bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and Predictors of Fractures in Children After Solid Organ Transplantation: A 5-Year Prospective, Population-Based Study
Authors: Helenius Ilkka , Remes Ville , Salminen Sari , Valta Helena , Mäkitie Outi , Holmberg Christer , Palmu Petri , Tervahartiala Pekka , Sarna Seppo , Helenius Miia , Peltonen Jari , Jalanko Hannu 
Published: April 2006

Abstract
In this population-based prospective follow-up study, children undergoing solid organ transplantation had a highly elevated risk for fractures: The incidence of all fractures was 6-fold higher (92 versus 14 fractures/1000 persons/year; p &lt; 0.001) and vertebral fractures was 160-fold higher (57 versus 0.35 fractures/1000 persons/year; p &lt; 0.001) in the study group compared with the control population. Thus, screening of vertebral fractures at regular intervals is recommended, and preventive strategies should be studied.
Introduction: The incidence and predictors of fractures after solid organ transplantation are not well documented in the pediatric age group.
Materials and Methods: A total of 196 children, which is 93% of patients surviving kidney, liver, and heart transplantation in our country, participated in a retrospective chart review at enrollment followed by a 5-year prospective follow-up study between January 1999 and December 2004. Hospital and medical records were reviewed. All children underwent clinical examinations and answered questionnaires concerning fracture history at the beginning and at the end of the prospective follow-up. Radiographs of the thoracic and lumbar spine were obtained. The fracture incidence was compared with data obtained from public health registries.
Results: Seventy-five (38%) of the transplant patients suffered from a total of 166 fractures after organ transplantation. The incidence of all fractures was 6-fold higher (92 versus 14 fractures/1000 persons/year; p &lt; 0.001) and vertebral fractures was 160-fold higher (57 versus 0.35 fractures/1000 persons/year; p &lt; 0.001) in the study group compared with the control population. The age- and sex-adjusted hazard ratios (95% CI) were 61.3 (40.7-92.4) for vertebral, 17.9 (8.96-35.8) for symptomatic vertebral, 0.99 (0.65-1.50) for nonvertebral, and 2.90 (2.25-3.73) for all fractures in the patients compared with the control population. In a multivariate analysis, older age (hazard ratio [95% CI]; 2.02 [1.07-3.83]), male sex (2.15 [1.22-3.81]), liver transplantation (1.78 [1.01-3.14]), and fractures before transplantation (2.02 [0.92-4.47]) were the most significant independent risk factors.
Conclusions: Children undergoing solid organ transplantation have a highly elevated risk for fractures. Screening of vertebral fractures at regular intervals is recommended, and preventive strategies should be studied.
On Our Age-Related Bone Loss: Insights from a New Paradigm
Authors: Frost Harold M. 
Published: April 2006

Abstract
Bone strength and “mass” normally adapt to the largest voluntary loads on bones. The loads come from muscles, not body weight. Bone modeling can increase bone strength and “mass,” bone remodeling can conserve or reduce them, and each can turn ON and OFF in response to its own threshold range of bone strains. During growth, the loads on bones from body weight and muscle forces increase, and modeling correspondingly increases bone strength and “mass.” In young adults those loads usually plateau, so bone strength can “catch up” and modeling can turn OFF. Meanwhile remodeling keeps existing bone. After about 30 years of age, muscle strength usually decreases. In aging adults this would put bones that had adapted to stronger young-adult muscles into partial disuse and make remodeling begin to reduce their strength and “mass,” as disuse regularly does in experimental situations in other mammals, both growing and adult. Those changes associate strongly with the size of the bone strains caused by the loads on bone. While nonmechanical effects associated with aging should contribute to that age-related bone loss too, a new skeletal paradigm suggests the above mechanical influences would dominate control of the process in time and anatomical space.
Chondrocytes Are Regulated by Cellular Adhesion Through CD44 and Hyaluronic Acid Pathway
Authors: Ishida Osamu , Tanaka Yoshiya , Morimoto Isao , Takigawa Masaharu , Eto Sumiya 
Published: April 2006

Abstract
The articular cartilage consists of resident chondrocytes embedded within the extracellular matrix which contains several components such as collagen and hyaluronic acids (HA). CD44 is a major cell surface receptor for HA and is homologous to cartilage-link proteins. Although CD44 is present in cartilage, it is not clear if chondrocytes adhere to HA through CD44 or whether such adhesion changes the function of chondrocytes. We studied the molecular mechanisms of CD44-related chondrocyte adhesion to HA and the effects of such adhesion on chondrocyte function. Experiments were performed using the human chondrosarcoma-derived chondrocyte-like cell line HCS-2/8. Our results showed that (a) HCS-2/8 cells highly expressed CD44; (b) HCS-2/8 cells efficiently adhered to HA without any stimuli; (c) monoclonal antibody (mAb)-blocking studies indicated that adhesion of HCS-2/8 cells to HA was mainly mediated by the CD44/HA pathway; (d) cellular adhesion to HA increased the proliferation of HCS-2/8 cells, independent of transforming growth factor-β (TGF-β), but this was inhibited by CD44 mAb; (e) the adhesion of chondrocytes to HA also induced c-myc mRNA expression and this was also inhibited by CD44 mAb; and (f) the adhesion of cells to HA augmented TGF-β mRNA expression, a process also reduced by CD44 mAb. Thus, HCS-2/8 cells effectively adhered to HA through cell surface CD44. The adhesion was also involved in cellular signaling which induced cellular proliferation and expression of c-myc mRNA as well as TGF-β mRNA expression within the cells. Our results indicate that CD44 on chondrocytes plays an important role in normal and abnormal functions of cartilage through its adhesion to HA, which induces a variety of stimulatory signals to regulate chondrocyte proliferation as well as matrix synthesis in cartilage microenvironment.
Human Stanniocalcin Inhibits Renal Phosphate Excretion in the Rat
Authors: Dr. Wagner Graham F. , Vozzolo Benito L. , Jaworski Ewa , Haddad Michel , Kline Robert L. , Olsen Henrik S. , Rosen Craig A. , Davidson Michael B. , Renfro J. Larry 
Published: April 2006

Abstract
Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fishes where it counteracts hypercalcemia by inhibiting gill calcium uptake and stimulating renal inorganic phosphate (Pi) reabsorption. Human STC (hSTC) has recently been cloned and sequenced and is highly homologous to the fish hormone at the amino acid level. The objective of this study was to examine the possible effects of hSTC on electrolyte homeostasis and renal function in the rat. Recombinant hSTC was expressed in bacteria and purified by metal-ion affinity chromatography and reverse-phase high performance liquid chromatography. Anesthetized animals were given bolus infusions of 1, 5, or 10 nmol hSTC per kilogram of body weight. Control animals received solvent alone. The most effective dosage was 5 nmol/kg, which caused significant reductions in both absolute and fractional phosphate excretion in comparison with control rats. The hSTC had no effect on the renal excretion of other ions, the glomerular filtration rate, renal blood flow, blood pressure, or plasma electrolytes (Na+, K+, Ca2+, Pi, Mg2+). The maximum effect of hSTC on phosphate excretion was observed 60–80 minutes postinjection. Lesser effects were obtained with higher and lower dosages of hormone. When renal cortical brush-border membrane vesicles were isolated from control and hormone-treated animals 80 minutes postinjection, the rate of Na+/Pi cotransport was found to be 40% higher in vesicles from hormone-treated animals (p &lt; 0.01; 5 nmol hSTC/kg). Together, the renal clearance and membrane vesicle data indicate that hSTC participates in the renal regulation of Pi homeostasis in mammals.
High-Impact Exercise Promotes Bone Gain in Well-Trained Female Athletes
Authors: Taaffe Dennis R. , Robinson Tracey L. , Snow Christine M. , Marcus Robert 
Published: April 2006

Abstract
Maximizing peak bone mass, as well as reducing its loss after menopause, is important for the prevention of osteoporosis. One mode of activity, gymnastics training, invokes high impact loading strains on the skeleton which may have powerful osteogenic effects. To examine the role of athletic activity, specifically gymnastics, on bone mineral density (BMD) accretion, we monitored longitudinal changes in regional and whole body BMD in collegiate women gymnasts and competitive athletes whose skeletons are exposed to differential loading patterns: runners and swimmers. Two cohorts were studied. Cohort I = 26 gymnasts (19.7 ± 1.2 years), 36 runners (21.1 ± 2.7 years) and 14 nonathletic women (19.3 ± 1.7 years) followed over an 8-month period. Cohort II = 8 gymnasts (18.9 ± 1.1 years), 11 swimmers (20.0 ± 2.3 years) and 11 nonathletic women (19.0 ± 1.2 years) followed over a 12-month period. Lumbar spine (L2–4), femoral neck, and whole body BMD (g/cm2) were assessed by dual-energy X-ray absorptiometry. For cohort I, the percent change in lumbar spine BMD after 8 months was significantly greater (p = 0.0001) in the gymnasts (2.8 ± 2.4%) than in the runners (−0.2 ± 2.0%) or controls (0.7 ± 1.3%). An increase in femoral neck BMD of 1.6 ± 3.6% in gymnasts was also greater (p &lt; 0.05) than runners (−1.2 ± 3.0%) and approached significance compared with controls (−0.9 ± 2.2%, p = 0.06). For cohort II, gymnasts gained 2.3 ± 1.6% at the lumbar spine which differed significantly (p &lt; 0.01) from changes in swimmers (−0.3 ± 1.5%) and controls (−0.4 ± 1.7%). Similarly, the change at the femoral neck was greater (p &lt; 0.001) in gymnasts (5.0 ± 3.4%) than swimmers (−0.6 ± 2.8%) or controls (2.0 ± 2.3%). The percent change in BMD at any site did not differ between eumenorrheic and irregularly menstruating athletes. These results indicate that bone mineral at clinically relevant sites, the lumbar spine and femoral neck, can respond dramatically to mechanical loading characteristic of gymnastics training in college-aged women. This occurred despite high initial BMD values and was independent of reproductive hormone status. The results provide evidence to support the view that high impact loading, rather than selection bias, underlies high BMD values characteristic of women gymnasts. Because all athletes underwent resistance training throughout the year of study, muscle strengthening activity did not appear to be a significant factor in the skeletal response observed in gymnasts. We conclude that activities resulting in high skeletal impacts may be particularly osteotropic for young women.
Identification and Characterization of the Insulin-like Growth Factor I Receptor in Mature Rabbit Osteoclasts
Authors: Hou Peng , Sato Takuya , Hofstetter Willy , Foged Niels Tækker 
Published: April 2006

Abstract
In this study, the insulin-like growth factor I (IGF-I) receptor was identified in rabbit osteoclasts at mRNA and protein levels by in situ hybridization and autoradiography, respectively. Using highly purified mature osteoclasts, the IGF-I receptor was characterized on the molecular level according to its size and its affinity and number per osteoclast by isolation of the receptor–ligand complex and by binding studies, respectively, and on the cellular level according to the response of mature osteoclasts to IGF-I stimulation. In situ hybridization and autoradiography experiments showed that osteoclasts express IGF-I receptor mRNA and IGF-I binding sites. Chemical cross-linking of125I-IGF-I bound to the purified mature osteoclasts and subsequent sodium dodecyl sulfide-polyacrylamide gel electrophoresis revealed the specific binding of125I-IGF-I in complexes with molecular masses of 130 and 230 kD consistent with binding to the IGF-I receptor. In competition experiments,125I-IGF-I binding to mature osteoclasts was dose-dependently reduced by unlabeled IGF-I in the picomolar range, whereas 20 nM insulin did not reduce the binding of125I-IGF-I binding. The calculated receptor number was 6000 per osteoclast, and the Kd was 0.10 nM. Searching for a role of the IGF-I receptor in mature osteoclasts, we found no significant influence of IGF-I on the levels of the proform of matrix metaloproteinase 9 and tartrate-resistant acid phosphatase. However, the induction of nuclear fragmentation in serum-depleted cultures of purified mature osteoclasts was dose-dependently inhibited by IGF-I in the picomolar range, but not by 1 nM insulin. These data show that functionally active IGF-I receptor is present in mature osteoclasts.
Fractal Properties of Subchondral Cancellous Bone in Severe Osteoarthritis of the Hip
Authors: Dr. Fazzalari N. L. , Parkinson I. H. 
Published: April 2006

Abstract
Primary osteoarthritis of the hip results in changes to the architecture of subchondral cancellous bone. These changes in architecture occur through the action of osteoclasts and osteoblasts in selectively removing and adding bone. The quantitative description of the bone architecture helps in understanding the etiology of primary osteoarthritis. Fractal analysis is a method for describing complex shapes, which is expressed numerically as the fractal dimension. A box counting method was used, where the perimeter of binary profiles of cancellous bone samples was measured for different box sizes. The fractal dimension was the absolute value of the slope of the straight line segments from the plot of the log number of boxes versus the log box size. Cancellous bone samples from two subchondral regions, superior and inferomedial, to the fovea were analyzed from primary severe osteoarthritic specimens taken following total hip replacement surgery (n = 19, aged 51–80 years) and autopsy controls (n = 25, aged 18–90 years). There were three straight line segments identified on the log–log plot, for each subject, indicating a fractal dimension over three different ranges of scale. The results show that in the superior region there is a highly significant difference between the groups (p &lt; 0.0001) for fractal 1 and pivot point 2. The histomorphometry shows significant differences for bone volume/total volume, bone surface/total volume, trabecular separation, and osteoid surface/total volume between groups. In the inferomedial region fractal 1 and fractal 2 are significantly different. For the histomorphometry, trabecular thickness and eroded surface/total volume are significantly different between the groups. The pivot points, i.e., the box size at which the fractal dimension changes, were of similar magnitude to the trabecular thickness and trabecular separation. These data suggest that the fractal geometry analysis of cancellous bone identifies architectural features not easily recognized by conventional bone histomorphometry. The fractal dimension is a descriptor of bone structure which simplifies the description of a complex structure and enables changes in cancellous bone architecture, due to disease, to be identified.
Cloning and Sequencing of Human PEX from a Bone cDNA Library: Evidence for Its Developmental Stage-Specific Regulation in Osteoblasts
Authors: Guo Rong , Quarles L. Darryl 
Published: April 2006

Abstract
Inactivating mutations of the neutral endopeptidase, PEX, have been identified as the cause of X-linked hypophosphatemia (XLH). Though the function of PEX is unknown, current information suggests that impaired renal phosphate conservation in XLH is due to the failure of PEX to either degrade an undefined phosphaturic factor or activate a novel phosphate-conserving hormone. The physiologically relevant target tissue for the XLH mutation has not been identified. An apparent intrinsic defect of osteoblast function in XLH implicates bone as a possible site of PEX expression. In the current investigation, we employed a polymerase chain reaction (PCR) strategy to amplify a PEX cDNA from a human bone cell cDNA library. We found that the human PEX cDNA encodes a 749 amino acid protein belonging to the type II integral membrane zinc-dependent endopeptidase family. The predicted PEX amino acid sequence shares 96.0% identity to the recently cloned mouse Pex cDNA and has 27–38% identity to other members of the metalloendopeptidase family. Using reverse transcriptase (RT)-PCR with PEX-specific primers, we detected PEX transcripts in both human osteosarcoma-derived MG-63 osteoblasts and in differentiated mouse MC3T3-E1 clonal osteoblasts but not in immature MC3T3-E1 preosteoblasts. The association of impaired mineralization of bone in XLH and the apparent developmental stage-specific expression of PEX in osteoblasts suggest that bone is a physiologically relevant site of PEX expression and that PEX may play an active role in osteoblast-mediated mineralization.
The BsmI Vitamin D Receptor Restriction Fragment Length Polymorphism (bb) Influences the Effect of Calcium Intake on Bone Mineral Density
Authors: Kiel Douglas P. , Myers Richard H. , Cupples L. ADRIENNE , Kong Xiang F. , Zhu Xue H. , Ordovas Jose , Schaefer Ernest J. , Felson David T. , Rush David , Wilson Peter W. F. , Eisman John A. , Holick Michael F. 
Published: April 2006

Abstract
Previous studies of the vitamin D receptor (VDR) polymorphisms and bone mineral density (BMD) have suggested that there may be differences in calcium absorption among groups of women with different VDR genotypes, and that the association may be stronger in younger women. To investigate the association between the VDR polymorphisms and BMD, this study was undertaken in the Framingham Study Cohort and a group of younger volunteers. Subjects from the Framingham Study (ages 69–90 years) included those who underwent BMD testing and who had genotyping for the VDR alleles (n = 328) using polymerase chain reaction methods and restriction fragment length polymorphisms with BsmI (B absence, b presence of cut site). A group of younger volunteer subjects (ages 18–68) also underwent BMD testing and VDR genotyping (n = 94). In Framingham Cohort subjects with the bb genotype, but not the Bb or BB genotypes, there were significant associations between calcium intake and BMD at five of six skeletal sites, such that BMD was 7–12% higher in those with dietary calcium intakes greater than 800 mg/day compared with those with intakes &lt;500 mg/day. The data also suggested that BMD was higher in persons with the bb genotype only in the group with calcium intakes above 800 mg/day. No significant differences were found in the Framingham Cohort for age-, sex-, and weight-adjusted BMD at any skeletal site between those with the BB genotype and those with the bb genotype regardless of 25-hydroxyvitamin D levels or country of origin. In the younger volunteers, BMD of the femoral neck was 5.4% higher (p &lt; 0.05) in the bb genotype group compared with the BB group and 11% higher (p &lt; 0.05) in males with the bb genotype compared with the BB group. There were no significant differences at the lumbar spine. In this study, the association between calcium intake and BMD appeared to be dependent upon VDR genotype. The finding of an association between dietary calcium intake and BMD only in the bb genotype group suggests that the VDR genotype may play a role in the absorption of dietary calcium. Studies that do not consider calcium intake may not detect associations between VDR genotype and BMD. In addition, the association between VDR alleles and BMD may become less evident in older subjects.
Tumor-Induced Osteomalacia: Clinical and Basic Studies
Authors: Shane Elizabeth , Parisien May , Henderson Janet E. , Dempster David W. , Feldman Frieda , Hardy Mark A. , Tohme Jack F. , Karaplis Andrew C. , Clemens Thomas L. 
Published: April 2006

Abstract
A patient with classic clinical and biochemical features of tumor-induced osteomalacia (hypophosphatemia, phosphaturia, and undetectable serum concentrations of 1,25-dihydroxyvitamin D [1,25(OH)2D]) was studied before and after resection of a benign extraskeletal chondroma from the plantar surface of the foot. Presurgical laboratory evaluation was notable for normal serum concentrations of calcium, intact parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), and osteocalcin, increased serum alkaline phosphatase activity, and frankly elevated urinary cyclic adenosine monophosphate (cAMP) and pyridinium cross-link excretion. Quantitative histomorphometry showed severe osteomalacia and deep erosions of the cancellous surface by active osteoclasts. After resection, serum 1,25(OH)2D normalized within 24 h, while renal tubular phosphorus reabsorption and serum phosphorus did not normalize until days 2 and 3, respectively; serum Ca declined slightly, and serum intact PTH, osteocalcin, and urinary pyridinium cross-link excretion increased dramatically. Urinary cAMP excretion declined immediately after resection and then began to increase concomitant with the increase in serum intact PTH. A second bone biopsy taken 3 months after resection demonstrated complete resolution of the osteomalacia, increased mineral apposition rate (1.09 μ/day), resorption surface (9.2%), mineralizing surface (71%), and bone formation rate (0.83 mm3/mm2/day), and marked decreases in cancellous bone volume (13.1%) and trabecular connectivity compared with the first biopsy. Tumor extracts did not affect phosphate transport in renal epithelial cell lines or 1α-hydroxylase activity in a myelomonocytic cell line. The patient's course suggests that the abnormal 1,25(OH)2D and phosphorus metabolism is due to a tumor product that may be acting via stimulation of adenylate cyclase activity. Increased bone resorption prior to surgical resection suggests that the tumor may also produce an osteoclast activator. The rise in resorption surface and pyridinium cross-link excretion, increase in serum osteocalcin and bone mineralization, normalization of osteoid width, and fall in cancellous bone volume after resection are consistent with healing of osteomalacia by rapid remodeling.
Normal Human Cementum-Derived Cells: Isolation, Clonal Expansion, and In Vitro and In Vivo Characterization
Authors: Grzesik Wojciech J. , Kuzentsov Sergei A. , Uzawa Katsuhiro , Mankani Mahesh , Robey Pamela Gehron , Yamauchi Mitsuo 
Published: April 2006

Abstract
Cultures of primary human cementum-derived cells (HCDCs) were established from healthy premolar teeth extracted for orthodontic reasons. Cementum was manually dissected, fragmented, and digested twice with collagenase. Following a thorough wash to remove liberated cells, the remaining cementum fragments were plated in Dulbecco's modified Eagle's medium/F12 medium containing 10% fetal bovine serum. Discrete colonies that contained cells exhibiting fibroblast-like morphology were visible after 14–21 days of culture. When the colonies became sufficiently large, cells from individual colonies were isolated and subcultured. Cementum-derived cells exhibited low levels or no alkaline phosphatase activity and mineralized in vitro to a lesser degree than human periodontal ligament (PDL) cells and human bone marrow stromal cell (BMSC) cultures. To study differentiation capacities of HCDCs, cells were attached to hydroxyapatite/tricalcium phosphate ceramic and transplanted subcutaneously into immunodeficient mice. The transplants were harvested 3, 6, and 8 weeks after transplantation and evaluated histologically. In human BMSC transplants, new bone tissue was formed with a prominent osteoblastic layer and osteocytes embedded in mineralized bone matrix. No osseous tissue was formed by PDL cells. Of six single colony-derived strains of HCDCs tested, three formed a bone-like tissue that featured osteocyte/cementocyte-like cells embedded within a mineralized matrix and which was lined with a layer of cells, although they were somewhat more elongated than osteoblasts. These results show that cells from normal human cementum can be isolated and expanded in vitro. Furthermore, these cells are capable of differentiating and forming mineralized tissue when transplanted into immunodeficient mice.