bluuebunny/crossref_metadata_2025_split huggingface dataset:
Markers of bone remodeling in the elderly subject: Effects of vitamin D insufficiency and its correction
Authors: Brazier M. , Kamel S. , Maamer M. , Agbomson F. , Elesper I. , Garabedian M. , Desmet G. , Sebert J.L. 
Published: February 2010

Abstract
The elderly subject is prone to both vitamin D insufficiency and calcium insufficiency due to a low calcium intake and calcium malabsorption. These two alterations may lead to secondary hyperparathyroidism, and thus to increased bone loss. We investigated 72 elderly subjects (16 men and 56 women) with vitamin D insufficiency and 25 healthy elderly women with normal vitamin D status, with respect to their indices of calcium metabolism and of bone remodeling: serum total alkaline phosphatases (AP), bone AP (BAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), urine hydroxyproline (HYP), and the 3-OH-pyridinium derivatives pyridinoline (PYD) and deoxypyridinoline (DPD), which are new markers of bone resorption. We then studied the modifications of these markers in the patients with vitamin D insufficiency at 3 months and 6 months after onset of a daily vitamin D and calcium supplementation. When compared with elderly subjects with normal vitamin D status, patients with vitamin D insufficiency had increased intact parathyroid hormone (iPTH) levels (60.1 ± 10.2 vs 30.2 ± 4.5, p &lt; 0.001) and a high bone turnover as reflected by increased values of most serum and urine markers of bone remodeling. PYD and DPD levels were significantly correlated with all indices of bone turnover, unlike HYP, which showed no correlation with bone formation markers (AP, BAP, and BGP). A daily supplement of 800 IU vitamin D3 and 1 g of elemental calcium increased 25(OH)D levels and induced a dramatic decrease of iPTH levels; at 3 and 6 months, the mean iPTH level decreased by 50% (p &lt; 0.0001), reaching the mean value of healthy vitamin D sufficient elderly women. All markers of bone turnover, except TRAP, decreased significantly at 3 and 6 months. The PYD/DPD ratio increased significantly at 3 and 6 months. The decrease of bone markers was more marked in patients with more severe hyperparathyroidism, the greatest variations being obtained with BAP (45%, p = 0.006) and DPD (43%, p = 0.036) levels. Most markers of bone remodeling are increased in elderly subjects with vitamin D insufficiency and vary with its correction. However, BAP and DPD are the most sensitive indicators of increased bone turnover due to secondary hyperparathyroidism.
Determinants of bone mineral density in older men
Authors: Glynn Warhaftig Nancy , Meilahn Elaine N. , Charron Martin , Anderson Stewart J. , Kuller Lewis H. , Dr. Cauley Jane A. 
Published: February 2010

Abstract
Osteoporosis is a significant health problem and contributor to disability and premature mortality among older men. Incidence rates for hip fracture have stabilized in women, but continue to increase in men. A major risk factor for hip fracture is bone mineral density level. The determinants of bone mineral density (BMD) are well defined in women, but not in men. The primary goal of the current research was to increase our understanding of the determinants of BMD of the proximal femur in a large community-based sample of older male volunteers. Eligibility requirements included age of 50 years or older, ambulatory, and not having undergone a bilateral hip replacement. Five hundred twenty-three men, mean age 66.6 years, met all eligibility requirements and participated in the Study of Osteoporotic Risk in Men or STORM. Information on demographics, medical history, anthropometry, leisure-time and occupational physical activity, muscular strength, cigarette smoking, alcohol consumption, dietary calcium intake, and medication use (thiazide diuretics and glucocorticoids) were obtained by questionnaire, interview, and examination. BMD of the proximal femur (femoral neck, greater trochanter, and Ward's triangle) was measured by dual-energy X-ray absorptiometry using the Hologic QDR-1000 and QDR-2000. The cross-sectional determinants of BMD included age, blond hair color, current body weight, thiazide diuretic use, historical physical activity, and quadriceps strength. Several variables commonly thought to be determinants of BMD were not related to BMD in this population of older men, including current cigarette smoking, alcohol consumption, current leisure-time physical activity, dietary calcium intake, vitamin D use, and caffeine intake. However, failure to find associations among BMD and some of the potential determinants may be due to lack of statistical power. Identification of the determinants of BMD could lead to the development of interventions aimed at maximizing BMD in men and could potentially decrease the risk of hip fractures.
Risk factors for hip fracture in european women: The MEDOS study
Authors: Johnell Olof , Gullberg Bo , Kanis John A. , Allander Erik , Elffors Lars , Dequeker Jan , Dilsen Guzin , Gennari Carlo , Vaz Lopes Antonio , Lyritis George , Mazzuoli Gianfranco , Miravet Livia , Passeri Mario , Cano Perez Ramon , Rapado Aurelio , Ribot Claude 
Published: February 2010

Abstract
The aims of this study were to determine common international risk factors for hip fracture in women aged 50 years or more. We studied women aged 50 years or more who sustained a hip fracture in 14 centers from Portugal, Spain, France, Italy, Greece, and Turkey over a 1-year period. Women aged 50 years or more selected from the neighborhood or population registers served as controls. Cases and controls were interviewed using a structured questionnaire on work, physical activity, exposure to sunlight, reproductive history and gynecologic status, height, weight, mental score, and consumption of tobacco, alcohol, calcium, coffee, and tea. Significant risk factors identified by univariate analysis included low body mass index (BMI), short fertile period, low physical activity, lack of sunlight exposure, low milk consumption, no consumption of tea, and a poor mental score. No significant adverse effects of coffee or smoking were observed. Moderate intake of spirits was a protective factor in young adulthood, but otherwise no significant effect of alcohol intake was observed. For some risks, a threshold effect was observed. A low BMI and milk consumption were significant risks only in the lowest 50% and 10% of the population, respectively. A late menarche, poor mental score, low BMI and physical activity, low exposure to sunlight, and a low consumption of calcium and tea remained independent risk factors after multivariate analysis, accounting for 70% of hip fractures. Excluding mental score and age at menarche (not potentially reversible), the attributable risk was 56%. Thus, about half of the hip fractures could be explained on the basis of the potentially reversible risk factors sought. In contrast, the use of risk factors to “predict” hip fractures had moderate sensitivity and specificity. We conclude that variations in lifestyle factors are associated with significant differences in the risk of hip fracture, account for a large component of the total risk, and may be of some value in selecting individuals at high risk.
Transmenopausal change of trabecular bone density and structural pattern assessed by peripheral quantitative computed tomography in Japanese women
Authors: Takagi Yasuyuki , Fujii Yoshio , Miyauchi Akimitsu , Goto Bunrei , Takahashi Keiichi , Fujita Takuo 
Published: February 2010

Abstract
Trabecular bone pattern, related to connectivity, was analyzed along with a separate measurement of cortical and trabecular bone mineral density (BMD) at the distal radius by peripheral quantitative computed tomography (pQCT) in 48 perimenopausal women, consisting of 25 premenopausal women aged 41 to 52 (mean 46.6 ± 2.9 years) and 23 early postmenopausal women aged 46 to 59 (mean 53.2 ± 3.2 years) within 5 years of the menopause (mean 2.7 ± 1.5 years). No significant difference was found in either cortical or trabecular bone density between premenopausal and postmenopausal women despite a significant difference in age (premenopause vs postmenopause: 46.7 ± 2.9 years vs 53.2 ± 3.1 years, p &lt; 0.00001), indicating a slow change of BMD, if any, before and within 5 years of the menopause. However, analysis of trabecular fragments and perforation revealed a significant increase of the number of perforations in postmenopausal compared with premenopausal women (premenopausal vs postmenopausal: 0.9 ± 1.6 vs 2.9 ± 2.3, p &lt; 0.002), indicating that disconnectivity has already increased before a significant reduction of BMD. Furthermore, chi-square analysis showed that even postmenopausal women with trabecular BMD more than 160 mg/cm3 were about 11 times more likely to have three or more perforations than premenopausal ones (odds ratio: 11.42, F = 0.030). These data suggest that trabecular bone connectivity is more sensitive than BMD in the detection of the early changes of postmenopausal osteoporosis.
Bone fragility in transgenic mice expressing a mutated gene for type I procollagen (COL1A1) parallels the age-dependent phenotype of human osteogenesis imperfecta
Authors: Pereira Ruth F. , Hume Eric L. , Halford Kenneth W. , Prockop Darwin J. 
Published: February 2010

Abstract
An inbred strain of transgenic mice that expressed a mutated gene for type I procollagen and that developed spontaneous fractures was used to study the effects of age on the phenotype of fragile bones. The mutated gene has been shown to cause depletion of type I collagen in the transgenic mice because it generated shortened proα1(I) chains that bound to and produced degradation of normal proα1(I) chains synthesized from the endogenous mouse COL1A1 gene. For this study, femurs from transgenic mice ranging in age from 0.5–24 months were examined. The results demonstrated that the level of expression of the transgene was independent of age. Femurs from the transgenic mice were more fragile than controls at 0.5 and 1.5 months, they were biomechanically normal at 6 months, and then they were more fragile at 24 months. The normal biomechanical properties of the bones from the transgenic mice at 6 months were accompanied by periosteal thickening of the bones together with an increase in the collagen content that was not associated with a proportional increase in mineral content. The results indicated that the effects of age, mechanical stress, and hormonal action produced a biological compensation for the mutated gene by either increasing collagen synthesis of bone, decreasing collagen degradation, or both. The biological compensation was apparently lost by 24 months when the outer diameters of the femurs were again less than in controls, the cortical thickness was about the same as in controls, and both the collagen and mineral contents were less than controls. The results demonstrated that bone fragility in the transgenic mice paralleled the age-dependent phenotype of human osteogenesis imperfecta. Therefore the transgenic mice appeared to be useful models for osteogenesis imperfecta. They also may be useful models for some forms of osteoporosis.
PTH/PTHrP receptor expression on osteoblasts and osteocytes but not resorbing bone surfaces in growing rats
Authors: Dr. Fermor Beverley , Skerry Timothy M. 
Published: February 2010

Abstract
Using in situ hybridization, we correlated the expression of mRNA for the parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) receptor with bone formation and resorption in undecalcified serial sections of bones from growing rats. In addition we investigated the presence of biologically active receptors in the same locations using an in vivo autoradiographic technique. In the ulnae of growing rats, there are well defined zones of cortical bone formation and resorption. These contribute to the modeling drifts by which the bone achieves its adult shape. Forming surfaces incorporate fluorochrome labels, are lined with osteoid, and have a layer of cuboidal osteoblasts that have a high alkaline phosphatase activity. Resorbing surfaces have no fluorochrome incorporation, no osteoid, and are lined with resorbing cells with high tartrate-resistant acid phosphatase (TRAP) activity. PTH/PTHrP receptor mRNA was expressed predominantly on forming but not on resorbing bone surfaces and colocalized with sites of binding of radiolabeled PTH after intravenous injection. PTH/PTHrP mRNA expression on osteocytes was inconclusive but radiolabeled PTH bound to a proportion of osteocytes in all regions of the cortex although binding was not specifically related to areas of bone formation or resorption. These results suggest that in growing animals the actions of PTH or PTHrP are connected more with bone formation than resorption. Such a role may be linked to the ability of PTH to induce bone formation in adults but does not explain the actions of the hormone in regulating resorption. Binding of PTH to osteocytes increases the evidence for a physiological role for these cells.
Cranial sutures require tissue interactions with dura mater to resist osseous obliteration in vitro
Authors: Opperman Lynne A. , Passarelli Ralph W. , Morgan Ellen P. , Reintjes Mark , Dr. Ogle Roy C. 
Published: February 2010

Abstract
A chemically defined serum-free medium, which supports the development of bones and fibrous tissues of rat calvaria from nonmineralized mesenchymal precursor tissues, was employed to investigate tissue interactions between the dura mater and overlying tissues. Fetal calvarial rudiments from stages prior to bone and suture morphogenesis (fetal days 19 and 20) and neonatal calvarial rudiments with formed sutures (day 1) were cultured with and without associated dura mater. Removal of calvaria for in vitro culture allowed the examination of suture morphogenesis in the absence of tensional forces exerted on the sutures via fiber tracts in the dura mater originating in the cranial base. Ossification of frontal and parietal bones proceeded in a fashion comparable to development in vivo, but the cranial (coronal) sutures—primary sites for subsequent skull growth—were obliterated by osseous tissue union in the absence of dura mater. Bony fusion did not occur when rudiments were cocultured with dura mater on the opposite sides of 0.45 μm polycarbonate transwell filters, suggesting that the influence of dura mater on sutural obliteration was mediated by soluble factors rather than cell—cell or cell—matrix interactions. These results indicate that cell signaling mechanisms rather than biomechanical tensional forces are required for morphogenesis of the calvaria.
Effects of aluminum on bone surface ion composition
Authors: Bushinsky David A. , Sprague Stuart M. , Hallegot Philippe , Girod Chantal , Chabala Jan M. , Levi-Setti Riccardo 
Published: February 2010

Abstract
Aluminum induces net calcium efflux from cultured bone. To determine whether aluminum alters the bone surface ion composition in a manner consistent with predominantly cell-mediated resorption, a combination of cell-mediated resorption and physicochemical dissolution or physicochemical dissolution alone, we utilized an analytic high-resolution scanning ion microprobe with secondary ion mass spectroscopy to determine the effects of aluminum on bone surface ion composition. We cultured neonatal mouse calvariae with or without aluminum (10−7 M) for 24 h and determined the relative ion concentrations of 23Na, 27AI, 39K, and 40Ca on the bone surface and eroded subsurface. Control calvariae have a surface (depth ∼6 nm) that is rich in Na and K compared with Ca (Na/Ca = 24.4 + 1.4, mean + 95% confidence limit of counts per second of detected secondary ions, K/Ca = 13.2 + 0.9). Aluminum is incorporated into the bone and causes a depletion of surface Na and K relative to Ca (Na/Ca = 9.6 + 0.7, K/Ca = 4.9 + 0.4; each p &lt; 0.001 versus control). After erosion (depth ∼50 nm), control calvariae have more Na and K than Ca (Na/Ca = 16.0 + 0.1, K/Ca = 7.5 + 0.1); aluminum again depleted Na and K relative to Ca (Na/Ca = 4.1 + 0.1, K/Ca = 1.9 + 0.1; each p &lt; 0.001 versus control). Aluminum produced a greater net efflux of Ca (362 ± 53, mean ± SE, nmol/bone/24 h) than control (60 ± 30, p &lt; 0.001). With aluminum, the fall in the ratios of both Na/Ca and K/Ca coupled with net Ca release from bone indicates that aluminum induces a greater efflux of Na and K than Ca from the bone surface and is consistent with an aluminum-induced removal of the bone surface. This alteration in surface ion concentration and calcium efflux is consistent with that observed when calcium is lost from bone through a combination of cell-mediated resorption and physicochemical dissolution.
Normal parathyroid hormone responsiveness of bone-derived cells from a patient with pseudohypoparathyroidism
Authors: Ish-Shalom Sophia , Rao Letitia G. , Levine Michael A. , Fraser Donald , Kooh Sang W. , Josse Robert G. , Mcbroom Robert , Wong Min-Min , Murray Timothy M. 
Published: February 2010

Abstract
Pseudohypoparathyroidism (PHP) is characterized by a lack of response to parathyroid hormone (PTH); however, normal skeletal responsiveness to PTH in some patients with PHP type la was previously suggested on the basis of clinical observations. To test this hypothesis, we measured cyclic adenosine monophosphate (cAMP) production in response to various agonists in bone-derived osteoblast-like (OBL) cells from trabecular explants obtained from an iliac crest biopsy of a 25-year-old woman with PHP. The patient was proved to have PHP type la on the basis of Albright's hereditary osteodystrophy and decreased activity of stimulatory guanine nucleotide-binding protein (Gs) in erythrocytes. Responsiveness of the patient's OBL cells was compared with OBL cells from eight subjects aged 18–39 years who had no evidence of metabolic bone disease. OBL cells from the patient responded to the following agonists (expressed in multiples of elevation of cAMP, stimulated/basal, mean ± SE, n = 3): PTH, 3.8 ± 0.3; forskolin, 8.2 ± 0.2; and cholera toxin, 56.8 ± 10.0. These responses were not significantly different from those of control OBL cells: PTH, 4.5 ± 1.1 (range 2.4–7.5); forskolin, 7.7 ± 1.4; and cholera toxin, 57.9 ± 16.2. The normal cholera toxin response indicated the presence of functional Gs. Bone cells from patients with PHP type la may exhibit a normal PTH receptor-coupled adenylyl cyclase system in vitro despite clinical evidence of impaired hormone-responsive adenylyl cyclase in other tissues, including the kidney. Skeletal responsiveness to PTH may explain the long periods of spontaneous normocalcemia observed in this patient.
Osteoblast hydraulic conductivity is regulated by calcitonin and parathyroid hormone
Authors: Hillsley Mechteld V. , Frangos John A. 
Published: February 2010

AbstractIt is our hypothesis that osteoblasts play a major role in regulating bone (re)modeling by regulating interstitial fluid (ISF) flow through individual bone compartments. We hypothesize that osteoblasts of the blood-bone membrane lining the bone surfaces are capable of regulating transosseous fluid flow. This regulatory function of the osteoblasts was tested in vitro by culturing a layer of rat calvarial osteoblasts on porous membranes. Such a layer of osteoblasts subjected to 7.3 mm Hg of hydrostatic pressure posed a significant resistance to fluid flow across the cell layer similar in magnitude to the resistance posed by endothelial monolayers in vitro. The hydraulic conductivity, the volumetric fluid flux per unit pressure drop, of the osteoblast layer was altered in response to certain hormones. Hydraulic conductivity decreased approximately 40% in response to 33 nM parathyroid hormone, while it exhibited biphasic behavior in response to calcitonin: increased 40% in response to 100 nM calcitonin and decreased 40% in response to 1000 nM calcitonin. Further, activation of adenylate cyclase by forskolin dramatically increased the hydraulic conductivity, while elevation of intracellular calcium, [Ca2+]i, by the calcium ionophore A23187 initially decreased the hydraulic conductivity at 5 minutes before increasing conductivity by 30 minutes. These results suggest that cyclic adenosine monophosphate (cAMP) and [Ca2+]i may mediate changes in the osteoblast hydraulic conductivity. The increase in hydraulic conductivity in response to 100 nM calcitonin and the decrease in response to PTH suggest that the stimulatory and inhibitory effects on bone formation of calcitonin and parathyroid hormone, respectively, may be due in part to alterations in bone fluid flow.
Maintaining bone mass by bisphosphonate incadronate disodium (YM175) sequential treatment after discontinuation of intermittent human parathyroid hormone (1-34) administration in ovariectomized rats
Authors: Takano Yuichi , Tanizawa Tatsuhiko , Mashiba Tasuku , Endo Naoto , Nishida Saburo , Takahashi Hideaki E. 
Published: February 2010

Abstract
Intermittent treatment with human parathyroid hormone (1-34) [hPTH(1-34)] stimulates bone formation and increases cancellous bone mass in ovariectomized (OVX) rats. But PTH-induced cancellous bone rapidly disappears upon cessation of treatment. The fate of cortical bone treated by PTH has not been well characterized. Incadronate disodium (disodium cycloheptylaminomethylenedisphosphonate monohydrate, YM175) was expected to be antiresorptive without inhibiting bone formation. The purposes of this study were to determine (1) whether PTH treatment increases new cancellous and cortical bone mass and bone formation, (2) whether the new bone could be maintained by YM175 sequential treatment, and (3) whether the maintenance effect is persistent after YM175 withdrawal. Eighty-eight 11-week-old Sprague-Dawley rats were divided into sham operation and OVX groups. The OVX rats were treated for 8 weeks with the subcutaneous intermittent injection of 30 μ/kg of hPTH(1–34) three times a week beginning 4 weeks after surgery, then PTH treatment was withdrawn and YM175 (10 μ/kg) was injected subcutaneously three times a week for 4 weeks. YM175 treatment was withdrawn for the last 8 weeks of the protocol. The results of microstructural assessment in proximal tibial metaphysis and bone mineral density in distal and proximal femur demonstrated that PTH treatment for 8 weeks restored bone mass to the sham control level. However, after cessation of PTH treatment, the PTH-induced tibial cancellous bone mass showed a decrease at 4 weeks and almost totally disappeared after 12 weeks. Conversely, YM175 treatment maintained the PTH-induced tibial cancellous bone mass, and the bone continued to be maintained after 8 weeks of withdrawal of the YM175. Cortical bone was not lost during PTH treatment. YM175 maintained the PTH-induced new tibial cancellous bone in OVX rats by suppressing remodeling.
Induction of apoptosis in murine clonal osteoblasts expressed by human T-cell leukemia virus type I tax by NF-κPB and TNF-α
Authors: Kitajima Isao , Nakajima Toshihiro , Imamura Takeshi , Takasaki Ikuko , Kawahara Koichi , Okano Toshihiro , Tokioka Takeshi , Soejima Yasuko , Abeyama Kazuhiro , Maruyama Ikuro 
Published: February 2010

Abstract
We investigated the effects of various cytokines in the presence of human T-cell leukemia virus type I (HTLV-I) tax protein in murine clonal osteoblasts, MC3T3-E1 cells. Skeletal remodeling by osteoclasts and osteoblasts is coordinated by cytokines, which are activated by HTLV-I tax protein via nuclear factor-κB (NF-κB). MC3T3-E1 cells were cocultured with an irradiated HTLV-I-producing lymphocyte cell line, MT-2. After coculture, the tumor necrosis factor-α (TNF-α) level in the medium was markedly elevated during the 7 days of culture, and MC3T3-E1 cells underwent apoptotic cell death. Marked apoptosis was also observed in MC3T3-E1 cells treated with MT-2 culture medium and in HTLV-I tax-expressing MC3T3-E1 clones, which both expressed high levels of TNF-α. This apoptosis was prevented by treatment with neutralizing anti-TNF-α antibody (αTNF). HTLV-I tax protein and TNF-α induced activation of NF-κB in apoptotic MC3T3-E1 cells. Decreased NF-κB activation was observed in HTLV-I tax-expressing MC3T3-E1 cells treated with αTNF. Our results suggest that HTLV-I tax activated NF-κB and subsequently TNF-α, leading to apoptosis of osteoblasts.