bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of continuous and intermittent administration and inhibition of resorption on the anabolic response of bone to parathyroid hormone
Authors: Hock J.M. , Gera I. 
Published: February 2010

Abstract
The role of resorption in the anabolic response of bone to parathyroid hormone (PTH) is not well understood. In contrast to the increase in bone mass induced by intermittent PTH in intact rats, continuous infusion of PTH into thyroparathyroidectomized (TPTX) rats failed to increase bone volume. The objectives of this study were to determine if continuous infusions of low doses of PTH were anabolic in intact rats and if inhibition of resorption would enhance or block an anabolic action of PTH. Young male rats were treated with either continuous infusion or intermittent injections of hPTH-(1-34) for 12 days. In experiment 1, PTH, infused daily at 4 μg per 100 g, increased femur calcium and dry weight. Unlike infusion of 8 μg PTH, which did not alter bone mass, intermittent PTH at 8 μg was anabolic and increased bone mass by increasing trabecular thickness and number. Infusion of 16 μg induced hypercalcemia and death. In experiment 2, lower dose daily infusions of 0.25–4 μg PTH per 100 g did not increase bone mass. In experiment 3, in rats pretreated with dichloromethylene diphosphonate (CI2MDP) to inhibit resorption and subsequently exhibiting decreased bone formation, PTH, irrespective of the method of administration, reversed the inhibitory effects of Cl2MDP on bone formation. Thus, intermittent and continuous PTH increase bone formation independently of effects on bone resorption, but only intermittent PTH increases bone mass consistently.
Effects of five daily 1 h infusions of alendronate in paget's disease of bone
Authors: O'Doherty D.P. , Gertz B.J. , Tindale W. , Sciberras D.G. , Survill T.T. , Kanis J.A. 
Published: February 2010

Abstract
We report a randomized placebo-controlled double-blind study of amino-hydroxybutylidene bisphosphonate (alendronate), infused over 1 h, in 15 patients with Paget's disease of bone. Alendronate, 10 mg/day for 5 days, suppressed urinary hydroxyproline to 44.9 ± 4.8% and serum alkaline phosphatase to 74.6 ± 5.4% of their pretreatment values within 1 month of the start of treatment. Within 5 months of the start of treatment serum alkaline phosphatase fell to 47.9 ± 6.3% of pretreatment values. These effects were associated with a decrease in serum calcium and phosphate and in urinary calcium excretion and with a rise in serum iPTH values. A transient fever was observed in 3 of 10 patients who received alendronate during the course of the infusions, and this was associated with a decrease in the total and differential white cell count. No adverse effects were noted on renal function as judged by glomerular filtration rate and indices of proximal and distal tubular function. This regimen may simplify the management of patients with Paget's disease of bone.
Lateral dual-energy radiography: Artifact error from rib and pelvic bone
Authors: Rupich Reta C. , Griffin Michael G. , Pacifici Roberto , Avioli Louis V. , Susman Noah 
Published: February 2010

Abstract
A lateral projection of the lumbar spine with dual-energy radiography (DER) may be a more sensitive tool for the detection of vertebral demineralization than the standard anterior-posterior (AP) DER measurement. The lateral view allows measurement of the vertebral body and selective measurement of the central trabecular compartment, excluding the majority of the cortical envelope and posterior vertebral elements. The lateral DER typically contains L2-4 in the region of interest. The present study was designed to investigate the frequency and bone mineral content (BMC) contribution of rib to the L2 vertebral body BMC measurement in a lateral view DER scan. In addition, the frequency of pelvic overlap of L4 was evaluated. All patients were scanned in the supine position. Abdominal CT images of L2 were examined in 20 women aged 28–82 years to determine the frequency of rib and pelvic interference. QCT images of L2 also were examined in an additional 35 women aged 20–82 years to further investigate the frequency of rib overlap and to calculate the potential contribution of rib superimposition to the L2 BMC in a lateral projection. Pelvic overlap of L4 occurred in 15% of the 20 cases reviewed. Rib overlapped the L2 vertebral body in 100% of the L2 images. The expected contribution of rib BMC to L2 BMC in a lateral DER scan was 10.4% on average. There was no relationship between the percentage of rib BMC contribution and age and relatively poor correlations between rib BMC and that of either the vertebral body or the central trabecular compartment of L2. We conclude that supine positioning allows routine inclusion of L3 and L4 in a lateral lumbar scan. Results also suggest that L2 should be excluded from DER scans on patients scanned in either the lateral decubitus or supine position.
Stimulation of bone formation in osteoporosis patients treated with fluoride associated with increased dna synthesis by osteoblastic cells in vitro
Authors: Marie Pierre J. , De Vernejoul Marie Christine , Lomri Abderrahim 
Published: February 2010

Abstract
In this study we evaluated whether the fluoride-induced increased bone formation in osteoporosis is mediated by stimulation of bone cell proliferation and/or differentiation. We analyzed the kinetics of DNA synthesis and the phenotypic features of osteoblastic cells isolated from the trabecular bone surface in relationship to histomorphometric indices of bone formation evaluated on the same bone biopsy in 12 osteoporotic patients treated with fluoride. Osteoblastic cells isolated from patients with a higher than normal bone formation rate, increased mean wall thickness of trabecular bone packets, and high trabecular bone volume after fluoride therapy displayed a higher than normal rate of DNA synthesis in vitro. The peak of [3H]thymidine incorporation into DNA, the maximal DNA synthesis, and the area under the growth curve of osteoblastic cells isolated from these patients were higher than the values in normal bone cells obtained from agematched controls. By contrast, in vitro parameters of osteoblastic cell proliferation were not different from normal in fluoride-treated osteoporosis patients in whom bone formation was not increased, although the duration of treatment and bone fluoride content were not different. Parameters of bone cell proliferation in vitro were increased in correlation with the mean wall thickness, and the latter correlated with the trabecular bone volume, indicating that the augmentation of bone formation and bone volume induced by fluoride was paralleled by an increased proliferation of osteoblastic cells. Basal osteocalcin production (corrected for cell protein) and alkaline phosphatase activity in vitro were comparable, and the response to 1,25-dihydroxyvitamin D3 (10 nmol/liter, 48 h) was not different in normal osteoblastic cells and in cells from fluoride-treated osteoporosis patients whether they had high or normal bone formation. The results show that the fluoride-induced increased bone formation in osteoporotic patients is associated with an increased in vitro proliferative capacity of osteoblastic cells lining the trabecular bone surface, whereas parameters of osteoblast differentiation are not affected. The data also suggest that induction of a higher than normal bone cell proliferation is prerequisite for the stimulation of bone formation by fluoride.
New approaches for interpreting projected bone densitometry data
Authors: Professor Carter Dennis R. , Bouxsein Mary L. , Marcus Robert 
Published: February 2010

Abstract
Bone densitometry using dual-photon absorptiometry (DPA) or dual-energy x-ray absorptiometry (DXA) has become a standard method for assessing bone mineral content in the spine and other skeletal regions. A projected areal density, referred to as bone mineral density (BMD,g/cm2), is normally calculated to assess regional bone density and strength. We demonstrate that this measure can be misleading when used to compare bones of different sizes due to inherent biases caused by bone thickness differences. For example, assuming that volumetric bone density remains constant and bony linear dimensions are proportional to height, a 20% increase in height would result in a 20% increase in both the thickness and the BMD of any bone. We describe new analysis methods to reduce the confounding effect of bone size, and we introduce a parameter, bone mineral apparent density (BMAD, g/cm3), that better reflects bone apparent density. Using this parameter, we calculate a quantity that serves as an index of bone strength (IBS, g2/cm4) for whole vertebral bodies. These analyses were applied to lumbar spine (L2–4) DXA measurements in a population of women 17–40 years old and appear to offer advantages to conventional techniques.
Effect of swimming on prednisolone-induced osteoporosis in elderly rats
Authors: Dr. Swissa-Sivan A. , Statter M. , Brooks G.A. , Azevedo J. , Viguie C. , Azoury R. , Greenfield C. , Oman S. , Leichter I. , Zinker B.A. , Menczel J. 
Published: February 2010

Abstract
We investigated the possible ameliorating and preventive effect of swimming on prednisolone-induced osteoporosis in elderly rats. A total of 48 female Sabra strain rats were randomly assigned to the following groups and treatments: (1) control (C), (2) swimming (S), (3) prednisolone-treated (CP), and (4) swimming + prednisolone (SP). An additional 8 rats were sacrificed and examined at the onset of the study. Groups C and S were sham injected; groups CP and SP were injected with prednisolone (Ultracorten), 80 mg/kg three times per week for 10 weeks. Groups S and SP swam 1 h daily, 5 days per week for 10 weeks. SP rats swam simultaneously with prednisolone administration. At the end of the swimming period, in vivo bone mineral content (BMC) measurements were performed on rat vertebrae L4-5 by single-photon absorptiometry. Later, the humerus and femur were removed for the following measurements: morphometric, bone density (BD) by Compton scattering technique, bone ion content by atomic absorption, and hydration fraction by proton magnetic resonance (PMR). We found that the humeral BD of S rats was greater by 14%for group S over C and 3% greater for group SP over CP (P &lt; 0.05). Vertebral BMC was higher by 15% in group S over C and 11% higher for group SP over CP (P &lt; 0.05). Femoral calcium (mg/g dry bone) ion content was higher by 5% in group S over C and 8% in group SP over CP group (P &lt; 0.05). The fraction of bound water was higher by 36% in group S over C and 8% in group SP over CP group (P &lt; 0.05). The hydration properties of the femur were examined by PMR determining the longitudinal (T1) and transverse (T2) relaxation times, referring to the freedom of the hydrogen proton movement of water molecules within bone tissue. T2 relaxation time was found to be significantly greater in swimming rats compared to controls (27%) and 58% in group SP over CP. T1 relaxation time was found to be significantly higher (23%) in group C over S and 17% in group CP over SP (P &lt; 0.05). No significant morphometric differences were found among the different treatment groups. These results support the notion that swimming partially prevents prednisolone-induced osteoporosis in elderly rats.
1,25-Dihydroxyvitamin D3 inhibits the passive transfer of cellular immunity by a myelin basic protein-specific T cell clone
Authors: Lemire Jacques M. , Adams John S. 
Published: February 2010

Abstract
1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] and related analogs have been shown to exert immunoinhibitory effects on activated lymphocytes in vitro. However, the effects of the hormone on the mammalian immune response in vivo have not been well studied. To examine the possible immunoactions of 1,25-(OH)2D3 in vivo, we employed a murine model of experimental autoimmune encephalomyelitis (EAE). In this model, T helper lymphocyte clones developed from lines of lymphocytes reactive to myelin basic protein (MBP) confer MBP immunoreactivity and demyelinating central nervous system disease on syngeneic, naive recipients of the T cell clone. Similar to peripheral blood mononuclear cells incubated with mitogen, the T cell clone evaluated in this study expressed a high-affinity specific receptor for 1,25-(OH)2D3 (VDR; Kin = 0.03 nM) upon exposure to MBP. The MBP-stimulated clone elicited a ninefold enhancement of the local delayed hypersensitivity (DTH) response when as few as 0.5 × 105 cells of the T cell clone were injected into the foot pad of recipient mice. The DTH response in the recipient was completely blocked when the clone was preincubated with ≥ 10−8 M 1,25-(OH)2D3 before transfer; the half-maximal inhibitory concentration of hormone (EC50) was 5 × 10−9 M. These data indicate that exposure of antigen-reactive T helper lymphocytes to a VDR saturating concentration of 1,25-(OH)2D3 can dramatically lessen the expression of immunoreactivity in vivo.
Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells
Authors: Franceschi Renny T. , Iyer Bhanumathi S. 
Published: February 2010

Abstract
The MC3T3-E1 mouse calvaria-derived cell line has been used to study the role of collagen synthesis in osteoblast differentiation. MC3T3-E1 cells, like several previously characterized osteoblast culture systems, expressed osteoblast markers and formed a mineralized extracellular matrix only after exposure to ascorbic acid. Mineralization was stimulated further by β-glycerol phosphate. Ultrastructural observations indicated that the extracellular matrix produced by ascorbic acid-treated cells was highly organized and contained well-banded collagen fibrils. Expression of osteoblast markers followed a clear temporal sequence. The earliest effects of ascorbic acid were to stimulate type I procollagen mRNA and collagen synthesis (24 h after ascorbate addition), followed by induction of alkaline phosphatase (48–72 h) and osteocalcin (96–144 h) mRNAs. Procollagen mRNA, which was expressed constitutively in the absence of ascorbate, increased only twofold after vitamin C addition. In contrast, alkaline phosphatase and osteocalcin mRNAs were undetectable in untreated cultures. Actions of ascorbic acid on osteoblast marker gene expression are mediated by increases in collagen synthesis and/or accumulation because (1) parallel dose-response relationships were obtained for ascorbic acid stimulation of collagen accumulation and alkaline phosphatase activity, and (2) the specific collagen synthesis inhibitors, 3,4-dehydroproline and cis-4-hydroxyproline, reversibly blocked ascorbic acid-dependent collagen synthesis and osteoblast marker gene expression.
Inhibition of bone resorption in vitro by human enkephalinase (EC 3.4.24.11), a neutral metalloendopeptidase
Authors: Dr. Ibbotson Kenneth J. , D'souza Sharyn M. , Deschodt-Lanckman Monique , Appelboom Thierry E. 
Published: February 2010

Abstract
Bone metabolism is regulated by a wide variety of both circulating and locally produced peptides. The activity of such agents must be regulated, and one potential regulating mechanism is the inactivation of these peptides by locally produced proteolytic enzymes. One candidate for such a class of enzymes is enkephalinase (EC 2.3.24.11), a membrane-bound neutral metalloendopeptidase that inhibits the activity of a range of biologically active peptides, including interleukin-1 (IL-1), a potent bone-resorbing agent. In this study, we examined the effects of human enkephalinase on bone resorption in cultures of fetal rat long bones. We found that partially purified and highly purified enkephalinase inhibited bone resorption stimulated by parathyroid hormone (PTH) and IL-1α. The effects on PTH-stimulated resorption were reversible, but enkephalinase did not inhibit prestimulated resorption. Enkephalinase also inhibited resorption induced by the nonpeptide stimulators 1,25-(OH)2D3, retinoic acid, and prostaglandin E2 (PGE2). In addition, preliminary studies confirmed a previous report of the presence of an enkephalinase-like activity in osteoblast-like osteosarcoma cells. These data are consistent with the hypothesis that proteolytic enzymes, such as enkephalinase, may play a role in the local regulation of bone resorption.
Developmental changes in calcium kinetics in children assessed using stable isotopes
Authors: Abrams Steven A. , Esteban Nora V. , Vieira Nancy E. , Sidbury James B. , Specker Bonny L. , Yergey Alfred L. 
Published: February 2010

Abstract
Total exchangeable calcium pool size (TEP) and bone calcium accretion rate (V0+) were measured using stable isotopes in healthy children and young adults. 42Ca or 46Ca was given intravenously to 10 children aged 10 months to 14 years and 3 women aged 23–33 years. Calcium kinetic parameters were determined using a two- or three-exponential curve of the resultant serum and urine tracer excesses. These data were compared with previously reported (radiotracer) kinetic studies of 21 children and 5 adults without known bone disease. Current results are comparable to those previously obtained, and the data from all studies were analyzed together. Total V0+ was significantly greater in children aged 3–16 years than in adults (2.8 ± 1.6 versus 0.7 ± 0.2 g/day, p &lt; 0.01). Both TEP and V0+ were significantly correlated to age independently on variations in body weight (p &lt; 0.01 for each). The ratio k0+ = V0+/TEP was greater in children than adults (0.36 ± 0.15 versus 0.12 ± 0.03 day−1, p &lt; 0.001). These data demonstrate increased bone flow of calcium associated with increases in exchangeable calcium pools in children compared to adults. V0+ and TEP may be maximum in early adolescence, associated with peak rates of net calcium accretion. The use of stable isotopes permits the safe evaluation of calcium kinetics in patients of all ages.
Parathyroid hormone sensitizes long bones to the stimulation of bone resorption by 1,25-dihydroxyvitamin D3
Authors: Dr. van Leeuwen J. P. T. M. , Birkenhäger J. C. , Bos M. P. , van der Bemd G. J. C. M. , Herrmann-Erlee M. P. M. , Pols H. A. P. 
Published: February 2010

Abstract
In response to hypocalcemia the serum PTH level increases rapidly followed by a PTH-induced rise in 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] production. Therefore, bone is first exposed to increased PTH levels before increased 1,25-(OH)2D3 levels. In the present study the effect of pretreatment with PTH on 1,25-(OH)2D3-induced bone resorption was examined. Bone resorption was measured as release of prelabeled 45Ca during culture from 17-day-old fetal mice radii/ulnae and metatarsals. Radii/ulnae and metatarsals are characterized by differences in development. In radii/ulnae mature osteoclasts are present, whereas in metatarsals only different stages of preosteoclasts can be found. Preincubation for 24 h but not 4 h with PTH increases the stimulation of bone resorption by 1,25-(OH)2D3 in fetal radii/ulnae but not in metatarsals. Coincubation of PTH and 1,25-(OH)2D3 did not result in a significant change in bone resorption compared to 1,25-(OH)2D3 alone. The observed difference in the effect of pretreatment with PTH between radii/ulnae and metatarsals indicates that PTH does not stimulate the development of early osteoclast precursors but that a certain level of differentiation of the osteoclast precursor is required. Pretreatment with prostaglandin E2 resulted in an effect similar to that of PTH. Inhibition of prostaglandin synthesis by indomethacin prevented the potentiation of 1,25-(OH)2D3-induced bone resorption by pretreatment with PTH. Thus, the present study demonstrates that PTH sensitizes responses to 1,25-(OH)2D3. PTH must be present before 1,25-(OH)2D3 to observe a potentiation of 1,25-(OH)2D3-induced bone resorption. Local production of prostaglandins seems to be involved in this action of PTH. Taken together, these data suggest that besides increased renal production of 1,25-(OH)2D3 PTH also sensitizes bone for the 1,25-(OH)2D3-induced bone resorption.
Mineral crystals in calcified tissues: A comparative study by SAXS
Authors: Fratzl P. , Groschner M. , Vogl G. , Plenk H. , Eschberger J. , Fratzl-Zelman N. , Koller K. , Dr. Klaushofer K. 
Published: February 2010

Abstract
The shape, the typical orientation, and the average size of mineral crystals in different types of mineralized tissues were investigated by means of small-angle x-ray scattering (SAXS). To rule out eventual artifacts due to sample preparation, four different standard preparation techniques were used and a comparison showed that the SAXS results were identical for all four methods. In mineralized turkey leg tendon, a frequently used model system for bone, the crystals were found to be typically plate-like with a thickness of the order of 2 nm. This stands in contrast to the case of bone (calvaria, femur, and iliac crest) from mouse, rat, and dog, where mainly needle-like crystals were found. The thickness of these crystals ranged from 3 to 4 nm but was remarkably constant for different bones of a given animal. The preferred orientation of the needle-like crystals was along the main axis of the femur and within the surface of the calvaria (for mouse, rat, and dog). The mineral plates in turkey leg tendon were located inside the hole zone and oriented along the fibril axis. Finally, no periodic arrangement of the crystals inside the hole zone of the collagen could be found.
Integrins on rat osteoclasts: Characterization of two monoclonal antibodies (F4 and F11) to rat β3
Authors: Helfrich Miep H. , Nesbitt Stephen A. , Horton Michael A. 
Published: February 2010

Abstract
Two monoclonal antibodies, F4 and F11, were raised to newborn rat bone cell suspensions. These antibodies are shown by immunocytochemistry on tissue sections to recognize an antigen shared between osteoclasts, megakaryocytes, and platelets. Immunoprecipitation analysis of the antigen from C6 rat glial cells followed by SDS-PAGE showed a heterodimeric molecule with a characteristic integrin-like shift in apparent molecular mass upon reduction (137/78 kD nonreduced; 118/100 kD reduced); the low-molecular-mass band comigrates with the β3 subunit precipitated with polyclonal antihuman vitronectin receptor antiserum, and the high-molecular-mass band comigrates with the αv subunit precipitated with a polyclonal antiserum to a C-terminal amino acid sequence of human αv. Antibody F4 strongly cross-reacts with human cells and is shown in cross-blocking experiments and immunoprecipitation analysis with a human melanoma cell line DX3 to recognize a seemingly identical molecule as identified by anti-αvβ3 monoclonal antibody 23C6. Expression of F4 and F11 is reduced in platelets from a patient heterozygous for Glanzmann's thrombasthenia. Taken together, these results indicate that F4 and F11 recognize rat CD61, the integrin β3 chain, which, as was confirmed with polyclonal anti CD61 antisera, is highly expressed in rat osteoclasts. These antibodies may be useful tools in investigating the biochemical nature and biologic function of β3 integrins in rat osteoclasts. Additionally, because high expression of β3 in vivo is restricted to osteoclasts, megakaryocytes, and platelets, these antibodies may be used to help identify osteoclasts in tissue sections and bone cell suspensions. Apart from β3, rat osteoclasts were found to express high levels of αv and β1 integrins.