bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Mineral Response to a 7-Month Randomized Controlled, School-Based Jumping Intervention in 121 Prepubertal Boys: Associations With Ethnicity and Body Mass Index
Authors: Mackelvie K. J. , Mckay H. A. , Petit M. A. , Moran O. , Khan K. M. 
Published: April 2006

Abstract
We examined the effects of a 7-month jumping intervention (10 minutes, 3 times per week) on bone mineral gain in prepubertal Asian and white boys (10.3 ± 0.6 years, 36.0 ± 9.2 kg) at 14 schools randomized to control (n = 60) and intervention (n = 61) groups. Intervention and control groups had similar mean baseline and change in height, weight, lean mass and fat mass, baseline areal bone mineral density (aBMD; g/cm2), bone mineral content (BMC; g; dual-energy X-ray absorptiometry [DXA], QDR 4500W), and similar average physical activity and calcium intakes. Over 7 months, the intervention group gained more total body (TB) BMC (1.6%, p &lt; 0.01) and proximal femur (PF) aBMD (1%, p &lt; 0.05) than the control group after adjusting for age, baseline weight, change in height, and loaded physical activity. We also investigated the 41 Asian and 50 white boys (10.2 ± 0.6 years and 31.9 ± 4.4 kg) who were below the 75th percentile (19.4 kg/m2) of the cohort mean for baseline body mass index (BMI). Boys in the intervention group gained significantly more TB and lumbar spine (LS) BMC, PF aBMD, and trochanteric (TR) aBMD (+ ∼2%) than boys in the control group (adjusted for baseline weight, final Tanner stage, change in height, and loaded physical activity). Bone changes were similar between Asians and whites. Finally, we compared the boys in the control group (n = 16) and the boys in the intervention group (n = 14) whose baseline BMI fell in the highest quartile (10.5 ± 0.6 years and 49.1 ± 8.2 kg). Seven-month bone changes (adjusted as aforementioned) were similar in the control and intervention groups. In summary, jumping exercise augmented bone mineral accrual at several regions equally in prepubertal Asian and white boys of average or low BMI, and intervention effects on bone mineral were undetectable in high BMI prepubertal boys.
Neuromuscular and Psychomotor Function in Elderly Subjects Who Fall and the Relationship With Vitamin D Status
Authors: Dr. Dhesi J. K. , Bearne L. M. , Moniz C. , Hurley M. V. , Jackson S. H. D. , Swift C. G. , Allain T. J. 
Published: April 2006

Abstract
Vitamin D and calcium supplementation significantly reduces the incidence of fractures. Evidence suggests vitamin D deficiency impairs neuromuscular function, causing an increase in falls and thereby fractures. The relationship between vitamin D, functional performance, and psychomotor function in elderly people who fall was examined in a prospective cross-sectional study. Patients were recruited from a falls clinic and stratified according to serum 25-hydroxyvitamin-D levels (25OHD): group 1, 25OHD &lt; 12 μg/liter; group 2 25OHD, 12-17 μg/liter; and group 3, 25OHD &gt; 17 μg/liter. Healthy elderly volunteers with 25OHD &gt; 17 μg/liter comprised group 4 (n = 20/group). Measures included aggregate functional performance time (AFPT, seconds), isometric quadriceps strength (Newtons), postural sway (degrees), and choice reaction time (CRT, seconds). Serum bone biochemistry, 25OHD, and parathyroid hormone levels were measured. Patients who fell had significantly impaired functional performance, psychomotor function, and quadriceps strength compared with healthy subjects (AFPT: 51.0 s vs. 32.8 s, p &lt; 0.05; CRT: 1.66 s vs. 0.98 s, p &lt; 0.05; strength: 223N vs. 271N, t = 2.35, p = 0.02). Group 1 had significantly slower AFPT (66.0 s vs. 44.8 s, t = 4.15, p &lt; 0.05) and CRT (2.37 s vs. 0.98 s, t = 3.59, p &lt; 0.05) than groups 2 and 3. Group 1 had the greatest degree of postural sway and the weakest quadriceps strength, although this did not reach significance. Multivariate analysis revealed 25OHD as an independent variable for AFPT, CRT, and postural sway. PTH was an independent variable for muscle strength. Older people who fall have impaired functional performance, psychomotor function, and muscle strength. Within this group, those with 25OHD &lt; 12 μg/liter are the most significantly affected.
Bone Mineral Content per Muscle Cross-Sectional Area as an Index of the Functional Muscle-Bone Unit
Authors: Schoenau Eckhard , Neu Christina Maria , Beck Bodo , Manz Friedrich , Rauch Frank 
Published: April 2006

Abstract
Bone densitometric data often are difficult to interpret in children and adolescents because of large inter- and intraindividual variations in bone size. Here, we propose a functional approach to bone densitometry that addresses two questions: Is bone strength normally adapted to the largest physiological loads, that is, muscle force? Is muscle force adequate for body size? To implement this approach, forearm muscle cross-sectional area (CSA) and bone mineral content (BMC) of the radial diaphysis were measured in 349 healthy subjects from 6 to 19 years of age (183 girls), using peripheral quantitative computed tomography (pQCT). Reference data were established for height-dependent muscle CSA and for the variation with age in the BMC/muscle CSA ratio. These reference data were used to evaluate results from three pediatric patient groups: children who had sustained multiple fractures without adequate trauma (n = 11), children with preterminal chronic renal failure (n = 11), and renal transplant recipients (n = 15). In all three groups mean height, muscle CSA, and BMC were low for age, but muscle CSA was normal for height. In the multiple fracture group and in renal transplant recipients the BMC/muscle CSA ratio was decreased (p &lt; 0.05), suggesting that bone strength was not adapted adequately to muscle force. In contrast, chronic renal failure patients had a normal BMC/muscle CSA ratio, suggesting that their musculoskeletal system was adapted normally to their (decreased) body size. This functional approach to pediatric bone densitometric data should be adaptable to a variety of densitometric techniques.
Localization of the Gene Causing Autosomal Dominant Osteopetrosis Type I to Chromosome 11q12-13
Authors: Van Hul Els , Gram Jeppe , Bollerslev Jens , Van Wesenbeeck Liesbeth , Mathysen Danny , Andersen Poul Erik , Vanhoenacker Filip , Van Hul Wim 
Published: April 2006

Abstract
The osteopetroses are a heterogeneous group of genetic conditions characterized by increased bone density due to impaired bone resorption by osteoclasts. Within the autosomal dominant form of osteopetrosis, the radiological type I (ADOI) is characterized by a generalized osteosclerosis, most pronounced at the cranial vault. The patients are often asymptomatic but some suffer from pain and hearing loss. ADOI is the only type of osteopetrosis not associated with an increased fracture rate. Linkage analysis in two families with ADOI from Danish origin enabled us to assign the disease-causing gene to chromosome 11q12-13. A summated maximum lod score of +6.54 was obtained with marker D11S1889 and key recombinants allowed delineation of a candidate region of 6.6 cM between markers D11S1765 and D11S4113. Previously, genes causing other conditions with abnormal bone density have been identified from this chromosomal region. The TCIRG1gene was shown to underly autosomal recessive osteopetrosis (ARO), and, recently, mutations in the LRP5gene were found both in the osteoporosis-pseudoglioma syndrome and the high bone mass trait. Because both genes map within the candidate region for ADOI, it can not be excluded that ADOI is caused by mutations in either the TCIRG1or the LRP5gene.
Impaired Vascular Invasion of Cbfa1-Deficient Cartilage Engrafted in the Spleen
Authors: Himeno Miki , Enomoto Hirayuki , Liu Wenguang , Ishizeki Kiyoto , Nomura Shintaro , Kitamura Yukihiko , Komori Toshihisa 
Published: April 2006

Abstract
Chondrocyte maturation and vascular invasion of cartilage are essential in the process of endochondral ossification. Cbfa1-deficient (Cbfa1−/−) mice displayed a complete absence of osteoblast and osteoclast maturation as well as severely inhibited chondrocyte maturation in most parts of the skeleton. Although chondrocyte maturation and mineralization were observed in restricted areas of Cbfa1−/− mouse skeleton, vascular invasion of calcified cartilage was never noted. To investigate the possibility of chondrocyte maturation and vascular invasion in Cbfa1−/− cartilage and the role of the hematopoietic system in the process of vascular invasion, we transplanted embryonic day 18.5 (E18.5) Cbfa1−/− femurs, which are composed of immature chondrocytes, into spleens of normal mice. One week later, the transplanted femurs contained terminally differentiated chondrocytes expressing osteopontin, bone sialoprotein (BSP), and matrix metalloproteinase (MMP) 13. In the diaphyses of the transplants, the cartilage matrix was mineralized and the cartilage was invaded by vascular vessels and osteoclasts. However, chondrocyte maturation and vascular invasion were severely retarded in comparison with transplants of E14.5 wild-type femurs, in which the cartilage was rapidly replaced by bone, and neither mature osteoblasts nor bone formation were observed. In primary culture of Cbfa1−/− chondrocytes, transforming growth factor (TGF) β1, platelet-derived growth factor (PDGF), interleukin (IL)-1β, and thyroid hormone (T3) induced osteopontin and MMP-13 expression. These findings indicated that factors in the hematopoietic system are able to support vascular invasion of cartilage independent of Cbfa1 but are less effective without it, suggesting that Cbfa1 functions in cooperation with factors from bone marrow in the process of growth plate vascularization.
Reduction of Osteoclasts in a Critical Embryonic Period Is Essential for Inhibition of Mouse Tooth Eruption
Authors: Yoshino Miya , Yamazaki Hidetoshi , Yoshida Hisahiro , Niida Shumpei , Nishikawa Shin-Ichi , Ryoke Kazuo , Kunisada Takahiro , Hayashi Shin-Ichi 
Published: April 2006

Abstract
Alveolar bone resorption by osteoclasts is essential for tooth eruption. Osteoclast-deficient Csfmop homozygous (op/op) mice, which lack functional macrophage colony-stimulating factor (M-CSF), suffer from osteopetrosis and completely lack tooth eruption. Although osteoclasts appear, and osteopetrosis is cured with age in op/op mice, tooth eruption is never seen. This fact suggests that there is a critical period when osteoclasts are required for tooth eruption. In this study, to detect the critical period, we administered an antagonistic antibody directed against c-Fms, a receptor for M-CSF, to inbred C57BL/6 mice for various periods. Administration of this antibody decreased tartrate-resistant acid phosphatase-positive (TRAP) osteoclasts, and incisor eruption was completely inhibited by continual administration of this antibody from embryonic day 15.5 (E15.5) until postnatal day 12.5 (D12.5). A 1-day delay of this administration abolished the inhibition of incisor eruption. The number of TRAP-positive osteoclasts was significantly reduced between E16.5 and E18.5 in the mice treated with antibody from E15.5 compared with those treated from E16.5. These results indicate that this period, during which the number of osteoclasts decreases significantly, is critical for inhibiting incisor eruption in C57BL/6 mice.
A Novel Immunoassay for The Determination of Tartrate-Resistant Acid Phosphatase 5b From Rat Serum
Authors: Alatalo Sari L , Peng Zhiqi , Janckila Anthony J , Kaija Helena , Vihko Pirkko , Väänänen H Kalervo , Halleen Jussi M 
Published: April 2006

Abstract
Osteoclasts secrete tartrate-resistant acid phosphatase 5b (TRACP 5b) into the circulation. We have developed an immunoassay for the determination of rat TRACP 5b activity. Intra-assay variation of the immunoassay was 4.5%, interassay variation was 3.8%, dilution linearity was 104.6 ± 7.6%, and recovery of recombinant rat TRACP was 99.1 ± 5.8%. We studied serum TRACP 5b as a marker of bone resorption using orchidectomized (ORC) rats as a model for osteoporosis and age-matched sham-operated rats as controls in a 6-month study. After the operation, trabecular bone mineral density decreased significantly more in the ORC group than in the sham group, whereas cortical bone mineral density increased similarly in both groups. Serum TRACP 5b activity was significantly elevated within the first week after ORC, returned to the control level in the third week, and was not increased above the sham level at any of the later time points. At 6 months, trabecular bone volume was 80% lower in ORC rats than in controls. Osteoclast number per trabecular bone perimeter was slightly increased, but the absolute number of osteoclasts in trabecular bone was significantly decreased. These results suggest that absolute bone resorption is increased within the first week after ORC. Later, it is decreased because there is less bone to be resorbed. However, relative bone resorption (compared with the amount of remaining bone) is still increased, leading to further bone loss. We conclude that serum TRACP 5b is a useful marker for monitoring changes in the bone resorption rate in rat ORC model.
Nitric Oxide Promotes Infectious Bone Resorption by Enhancing Cytokine-Stimulated Interstitial Collagenase Synthesis in Osteoblasts
Authors: Lin Sze-Kwan , Kok Sang-Heng , Kuo Mark Yen-Ping , Lee Ming-Shu , Wang Chih-Chiang , Lan Wan-Hong , Hsiao Michael , Goldring Steven R , Hong Chi-Yuan 
Published: April 2006

Abstract
This experiment was undertaken to determine the role of macrophage-derived nitric oxide (NO) in mediating lipopolysaccharide (LPS)-induced bone resorption by using an in vitro co-culture system and an in vivo model of infectious bone resorption. Our results demonstrated that LPS stimulated the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α mRNAs and nitrite synthesis in the J774 mouse macrophage cell line but not in the UMR-106 (rat) and MC3T3-E1 (mouse) osteoblast cell lines. Conditioned media (CM) from LPS-stimulated J774 triggered only low to moderate levels of iNOS mRNAs in MC3T3-E1 and a trivial effect in UMR-106. On the other hand, CM induced matrix metalloproteinase-1 (MMP-1) gene expression in both osteoblast cell lines. The NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) did not alter this effect in MC3T3-E1 and UMR-106, whereas TNF-α antibody diminished the CM-induced MMP-1 gene expression in both cell lines. Interestingly, SNAP, a NO donor, although by itself is not a MMP-1 stimulator for UMR-106, augmented the TNF-α-stimulated MMP-1 mRNA production in UMR-106. In a J774/UMR-106 co-culture system, LPS stimulated significant MMP-1 gene expression in UMR-106, and this upregulation was abolished by L-NMMA and TNF-α antibodies. Immunohistochemical analysis in a rat model of infectious bone resorption (periapical lesion) showed co-distributions of iNOS+ macrophages and MMP-1+ osteoblasts around the osteolytic areas. Administration of L-NMMA markedly reduced the extent of bone loss and the percentage of MMP-1-synthesizing osteoblasts. These data suggest that NO derived from macrophages after LPS stimulation may enhance bone loss by augmenting the cytokine-induced MMP-1 production in osteoblasts.
Chloride Channel ClCN7 Mutations Are Responsible for Severe Recessive, Dominant, and Intermediate Osteopetrosis
Authors: Frattini Annalisa , Pangrazio Alessandra , Susani Lucia , Sobacchi Cristina , Mirolo Massimiliano , Abinun Mario , Andolina Marino , Flanagan Adrienne , Horwitz Edwin M , Mihci Ercan , Notarangelo Luigi D , Ramenghi Ugo , Teti Anna , Van Hove Johan , Vujic Dragana , Young Terri , Albertini Alberto , Orchard Paul J , Vezzoni Paolo , Villa Anna 
Published: April 2006

Abstract
Among 94 osteopetrotic patients presenting with a severe clinical picture and diagnosed early in life, 12 bore mutations in the ClCN7 gene, but only 7 of them had the expected two recessive mutations. The remaining five patients seem to be heterozygous for a ClCN7 mutation, and significant variations were observed in the clinical manifestations of their disease, even within the same family.
Introduction: Human osteopetroses are a heterogeneous group of diseases that include both infantile severe, autosomal recessive (ARO) and adult autosomal dominant (ADO) forms. Two genes, Atp6a3 (TCIRG1) and ClCN7, have been shown to be associated with human ARO, the latter of which is also thought to be responsible for ADO-II. However, patients with an intermediate phenotype have been described: the genetic basis of these observances is unknown.
Materials and Methods: In this study, we report the clinical and molecular analysis of 94 patients in which a diagnosis of severe osteopetrosis was made within the first 2 years of age. Both TCIRG1 and CLCN7 genes were sequenced in all patients and the molecular findings were correlated to clinical parameters.
Results and Conclusions: In 56 of 94 patients with a classical picture of ARO, TCIRG1-dependent recessive mutations were found. In contrast, ClCN7 mutations were found in 12 cases (13%) of severe osteopetrosis, but only 7 of them had two recessive mutations identified: in 6 of these 7 cases, central nervous system manifestations were noted, and these patients had a poor prognosis. The remaining five cases were heterozygous for a ClCN7 mutation, including two brothers from a large family with a history of ADO-II in which the presence of a second ClCN7 mutation was formally excluded. Despite an early and severe clinical presentation, these five patients all reached adulthood, suggesting that the degree of dominant interference with chloride channel function can vary widely. Our findings suggest that recessive ClCN7-dependent ARO may be associated with CNS involvement and have a very poor prognosis, whereas heterozygous ClCN7 mutations cause a wide range of phenotypes even in the same family, ranging from early severe to nearly asymptomatic forms. These findings have prognostic implications, might complicate prenatal diagnosis of human osteopetroses, and could be relevant to the management of these patients.
A Single Nucleotide Polymorphism Under the Reverse Primer Binding Site May Lead to BsmI Mis-Genotyping in the Vitamin D Receptor Gene
Authors: Zajíčková K , Křepelová A , Žofková I 
Published: April 2006

Abstract
The BsmI polymorphism in the VDR gene has been extensively investigated by PCR and restriction digestion in bone genetics. A SNP within the corresponding region for the previously published reverse primer was observed and confirmed by DNA sequencing. BsmI mis-genotyping caused by this SNP could confound genetic findings.
Introduction: By analyzing the FokI, BsmI, ApaI, and TaqI polymorphisms in the vitamin D receptor (VDR) gene, we observed a significantly different genotype distribution in the BsmI polymorphic locus with a deviation from Hardy-Weinberg equilibrium. One of the reasons for polymerase chain reaction (PCR) non-amplification may be a mismatched base at the primer binding region. Therefore, the aim of this study was to analyse whether a single nucleotide polymorphism (SNP), which has been recently described as TruI, is responsible for the discrepancy between expected and observed genotype frequencies.
Materials and Methods: The VDR genotypes were identified in a cohort of 165 peri- and postmenopausal women of white origin. PCR amplification was carried out using the originally published primers and followed by restriction cleavage. The BsmI genotypes were further verified with a reverse primer external to the original binding site. The presence of the TruI polymorphism under the previously published reverse primer was confirmed by a restriction digestion and DNA sequencing. In Bb subjects, the colocalization of b allele with the TruI restriction site on the same chromosome was confirmed by a simultaneous digestion of the PCR product with both BsmI and TruI restriction enzymes.
Results: The BsmI reanalysis with an external primer provided a higher number of heterozygous subjects with a proportionally smaller number of BB subjects, and the changed genotype distribution was under Hardy-Weinberg equilibrium (BB, 31; Bb, 80; bb, 54; r = 0.0203; p = 0.90). In our primary analysis, the presence of the TruI polymorphism led to a drop out of b allele during PCR amplification and thus to the false prevalence of BB genotypes (BB, 50; Bb, 61; bb, 54; r = 11.17; p = 0.01).
Conclusion: The SNP in the region corresponding to the reverse primer may lead to BsmI mis-genotyping, which may have confounded some previous genetic studies.
Bone Remodeling at the Endocortical Surface of the Human Femoral Neck: A Mechanism for Regional Cortical Thinning in Cases of Hip Fracture
Authors: Power J , Loveridge N , Lyon A , Rushton N , Parker M , Reeve J 
Published: April 2006

Abstract
Endocortical remodeling and wall thickness (W.Th.) were measured in femoral neck bone from 12 female fracture cases (81.3 ± 1.5 years) and 12 sex-matched controls (81.9 ± 1.9 years). Regionally, osteoid and eroded surface were increased, whereas W.Th. was reduced. These processes likely contribute to cortical bone loss seen in hip fracture.
Introduction: Because periosteal expression of alkaline phosphatase was similar between cases and controls, we hypothesized that the mechanism causing the marked femoral neck cortical thinning associated with hip fracture may be net endocortical bone loss.
Methods: Twelve female cases of femoral neck fracture (mean age = 81.3 ± 1.5 years) and 12 age- and sex-matched postmortem controls (mean age = 81.9 ± 1.9 years) were included in the study. Samples of their femoral neck bone were embedded in methyl methacrylate, sectioned at 10 μm, and stained with Solochrome cyanine R and Goldner's trichrome for the detection of osteoid (%OS/BS) and resorption surfaces (%ES/BS) respectively. In addition, wall thickness (W.Th.) and lamellar thickness (Lm.Th.) data were also collected from identifiable endocortical bone packets as a measure of formative potential.
Results and Conclusions: %OS/BS was significantly elevated in the anterior (control = 3.4 ± 0.7: fracture = 11.0 ± 2.3; p = 0.0001), inferior (3.4 ± 1.0: 9.9 ± 3.0; p = 0.0009), and posterior quadrants (3.2 ± 0.8: 9.1 ± 2.3; p = 0.0021). Only for anterior region was increased %ES/BS demonstrated in the fracture group (2.8 ± 0.6: 5.3 ± 0.7; p = 0.055). W.Th. (mm) was reduced only in the inferior region of the fracture cases (control = 33.7 ± 1.2: fracture = 30.6 ± 0.9; p = 0.013), whereas Lm.Th. was also reduced inferiorly (control = 2.7 ± 0.08: fracture = 2.5 ± 0.08; p = 0.042). These data suggest that an endocortical remodeling imbalance involving reduced bone formation within inferior region coupled with elevated anterior resorption may make an important contribution to the cortical thinning observed in cases of femoral neck fracture.