bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Ultrasound: Use in Screening for Susceptibility to Stress Fractures in Female Army Recruits
Authors: Lappe Joan , Davies Kennard , Recker Robert , Heaney Robert 
Published: April 2006

Abstract
QUS measurements were made on 4139 female Army recruits at the beginning of basic training (BT). QUS predicted stress fracture in female recruits as well as it predicts hip fracture in elderly women. Recruits with low QUS values and a history of smoking and not exercising had an extremely high risk of stress fracture.
Introduction: Stress fractures during basic military training (BT) cause morbidity for the recruits and expense for the Military Services. Females have a higher incidence than males. If recruits at high risk for stress fracture could be accurately identified before they began BT, the military might find it advantageous to provide adaptive training programs for them. Currently no accurate methods of risk identification are available. We measured quantitative ultrasound (QUS) in a population sample of female Army recruits to determine if QUS is a useful tool for determining soldiers at high risk of stress fracture during BT.
Materials and Methods: We recruited 93% of the population of female recruits entering BT at Fort Leonard Wood, MO, during a 10-month period. We measured calcaneal QUS and administered a risk factor questionnaire at baseline and ascertained stress fractures during the 8 weeks of BT. Logistic regression was used to calculate relative risk (RR) of stress fracture. The area under the receiver-operating characteristic (ROC) curve was also analyzed to determine the sensitivity and specificity of speed of sound (SOS) in predicting stress fracture.
Results: The incidence of stress fracture was 4.7%. SOS was significantly related to the risk of stress fracture. (p &lt; 0.000) The area under the ROC curve was 0.70. The relative risk (RR) of fracture of those in the lowest quintile (Q1) of SOS was 6.7. The highest risk of stress fracture was found in the subgroup of white women in Q1 of SOS who smoked and didn't exercise (RR, 14.4). Over 16% of the fractures occurred in this subgroup, which indicates that about six of these women would need to be assigned to an alternate BT regimen to prevent one stress fracture.
Conclusions: The combination of QUS measurements with evaluation of individual risk factors can identify recruits who are at the very highest risk of stress fracture. The military may find these data helpful to determine the cost-effectiveness of alternate BT regimens.
Underdiagnosis of Vertebral Fractures Is a Worldwide Problem: The IMPACT Study
Authors: Delmas Pierre D , van de Langerijt Lex , Watts Nelson B , Eastell Richard , Genant Harry , Grauer Andreas , Cahall David L 
Published: April 2006

Abstract
Accurate radiographic diagnosis of vertebral fractures is important. This multicenter, multinational study assessed radiographic diagnoses of vertebral fracture in 2451 postmenopausal women with osteoporosis. Comparison between local and central readings yielded a false-negative rate of 34%. Underdiagnosis of vertebral fracture is a worldwide problem.
Introduction: Vertebral fractures are the most common complication of osteoporosis. Although they are associated with significant morbidity, they frequently do not come to clinical attention. Accurate radiographic diagnosis is important.
Materials and Methods: In a multicenter, multinational prospective study (the IMPACT trial), the accuracy of radiographic diagnosis of vertebral fracture was evaluated in postmenopausal women 65–80 years of age newly diagnosed with osteoporosis (based on BMD measurement). Lateral radiographs of the thoracolumbar spine were evaluated for identification of vertebral fractures, first locally and subsequently at a central reading center, using a validated semiquantitative method. False-positive and false-negative rates were calculated based on adjudicated discrepancies between the initial interpretation at the local site and the subsequent central reading, considered the “reference standard.”
Results: Of 2451 women with an evaluable radiograph both centrally and locally, 789 (32%) had at least one vertebral fracture. Adjudicated discrepancies (n = 350 patients) between local and central readings because of undetected vertebral fracture (68%) or equivocal terminology in the local radiology report (32%) yielded a false-negative rate of 34%.
Conclusions: Underdiagnosis of vertebral fractures was observed in all geographic regions (false-negative rates: North America, 45.2%; Latin America, 46.5%; Europe/South Africa/Australia, 29.5%). The false-positive rate was 5% globally. Underdiagnosis of vertebral fracture is a worldwide problem attributable in part to a lack of radiographic detection, use of ambiguous terminology in the radiology report, or both. Efforts to improve accuracy and reduce variability in terminology and interpretation may increase the effectiveness of spinal radiography for detecting vertebral fractures in patients with osteoporosis.
Long-Term Fracture Risk Among Children With Asthma: A Population-Based Study
Authors: Melton L Joseph , Patel Ashok , Achenbach Sara J , Oberg Ann L , Yunginger John W 
Published: April 2006

Abstract
Fracture risk among patients diagnosed with asthma in childhood is greater in males and oral corticosteroid users, but most fractures are of the appendicular skeleton and may relate to impaired skeletal development.
Introduction: There are no population-based data on fracture outcomes among the growing number of patients with asthma diagnosed in childhood.
Materials and Methods: We conducted a population-based retrospective (historical) cohort study among 279 Rochester, Minnesota, residents who were &lt;35 years of age (mean, 6.2 years) when first diagnosed with asthma. Fractures were ascertained by review of comprehensive community medical records, and cases were compared directly with age- and sex-matched controls in a stratified proportional hazards model. Risk factors for fractures among the asthma cases were assessed using Andersen-Gill time-to-fracture regression models.
Results: During 6649 person-years of follow-up (median, 24.3 years/subject), 107 asthma patients experienced 189 fractures, for a crude fracture incidence rate of 2.8 per 100 person-years. The actuarially estimated cumulative fracture incidence after 20 years was 40% compared with 34% among controls (p = 0.122). There was no significant increase in overall fracture risk among cases compared to their age- and sex-matched controls (hazard ratio [HR], 1.3; 95% CI, 0.9-1.9), but males with asthma had a 2.6-fold greater risk of hand and finger fractures than control males. The independent predictors of overall fracture risk among the asthma patients included male gender (HR, 2.2; 95% CI, 1.5-3.2) and use of oral corticosteroids (HR, 2.0; 95% CI, 1.2-3.1) or anti-cholinergic agents (HR, 3.9; 95% CI, 1.5-10).
Conclusions: Rather than osteoporotic fractures of the axial skeleton, oral corticosteroid therapy was associated here with limb fractures, suggesting a relationship with impaired development of a biomechanically competent skeleton. Additional studies are needed to assess this possibility.
Decrease in Thoracic Vertebral Bone Attenuation With Calcium-Based Phosphate Binders in Hemodialysis
Authors: Raggi Paolo , James George , Burke Steven K , Bommer Jürgen , Chasan-Taber Scott , Holzer Herwig , Braun Johan , Chertow Glenn M 
Published: April 2006

Abstract
We performed a posthoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. Subjects randomized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation, in association with higher concentrations of serum calcium, lower concentrations of PTH, and reduced total and bone-specific alkaline phosphatase.
Introduction: In patients with chronic kidney disease, hyperphosphatemia is associated with osteodystrophy, vascular and soft tissue calcification, and mortality. Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism. Clinicians and investigators have presumed that, in hemodialysis patients, calcium exerts beneficial effects on bone.
Materials and Methods: We performed a posthoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover.
Results and Conclusions: The average serum phosphorus and calcium × phosphorus products were similar for both groups, although the average serum calcium concentration was significantly higher in the calcium-treated group. Compared with sevelamer-treated subjects, calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation (p = 0.01) and a trend toward decreased cortical bone attenuation. More than 30% of calcium-treated subjects experienced a 10% or more decrease in trabecular and cortical bone attenuation. On study, sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase, osteocalcin, and PTH (p &lt; 0.001). When used to correct hyperphosphatemia, calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation. Calcium salts may paradoxically decrease BMD in hemodialysis patients.
Bone Adaptation to a Mechanical Loading Program Significantly Increases Skeletal Fatigue Resistance
Authors: Warden Stuart J , Hurst Julie A , Sanders Megan S , Turner Charles H , Burr David B , Li Jiliang 
Published: April 2006

Abstract
Using a mechanical loading program to induce bone adaptation, we found that small (&lt;2-fold) changes in the structural properties of the rat ulna increased its fatigue resistance &gt;100-fold. This indicates that a moderate exercise program may be an effective preventative strategy for stress fractures.
Introduction: There are currently limited preventative strategies for stress fractures. Because stress fracture risk is directly influenced by skeletal properties, it has been hypothesized that modification of these properties using a mechanical loading program may positively influence risk. The aim of this study was to investigate whether the bone changes associated with a mechanical loading program can enhance skeletal fatigue resistance.
Materials and Methods: Site-specific mechanical loading was performed on one forearm of adult female Sprague-Dawley rats using the axial compression loading model. Loading was performed 3 days/week for 5 consecutive weeks to induce adaptation. The loaded and nonloaded ulnas in each animal were removed after the loading program, and their material and structural properties were determined. The ulna pairs were subsequently loaded until fatigue failure at the same constant peak axial load.
Results: Mechanical loading induced consistent and predictable changes in the structural properties of loaded ulnas, with the largest change being a nearly 2-fold increase in midshaft minimum second moment of area (IMIN). The mechanical-loading induced bone changes resulted in a &gt;100-fold increase in fatigue resistance in loaded ulnas, with resistance being exponentially related to the structural properties of the ulna.
Conclusions: This study found that by enhancing the structural properties of a bone through a mechanical loading program, its fatigue resistance could be significantly improved. This indicates that an exercise program aimed at modifying bone structure may be used as a possible prevention strategy for stress fractures.
Combined Angiogenic and Osteogenic Factor Delivery Enhances Bone Marrow Stromal Cell-Driven Bone Regeneration
Authors: Huang Yen-Chen , Kaigler Darnell , Rice Kevin G , Krebsbach Paul H , Mooney David J 
Published: April 2006

Abstract
Bone formation is a coordinated process involving various biological factors. We have developed a scaffold system capable of sustained and localized presentation of osteogenic (BMP-4) and angiogenic (VEGF) growth factors and human bone marrow stromal cells to promote bone formation at an ectopic site. Combined delivery of these factors significantly enhanced bone formation compared with other conditions.
Introduction: Tissue regeneration entails complex interactions between multiple signals and materials platforms. Orchestrating the presentation of these signals may greatly enhance the regeneration of lost tissue mass. Bone formation, for example, is dependent on the signaling of BMPs, molecules initiating vascularization (e.g., vascular endothelial growth factor [VEGF]), and osteogenic precursor cells capable of responding to these cues and forming bone tissue. It was hypothesized that combined and concerted delivery of these factors from biodegradable scaffolds would lead to enhanced bone formation.
Materials and Methods: Poly(lactic-co-glycolic acid) scaffolds containing combinations of condensed plasmid DNA encoding for BMP-4, VEGF, and human bone marrow stromal cells (hBMSCs) were implanted into the subcutaneous tissue of SCID mice. Implants (n = 6) were retrieved at 3, 8, and 15 weeks after implantation. Bone and blood vessel formation was determined qualitatively and quantitatively by methods including histology, immmunostaining, and μCT.
Results: Scaffolds delivering VEGF resulted in a prominent increase in blood vessel formation relative to the conditions without VEGF. BMP-4 expression in scaffolds encapsulating condensed DNA was also confirmed at the 15-week time-point, showing the characteristic of long-term delivery in this system. Combined delivery of all three types of factors resulted in a significant increase in the quantity of regenerated bone compared with any factor alone or any two factors combined, as measured with DXA, X-ray, and histomorphometric analysis. Furthermore, bone formed with all three factors had elastic moduli significantly higher than any other condition.
Conclusions: Concerted delivery of BMP-4, VEGF, and hBMSCs promoted greater bone formation relative to any single factor or combination of two factors. Materials systems that allows multifactorial presentation more closely mimic natural developmental processes, and these results may have important implications for bone regeneration therapeutics.
Identification and Characterization of cis-Acting Elements in the Human and Bovine PTH mRNA 3′-Untranslated Region
Authors: Bell Osnat , Silver Justin , Naveh-Many Tally 
Published: April 2006

Abstract
The human PTH mRNA 3′-UTR has a cis element homologous to the rat cis-acting instability element and a more proximal element identical to the single binding element identified in bovine PTH mRNA 3′-UTR. The function of the elements was shown in vitro.
Introduction: In the rat, Ca2+ and phosphate regulate PTH mRNA stability by the interaction of trans-acting proteins with a defined cis-acting instability element in the distal region of the PTH mRNA 3′-untranslated region (UTR). This element has been characterized in the rat and is conserved in human, canine, feline, and murine 3′-UTRs but not in bovine and porcine 3′-UTRs.
Materials and Methods: Parathyroid protein-binding assays to the PTH mRNA transcripts were performed. Functionality was studied in reporter genes that were transiently transfected into HEK293 cells.
Results: Protein-RNA binding experiments identified an element in bovine PTH mRNA at the proximal end of the 3′-UTR that is different from the rat protein-binding element. The human 3′-UTR contains both elements, but only the distal element binds proteins. Functional studies with HEK293 cells transiently transfected with reporter genes containing the different elements and flanking nucleotides (nt) showed that the human distal element destabilized a reporter mRNA similar to the effect of this element in the rat. A reporter mRNA containing the single bovine PTH mRNA protein-binding element was also destabilized, and this was prevented by coexpression of AU-rich element binding factor 1 (AUF1).
Conclusion: Our results identify a new protein-binding element in the PTH mRNA 3′-UTR. In bovine PTH mRNA, it is the only element, and it is functional in destabilizing a reporter gene. It is also present in other species, including human PTH mRNA, where it is not functional, possibly because of differences in flanking sequences. The human PTH mRNA 3′-UTR distal element is highly homologous to the rat cis-acting instability element and destabilized a reporter gene, indicating its functionality. Therefore, different species have alternative cis-acting protein-binding elements that may determine the regulation of PTH mRNA stability in response to changes in serum calcium and phosphate.
Functional Analysis of the Single Nucleotide Polymorphism (787T&gt;C) in the Tissue-Nonspecific Alkaline Phosphatase Gene Associated With BMD
Authors: Goseki-Sone Masae , Sogabe Natsuko , Fukushi-Irie Mariko , Mizoi Lena , Orimo Hideo , Suzuki Takao , Nakamura Hiroyuki , Orimo Hajime , Hosoi Takayuki 
Published: April 2006

Abstract
Polymorphisms of the TNSALP gene have not previously been studied as a possible determinant for variations in BMD or as a predisposing genetic factor for osteoporosis. This study showed a significantly higher association between the 787T&gt;C (Tyr246His) TNSALP gene and BMD among 501 postmenopausal women. Furthermore, the effects of amino acid substitution on the catalytic property of the protein translated from the 787T&gt;C gene were examined.
Introduction: Alkaline phosphatase (ALP) is present mainly on the cell membrane in various tissues and hydrolyzes a variety of monophosphate esters into inorganic phosphoric acid and alcohol. Human ALPs are classified into four types: tissue-nonspecific, intestinal, placental, and germ cell types. Based on studies of hypophosphatasia, which is a systemic skeletal disorder resulting from a tissue-nonspecific ALP (TNSALP) deficiency, TNSALP was suggested to be indispensable for bone mineralization.
Materials and Methods: We explored the possibility that the TNSALP gene may contribute to age-related bone loss in humans by examining the association between TNSALP gene polymorphisms and BMD in 501 Japanese postmenopausal women. To analyze the protein translated from the TNSALP gene associated with BMD, we constructed a TNSALP cDNA expression plasmid.
Results: We genotyped two single nucleotide polymorphisms (787T&gt;C[Tyr246His] and 876A&gt;G[Pro275Pro]), which proved to be in complete linkage disequilibrium. There was a significant difference in BMD and the BMD score adjusted for age and body weight (Z score) among haplotypes (p = 0.041), which was lowest among 787T/876A homozygotes, highest among 787T&gt;C/876A&gt;G homozygotes, and intermediate among heterozygotes. In subgroups divided by age, haplotypes were significantly associated with BMD in older postmenopausal women (&gt;74 years; p = 0.001), but not in younger postmenopausal women (&lt;74 years; p = 0.964). Expression of the 787T&gt;C TNSALP gene using COS-1 cells showed that the protein translated from 787T&gt;C had ALP-specific activity similar to that of 787T. Interestingly, the Km value for TNSALP in cells transfected with the 787T&gt;C TNSALP gene was decreased significantly compared with that of cells bearing the 787T gene, reflecting the higher affinity.
Conclusions: These results suggest that variation in TNSALP may be an important determinant of age-related bone loss in humans and that the phosphate metabolism pathway may provide a novel target for the prevention and treatment of osteoporosis.
Low Skeletal Muscle Mass Is Associated With Poor Structural Parameters of Bone and Impaired Balance in Elderly Men—The MINOS Study
Authors: Szulc Pawel , Beck Tom J , Marchand François , Delmas Pierre D 
Published: April 2006

Abstract
In 796 men, 50-85 years of age, decreased relative skeletal muscle mass index was associated with narrower bones, thinner cortices, and a consequent decreased bending strength (lower section modulus), as well as with impaired balance and an increased risk of falls.
Introduction: In men, appendicular skeletal muscle mass (ASM) is correlated positively with BMC and areal BMD (aBMD). In elderly men, low muscle mass and strength (sarcopenia) is associated with difficulties in daily living activities. The aim of this study was to evaluate if ASM is correlated with bone size, mechanical properties of bones, balance, and risk of falls in elderly men.
Materials and Methods: This study used 796 men, 50-85 years of age, belonging to the MINOS cohort. Lifestyle factors were evaluated by standardized questionnaires. Estimates of mechanical bone properties were derived from aBMD measured by DXA. ASM was estimated by DXA. The relative skeletal muscle mass index (RASM) was calculated as ASM/(body height)2.3.
Results: After adjustment for age, body size, tobacco smoking, professional physical activity, and 17β-estradiol concentration, RASM was correlated positively with BMC, aBMD, external diameter, and cortical thickness (r = 0.17-0.34, p &lt; 0.0001) but not with volumetric BMD. Consequently, RASM was correlated with section modulus (r = 0.29-0.39, p &lt; 0.0001). Men in the lowest quartile of RASM had section modulus of femoral neck and distal radius lower by 12-18% in comparison with men in the highest quartile of RASM. In contrast, bone width was not correlated with fat mass, reflecting the load of body weight (except for L3), which suggests that the muscular strain may exert a direct stimulatory effect on periosteal apposition. After adjustment for confounding variables, a decrease in RASM was associated with increased risk of falls and of inability to accomplish clinical tests of muscle strength, static balance, and dynamic balance (odds ratio per 1 SD decrease in RASM, 1.31-2.23; p &lt; 0.05-0.001).
Conclusions: In elderly men, decreased RASM is associated with narrower bones and thinner cortices, which results in a lower bending strength. Low RASM is associated with impaired balance and with an increased risk of falls in elderly men. It remains to be studied whether low RASM is associated with decreased periosteal apposition and with increased fracture risk in elderly men, and whether the difference in skeletal muscle mass between men and women contributes to the between-sex difference in fracture incidence.