bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Investigation of Unique and Shared Gene Effects on Speed of Sound and Bone Density Using Axial Transmission Quantitative Ultrasound and DXA in Twins
Authors: Knapp Karen M , Andrew Toby , MacGregor Alex J , Blake Glen M , Fogelman Ignac , Spector Tim D 
Published: April 2006

Abstract
The genetic influences of speed of sound (SOS) and BMD were evaluated using 215 pairs of healthy female twins. Genetic influences were found for all SOS and BMD measurements. A combination of shared and unique genetic influences was found to control BMD and SOS at the radius.
Introduction: The aim of this study was to investigate to what extent axial transmission speed of sound (SOS) measurements in cortical bone at multiple, peripheral skeletal sites will be influenced by genetic factors and to estimate the proportion of shared and unique genetic influences controlling bone mineral density (BMD) and SOS at a single site, the radius.
Materials and Methods: The study population consisted of 215 pairs of healthy female twins. Of these, 85 pairs were monozygotic (MZ) and 130 pairs were dizygotic (DZ). The twins had measurements of the nondominant third proximal phalanx, one-third radius, midshaft tibia, and fifth metatarsal using the Sunlight Omnisense and DXA measurements of the lumbar spine, nondominant proximal femur, nondominant radius, and whole body using Hologic QDR-4500W densitometers. Calcaneal quantitative ultrasound (QUS) measurements were performed using the McCue CUBA clinical. Intraclass correlations were calculated, and heritability was estimated using multiple regression analysis. Bivariate analysis of site-matched SOS and BMD measurements at the radius was performed using a variance components analysis program.
Results: Age- and body mass index-adjusted heritability estimates ranged from 0.51 (95% CI, 0.32–0.70) to 0.56 (0.37–0.76) for SOS measurements, 0.58 (0.41–0.75) for broadband ultrasound attenuation (BUA), 0.72 (0.58–0.86) to 0.77 (0.63–0.91) for axial BMD, and 0.53 (0.16–0.90) to 0.63 (0.26–1.00) for radius and whole body BMD. The correlation between SOS and DXA at the radius was r = 0.34 (0.29–0.47). Thirty-eight percent (16–57%) of the genetic variance explained by SOS at the radius was also explained by BMD (one-third radius region of interest), with 62% being unique.
Conclusion: In conclusion, genetic influences were demonstrated for SOS measurements in cortical bone at multiple sites, axial BMD, calcaneal BUA, radius, and whole body BMD. At the radius, up to 38% of the genetic influence is shared by genes controlling BMD and SOS. Clarifying the site specificity and pleiotropic effects of bone genes should help our understanding of these complex pathways.
Carbonated Soft Drink Consumption and Bone Mineral Density in Adolescence: The Northern Ireland Young Hearts Project
Authors: McGartland C , Robson PJ , Murray L , Cran G , Savage MJ , Watkins D , Rooney M , Boreham C 
Published: April 2006

Abstract
In an observational study of 1335 boys and girls aged 12 and 15 years, higher intakes of carbonated soft drinks (CSDs) were significantly associated with lower bone mineral density at the heel, but only in girls. Owing to the upward trend in CSD intake in adolescence, this finding may be of concern.
Introduction: High consumption of carbonated soft drinks (CSD) during adolescence may reduce bone mineral accrual and increase fracture risk. The aim of this study was to examine the relationship between CSD consumption and bone mineral density (BMD) in a representative sample of adolescents.
Materials and Methods: This was a cross-sectional observational study in 36 postprimary schools in Northern Ireland. Participants included 591 boys and 744 girls either 12 or 15 years old. BMD was measured by DXA, and usual beverage consumption was assessed by the diet history method. Adjusted regression modeling was used to investigate the influence of CSD on BMD.
Results: A significant inverse relationship between total CSD intake and BMD was observed in girls at the dominant heel (β, −0.099; 95% CI, −0.173 to −0.025). Non-cola consumption was inversely associated with dominant heel BMD in girls (β, −0.121; 95% CI, −0.194 to −0.048), and diet drinks were also inversely associated with heel BMD in girls (β, −0.087; 95% CI, −0.158 to −0.016). However, no consistent relationships were observed between CSD intake and BMD in boys. Cola consumption and nondiet drinks were not significantly related to BMD in either sex.
Conclusion: CSD consumption seems to be inversely related to BMD at the dominant heel in girls. It is possible that the apparent association results from the displacement of more nutritious beverages from the diet. Although the inverse association observed between CSD consumption and BMD is modest and confined to girls, this finding may have important public health implications given the widespread use and current upward trend in CSD consumption in Western populations.
Characterization of Bone Structure in Leptin Receptor-Deficient Zucker (fa/fa) Rats
Authors: Tamasi Joseph A , Arey Brian J , Bertolini Donald R , Feyen Jean HM 
Published: April 2006

Abstract
To investigate the role of leptin in bone formation, the skeleton of the obese female leptin receptor-deficient Zucker rat was examined using pQCT, μCT, and histomorphometry. A trend toward decreasing structural and bone formation parameters in these rats as they age suggest that leptin has a small positive effect on bone.
Introduction: Evidence in the literature has suggested the possible role of leptin in bone formation. Leptin deficiency or leptin receptor deficiency results in higher bone mass. In an attempt to further investigate leptin's role in bone formation, we examined the skeleton of obese leptin receptor-deficient Zucker rats.
Methods: Female leptin receptor-deficient Zucker (fa/fa) rats and their homozygous (Fa/Fa) and heterozygous (Fa/fa) lean controls were used at 9 and 15 weeks of age (n = 5). Bone mineral density of the proximal tibia was measured by peripheral quantitative computed tomography (pQCT). Microcomputed tomography (μCT) was used for the analysis of trabecular architecture in the proximal tibia metaphysis and cortical bone at the tibia-fibula junction. Static and dynamic parameters of bone resorption and formation were quantitated by histomorphometry. Statistical analysis was performed by Dunnett's one-way ANOVA.
Results: Analysis of the proximal tibia by pQCT show no significant differences in the bone mineral density of obese rats compared with their corresponding lean controls in either age group. Trabecular architecture measured by μCT indicate a trends toward decreasing bone volume (BV/TV) in the obese animals, evident by a decrease in trabecular number and thickness with an increase in trabecular separation. Histomorphometric evaluation further shows significant increases in osteoclast surface in the obese rats at both 9 and 15 weeks without a change in osteoclast number. Osteoid surface in the obese animals was also found to be decreased by 15 weeks of age. Fluorescent-based measurements of bone formation were not significantly different. Differences in the cortical compartment were not observed at either age.
Conclusion: Based on the observed skeletal phenotype of the Zucker (fa/fa) rat, it is suggested that leptin exerts a positive effect on bone.
Determinants of Bone Density in 30- to 65-Year-Old Women: A Co-Twin Study
Authors: MacInnis RJ , Cassar C , Nowson CA , Paton LM , Flicker L , Hopper JL , Larkins RG , Wark JD 
Published: April 2006

Abstract
Reported effects of body composition and lifestyle on bone mineral density in pre-elderly adult women have been inconsistent. In a co-twin study, we measured bone mineral density, lean and fat mass, and lifestyle factors. Analyzing within pair differences, we found negative associations between bone mineral density and tobacco use (2.3–3.3% per 10 pack-years) and positive associations with sporting activity and lean and fat mass.
Introduction: Reported effects of body composition and lifestyle of bone mineral density in pre-elderly adult women have been inconsistent.
Methods: In a co-twin study of 146 female twin pairs aged 30 to 65 years, DXA was used to measure bone mineral density at the lumbar spine, total hip, and forearm, total body bone mineral content, and lean and fat mass. Height and weight were measured. Menopausal status, dietary calcium intake, physical activity, current tobacco use, and alcohol consumption were determined by questionnaire. Within-pair differences in bone measures were regressed through the origin against within-pair differences in putative determinants.
Results: Lean mass and fat mass were associated with greater bone mass at all sites. A discordance of 10 pack-years smoking was related to a 2.3–3.3% (SE, 0.8–1.0) decrease in bone density at all sites except the forearm, with the effects more evident in postmenopausal women. In all women, a 0.8% (SE, 0.3) difference in hip bone mineral density was associated with each hour per week difference in sporting activity, with effects more evident in premenopausal women. Daily dietary calcium intake was related to total body bone mineral content and forearm bone mineral density (1.4 ± 0.7% increase for every 1000 mg). Lifetime alcohol consumption and walking were not consistently related to bone mass.
Conclusion: Several lifestyle and dietary factors, in particular tobacco use, were related to bone mineral density. Effect sizes varied by site. Characterization of determinants of bone mineral density in midlife and thereafter may lead to interventions that could minimize postmenopausal bone loss and reduce osteoporotic fracture risk.
Height and Lower Extremity Length as Predictors of Hip Fracture: Results of the NHANES I Epidemiologic Follow-up Study
Authors: Opotowsky Alexander R , Su Brian W , Bilezikian John P 
Published: April 2006

Abstract
The relationship between height, lower extremity length (LEL), and hip fracture was examined in 4264 women followed for 22 years. Greater height predicted fracture among younger women, whereas LEL predicted risk for all ages. LEL is a better predictor of hip fracture risk than height among older women.
Introduction: The significance of height as a risk factor for hip fracture is controversial. Age-related height loss, caused by nonpathological processes and vertebral deformities, may confound the relationship between standing height and hip fracture. In contrast, LEL might be less subject to age-related changes and thus be a better index of fracture risk for older individuals.
Methods: We evaluated data available from 4264 white women who participated in the NHANES I Epidemiologic Follow-up Survey. There were 203 incident hip fractures over the 22-year follow-up period. The effect of height and LEL on hip fracture risk was determined for three age groups: 40–59, 60–69, and 70–74 year olds.
Results: After controlling for potential confounders, the hazard ratio (HR) for hip fracture for each SD greater standing height was 1.81 for the youngest age group (p = 0.002), 1.29 for 60–69 year olds (p = 0.02), and 1.10 for 70–74 year olds (p = 0.49). In contrast, LEL predicted hip fracture risk for all age groups, with HRs of 1.43 (p = 0.02), 1.30 (p = 0.002), and 1.33 (p = 0.02), respectively. Similarly, higher tertile of standing height did not confer increased hip fracture risk among the oldest women, but higher tertile of LEL did. Among women that were 70–74 years old, those in the highest tertile of LEL had a 1.83-fold (p &lt; 0.05) greater risk of hip fracture than those in the lowest tertile.
Conclusions: The results support the hypothesis that LEL is a better predictor of hip fracture than standing height among older women, the group at highest risk for these fractures.
Abnormalities in Bone Mineral Density and Bone Histology in Thalassemia
Authors: Domrongkitchaiporn Somnuek , Sirikulchayanonta Vorachai , Angchaisuksiri Pantep , Stitchantrakul Wasana , Kanokkantapong Chavasak , Rajatanavin Rajata 
Published: April 2006

Abstract
This study demonstrated that there was extensive iron staining on trabecular surface and marked reduction in trabecular bone volume without significant alteration in bone formation and bone resorption rates as well as significant reduction in bone mineral density in 18 thalassemic patients. Serum IGF-I was reduced and may modulate the reduction of bone mass.
Introduction: Bone histomorphometric studies in thalassemia to show alterations in bone histology and their relationship to biochemical parameters are very limited. Therefore, this study was systematically conducted to determine the alterations in thalassemia patients.
Methods: Serum biochemical parameters, trans-iliac crest bone biopsy, and determination of bone mineral density of femur and lumbar spine were done in 18 thalassemic patients (10 females and 8 males).
Results: Serum osteocalcin, carboxy terminal teleopeptide fragment of type I collagen, and parathyroid hormone levels were within normal limits, but serum 25(OH) vitamin D (19.3 ± 1.6 ng/ml) and 1,25(OH)2 vitamin D (33.77 ± 1.51 pg/ml) levels were decreased. Serum insulin-like growth factor I (IGF-I; 145.2 ± 20 ng/ml) was suppressed, whereas serum ferritin (1366.6 ± 253.9 ng/ml) was markedly elevated. Reduced bone mineral density was found in all studied areas. Trabecular bone volume was significantly decreased (16.65 ± 1.12%), whereas bone formation rate, eroded surface, and other bone histomorphometric parameters were within normal limits. The trabecular bone volume varied significantly with bone mineral density of total femur (r = 0.48, p = 0.04). There was an extensive stainable iron surface on the mineral front (9–60%). Significant correlation between serum IGF-I, serum ferritin, stainable iron surface, and bone mineral density, lumbar spine, and total femur were found. Serum IGF-I correlated with trabecular bone volume (r = 0.6, p = 0.03), inversely with both serum ferritin level (r = −0.6, p &lt; 0.01), and inversely with stainable iron surface (r = −0.53, p = 0.02). Multiple regression analysis demonstrated that IGF-I was the only independent variable that determined bone mineral density of lumbar spine and total femur.
Conclusion: Low bone mineral density and reduced trabecular bone volume with extensive iron deposition are the predominant findings in thalassemic patients. There was no evidence of increased bone resorption or mineralization defect. A reduction in circulatory IGF-I may modulate the reduction of bone mass.
Osteopontin Expression in Osteoblasts and Osteocytes During Bone Formation Under Mechanical Stress in the Calvarial Suture In Vivo
Authors: Morinobu Mikihiko , Ishijima Muneaki , Rittling Susan R , Tsuji Kunikazu , Yamamoto Haruyasu , Nifuji Akira , Denhardt David T , Noda Masaki 
Published: April 2006

Abstract
To clarify the role of OPN in bone formation under mechanical stress, we examined the expression and the function of OPN in bone using an expansion force-induced osteogenesis model. Our results indicated that OPN expression was enhanced during the bone formation and that OPN would be one of the positive factors for the bone formation under mechanical stress.
Introduction: Bone formation is known to be stimulated by mechanical stress; however, molecules involved in stress-dependent regulation of bone formation have not yet been fully characterized. Extracellular matrix proteins such as osteopontin (OPN) could play a role in mediation of the mechanical stress signal to osteoblasts. However, the function of OPN in bone formation under mechanical force is not known. Therefore, we examined the expression and the role of OPN in bone formation in vivo under tensile mechanical stress.
Materials and Methods: Sagittal sutures of mice were subjected to expansion mechanical stress by setting orthodontic spring wires, and OPN expression during bone formation within the suture gap was examined.
Results: Expansion of the sutures resulted in bone formation at the edges of the parietal bones within the sagittal suture. Immunohistochemical analysis revealed abundant accumulation of OPN protein in the matrix of newly formed bone on the inner edge of the parietal bone within the mechanically expanded sutures. Osteoblasts forming bone within the suture subjected to tensile stress also exhibited high levels of OPN protein expression. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated that OPN mRNA expression was enhanced in wild-type calvariae subjected to expansion force compared with the control calvariae where dead spring wires were set without expansion stress. In addition, type I collagen mRNA was also expressed in the calvariae under the mechanical stimuli. To understand the function of OPN, sagittal sutures in OPN-deficient mice were subjected the expansion stress, and bone formation within the suture to fill the expanded gap was compared with that observed in wild-type mice. OPN deficiency reduced bone formation at the edge of the parietal bone in contact with the expanded suture gap.
Conclusions: These observations revealed that OPN plays a pivotal role in bone formation under tensile mechanical stress.
Identification of Biphenylcarboxylic Acid Derivatives as a Novel Class of Bone Resorption Inhibitors
Authors: van 't Hof Rob J , Idris Aymen I , Ridge Susan A , Dunford James , Greig Iain R , Ralston Stuart H 
Published: April 2006

Abstract
A novel class of biphenylcarboxylic acid derivatives are described that inhibit osteoclastic bone resorption in vitro by promoting osteoclast apoptosis and that prevent ovariectomy-induced bone loss in vivo. The compounds act by a novel mechanism that seems to be distinct from existing antiresorptive drugs.
Introduction: Many common bone diseases such as osteoporosis, Paget's disease, and cancer-associated bone disease are characterized by excessive bone loss caused by increased osteoclastic activity. Successful treatment of these diseases is based on osteoclast inhibition. The osteoclast inhibitory drugs that are currently available fall into relatively few mechanistic classes, indicating the need to identify novel antiresorptives. Here we describe a series of biphenylcarboxylic acid derivatives that have potent inhibitory effects on osteoclastic bone resorption in vitro and on ovariectomy-induced bone loss in vivo.
Materials and Methods: Compounds were tested for inhibitory effects on bone resorption in vitro using mouse osteoblast-bone marrow co-cultures, isolated rabbit osteoclasts, and mouse osteoclasts generated from bone marrow. Some experiments were also performed on human osteoclasts generated from peripheral blood mononuclear cells. We also investigated the effects of specific compounds on ovariectomy-induced bone loss in vivo in mice.
Results: One of the most potent compounds identified was the butanediol ester of biphenyl carboxylic acid (ABD056), which inhibited osteoclast formation in mouse osteoblast-bone marrow co-cultures by 50% (IC50) at a concentration of 26 μM and in macrophage-colony stimulating factor (M-CSF)- and RANKL-stimulated mouse bone marrow cultures with an IC50 of 8 μM. Mechanistic studies showed that ABD056 caused osteoclast apoptosis and inhibited TNFα-induced NF-κB activation. No inhibitory effects on osteoblast growth or differentiation were observed at concentrations of up to 100 μM. When administered to mice at doses of 5 and 10 mg/kg/day, ABD056 prevented ovariectomy-induced bone loss.
Conclusions: Butanediol biphenylcarboxylic acid derivatives represent a new class of antiresorptive drug that might be of therapeutic value in the prevention and treatment of diseases characterized by osteoclast activation such as osteoporosis, cancer-associated bone disease, and Paget's disease of bone.
Localization of the Gene Causing the Osteopetrotic Phenotype in the Incisors Absent (Ia) Rat on Chromosome 10q32.1
Authors: van Wesenbeeck Liesbeth , Odgren Paul R , Mackay Carole A , Van Hul Wim 
Published: April 2006

Abstract
The incisors absent rat is an osteopetrotic animal model. Segregation analysis in 37 affected animals from an outcross enabled us to assign the disease causing gene to a 4.7-cM interval on rat chromosome 10q32.1. Further analysis of the genes mapped in this region will provide more insight into the underlying pathogenesis.
Introduction: Many of the insights into the factors that regulate the differentiation and activation of osteoclasts are gained from different spontaneous and genetically induced osteopetrotic animal models. The osteopetrotic incisors absent (ia) rat exhibits a generalized skeletal sclerosis and a delay of tooth eruption. Although the ia rat has well been studied phenotypically, the genetic defect still remains unknown.
Material and Methods: To map the ia locus, we outcrossed the inbred ia strain with the inbred strain Brown Norway. Intercrossing F1 animals produced the F2 generation. Thirty-one mutant F2 animals and six mutant F4 animals were available for segregation analysis.
Results: Segregation analysis enabled us to assign the disease causing gene to rat chromosome 10q32.1. Homozygosity for the ia allele was obtained for two of the markers analyzed (D10Rat18 and D10Rat84). Key recombinations delineate a candidate region of 4.7 cM flanked by the markers D10Rat99 and D10Rat17.
Conclusion: We have delineated a 4.7-cM region on rat chromosome 10q32.1 in which the gene responsible for the osteopetrotic phenotype of the ia rat is located. Although the sequence of this chromosomal region is not complete, over 140 known or putative genes have already been assigned to this region. Among these, several candidate genes with a putative role in osteoclast functioning can be identified. However, at this point, it cannot be excluded that one of the genes with a currently unknown function is involved in the pathogenesis of the ia rat. Further analysis of the genes mapped in this region will provide us more insight into the pathogenesis of this osteopetrotic animal model.
Negative Regulation of Chondrocyte Differentiation by Transcription Factor AP-2α
Authors: Huang Zhengmin , Xu Haiming , Sandell Linda 
Published: April 2006

Abstract
This study investigated the role of transcription factor AP-2α in chondrocyte differentiation in vitro. AP-2α mRNA declined during differentiation, and overexpression of AP-2α inhibited differentiation. The results demonstrated that AP-2α plays a negative role in chondrocyte differentiation.
Introduction: Transcription factor AP-2α has been detected in growth plate and articular chondrocytes and has been shown to regulate cartilage matrix gene expression in vitro. However, the precise functional role of AP-2α in chondrocyte differentiation is not known. In this study, we assessed the expression and the function of AP-2α in chondrocyte differentiation of ATDC5 cells.
Materials and Methods: Chondrocyte differentiation of ATDC5 cells was induced with insulin or transforming growth factor β (TGF-β). Proteoglycan production was assessed by alcian blue staining, and expression levels of chondrocyte marker genes and AP-2 gene family were determined by quantitative real time reverse transcriptase-polymerase chain reaction (RT-PCR). Overexpression of AP-2α in ATDC5 cells was accomplished by retroviral infection. Infected cells were selected for G418 resistance and pooled for further analysis.
Results and Conclusions: Quantitative real time RT-PCR analysis showed that among the four members of the AP-2 gene family, AP-2α mRNA was the most abundant. AP-2α mRNA levels progressively declined during the differentiation induced by either insulin or TGF-β treatment. Retroviral expression of AP-2α in ATDC5 cells prevented the formation of cartilage nodules, suppressed the proteoglycan production, and inhibited the expression of type II collagen, aggrecan, and type X collagen. Expression profile analysis of key transcription factors involved in chondrogenesis showed that overexpression of AP-2α maintained the expression of Sox9 but suppressed the expression of Sox5 and Sox6. Taken together, we provide, for the first time, molecular and cellular evidence suggesting that AP-2α is a negative regulator of chondrocyte differentiation.