bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Exclusion of High Trauma Fractures May Underestimate the Prevalence of Bone Fragility Fractures in the Community: The Geelong Osteoporosis Study
Authors: Sanders K. M. , Pasco J. A. , Ugoni A. M. , Nicholson G. C. , Seeman E. , Martin T. J. , Skoric B. , Panahi S. , Kotowicz M. A. 
Published: April 2006

Abstract
Fractures associated with severe trauma are generally excluded from estimates of the prevalence of osteoporotic fractures in the community. Because the degree of trauma is difficult to quantitate, low bone mass may contribute to fractures following severe trauma. We ascertained all fractures in a defined population and compared the bone mineral density (BMD) of women who sustained fractures in either “low” or “high” trauma events with the BMD of a random sample of women from the same population. BMD was measured by dual-energy X-ray absorptiometry and expressed as a standardized deviation (Z score) adjusted for age. The BMD Z scores (mean ± SEM) were reduced in both the low and high trauma groups, respectively: spine-posterior-anterior (−0.50 ± 0.05 and −0.21 ± 0.08), spine-lateral (−0.28 ± 0.06 and −0.19 ± 0.10), femoral neck (−0.42 ± 0.04 and −0.26 ± 0.09), Ward's triangle (−0.44 ± 0.04 and −0.28 ± 0.08), trochanter (−0.44 ± 0.05 and −0.32 ± 0.08), total body (−0.46 ± 0.06 and −0.32 ± 0.08), ultradistal radius (−0.47 ± 0.05 and −0.42 ± 0.07), and midradius (−0.52 ± 0.06 and −0.33 ± 0.09). Except at the PA spine, the deficits were no smaller in the high trauma group. Compared with the population, the age-adjusted odds ratio for osteoporosis (t-score &lt; −2.5) at one or more scanning sites was 3.1 (95% confidence interval 1.9, 5.0) in the high trauma group and 2.7 (1.9, 3.8) in the low trauma group. The data suggest that the exclusion of high trauma fractures in women over 50 years of age may result in underestimation of the contribution of osteoporosis to fractures in the community. Bone density measurement of women over 50 years of age who sustain fractures may be warranted irrespective of the classification of trauma.
Mutations of CTSK Result in Pycnodysostosis via a Reduction in Cathepsin K Protein
Authors: Ho Nicola , Punturieri Antonello , Wilkin Douglas , Szabo Jinny , Johnson Maureen , Whaley Justine , Davis Joie , Clark Alison , Weiss Stephen , Francomano Clair 
Published: April 2006

Abstract
Pycnodyostosis, an autosomal recessive osteosclerosing skeletal disorder, has recently been shown to result from mutations in the cathepsin K gene. Cathepsin K, a lysosomal cysteine protease with an abundant expression in osteoclasts, has been implicated in osteoclast-mediated bone resorption and remodeling. DNA sequence analysis of the cathepsin K gene in a nonconsanguineous family demonstrated compound heterozygozity for mutations in two affected siblings. We have identified a missense mutation with a single base G→A transition at cDNA nucleotide 236, resulting in conversion of a conserved glycine to a glutamine residue (G79E). The other mutation is an A→T transition at nucleotide 154, leading to the substitution of a lysine residue by a STOP codon (K52X) predicting premature termination of the precursor cathepsin K polypeptide. Sequencing of genomic and cDNAs from the parents demonstrated that the missense mutation was inherited from the father and the nonsense mutation from the mother. Protein expression in both affected children was virtually absent, while in the parents was reduced by 50–80% compared with controls. The protein studies demonstrate that even significantly reduced cathepsin K levels do not have any phenotypic effect, whereas absent cathepsin K results in pycnodysostosis.
Growth Retardation in Children with Chronic Renal Failure
Authors: Kuizon Beatriz D. , Salusky Isidro B. 
Published: April 2006

Abstract
Growth retardation is a major obstacle to full rehabilitation of children with chronic renal failure (CRF). Several factors have been identified as contributors to impaired linear growth and they include protein and calorie malnutrition, metabolic acidosis, growth hormone resistance, anemia, and renal osteodystrophy. Although therapeutic interventions such as the use of recombinant human growth hormone, recombinant human erythropoietin, and calcitriol have made substantial contributions, the optimal therapeutic strategy remains to be defined. Indeed, growth failure persists in a substantial proportion of children with renal failure and those treated with maintenance dialysis. In addition, the increasing prevalence of adynamic lesions of renal osteodystrophy and its effect on growth have raised concern about the continued generalized use of calcitriol in children with CRF. Recent studies have shown the critical roles of parathyroid hormone–related protein (PTHrP) and the PTH/PTHrP receptor in the regulation of endochondral bone formation. The PTH/PTHrP receptor mRNA expression has been shown to be down-regulated in kidney and growth plate cartilage of animals with renal failure. Differences in the severity of secondary hyperparathyroidism influence not only growth plate morphology but also the expression of selected markers of chondrocyte proliferation and differentiation in these animals. Such findings suggest potential molecular mechanisms by which cartilage and bone development may be disrupted in children with CRF, thereby contributing to diminished linear growth.
Intermittent Administration of Human Parathyroid Hormone(1–34) Prevents Immobilization-Related Bone Loss by Regulating Bone Marrow Capacity for Bone Cells in ddY Mice
Authors: Sakai Akinori , Sakata Takeshi , Ikeda Satoshi , Uchida Soshi , Okazaki Ryuji , Norimura Toshiyuki , Hori Masayuki , Nakamura Toshitaka 
Published: April 2006

Abstract
ddY mice, 6 weeks of age, were neurectomized (Nx) in the right hindlimbs and sham-operated (Sham) in the left limbs for evaluation of the effects of intermittent injections of human parathyroid hormone (hPTH) on trabecular bone turnover and bone marrow cell development in unloaded and loaded limbs. Mice were given subcutaneous injections of hPTH(1–34) five times a week at a dose of 0 (vehicle), 4 (low dose), or 40 (high dose) μg/kg of body weight for 2, 4, or 6 weeks. Histomorphometric analyses of the trabecular bone of the proximal tibiae revealed that high-dose hPTH injections preserved the trabecular bone volume of the Nx limbs, which was reduced after neurectomy, at the same level as that of the contralateral Sham limbs. The mineral apposition rate in the Nx limbs was elevated to values above even that of the Sham limbs by high-dose hPTH injections. The bone formation rate reduced by neurectomy was maintained at the Sham level by low- and high-dose hPTH injections. The neurectomy-induced increase in osteoclast number was suppressed by high-dose hPTH injections. In the bone marrow cells, the numbers of nonadherent and adherent cells per tibia obtained from the Nx and Sham limbs did not change. The hPTH injections decreased the numbers of nonadherent cells and increased those of adherent cells in both the Nx and the Sham limbs, but the effects were less marked in the Nx than in the Sham limbs even at high-dose injections. The formation of osteogenic nodules in the marrow cultures obtained from the Nx limbs was decreased after surgery and was maintained at the level of the Sham limbs by high-dose hPTH injections. The number of osteoclast-like multinucleated cells was reduced in the Sham limbs by high-dose hPTH injections. The value was increased at 2 weeks after neurectomy, but it was maintained at the Sham level by high-dose hPTH injections through the experimental period. The numbers of colony forming units-fibroblastic, which were reduced by neurectomy, and those of colony forming units for granulocytes and macrophages were not altered by hPTH injections. These results demonstrate that intermittent high-dose hPTH administration in the Nx limbs as well as in the contralateral Sham limbs has similar anabolic effects, stimulating osteoblast cell lineage and suppressing osteoclast cell lineage. The anabolic effects at 4 μg were reduced, but the effects at 40 μg seemed to be less affected by unloading due to sciatic neurectomy.
Sphingosine 1-Phosphate Induces Heat Shock Protein 27 via p38 Mitogen-Activated Protein Kinase Activation in Osteoblasts
Authors: Kozawa Osamu , Niwa Masayuki , Matsuno Hiroyuki , Tokuda Haruhiko , Miwa Masaichi , Ito Hidenori , Kato Kanefusa , Uematsu Toshihiko 
Published: April 2006

Abstract
We previously showed that sphingosine 1-phosphate acts as a second messenger for tumor necrosis factor α–induced interleukin-6 synthesis in osteoblast-like MC3T3-E1 cells and that the synthesis by sphingosine 1-phosphate is dependent on p42/p44 mitogen-activated protein (MAP) kinase activation. In the present study, we investigated the effect of sphingosine 1-phosphate on the induction of heat shock protein 27 (HSP27) in MC3T3-E1 cells. Not C2-ceramide, but sphingosine and sphingosine 1-phosphate significantly induced HSP27 accumulation dose dependently in the range between 1μM and 30 μM. DL-threo-dihydrosphingosine, an inhibitor of sphingosine kinase, markedly inhibited the sphingosine-induced HSP27 accumulation. Sphingosine 1-phosphate induced increase in the levels of the mRNA for HSP27. Sphingosine 1-phosphate stimulated the phosphorylation of p38 MAP kinase. The sphingosine 1-phosphate–induced HSP27 accumulation was dose dependently suppressed by SB203580, an inhibitor of p38 MAP kinase, but not PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase. SB203580 reduced the sphingosine 1-phosphate–induced increase of mRNA for HSP27. These results strongly suggest that sphingosine 1-phosphate–stimulated HSP27 induction is mediated via p38 MAP kinase activation in osteoblasts.
Early Estrogen Replacement Therapy Reverses the Rapid Loss of Trabecular Bone Volume and Prevents Further Deterioration of Connectivity in the Rat
Authors: Lane Nancy E. , Haupt David , Kimmel Donald B. , Modin Gunnar , Kinney John H. 
Published: April 2006

Abstract
To evaluate the ability of estrogen replacement therapy (ERT) to prevent changes in trabecular bone volume (BV/TV) and connectivity beginning either at ovariectomy (OVX) or 5–13 days after OVX in adult female rats, the right proximal tibial was examined by three-dimensional X-ray tomographic microscopy (XTM) in vivo. Animals had XTM scans of the right tibia and then were randomized into six groups (n = 9). Groups 2–6 had bilateral (OVX), while group 1 was sham-ovariectomized (OVXd) on day 0. Animals were treated with vehicle (groups 1 and 2) or 17β-estradiol therapy (ERT) at 10 μ g/kg three times per week starting at days 0, 5, 8, and 13 post-OVX (groups 3, 4, 5, and 6), until day 50 when they were rescanned by XTM and sacrificed. Trabecular bone structural variables were calculated from XTM data (BV/TVx and β1/BV/TVx) and standard histomorphometry. Trabecular bone volume (BV/TVx) and the trabecular connections per cubic millimeter of trabecular bone (β1/BV/TVx) were maintained in both sham-OVXd animals and OVX animals given ERT from the time of OVX. However, OVX + vehicle–treated animals lost 54% BV/TVx and 46% β1/BV/TVx (p &lt; 0.01 from day 0). BV/TVx and β1/BV/TVx decreased rapidly post-OVX to −22% and −25% at day 13 (p &lt; 0.01 from day 0). ERT initiated at day 5, 8, and 13 post-OVX restored BV/TVx to baseline values at day 50 by modestly increasing trabecular plate thickness; however, β1/BV/TVx was reduced in all OVX groups when compared with their baseline values. ERT also caused a significant reduction in bone turnover compared with OVX + vehicle; however, resorption was suppressed more than formation. These results demonstrate that ERT can restore the lost trabecular bone, but not trabecular connectivity, that occurs soon after OVX by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. This may be the mechanism by which prompt intervention with estrogen and other antiresorptive agents can restore bone mass that has been lost from the increase in remodeling space, and thereby reduce the risk of osteoporotic fractures in postmenopausal women.
Smoking Increases Bone Loss and Decreases Intestinal Calcium Absorption
Authors: Krall Elizabeth A. , Dawson-Hughes Bess 
Published: April 2006

Abstract
Cigarette use is a risk factor for increased bone mineral density (BMD) loss but the mechanisms are not well understood. The relationship of smoking to rates of BMD change at the femoral neck, spine, and total body, and to intestinal calcium absorption were examined in 402 elderly men and women (32 smokers, 370 nonsmokers) who participated in a 3-year placebo-controlled study of calcium and vitamin D supplementation. Subjects in the supplemented group took 500 mg/day of elemental calcium and 700 IU/day of cholecalciferol. Two-hour calcium absorption fraction was determined three times, at 18, 30, and 36 months, with a single isotope method utilizing45Ca in a subset of 333 subjects. Annualized rates of BMD loss (adjusted for baseline BMD, weight, age, gender, supplementation status, and dietary calcium intake) were higher in smokers than nonsmokers at the femoral neck (−0.714 ± 0.285 %/year vs. +0.038 ± 0.084 %/year, p &lt; 0.02), and total body (−0.360 ± 0.101 %/year vs. −0.152 ± 0.030 %/year, p &lt; 0.05). No significant difference was observed at the spine (+0.260 ± 0.252 %/year in smokers vs. +0.593 ± 0.074 %/year in nonsmokers, p = 0.21). The mean (± SEM) calcium absorption fraction was lower in smokers (12.9 ± 0.8%, n = 23) than nonsmokers (14.6 ± 0.2%, n = 310, p &lt; 0.05) after adjustment for gender, age, supplementation status, and dietary calcium and vitamin D intakes. Smokers of at least 20 cigarettes per day (n = 15) had the lowest mean absorption fraction (12.1 ± 1.1%). With calcium and vitamin D supplementation, the proportionate increase in urinary calcium/creatinine excretion was lower in smokers (44 ± 12%) than nonsmokers (79 ± 9%, p &lt; 0.05). These results suggest that smoking accelerates bone loss from the femoral neck and total body in the elderly and that less efficient calcium absorption may be one contributing factor.
Expression of Gelatinase A and Its Activator MT1-MMP in the Inflammatory Periprosthetic Response to Polyethylene
Authors: Dr. Nawrocki Béatrice , Polette Myriam , Burlet Henriette , Birembaut Philippe , Adnet Jean-Jacques 
Published: April 2006

Abstract
Wear debris of polyethylene prosthetic components is known to induce a host granulomatous reaction which recruits numerous macrophages and multinucleated giant cells. By releasing cellular mediators of a nonspecific inflammatory reaction, activated phagocytic cells are thought to play a key role in osteolysis leading to aseptic loosening of the prosthesis. Matrix metalloproteinases (MMPs) have been implicated in this destructive process by their ability to degrade extracellular matrix components of bone and adjacent connective tissue. To investigate the roles of gelatinase A, its activator MT1-MMP, and the MMP inhibitors TIMP-1 and TIMP-2 in aseptic loosening of polyethylene prostheses, immunohistochemistry (IHC) and in situ hybridization (ISH) were performed on periprosthetic pseudosynovial interface tissues. Gelatinase A and MT1-MMP were strongly detected immunohistochemically in macrophages and multinucleated giant cells in contact with polyethylene wear debris. In contrast to MT1-MMP, gelatinase A mRNAs were not found in phagocytic cells but in surrounding fibroblasts, thereby suggesting cooperation between macrophages and fibroblasts in this process. While TIMP-1 was expressed essentially in hyperplastic pseudosynoviocytes as assessed by IHC and ISH, TIMP-2, MT1-MMP, and gelatinase A were colocalized in phagocytic cells. These data support the concept of progelatinase A activation involving a trimolecular complex (MT1-MMP–TIMP-2–gelatinase A) mechanism. Thus, this study demonstrated that gelatinase A and its activator might contribute to the aseptic loosening of polyethylene prostheses.
Internalization of Phospholipids from the Plasma Membrane of Human Osteoblasts Depends on the Lipid Head Group
Authors: Libera Jeanette , Pomorski Thomas , Josimović-Alasević Oliviera , Fritsch Karl-Gerd , Herrmann Andreas 
Published: April 2006

Abstract
The redistribution of spin- or fluorescence-labeled phospholipid analogs across the plasma membrane of human osteoblast cells, either in suspension or grown as monolayers, was investigated. After incorporation into the outer membrane leaflet, analogs of the aminophospholipids phosphatidylserine and phosphatidylethanolamine moved rapidly to the inner monolayer, whereas the choline-containing analogs of phosphatidylcholine and sphingomyelin disappeared more slowly from the outer leaflet. The fast inward movement of the aminophospholipids became reduced after lowering the intracellular ATP, suggesting the presence of an aminophospholipid translocase activity in the plasma membrane of these cells. From these data, a transverse phospholipid asymmetry in osteoblasts can be inferred with the aminophospholipids mainly concentrated in the inner monolayer and the choline-containing phospholipids in the outer leaflet. A similar pattern of phospholipid internalization was inferred for osteoblasts from human osteoporotic bones and for a human osteosarcoma cell line. The relevance of the enrichment of phosphatidylserine in the cytoplasmic membrane leaflet for calcification in skeletal tissues is emphasized.
Association Between Calcium Ingested from Drinking Water and Femoral Bone Density in Elderly Women: Evidence from the EPIDOS Cohort
Authors: Aptel Isabelle , Cance-Rouzaud Anne , Dr. Grandjean Hélène ,   for the Epidos Study Group:
Published: April 2006

Abstract
Although the main source of dietary calcium is dairy products, the calcium contained in mineral water, which is as available as that of milk, could provide a valuable source of calcium. We analyzed the data from the EPIDOS multicenter study to evaluate the relationship between both dietary calcium and that supplied by drinking water and bone density measured at the femoral neck by dual-energy X-ray absorptiometry. The study included 4434 women over 75 years of age who had not received any treatment likely to interfere with calcium metabolism. A significant correlation was found between total calcium intake and bone density at the femoral neck (r = 0.10, p &lt; 0.001). After adjustment for the main variables influencing bone density, an increase of 100 mg/day in calcium from drinking water was associated to a 0.5% increase in femoral bone density, while a similar increase in dietary calcium from other sources only led to a 0.2% increase; however, this difference was not significant. The consumption of calcium-rich mineral water may be of interest, especially in older women who consume little calcium from dairy products.
Age- and Gender-Related Differences in Vertebral Bone Mass, Density, and Strength
Authors: Ebbesen Ebbe N. , Thomsen Jesper S. , Beck-Nielsen Henning , Nepper-Rasmussen Hans J. , Mosekilde Lis 
Published: April 2006

Abstract
This study was designed to evaluate age- and gender-related differences in vertebral bone mass, density, and strength by dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), peripheral QCT (pQCT), ash measurements, and biomechanical testing. The material comprised human lumbar vertebral bodies (L3) from 51 females and 50 males (age-range: 18–96 years). The results showed that females had significantly lower vertebral body bone mass (ash weight) than males at any given age. The decline in bone mass with age was parallel for females and males. The different bone density measurements—cancellous ash density, total vertebral body ash density, DXA bone mineral density, QCT, and pQCT—showed no gender-related difference concerning numeric value or changes with age. Morphometrical measurements showed that females had smaller vertebral bodies (volumes) than males. Hence the females had significantly smaller cross-sectional area (CSA) of L3 than males (11.6 cm2 and 14.4 cm2, respectively). This led to females having lower maximum compressive load (N) than males at all ages, whereas maximum compressive stress (load/CSA) showed no gender-related difference. In conclusion, females have lower vertebral body bone mass than males at any given age, due to smaller vertebral bodies. Hence, maximum compressive load (strength not corrected for size) was lower in females. Vertebral body cancellous bone density and total-vertebral body density were equal when comparing genders, and no gender differences were found in the size-corrected strength: maximum compressive stress. The decrease with age in vertebral body compressive strength decrease was twice as large as the age decrease in density.
Functional Characterization of Two Promoters in the Human Bone Morphogenetic Protein-4 Gene
Authors: van den Wijngaard Arthur , Pijpers Marie-Antonette , Joosten Paul H. L. J. , Roelofs José M. A. , Van Zoelen Everardus J. J. , Olijve Wiebe 
Published: April 2006

Abstract
Bone morphogenetic protein-4 (BMP-4) is a member of the BMP family, which consists of important regulators of bone formation and embryonic development. We have previously isolated the human BMP-4 encoding gene, which is associated with the heritable disorder Fibrodysplasia Ossificans Progressiva. In this study, we describe the molecular cloning and functional characterization of two promoters involved in the transcriptional regulation of the human BMP-4 gene, one upstream of exon 1, the second located in intron 1, upstream of exon 2. These two promoters give rise to different transcripts in a cell type– and differentiation-dependent manner. Mutational analysis showed cell type–specific regulation of both promoter activities. Gel mobility shift assays indicated the presence of cell type–specific transcription factor binding sites in promoter 1. In addition, evidence was found for a novel BMP-4 transcript. Since various human diseases can be linked directly to aberrant expression of BMP genes, the present findings are of great importance in attempts to develop strategies for therapeutic interference with such diseases.
Discordance Between Bone Turnover and Bone Loss: Effects of Aging and Ovariectomy in the Rat
Authors: Baldock Paul A. J. , Need Allan G. , Moore Robert J. , Durbridge Timothy C. , Dr. Morris Howard A. 
Published: April 2006

Abstract
Mechanical strain maintains bone architecture even under conditions of increased bone turnover such as occurs with ovarian hormone deficiency. The rat distal femur contains two sites that apparently experience different levels of mechanical strain and therefore the rat is a suitable model for investigating such effects. The femoral epiphysis experiences higher strain energy compared with the metaphysis and we report the effects of aging between 7 and 12 months and the postovariectomy effects over the same time period on cancellous bone variables measured at these two sites. Age-related bone loss in sham-operated (Sham) animals occurred in both regions, with a greater fall in the metaphysis than in the epiphysis (trabecular bone volume [BV/TV, %] Mean [SEM] Metaphysis: day 0, 25.9 [2.4]; day 150, 8.8 [1.3]: Epiphysis: day 0, 44.8 [1.7]; day 150, 36.7 [1.4] [p &lt; 0.0001]). With ovariectomy (OVX) there was a 73% reduction in cancellous bone at the metaphysis compared with no specific loss at the epiphysis (BV/TV [%] OVX: Metaphysis: day 150, 2.4 [0.4] [p &lt; 0.01 compared with Sham]: Epiphysis: day 150 29.3 [2.7] [NS]). Osteoblast cell activity and osteoclast surface were increased after ovariectomy in both regions. The mineral apposition rate decreased at 9.5 months of age in both regions (p &lt; 0.0001), independent of ovariectomy, and was coincident with a reduction in trabecular number in the epiphyses of both operative groups and in the metaphysis of the ovary-intact group. These data suggest that local mechanical strain governs bone balance with aging and that architectural changes resulting from age-related bone loss may mirror those following estrogen deficiency but occur via a different cellular mechanism.