bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes Is Associated Independently of Body Composition With BMD and Bone Volume in Older White and Black Men and Women: The Health, Aging, and Body Composition Study
Authors: Strotmeyer Elsa S , Cauley Jane A , Schwartz Ann V , Nevitt Michael C , Resnick Helaine E , Zmuda Joseph M , Bauer Douglas C , Tylavsky Frances A , de Rekeneire Nathalie , Harris Tamara B , Newman Anne B 
Published: April 2006

Abstract
The association between type 2 diabetes, BMD, and bone volume was examined to determine the effect of lean and fat mass and fasting insulin in the Health, Aging, and Body Composition Study, which included white and black well-functioning men and women 70-79 years of age (N = 2979). Diabetes predicted higher hip, whole body, and volumetric spine BMD, and lower spine bone volume, independent of body composition and fasting insulin.
Introduction: The purpose of this study was to determine if the association between type 2 diabetes and higher BMD observed in older white women is seen in elderly white men and blacks and to evaluate if higher BMD in diabetic individuals is accounted for by lean mass, fat mass, or fasting insulin differences.
Materials and Methods: In the Health, Aging, and Body Composition Study, which included white and black well-functioning men and women 70-79 years of age (N = 2979), 19% of participants had diabetes at baseline. Of those with diabetes, 57% were men, and 62% were black. Multivariate linear regression models examined independent effects of diabetes, lean mass, fat mass, visceral fat, and fasting insulin on BMD and bone volume while adjusting for relevant covariates.
Results and Conclusions: Fasting insulin, visceral fat, and volumetric spine BMD, assessed by CT, and lean mass, fat mass, and total hip and whole body BMD, assessed by DXA, were higher (p ≤ 0.05 for all) for those with diabetes. Hip BMD was higher in white men (0.99 ± 0.14 versus 0.93 ± 0.14 g/cm2, p &lt; 0.001), black men (1.06 ± 0.17 versus 1.00 ± 0.15 g/cm2, p &lt; 0.001), white women (0.83 ± 0.13 versus 0.76 ± 0.13 g/cm2, p &lt; 0.001), and black women (0.90 ± 0.15 versus 0.85 ± 0.15 g/cm2, p &lt; 0.001) with diabetes compared with those without diabetes, although the relationship was attenuated by body composition. In multiple regression models, diabetes was an independent predictor of higher hip, whole body, and volumetric spine BMD in all participants (p ≤ 0.001), but lower spine volume (p = 0.01) and higher hip BMD for each race-gender group (p ≤ 0.01). Type 2 diabetes was associated with a 4-5% higher total hip BMD in all race-gender groups of elderly adults, independent of body composition and fasting insulin levels.
Role of TAFII-17, a VDR Binding Protein, in the Increased Osteoclast Formation in Paget's Disease
Authors: Kurihara Noriyoshi , Reddy Sakamuri V , Araki Norie , Ishizuka Seiichi , Ozono Keiichi , Cornish Jillian , Cundy Tim , Singer Frederick R , Roodman G David 
Published: April 2006

Abstract
In contrast to normal OCL precursors, pagetic OCL precursors express MVNP and form OCL at physiologic concentrations of 1,25(OH)2D3, as do normal OCL precursors transfected with the MVNP gene. Using a GST-VDR chimeric protein, we identified TAFII-17 as VDR binding protein expressed by pagetic OCL precursors and MVNP transduced normal OCL precursors. TAFII-17 was in part responsible for the increased 1,25(OH)2D3 responsivity of pagetic OCL precursors.
Introduction: Pagetic osteoclasts (OCLs) and their precursors express measles virus nucleocapsid protein (MVNP) and form large numbers of OCLs at low concentrations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Similarly, normal OCL precursors transfected with MVNP also form OCLs at low concentrations of 1,25(OH)2D3. These results suggest that expression of MVNP in OCL precursors enhances vitamin D receptor (VDR)-mediated gene transcription.
Materials and Methods: To determine the mechanism for the increased OCL formation capacity of pagetic OCL precursors in response to 1,25(OH)2D3, lysates from pagetic and MVNP-transduced normal OCL precursors were incubated with a GST-VDR chimeric protein.
Results: A 17-kDa peptide that bound VDR was detected in MVNP-transduced cells and pagetic OCL precursors treated with 1,25(OH)2D3. This peptide was identified as TAFII-17, a component of the TFIID transcription complex. Expression of increased levels of TAFII-17 in cells allowed TAFII-17 to bind to VDR at low concentrations of 1,25(OH)2D3. An antisense oligonucelotide (AS-ODN) to TAFII-17 significantly decreased OCL formation in response to 1,25(OH)2D3 in pagetic but not normal marrow cultures by ∼40%. Transfection of TAFII-17 or MVNP into NIH3T3 cells increased VDR transcriptional activity as measured by DR-3 reporter assays.
Conclusion: These data show that expression of the MVNP gene in OCL precursors results in increased levels of TAFII-17. TAFII-17 can bind VDR at low concentrations of 1,25(OH)2D3. These results suggest that MVNP expression in Paget's OCL precursors increases expression of a component(s) of the VDR transcription complex that can increase OCL formation.
Macrophage Inflammatory Protein-1α Induces Hypercalcemia in Adult T-Cell Leukemia
Authors: Okada Yosuke , Tsukada Junichi , Nakano Kazuhisa , Tonai Shinichi , Mine Shinichiro , Tanaka Yoshiya 
Published: April 2006

Abstract
Hypercalcemia is observed in &gt;80% of ATL. Serum MIP-1α levels were elevated in all 24 ATL with hypercalcemia but undetectable in all 10 patients with humoral hypercalcemia of malignancy with solid tumors and in 34 of 37 ATL without hypercalcemia. We propose that serum MIP-1α is a clinical hallmark for hypercalcemia in ATL.
Introduction: High serum cytokines levels are not always associated with hypercalcemia in patients with adult T-cell leukemia (ATL), suggesting that other factors are involved in the pathogenesis of ATL patients with hypercalcemia. This study was designed to determine the role of macrophage inflammatory protein-1α (MIP-1α), a chemokine recently described as an osteoclast stimulatory factor, in ATL-associated hypercalcemia.
Materials and Methods: We measured serum interleukin (IL)-1β, IL-6, TNF-α, parathyroid hormone-related protein (PTHrP), and MIP-1α levels in ATL patients by enzyme-linked immunosorbent assays. FACScan was used to measure the expression of RANKL on ATL cells. Osteoclast formation in cocultures of ATL cells and peripheral blood mononuclear cells (PBMCs) was evaluated by TRACP staining.
Results: High serum MIP-1α levels were noted in all 24 ATL patients with hypercalcemia and in 3 of 37 ATL patients without hypercalcemia. The elevated levels of MIP-1α and calcium in ATL patients decreased after effective chemotherapy, emphasizing the role of MIP-1α in ATL hypercalcemia. ATL cells spontaneously produced MIP-1α. MIP-1α significantly enhanced human monocyte (precursor cells of osteoclasts) migration and induced RANKL expression on ATL cells. ATL cell-induced osteoclast formation from PBMCs was inhibited by anti-MIP-1α antibody and osteoprotegerin.
Conclusion: Our results suggest that MIP-1α can induce RANKL on ATL cells in autocrine fashion and that RANKL seems to mediate the hypercalcemic effect of MIP-1α in ATL. We propose that MIP-1α is the clinical hallmark of hypercalcemia in ATL and could be a potentially useful therapeutic target.
Osteoporosis and the Global Competition for Health Care Resources
Authors: Melton L Joseph , Johnell Olof , Lau Edith , Mautalen Carlos A , Seeman Ego 
Published: April 2006

Abstract
Global aging superimposed on existing infectious diseases and trauma will aggravate competition for health care resources to diagnose and treat osteoporosis. Efforts to implement public health measures are needed, but the targeted approach to assessment and treatment of high-risk individuals must also be refined.
Increases in the elderly population worldwide will cause a dramatic rise in osteoporotic fractures, but other age-related diseases will increase as well. Changes will be superimposed on existing public health problems (e.g., malaria, alcoholism), and these acute health care needs will take priority in some areas. Societies in most parts of the world may have to limit osteoporosis control to broad public health measures, and such efforts (e.g., calcium and vitamin D supplementation) should be supported. In these regions, clinical decision-making will generally be limited to treating patients with fractures (who presumably have already failed any public health measures in place), or in a few wealthy countries, to patients with low bone density identified by case-finding. Case-finding approaches will vary with the resources available, although unselective (mass) screening by bone densitometry is largely ineffective and unaffordable anywhere. The key to clinical decision-making on behalf of individuals will be an assessment of absolute fracture risk, and the tools needed to predict the risk of an osteoporotic fracture over the next 10 years are now being developed. These include bone density measures, but also incorporate other risk factors (e.g., fracture history, corticosteroid use), which may allow extension of fracture risk prediction to nonwhite populations and to men. Even with a universal risk prediction tool, cost-effective treatment thresholds will vary by country based on the level of fracture risk in the region and on the resources available for health care. To better compete for these resources, efforts should be made to lower the cost of osteoporosis interventions. Additionally, evidence is needed that these interventions are really effective in reducing fractures in the community.
Characterization of a Novel Bipotent Hematopoietic Progenitor Population in Normal and Osteopetrotic Mice
Authors: Blin-Wakkach Claudine , Wakkach Abdelilah , Rochet Nathalie , Carle Georges F 
Published: April 2006

Abstract
Several reports indicate that osteoclasts and B-lymphocytes share a common progenitor. This study focuses on the characterization of this bipotent progenitor from the bone marrow of the osteopetrotic oc/oc mouse, where the bipotent progenitor population is amplified, and of normal mice.
Introduction: Osteoclasts have a myelomonocytic origin, but they can also arise in vitro from pro-B-cells, suggesting that a subset of normal pro-B-cells is uncommitted and may reorient into the myeloid lineage representing a B-lymphoid/osteoclastic progenitor. The aim of this study was to characterize this progenitor population.
Materials and Methods: The osteopetrotic oc/oc mouse was used as a choice model because it displays an increased number of both osteoclasts and pro-B-cells in the bone marrow. Our results have been confirmed in normal littermates. Bone marrow cells from these animals were analyzed by flow cytometry. After sorting, the cells were cultured under different conditions to assess their differentiation capacity.
Results: Pro-B-cells from oc/oc and normal mice include an unusual biphenotypic population expressing markers from the B-lymphoid (CD19, CD43, CD5) and the myeloid (F4/80) lineages. This population also expresses progenitor markers (CD34 and Flt3) and is uncommitted. After sorting from the oc/oc bone marrow, this population is able to differentiate in vitro into osteoclast-like cells in the presence of RANKL and macrophage colony-stimulating factor (M-CSF), into dendritic-like cells in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4, and TNFα, and into immature B-cells when seeded onto ST2 cells in the presence of IL-7.
Conclusion: Our results show the existence of a novel bipotent biphenotypic hematopoietic progenitor population present in the bone marrow that has retained the capacity to differentiate into myeloid and B-lymphoid cells.
RANKL Coordinates Cell Cycle Withdrawal and Differentiation in Osteoclasts Through the Cyclin-Dependent Kinase Inhibitors p27KIP1 and p21CIP1
Authors: Sankar Uma , Patel Krupen , Rosol Thomas J , Ostrowski Michael C 
Published: April 2006

Abstract
The coordination of cell cycle progression and osteoclast differentiation by RANKL signaling was studied. Experiments with mouse genetic models revealed that RANKL promoted cell cycle withdrawal of osteoclast precursors dependent on the cyclin kinase inhibitor p27-KIP1, but that both p27-KIP1 and p21-CIP1 were required for osteoclast differentiation. These cyclin inhibitors may directly regulate osteoclast differentiation in addition to regulating cell cycle withdrawal.
Introduction: RANKL stimulates mononuclear precursor cells of the myeloid lineage to differentiate into multinuclear osteoclasts, thus providing a system to study the fundamental problem of coordination of cell cycle progression with cell differentiation.
Materials and Methods: Mice that lack expression of functional cyclin inhibitors p27KIP1and p21CIP1 were used to study cell cycle progression and differentiation of osteoclast precursors in vitro and in vivo.
Results and Conclusions: Experiments with cells derived from p27KIP1- and p21CIP1-deficient mice indicated that p27KIP1 function alone was necessary for RANKL-mediated cell cycle withdrawal by osteoclast precursors, but osteoclasts from mice with single mutations in either of these two genes differentiated normally. In contrast, p21/p27 double knockout mice developed osteopetrosis, with fewer osteoclasts that exhibited lower TRACP activity and abnormal cell morphology present in long bone. Moreover, isolated osteoclast progenitors from p21/p27 double knockout mice were defective in RANKL-mediated differentiation in vitro, expressing low levels of osteoclast-specific genes like TRACP and cathepsin K. Taken together, these data suggest p27KIP1 and p21CIP1 play roles in osteoclast differentiation in response to RANKL signaling distinct from their roles in promoting cell cycle withdrawal.
Lysyl Hydroxylase-2b Directs Collagen Cross-Linking Pathways in MC3T3-E1 Cells
Authors: Pornprasertsuk Suchaya , Duarte Wagner R , Mochida Yoshiyuki , Yamauchi Mitsuo 
Published: April 2006

Abstract
To elucidate the roles of LH2b in collagen cross-linking, MC3T3-E1 cell clones expressing higher (S) or lower (AS) levels of LH2b were established. Compared with controls, the collagen cross-linking pattern was shifted toward hydroxylysine-aldehyde (S clones)- or lysine-aldehyde (AS clones)-derived pathways. The data indicate that LH2b directs collagen cross-linking pathways through its action on telopeptidyl lysine residues.
Introduction: Lysine (Lys) hydroxylation is a post-translational modification of collagen critical for cross-linking and glycosylation. Currently, three isoforms of lysyl hydroxylase (LH) have been identified, but their specific functions are still not well defined. Recently, we proposed that LH2 might modulate collagen cross-linking pattern through its action on Lys residues located in the telopeptide domains of collagen.
Materials and Methods: To directly test this hypothesis, several MC3T3-E1 cell-derived clones expressing higher (sense [S]) or lower (antisense [AS]) levels of LH2b, the predominant form of LH2 in this cell line, were established and cultured for 2 weeks, and collagen cross-links and precursor aldehydes in the matrices were analyzed.
Results: In S clones tested, the ratio of dihydroxylysinonorleucine (DHLNL) to hydroxylysinonorleucine (HLNL) was significantly higher than the average of controls (76% and 140% increase, respectively), and the level of pyridinoline (Pyr) was elevated (100% and 150% increase, respectively). In contrast, when MC3T3-E1 cells were transfected with a LH2b antisense construct (AS clones), the DHLNL/HLNL ratios were significantly lower than that of controls (56% and 73% decrease, respectively), and Pyr was not detected. Furthermore, significant amounts of an aldol-derived cross-link, dehydrohistidinohydroxymerodesmosine, were produced (∼0.3 mol/mol of collagen) in AS clones.
Conclusions: The data clearly show a critical role of LH2b in determining collagen cross-linking pathways, most likely through its action on telopeptidyl Lys residues.
Association of Multiple Nucleotide Variations in the Pituitary Glutaminyl Cyclase Gene (QPCT) With Low Radial BMD in Adult Women
Authors: Ezura Yoichi , Kajita Mitsuko , Ishida Ryota , Yoshida Shoko , Yoshida Hideyo , Suzuki Takao , Hosoi Takayuki , Inoue Satoshi , Shiraki Masataka , Orimo Hajime , Emi Mitsuru 
Published: April 2006

Abstract
Correlation between 13 genetic variations of the glutaminyl-peptide cyclotransferase gene and adjusted aBMD was tested among 384 adult women. Among 13 variations with strong linkage disequilibrium, R54W showed a prominent association (p = 0.0003), which was more striking when examined among 309 elder subjects (≥50 years; p = 0.0001). Contribution for postmenopausal bone loss was suggested.
Introduction: Alterations in homeostatic regulation of estrogen through the hypothalamus-pituitary-gonadal axis (HPG axis) importantly affect the pathogenesis of osteoporosis. Osteoporosis-susceptibility genes have been proposed in this hormonal axis, such as estrogen receptor genes and the gonadotropin-releasing hormone gene (GnRH). Here we report another example of genes: glutaminyl-peptide cyclotransferase gene (QPCT), an essential modifier of pituitary peptide hormones, including GnRH.
Materials and Methods: Analyses of association of 13 single nucleotide polymorphisms (SNPs) at the QPCT locus with adjusted areal BMD (adj-aBMD) were carried out among 384 adult women. Linkage disequilibrium (LD) was analyzed by haplotype estimation and calculation of D′ and r2. Multiple regression analysis was applied for evaluating the combined effects of the variations.
Results and Conclusions: LD analysis indicated strong linkage disequilibrium within the entire 30-kb region of the QPCT gene. Significant correlations were observed between the genotypes of the six SNPs and the radial adj-aBMD, among which R54W (nt + 160C&gt;T) presented the most prominent association (p = 0.0003). Striking association was observed for these SNPs among the 309 subjects &gt;50 years of age (R54W, p = 0.0001; −1095T&gt;C, p = 0.0002; −1844C&gt;T, p = 0.0002). Multiple regression analyses indicated that multiple SNPs in the gene might act in combination to determine the radial adj-aBMD. These results indicate that genetic variations in QPCT are the important factors affecting the BMD of adult women that contribute to susceptibility for osteoporosis. The data should provide new insight into the etiology of the disease and may suggest a new target to be considered during treatment.
Quantitative Ultrasound Assessment in Children With Fractures
Authors: Schalamon Johannes , Singer Georg , Schwantzer Gerold , Nietosvaara Yrjänä 
Published: April 2006

Abstract
BMD of children with fractures was compared with healthy controls using QUS. We found significantly lower SOS values in children suffering from fractures. None of the studied environmental factors could explain the difference in BMD measurements.
Introduction: The aims of this study were to compare the results of quantitative ultrasound (QUS) in children with fractures with the respective values in children without fractures and to identify possible environmental factors influencing speed of sound (SOS) in our study cohort.
Materials and Methods: BMD was measured by QUS in 50 children who had sustained an acute fracture and in 154 healthy children as controls. SOS values were obtained from the proximal phalanges of the last four fingers of the dominant hand. Nutritional habits and activity level of the children were documented by a standardized questionnaire.
Results: Children with fractures had a significantly lower SOS compared with children without a history of fractures. This difference in SOS could not be explained by differences in diet, body mass index, or physical activity.
Conclusions: Previous studies have suggested that low BMD levels might contribute to an increased prevalence of fractures in patients with systemic diseases. Our study showed that, in an otherwise healthy pediatric population, the SOS values are lower in children with fractures compared with healthy controls. Despite statistical significance, the biological impact of the results remains unclear. The difference in SOS values could not be explained by any of the studied environmental factors.
Continuous Parathyroid Hormone Induces Cortical Porosity in the Rat: Effects on Bone Turnover and Mechanical Properties
Authors: Lotinun Sutada , Evans Glenda L , Bronk James T , Bolander Mark E , Wronski Thomas J , Ritman Erik L , Turner Russell T 
Published: April 2006

Abstract
We examined the time course effects of continuous PTH on cortical bone and mechanical properties. PTH increased cortical bone turnover and induced intracortical porosity with no deleterious effect on bone strength. Withdrawal of PTH increased maximum torque to failure and stiffness with no change in energy absorbed.
Introduction: The skeletal response of cortical bone to parathyroid hormone (PTH) is complex and species dependent. Intermittent administration of PTH to rats increases periosteal and endocortical bone formation but has no known effects on intracortical bone turnover. The effects of continuous PTH on cortical bone are not clearly established.
Materials and Methods: Eighty-four 6-month-old female Sprague-Dawley rats were divided into three control, six PTH, and two PTH withdrawal (WD) groups. They were subcutaneously implanted with osmotic pumps loaded with vehicle or 40 μg/kg BW/day human PTH(1-34) for 1, 3, 5, 7, 14, and 28 days. After 7 days, PTH was withdrawn from two groups of animals for 7 (7d-PTH/7d-WD) and 21 days (7d-PTH/21d-WD). Histomorphometry was performed on periosteal and endocortical surfaces of the tibial diaphysis in all groups. μCT of tibias and mechanical testing by torsion of femora were performed on 28d-PTH and 7d-PTH/21d-WD animals.
Results and Conclusions: Continuous PTH increased periosteal and endocortical bone formation, endocortical osteoclast perimeter, and cortical porosity in a time-dependent manner, but did not change the mechanical properties of the femur, possibly because of addition of new bone onto periosteal and endocortical surfaces. Additionally, withdrawal of PTH restored normal cortical porosity and increased maximum torque to failure and stiffness. We conclude that continuous administration of PTH increased cortical porosity in rats without having a detrimental effect on bone mechanical properties.