characteristics of estrogen-deficient osteopenia. The purpose of this study was to extend our understanding of this animal model to include the mechanical properties of cancellous bone in the proximal tibia. Female Sprague–Dawley rats were divided into two groups (n = 13 each) at 14 weeks of age: an ovariectomized group (OVX) and a sham-operated control group (sham). The study terminated after a duration of 5 weeks. Specimens 2 mm long were cut from the proximal tibial metaphysis just below the growth plate and tested using two methods: (1) “whole-slice” compression, in which the entire specimen is loaded between two larger flat platens and (2) “reduced-platen” compression (RPC), which uses platens sized and aligned to load only the cancellous bone in the center of the sample. Three-point bending tests also were conducted on the femur. The short duration of estrogen deficiency yielded only minimal differences (&lt; 10%) in femoral cortical bone but dramatic reductions (∼60%) in cancellous bone properties as determined by the RPC method. Ultimate stress was 7.23 MPa ± 1.97 MPa for OVX versus 18.1 MPa ± 5.21 MPa for sham; and elastic modulus was 252 MPa ± 104 MPa for OVX versus 603 MPa ± 180 MPa for sham. These changes in mechanical properties are similar in many respects to the dramatic effects reported in histomorphometric studies. For the whole-slice method, differences in mechanical properties between the two groups were not as large because the test directly loads both cancellous and cortical bone, and the latter is not affected as severely by estrogen deficiency. In this case, ultimate stress and elastic modulus were only 30% (or less) lower for the OVX group. (J Bone Miner Res 2000;15:284–292)
Growth Hormone Treatment in Adults with Adult-Onset Growth Hormone Deficiency Increases Iliac Crest Trabecular Bone Turnover: A 1-Year, Double-Blind, Randomized, Placebo-Controlled Study
Authors: Brixen Kim , Hansen Tony Bill , Hauge Ellen , Vahl Nina , Jørgensen Jens Otto Lunde , Christiansen Jens Sandahl , Mosekilde Leif , Hagen Claus , Melsen Flemming 
Published: April 2006

Abstract
The effects of growth hormone (GH) substitution on bone metabolism were evaluated by dynamic histomorphometry on iliac crest bone biopsies. Twenty-nine patients, aged 21–61 years (mean 45.5 years), with adult-onset GH deficiency (GHD) were randomized to receive subcutaneous injections with GH (2 IU/m2/day = 0.67 mg/m2/day) or placebo for 12 months. Serum insulin-linke growth factor I (IGF-I) levels increased 263 ± 98% (mean ± SD) during GH treatment (p &lt; 0.0001). In the GH group, osteoid surface increased during treatment from 11% (3–15%) (median [25–75 percentiles]) to 21% (10–27%) (p = 0.01) and mineralizing surface from 4% (1–8%) to 11% (7–16%) (p = 0.04). Moreover, erosion surface tended to increase in the GH group from 2% (1–3%) to 4% (3–5%) (p = 0.07). The quiescent surface decreased in the GH group from 87% (83–96%) to 74% (68–87%) (p = 0.01). The adjusted appositional rate, mineral apposition rate, bone formation rate, bone erosion rate, mineralization lag time, and osteoid thickness remained unchanged during treatment Erosion depth showed a trend toward increase in the GH group (p = 0.09), whereas wall thickness was unchanged. Bone balance at the remodeling unit level and activation frequency were unchanged. At the tissue level, bone erosion rate increased significantly from 26% (17–36%)/year to 39% (23–72%)/year (p = 0.03). Similarly, the bone formation rate at the tissue level tended to increase, from 24% (15–31%)/year to 36% (17%-63%)%/year (p = 0.06). Finally, bone balance at the tissue level decreased significantly from 1% (–2–2%)/year to −5% (−13–1%)/year (p = 0.01). No significant difference in change was seen in the cancellous bone volume. We conclude that 12 months of GH substitution therapy increases trabecular bone turnover. Moreover, our data suggest that bone balance at the bone multicellular unit level is not changed to positive. (J Bone Miner Res 2000;15:293–300)
Study of the Nonresorptive Phenotype of Osteoclast-like Cells from Patients with Malignant Osteopetrosis: A New Approach to Investigating Pathogenesis
Authors: Flanagan Adrienne M. , Sarma Usha , Steward Colin G. , Vellodi Ashok , Horton Michael A. 
Published: April 2006

Abstract
Osteopetrosis manifests as failure of osteoclastic bone resorption. The cause of the disease lies either in the hematopoietic lineage or in the bone marrow stromal microenvironment. It has not been possible to define the cell type involved in the various forms of the human disease because of the inability to form human osteoclasts in vitro. Using the recently described method for generating human osteoclasts from peripheral blood in coculture with rat osteoblastic UMR 106 cells, we demonstrate that a defect lies in the mature osteoclast-like cells in four cases of this disease. Control and osteopetrotic cocultures generated large numbers of osteoclast-like cells (calcitonin and vitronectin receptor positive, and F-actin ring–positive cells) with similar morphology. Bone resorption did not occur in three of the four osteopetrotic cultures. In case 1, in which bone resorption was identified, the area of resorption was negligible compared with the number of osteoclast-like cells in the culture and was detected only by scanning electron microscopy. In contrast, up to 20% of the bone surface in controls was resorbed. The normal and osteopetrotic osteoclast-like cells had a similar phenotype except that two of the osteopetrotic cases did not express CD44 and two expressed CD44 weakly, whereas CD44 was strongly expressed in the controls. This study shows that it is possible to reproduce in vitro the pathological features of human osteopetrosis, and the assay provides a means of acquiring a greater understanding of the pathogenesis of human osteopetrosis. (J Bone Miner Res 2000;15:352–360)
Genetic Epidemiological Approaches to the Search for Osteoporosis Genes
Authors: Nguyen T. V. , Blangero J. , Eisman J. A. 
Published: April 2006

Abstract
Important progress has been made in the identification of specific environmental factors and estimation of hereditary components in bone density, quantitative ultrasound (QUS), and bone turnover indices. By contrast, the search for specific genes that regulate bone mass has progressed rather slowly, and the results are more difficult to interpret and reproduce. This article reviews the genetics of osteoporosis and problems plaguing genetic research. It is argued that the search for genes involved in the expression of osteoporotic phenotypes should be based on linkage studies in relatively homogeneous populations. Strategies for increasing the power of studies, such as making use of information from extended pedigrees and multivariate analysis, are discussed. With the advent of a comprehensive human genetic linkage map, a complete identification of genes for osteoporosis appears feasible. Understanding the genetic mechanisms and their interactions with environmental factors should allow more focused and cost-effective osteoporosis prevention and treatment strategies.
Prevalence of Pelvic Paget's Disease of Bone in the United States
Authors: Altman R. D. , Bloch D. A. , Hochberg M. C. , Murphy W. A. 
Published: April 2006

Abstract
The objective of this article was to estimate the prevalence of Paget's disease of bone in the United States from a statistically derived sample of the general population. Pelvic radiographs obtained in the First National Health and Nutrition Examination Survey (NHANES-I) were reviewed for the presence of Paget's disease. Age, sex, and geographic distribution of Paget's disease of the pelvic region were determined. The overall prevalence of Paget's disease in the United States was estimated. Pelvic Paget's disease is estimated to be present in 0.71 + 0.18% of the radiographs of the general population. The disease was higher in frequency in people who were in the older decades of life with the highest prevalence of 2.32 + 0.54% in the 65- to 74-year-old people. There is a slight male predominance in the 45- to 74-year age group. The regional distribution suggests the highest prevalence in the Northeast (1.48 + 0.52%) with the lowest prevalence in the South (0.26 + 0.25%). The prevalence was equal in white people and black people. An estimate of the overall prevalence of Paget's disease in the United States was at least 1% and perhaps as much as 2% of the general population with near equal sex distribution and the highest prevalence in the northeastern United States.
Decreased Nitric Oxide Levels Stimulate Osteoclastogenesis and Bone Resorption Both in Vitro and in Vivo on the Chick Chorioallantoic Membrane in Association with Neoangiogenesis
Authors: Collin-Osdoby Patricia , Rothe Linda , Bekker Simon , Anderson Fred , Osdoby Philip 
Published: April 2006

Abstract
High nitric oxide (NO) levels inhibit osteoclast (OC)-mediated bone resorption in vivo and in vitro, and nitrate donors protect against estrogen-deficient bone loss in postmenopausal women. Conversely, decreased NO production potentiates OC bone resorption in vitro and is associated with in vivo bone loss in rats and humans. Previously, we reported that bone sections from rats administered aminoguanidine (AG), a selective inhibitor of NO production via inducible NO synthase, exhibited both increased OC resorptive activity as well as greater numbers of OC. Here, we investigated further whether AG promoted osteoclastogenesis, in addition to stimulating mature OC function, using a modified in vivo chick chorioallantoic membrane (CAM) system and an in vitro chick bone marrow OC-like cell developmental model. AG, focally administered in small agarose plugs placed directly adjacent to a bone chip implanted on the CAM, dose-dependently elicited neoangiogenesis while stimulating the number, size, and bone pit resorptive activity of individual OC ectopically formed in vivo. In addition to enhancing OC precursor recruitment via neoangiogenesis, AG also exerted other vascular-independent effects on osteoclastogenesis. Thus, AG promoted the in vitro fusion and formation from bone marrow precursor cells of larger OC-like cells that contained more nuclei per cell and exhibited multiple OC differentiation markers. AG stimulated development was inversely correlated with declining medium nitrite levels. In contrast, three different NO donors each dose-dependently inhibited in vitro OC-like cell development while raising medium nitrite levels. Therefore, NO sensitively regulates OC-mediated bone resorption through affecting OC recruitment (angiogenesis), formation (fusion and differentiation), and bone resorptive activity in vitro and in vivo. Possibly, the stimulation of neoangiogenesis and OC-mediated bone remodeling via AG or other pro-angiogenic agents may find clinical applications in reconstructive surgery, fracture repair, or the treatment of avascular necrosis.
Vascular Endothelial Growth Factor Is Expressed in Human Fetal Growth Cartilage
Authors: Garcia-Ramirez Marta , Toran Nuria , Andaluz Pilar , Carrascosa Antonio , Audi Laura 
Published: April 2006

Abstract
Angiogenesis is a crucial event in endochondral ossification. Chemoattractants and mitogens for endothelial cells (such as basic fibroblast growth factor [bFGF] and transforming growth factor β [TGF-β]), which act as local regulators of the process, are synthesized by chondrocytes under several stimuli and in relation to the differentiation stage of the cartilage. Vascular endothelial growth factor (VEGF) is a 44-kDa protein well known as a potent angiogenic molecule owing to its mitogenic and permeability-causing properties. In this work, VEGF was located by immunohistochemistry in growth plate cartilage of human fetuses (20–22 weeks old) and its expression was demonstrated by reverse-transcription polymerase chain reaction (RT-PCR). Primary culture of human fetal epiphyseal chondrocytes (HFEC) maintained VEGF expression at protein and messenger RNA (mRNA) levels and this expression was stimulated by cartilage-promoting growth factors incorporated into the culture media (rFGF-b, rTGF-β1, and insulin-like growth factor [rIGF-I] at 50 ng/ml). The conditioned medium (CM) of HFEC stimulated the proliferation of endothelial cells, and this was partially blocked by anti-VEGF antibody. These studies showed VEGF production by chondrocytes of the epiphyseal growth cartilage and suggested a role of this factor in cartilage physiology and the angiogenic process.