bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fracture Prediction From Bone Mineral Density in Japanese Men and Women
Authors: Fujiwara Saeko , Kasagi Fumiyoshi , Masunari Naomi , Naito Kumiko , Suzuki Gen , Fukunaga Masao 
Published: April 2006

AbstractIn a cohort of 2356 Japanese elderly, after adjusting for age and prevalent vertebral fracture, baseline BMD predicted the risk of spine and hip fracture with similar RR to that obtained from previous reports in whites. The RR per SD decrease in BMD for fracture declined with age.Introduction: Low bone mineral density (BMD) is one of the most important predictors of a future fracture. However, we are not aware of any reports among Japanese in Japan.Materials and Methods: We examined the association of BMD with risk of fracture of the spine or hip among a cohort of 2356 men and women aged 47–95 years, who were followed up by biennial health examinations. Follow-up averaged 4 years after baseline measurements of BMD that were taken with the use of DXA. Vertebral fracture was assessed using semiquantitative methods, and the diagnosis of hip fracture was based on medical records. Poisson and Cox regression analysis were used.Results: The incidence was twice as high in women as in men, after adjusting for age. After adjusting for baseline BMD and prevalent vertebral fracture, however, the gender difference was no longer significant. Age, baseline BMD of spine and femoral neck, and prior vertebral fracture predicted vertebral fracture and hip fracture. Loss of absolute BMD of the femoral neck predicted spine fracture, after adjusting for baseline BMD; rates of change in percent BMD, weight, height, body mass index, and age at menopause did not. The predictive value of baseline BMD for vertebral fracture risk was similar in men and women. The relative risk (RR) for vertebral fracture and hip fracture per SD decrease in BMD declined with age, after adjustment for prevalent vertebral fractures.Conclusions: Baseline BMD, loss of femoral neck BMD, and prior vertebral fracture predict the risk of spine and hip fracture in Japanese with similar RR to that obtained from previous reports in whites. The RR per SD decrease in BMD for fracture declined with age, suggesting that factors other than BMD might play a greater role in the elderly.
Impaired Fracture Healing in the Absence of TNF-α Signaling: The Role of TNF-α in Endochondral Cartilage Resorption
Authors: Gerstenfeld LC , Cho T-J , Kon T , Aizawa T , Tsay A , Fitch J , Barnes GL , Graves DT , Einhorn TA 
Published: April 2006

Abstract
TNF-α is a major inflammatory factor that is induced in response to injury, and it contributes to the normal regulatory processes of bone resorption. The role of TNF-α during fracture healing was examined in wild-type and TNF-α receptor (p55−/−/p75−/−)-deficient mice. The results show that TNF-α plays an important regulatory role in postnatal endochondral bone formation.
Introduction: TNF-α is a major inflammatory factor that is induced as part of the innate immune response to injury, and it contributes to the normal regulatory processes of bone resorption.
Methods: The role of TNF-α was examined in a model of simple closed fracture repair in wild-type and TNF-α receptor (p55−/−/p75−/−)-deficient mice. Histomorphometric measurements of the cartilage and bone and apoptotic cell counts in hypertrophic cartilage were carried out at multiple time points over 28 days of fracture healing (n = 5 animals per time point). The expression of multiple mRNAs for various cellular functions including extracellular matrix formation, bone resorption, and apoptosis were assessed (triplicate polls of mRNAs).
Results and Conclusions: In the absence of TNF-α signaling, chondrogenic differentiation was delayed by 2–4 days but subsequently proceeded at an elevated rate. Endochondral tissue resorption was delayed 2–3 weeks in the TNF-α receptor (p55−/−/p75−/−)-deficient mice compared with the wild-type animals. Functional studies of the mechanisms underlying the delay in endochondral resorption indicated that TNF-α mediated both chondrocyte apoptosis and the expression of proresorptive cytokines that control endochondral tissue remodeling by osteoclasts. While the TNF-α receptor ablated animals show no overt developmental alterations of their skeletons, the results illustrate the primary roles that TNF-α function contributes to in promoting postnatal fracture repair as well as suggest that processes of skeletal tissue development and postnatal repair are controlled in part by differing mechanisms. In summary, these results show that TNF-α participates at several functional levels, including the recruitment of mesenchymal stem, apoptosis of hypertrophic chondrocytes, and the recruitment of osteoclasts function during the postnatal endochondral repair of fracture healing.
A Missense Mutation in the Mouse Col2a1 Gene Causes Spondyloepiphyseal Dysplasia Congenita, Hearing Loss, and Retinoschisis
Authors: Donahue Leah Rae , Chang BO , Mohan Subburaman , Miyakoshi Nao , Wergedal Jon E , Baylink David J , Hawes Norman L , Rosen Clifford J , Ward-Bailey Patricia , Zheng Qing Y , Bronson Roderick T , Johnson Kenneth R , Davisson Muriel T 
Published: April 2006

Abstract
A missense mutation in the mouse Col2a1 gene has been discovered, resulting in a mouse phenotype with similarities to human spondyloepiphyseal dysplasia (SED) congenita. In addition, SED patients have been identified with a similar molecular mutation in human COL2A1. This mouse model offers a useful tool for molecular and biological studies of bone development and pathology.
Introduction: A new mouse autosomal recessive mutation has been discovered and named spondyloepiphyseal dysplasia congenita (gene symbol sedc).
Materials and Methods: Homozygous sedc mice can be identified at birth by their small size and shortened trunk. Adults have shortened noses, dysplastic vertebrae, femora, and tibias, plus retinoschisis and hearing loss. The mutation was mapped to Chr15, and Col2a1 was identified as a candidate gene.
Results: Sequence analyses revealed that the affected gene is Col2a1, which has a missense mutation at exon 48 causing an amino acid change of arginine to cysteine at position 1417. Two human patients with spondyloepiphyseal dysplasia (SED) congenita have been reported with the same amino acid substitution at position 789 in the human COL2A1 gene.
Conclusions: Thus, sedc/sedc mice provide a valuable model of human SED congenita with molecular and phenotypic homology. Further biochemical analyses, molecular modeling, and cell culture studies using sedc/sedc mice could provide insight into mechanisms of skeletal development dependent on Col2a1 and its role in fibril formation and cartilage template organization.
Noninvasive In Vivo Monitoring of Bone Architecture Alterations in Hindlimb-Unloaded Female Rats Using Novel Three-Dimensional Microcomputed Tomography
Authors: David Valentin , Laroche Norbert , Boudignon Benjamin , Lafage-Proust Marie-Hélène , Alexandre Christian , Ruegsegger Peter , Vico Laurence 
Published: April 2006

Abstract
We tested a novel microcomputed tomograph designed to longitudinally and noninvasively monitor bone alterations in hindlimb-unloaded female rats at a resolution of 26 μm over a period of 3 weeks. This prototype has a potential to detect three-dimensional trabecular microarchitectural changes induced by growth and unloading.
Introduction: Until now, data concerning structural changes of cancellous bone have only been available after necropsy of animals. In this study, we tested a novel microcomputed tomography (μCT) technique designed to monitor such changes repeatedly at a resolution of 26 μm with an acquisition time of about 10 minutes to map the entire proximal tibial metaphysis.
Materials and Methods: Four-month-old female Wistar rats were randomized to seven groups of 10 animals to be either tail-suspended or to act as controls. μCT and DXA measurements were performed at 0, 7, 14, and 23 days in suspended and control rats. One group was killed at each of these time points, and bone samples were processed for histomorphometry and ex vivo μCT.
Results: We verified that a good correlation was obtained between two-dimensional bone parameters evaluated in longitudinal tibial sections either by histomorphometry or μCT and μCT parameters obtained from either in vivo or ex vivo tibias. The longitudinal survey allowed earlier detection of both growth and unloading-related bone changes than the transverse survey. In controls, aging induced denser bones, reorganization of the trabecular network toward a more oriented plate-like structure, and an isotropic pattern. Unloading first inhibited cortical and cancellous bone growth and then induced bone loss characterized by fewer trabeculae, reduced connectivity density, and enhanced structure model index (SMI), revealing a lighter cancellous structure with development of rod-like characteristics.
Conclusion: We show for the first time that this μCT prototype has a great potential to accurately, repeatedly, reliably, and rapidly investigate alterations of three-dimensional trabecular microarchitecture.
Cdx-2 Polymorphism in the Promoter Region of the Human Vitamin D Receptor Gene Determines Susceptibility to Fracture in the Elderly
Authors: Fang Yue , Van Meurs Joyce BJ , Bergink Arjan P , Hofman Albert , Van Duijn Cornelia M , Van Leeuwen Johannes Ptm , Pols Huibert AP , Uitterlinden André G 
Published: April 2006

Abstract
A Cdx-2 binding site polymorphism (G to A) in the promoter region of the human vitamin D receptor gene was reported. In an ecological study in eight ethnic groups and an association study in 2848 elderly whites, we found the A-allele to be associated with decreased fracture risk. Our findings expand previous similar findings in a Japanese study to whites and show a relationship with fracture risk of this functional polymorphism.
Introduction: A single nucleotide polymorphism (SNP) within a binding site of the intestinal-specific transcription factor Cdx-2 in the promoter region of the human vitamin D receptor (VDR) gene was previously reported. It was found to modulate the transcription of the hVDR gene and to be associated with decreased bone mineral density in a small group of postmenopausal Japanese women. In this study, we investigated the relationship between the VDR Cdx-2 genotype and risk of fracture.
Methods: We first determined the location of this SNP in the VDR gene by sequencing analysis, and we developed an allele-specific multiplex polymerase chain reaction test to determine the Cdx-2 genotype. We then performed an ecological study in eight ethnic groups and an association analysis in a large epidemiological cohort of 2848 Dutch white men and women, ≥55 years old.
Results and Conclusions: The location of the G to A substitution was found in the promoter region of exon 1e (1e-G−1739A) of the VDR gene. By comparing the frequency of the A-allele in eight different ethnic groups, we observed a negative correlation between prevalence of the A-allele and published hip fracture incidence rates in these ethnic groups (p = 0.006 for men and p = 0.02 for women), suggesting a protective effect of this allele on fracture risk. Subsequently, in the association study, the A-allele (population frequency 19%) was observed to have a protective effect on occurrence of osteoporotic fractures, especially for nonvertebral fracture in women (relative risk of AA versus GG genotype is 0.2; 95% CI, 0.05–0.8). This effect remained after adjustment for age, weight, and bone mineral density. We conclude that the A-allele of the VDR Cdx-2 polymorphism is present in whites, albeit at low frequency, and show a protective effect of this allele on risk of fracture.
Reduced Iliac Cancellous Osteocyte Density in Patients With Osteoporotic Vertebral Fracture
Authors: Qiu Shijing , Rao D Sudhaker , Palnitkar Saroj , Parfitt A Michael 
Published: April 2006

Abstract
Iliac cancellous osteocyte density declines with age, but its relationship to vertebral fracture pathogenesis is unknown. We performed iliac bone biopsy in 44 women with clinical vertebral fracture and 56 healthy women. The fracture patients had 34% fewer osteocytes but no reduction in percent occupied lacunae. Some patients destined to sustain vertebral fracture make cancellous bone with fewer osteocytes.
Introduction: Patient's with vertebral fracture have less bone than appropriate healthy controls, but other factors may contribute to bone fragility. Iliac cancellous osteocyte density declines with age in healthy women; we asked whether this variable differed between fracture patients and healthy controls.
Methods: Two groups of women were assembled. Forty-four (mean age, 66.2 years) had unequivocal evidence of bone fragility manifested as painful nontraumatic vertebral fracture, and 56 (mean age, 62.2 years) were skeletally healthy. All subjects underwent iliac bone biopsy. From archival embedded biopsy cores, new sections were stained with Goldner's trichrome, in which we enumerated osteocyte-occupied lacunae (stained), empty lacunae (unstained), and total lacunae per bone area.
Results: Cancellous osteocyte density was 34% lower in the fracture group than in the controls (p &lt; 0.001); this difference was not a consequence of higher turnover, having less bone, or the small difference in age. The area under the receiver operating characteristic (ROC) curve for discrimination between the groups was &gt;90% for osteocyte density and &lt;75% for bone volume/tissue volume (BV/TV). The disease-related osteocyte deficit was accompanied by a proportionate reduction in empty lacunae and no change in percent occupied lacunae; therefor, it was not the result of premature death. Both superficial bone (&lt;25 μm from the surface) and deep bone (&gt;45 μm from the surface) were affected. In contrast, the age-related deficit is accompanied by an increase in empty lacunae and fall in percent osteocyte-occupied lacunae and occurs only in deep bone, but not in superficial bone.
Conclusions: In some patients destined to sustain spontaneous vertebral compression fracture, iliac cancellous bone is made with fewer osteocytes than normal; the mechanism of osteocyte incorporation into bone needs more detailed study. Osteocyte deficiency could contribute to bone fragility, either by impairing the detection of fatigue microdamage or by reducing canalicular fluid flow. Current practices of defining vertebral fracture based on morphometry alone regardless of symptoms, and diagnosing osteoporosis based on bone densitometry alone regardless of fracture history, should be reexamined.
Determinants of the Size of Incident Vertebral Deformities in European Men and Women in the Sixth to Ninth Decades of Age: The European Prospective Osteoporosis Study (EPOS)
Authors: Reeve J 
Published: April 2006

Abstract
More severe vertebral fractures have more personal impact. In the European Prospective Osteoporosis Study, more severe vertebral collapse was predictable from prior fracture characteristics. Subjects with bi-concave or crush fractures at baseline had a 2-fold increase in incident fracture size and thus increased risk of a disabling future fracture.
Introduction: According to Euler's buckling theory, loss of horizontal trabeculae in vertebrae increases the risk of fracture and suggests that the extent of vertebral collapse will be increased in proportion. We tested the hypothesis that the characteristics of a baseline deformity would influence the size of a subsequent deformity.
Methods: In 207 subjects participating in the European Prospective Osteoporosis Study who suffered an incident spine fracture in a previously normal vertebra, we estimated loss of volume (fracture size) from plane film images of all vertebral bodies that were classified as having a new fracture. The sum of the three vertebral heights (anterior, mid-body, and posterior) obtained at follow-up was subtracted from the sum of the same measures at baseline. Each of the summed height loss for vertebrae with a McCloskey-Kanis deformity on the second film was expressed as a percentage.
Results and Conclusions: In univariate models, the numbers of baseline deformities and the clinical category of the most severe baseline deformity were each significantly associated with the size of the most severe incident fracture and with the cumulated sum of all vertebral height losses. In multivariate modeling, age and the clinical category of the baseline deformity (crush &gt; bi-concave &gt; uni-concave &gt; wedge) were the strongest determinants of both more severe and cumulative height loss. Baseline biconcave and crush fractures were associated at follow-up with new fractures that were approximately twice as large as those seen with other types of deformity or who previously had undeformed spines. In conclusion, the characteristics of a baseline vertebral deformity determines statistically the magnitude of vertebral body volume lost when a subsequent fracture occurs. Because severity of fracture and number of fractures are determinants of impact, the results should improve prediction of the future personal impact of osteoporosis once a baseline prevalent deformity has been identified.
Relationship Between Dental Panoramic Radiographic Findings and Biochemical Markers of Bone Turnover
Authors: Taguchi Akira , Sanada Mitsuhiro , Krall Elizabeth , Nakamoto Takashi , Ohtsuka Masahiko , Suei Yoshikazu , Tanimoto Keiji , Kodama Ichiro , Tsuda Mikio , Ohama Koso 
Published: April 2006

Abstract
We investigated whether mandibular cortical measures on dental panoramic radiographs are associated with biochemical markers of bone turnover in 82 postmenopausal women. Mandibular cortical shape was significantly associated with biochemical markers and spinal BMD. Our results suggest that dentists may be able to identify postmenopausal women with low BMD by using dental panoramic radiographs.
Introduction: Recent studies suggest that mandibular inferior cortical shape and width on dental panoramic radiographs may be useful screening tools for low skeletal bone mineral density (BMD) or increased risk of osteoporotic fracture. However, little is known as to whether these measures are associated with bone turnover. We investigated relationships among dental panoramic radiographic findings, spine BMD, and biochemical markers of bone turnover in postmenopausal women.
Materials and Methods: Of 609 women who visited our clinic for BMD assessment between 1996 and 2002, 82 Japanese postmenopausal women, 46–68 years of age (54.1 ± 4.9 years), were recruited for this study. Mandibular inferior cortical shape (normal, mild/moderate erosion, severe erosion) and width were evaluated on dental panoramic radiographs. BMD at the lumbar spine (L2–L4) was measured by DXA and categorized as normal (T-score &gt; −1.0), osteopenia (T-score, −1.0 to −2.5), or osteoporosis (T-score &lt; −2.5). Bone turnover was estimated by serum total alkaline phosphatase (ALP) and urinary N-telopeptide cross-links of type I collagen (NTx), corrected for creatinine.
Results: The odds of low spine BMD in subjects with any cortical erosion were 3.8 (95% CI, 1.2–12.5). Mandibular cortical erosion was significantly associated with increased NTx (p &lt; 0.001) and ALP (p &lt; 0.05) levels. The associations of spine BMD with NTx and ALP were similar. Mandibular cortical width was significantly associated with spine BMD but not with NTx and ALP levels.
Conclusions: Our results suggest that mandibular inferior cortical shape on dental panoramic radiographs may be an indicator of bone turnover and spine BMD in postmenopausal women. Dentists may be able to identify postmenopausal women with increased risk of osteopenia and osteoporosis on routine dental panoramic radiographs.
Adenovirus Mediated BMP-13 Gene Transfer Induces Chondrogenic Differentiation of Murine Mesenchymal Progenitor Cells
Authors: Nochi Hitoshi , Sung Jin Hyung , Lou Jueren , Adkisson H Davis , Maloney William J , Hruska Keith A 
Published: April 2006

Abstract
Chondrogenic/osteogenic differentiation of a mesenchymal progenitor stimulated by BMP-13 (CDMP-2) was studied. C3H10T1/2 cells were transduced by an adenoviral construct containing BMP-13 or BMP-2. BMP-13 supported chondrogenesis but not terminal differentiation, whereas BMP-2 stimulated endochondral ossification. The studies show that BMP-13 may fail to support terminal chondrocyte differentiation.
Introduction: Bone morphogenetic protein (BMP)-13 is a member of the transforming growth factor β (TGF-β) superfamily of growth factors. Although the biological functions of BMP-13 remain poorly understood, continued postnatal expression of BMP-13 in articular cartilage suggests that this protein may function in an autocrine/paracrine fashion to regulate growth and maintenance of articular cartilage. The purpose of this study was to elucidate the role of BMP-13 in chondrogenic differentiation.
Materials and Methods: Replication-deficient adenoviruses carrying human BMP-13 (Adv-hBMP13), bacterial β-galactosidase (Adv-βgal), and human BMP-2 (Adv-hBMP2) were constructed. Murine mesenchymal progenitor cells (C3H10T1/2) were transduced with these vectors, and differentiation to the chondrogenic lineage was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), biochemical, and histological analyses.
Results and Conclusions: Our findings revealed that hBMP-13 transduced cells differentiated into round cells that stained with Alcian blue. Analysis of gene expression in hBMP-13-transduced cells demonstrated presence of cartilage-specific markers, absence of hypertrophic chondrocyte specific markers, and upregulation of proteoglycan biosynthesis. In particular, hBMP-13-transduced cells had significantly less and delayed expression of alkaline phosphatase activity and calcium mineral accumulation than hBMP-2-transduced cells. Except for BMPR-IB/ALK-6, expression of BMP receptors was identified constitutively in C3H10T1/2 cells and was not affected by the presence of either of the BMPs. In summary, hBMP-13, while stimulating chondrogenesis, failed to support differentiation to hypertrophic chondrocytes and endochondral ossification similar to hBMP-2. Thus, this may prove to be a useful strategy for cell-based regeneration of articular cartilage.