bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive assessment of ulnar bending stiffness in women
Authors: McCabe Frances , Zhou L.-J. , Steele Charles R. , Marcus Robert 
Published: February 2010

Abstract
The load-carrying capacity of cortical bone is closely related to its geometry and to its fundamental material properties, including mineral content (BMC). Together these determine the bending stiffness EI, where I is the cross-sectional moment of inertia and E is Young's modulus of elasticity. To assess the relationship of BMC and bone width (BW) to EI in healthy women, we used mechanical response tissue analysis (MRTA), a noninvasive method that involves analysis of tissue responses to ulnar vibration. A total of 48 healthy women were enrolled into an older (64 ± 1y, n = 25) and a younger (25 ± 0.6y, n = 23) group. BMC and BW of the dominant ulna were measured by single-photon absorptiometry (SPA). EI was determined by MRTA. BMC (0.75 ± 0.02 versus 0.63 ± 0.02 g/cm), BMC/BW (0.75 ± 0.02 versus 0.63 ± 0.02 g/cm2), and EI (21.7 ± 1.3 versus 21.3 ± 1.1 N ṁ m2) were significantly greater (p &lt; 0.005) in the young subjects. BW did not change with age (1.00 ± 0.01 versus 1.01 ± 0.01 cm). In young women, simple correlations of BMC and BW with EI were both significant. By multiple regression analysis only BW independently predicted EI (EI = −0.35 + 39.1 × BMC, R2 = 0.52). In older women BMC and BW correlated with EI, but in multiple regression only BMC was significant (EI = −34.5 + 62.1 × BW; R2 = 0.45). When this analysis of older women included only those whose BMC values were within 2 SD of the young mean, BMC remained the only significant predictor of EI. We conclude that ulnar dimensions make important contributions to axial loading strength in healthy young women, whereas changes in internal architecture, porosity, or bone material properties increase the importance of BMC as a determinant of ulnar stiffness for older women.
Urinary excretion of parathyroid hormone-related protein fragments in patients with humoral hypercalcemia of malignancy and hypercalcemic tumor-bearing nude mice
Authors: Imamura Hidehito , Dr. Sato Kanji , Shizume Kazuo , Satoh Tomoko , Kasono Keizo , Ozawa Minoru , Ohmura Eiji , Tsushima Toshio , Demura Hiroshi 
Published: February 2010

Abstract
To investigate whether parathyroid hormone-related protein (PTHrP), a hypercalcemia-inducing factor responsible for malignancy-associated hypercalcemia (MAH), is excreted into urine of these patients, radioimmunoassay was established using antiserum specific for the C-terminal region of PTHrP-(127–141).
Immunoreactive PTHrP (iPTHrP) was detected in the urine of all patients with MAH (n = 6) in whom nephrogenous cyclic AMP excretion was elevated. However, iPTHrP was not detected in the urine of normal subjects (n = 25) or hypercalcemic patients with primary hyperparathyroidism (n = 8). In normocalcemic patients with malignant disorders iPTHrP was not detected in the urine in most cases (24 of 25 patients) but was detectable in 1 of 25 patients. iPTHrP was also detected in the urine of hypercalcemic nude mice transplanted with PTHrP-producing tumors, but not in the urine of control and normocalcemic nude mice transplanted with PTHrP-nonproducing tumor. Furthermore, size-exclusion high-performance liquid chromatography revealed that the molecular weight of iPTHrP is about 2000–6000 daltons in the urine of patients as well as tumor-bearing nude mice.
These data indicate that the fragments of the C-terminal region of PTHrP are excreted into the urine of patients with MAH and in a few normocalcemic patients with malignancies, suggesting that the measurement of iPTHrP in the urine is potentially useful in the differential diagnosis of hypercalcemia, particularly in differentiating humoral hypercalcemia of malignancy and primary hyperparathyroidism.
Interrelationship among vitamin D metabolism, true calcium absorption, parathyroid function, and age in women: Evidence of an age-related intestinal resistance to 1,25-dihydroxyvitamin D action
Authors: Eastell Richard , Yergey Alfred L. , Vieira Nancy E. , Cedel Sandra L. , Kumar Rajiv , Dr. Riggs B. Lawrence 
Published: February 2010

Abstract
We studied the mechanism of impaired calcium absorption with aging in 51 healthy women whose ages ranged from 26 to 88 years. Serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D, mean of four measurements per subject] increased with age by 22% (P &lt; 0.05) but, by split-point analysis, plateaued or decreased slightly after age 65. In a subset of 20 subjects, [3H]1,25-(OH)2D3 kinetic analysis showed that this increase with age resulted from both increased production and decreased metabolic clearance of 1,25-(OH)2D. Despite the increase in serum 1,25-(OH)2D concentration, true calcium absorption did not change with age. The expected inverse correlation between true fractional calcium absorption and dietary calcium intake, however, was easily demonstrated (r = 0.66, P &lt; 0.001). Serum intact parathyroid hormone (PTH) increased with age by 35% (P &lt; 0.02) and serum bone gla protein (BGP, osteocalcin) increased by 47% (P &lt; 0.001); the increases in serum PTH and serum BGP were directly correlated (r = 0.32, P &lt; 0.05). The data are consistent with the following hypothetical model: (1) intestinal resistance to 1,25-(OH)2D action accounts for the increase in serum 1,25-(OH)2D concentrations with aging with no change in true calcium absorption; (2) this results in a compensatory increase in PTH secretion and in 1,25-(OH)2D production that prevents true calcium absorption from decreasing; (3) the previously described defect in 25-hydroxyvitamin D (25-OHD) 1α-hydroxylase activity in aging animals and humans acccounts for the leveling off in serum 1,25-(OH)2D concentration after age 65 years; and (4) the secondary hyperparathyroidism leads to increased bone turnover and thus contributes to age-related bone loss.
Osteotropic factor responsiveness of highly purified populations of early and late precursors for human multinucleated cells expressing the osteoclast phenotype
Authors: Kurihara Noriyoshi , Civin Curt , Roodman G. David 
Published: February 2010

Abstract
Recently we have adapted human long-term bone marrow cultures to form multinucleated cells (MNC) that express the osteoclast phenotype and used semisolid culture techniques to identify early (bipotent) and late (unipotent) mononuclear precursors for these MNC. The early precursor can form both osteoclast-like MNC and macrophage polykaryons; the late precursor forms only osteoclast-like MNC. In this study we examined the effects of osteotropic hormones and cytokines of MNC formation from highly purified populations of these early or late mononuclear precursor cells. MNC expressing the osteoclast phenotype were identified by their cross-reactivity with the 23c6 monoclonal antibody, which preferentially identifies osteoclasts. 1,25-(OH)2D3 (10−8 M), IL-1β (10 u/ml), and IL-6 (100 pg/ml) stimulated formation of 23c6-positive MNC from highly purified populations of early or late precursor cells. In contrast, PTH (50 ng/ml) did not act directly on late precursor cells but only stimulated 23c6-positive MNC formation from early precursors. These results show that (1) 1,25-(OH)2D3, IL-1β, and IL-6 can stimulate 23c6-positive MNC formation from a highly enriched population of early and late precursors, and (2) PTH does not act on late precursors but may act indirectly on the late precursors.
Comparison of dual-photon absorptiometry systems for total-body bone and soft tissue measurements: Dual-energy X-rays versus gadolinium 153
Authors: Russell-Aulet Mary , Wang Jack , Thornton John , Pierson Richard N. 
Published: February 2010

Abstract
A total of 81 subjects (41 males and 40 females) were scanned by dual-photon absorptiometry by 153Gd source (DPA; Lunar DP4) and by dual-energy x-ray absorptiometry (DEXA; Lunar-DPX) within a 24 h period. Total-body bone mineral density (TBMD), calcium content (Ca), and soft tissue mass (ST) were determined with a precision of about 1–1.5% using DPA and 0.5–1.0% using DEXA. Measurements of TBMD, Ca, ST, bone area (area), percentage fat, and regional bone mineral densities (BMD) were compared. Paired t-tests showed small but significant differences between all measurements. Correlations (r) for TBMD, Ca, area, ST, percentage fat, arm BMD, leg BMD, and trunk BMD were 0.99, 0.99, 0.97, 0.99, 0.97, 0.99, 0.99, and 0.98. There were small systematic differences for TBMD (&lt;1%), calcium (3%), bone area (3%), soft tissue mass (7%), and percentage fat (9%) between the two approaches. Regression equations are given relating these measurements.
Acute effect of 1,25-dihydroxyvitamin D3, prednisone, and 1,25-dihydroxyvitamin D3 plus prednisone on serum osteocalcin in normal individuals
Authors: Nielsen Henning K. , Brixen Kim , Kassem Mustapha , Mosekilde Leif 
Published: February 2010

Abstract
Suppression of osteoblastic function plays an important pathogenic role for the development of glucocorticosteroid-induced osteoporosis. Serum osteocalcin (OC) is a sensitive marker of bone formation. The diurnal rhythm in serum OC can be changed by administration of single doses of either 1,25-(OH)2D3 or prednisone. However, the two steroids have opposing effects: 1,25-(OH)2D3 increases and prednisone decreases serum OC. The aim of the present study was to examine whether 1,25-(OH)2D3 can oppose the acute suppressive effect of prednisone on serum OC in normal subjects. We compared the effect of a combined dose of 2 μg 1,25-(OH)2D3 and 10 mg prednisone on the diurnal rhythm of serum OC with the effect of 2 μg 1,25-(OH)2D3 + placebo in a crossover study. Seven normal subjects aged 23–36 years were investigated twice at an interval of 1 week. Blood samples were collected every 60 minutes from 1900 until 1100 h the following day. Study drugs were given at 2000 h. The data from the present investigation were compared with data obtained from a similar study with placebo and prednisone in the same subjects. After administration of 1,25-(OH)2D3 serum OC followed the placebo curve during the first 8 h, but in contrast to the placebo curve it then continued to increase and remained elevated throughout the observation period (p &lt; 0.05). Prednisone inhibited and reversed the nocturnal rise in serum OC levels (p &lt; 0.01). The course of serum OC after administration of 1,25-(OH)2D3 + prednisone almost paralleled the course after placebo. We conclude that 1,25-(OH)2D3 and prednisone have opposing effects on serum OC.
Bradykinin induces formation of inositol phosphates and causes an increase in cytoplasmic Ca2+ in the osteoblastic cell line MC3T3-E1
Authors: Ljunggren Östen , Johansson Hans , Ljunghall Sverker , Fredholm Bertil B. , Lerner Ulf H. 
Published: February 2010

Abstract
Recordings of fura-2 fluorescence from single osteoblastic MC3T3-E1 cells showed that bradykinin (BK, 1 μM) induced a rapid increase in cytoplasmic free Ca2+ (Cai2+, from 114 + 13 to 239 + 17 nM, mean + SEM). Following this initial transient (&lt;1 minute) increase there was a second slow increase in Cai2+ (from 117 + 11 to 151 + 12 nM). Incubation in buffer with no Ca2+ did not affect the first rapid BK-induced increase in Cai2+ but eliminated the second slow increase. Addition of indomethacin or hydrocortisone to the incubation buffer did not inhibit the effect of BK on Cai2+. BK caused a dose-dependent initial rapid increase in Cai2+ with threshold at 1 nM and a maximal effect (241 + 30% of basal Cai2+ concentration) at 0.1 μM. The B1 BK receptor agonist des-Arg9-BK (1 μM) caused only a small increase in Cai2+ in MC3T3-E1 cells (from 101 + 20 to 140 + 4 nM). BK dose and time dependently stimulated the formation of inositol phosphates in MC3T3-E1 cells with EC50 at 2.4 nM and a significant increase in inositol trisphosphate already seen after 15 s. The Ca2+ ionophore ionomycin induced a rapid increase in Cai2+ and prostaglandin E2 (PGE2) formation in MC3T3-E1 cells. Forskolin (10–30 μM) increased cyclic AMP accumulation but did not affect Cai2+ or PGE2 formation. Depletion of extracellular Ca2+ significantly reduced (but did not abolish) BK-induced PGE2 formation. The initial action of BK on Cai2+ is probably due to an inositol-(1,4,5)-trisphosphate-mediated rapid release of Ca2+ from intracellular stores in osteoblasts and is followed by an influx of extracellular Ca2+. The effect is due to B2 BK receptor occupancy and is not secondary to the prostaglandin synthesis. The BK-induced breakdown of phosphatidylinositol-(4,5)-bisphosphate with a subsequent increase in Cai2+ may be involved in BK-induced prostaglandin formation in osteoblasts.
Osteogenesis imperfecta: Changes in noncollagenous proteins in bone
Authors: Vetter U. , Fisher L.W. , Mintz K.P. , Kopp J.B. , Tuross N. , Termine J.D. , Robey P. Gehron 
Published: February 2010

Abstract
The noncollagenous proteins osteonectin, bone sialoprotein, osteocalcin, the small proteoglycan decorin (PG II), and α2-HS glycoprotein (which is synthesized in the liver but highly concentrated in bone) were measured in extracts of cortical bone from 3 type I, 2 type II, 8 type III and 13 type IV patients with osteogenesis imperfecta (OI) and from 7 control subjects.
Osteonectin was found to be reduced in the bone of all OI patients. The bone from severely affected type III OI patients contained the lowest levels of osteonectin. In contrast, bone sialoprotein was found to be elevated in the bones of OI patients. The highest levels were found in individuals classified as type IV patients. Osteocalcin and α2-HS glycoprotein concentrations were increased in all OI patients. Decorin levels were not significantly altered in OI bones compared to controls.
These changes in the concentrations of the noncollagenous proteins may contribute to the fragility of the OI bone by interfering with complete mineralization and/or normal tissue architecture.
Establishment and characterization of two immortalized cell lines of the osteoblastic lineage
Authors: Hofstetter W. , Guenther H.L. , Stutzer A. , Schenk R. , Fleisch H. , Friis R. 
Published: February 2010

Abstract
Osteoblastic cells were cloned by culturing rat calvariae cells in agarose in the presence of TGF-β and EGF. Two bone cell lines were established by immortalizing such an osteoblastic clonal cell population by the introduction of the avian v-mycOK10 gene in the form of a mouse ecotropic retrovirus. Although originating from the same clonal cell population, the two lines exhibited somewhat differing properties. IRC10/30-mycl expressed alkaline phosphatase (AP), showed PTH- and PGE2-induced cAMP production, synthesized mainly collagen type I and a minor fraction of type III, and produced mRNA for the bone-specific protein osteocalcin. IRC10/30-myc3 did not express AP, showed no PTH responsiveness, and synthesized only about one-third as much collagen as IRC10/30-mycl (4 versus 12% of total protein synthesis). However, the cell line IRC10/30-myc3 was induced to synthesize cAMP by PGE2 and produced osteocalcin mRNA. When cultured in vivo in diffusion chambers, both lines proved to be osteogenic. Besides bone, both lines also formed cartilage and fibrous tissue. Thus, by immortalizing a clonal cell population of the osteoblastic phenotype, cell lines expressing varying properties can emerge. Furthermore, the expression of alkaline phosphatase and PTH-inducible adenylate cyclase are not prerequisites for a cell to form bone in vivo. Finally, cells expressing the phenotype of differentiated osteoblasts, including osteocalcin synthesis, still have a multipotential differentiation capacity and form bone and cartilage in vivo.
Urinary excretion of pyridinoline crosslinks correlates with bone turnover measured on iliac crest biopsy in patients with vertebral osteoporosis
Authors: Dr. Delmas Pierre D. , Schlemmer Annette , Gineyts Evelyne , Riis Bente , Christiansen Claus 
Published: February 2010

Abstract
Vertebral osteoporosis, a common disorder in elderly women, is characterized by a wide spectrum of bone turnover abnormalities on iliac crest biopsy. The level of bone formation can be assessed noninvasively by measuring serum osteocalcin, whereas conventional biochemical markers of bone resorption lack specificity and do not reflect bone resorption assessed from histology. We measured the urinary excretion of pyridinoline crosslinks Pyr and D-Pyr, a specific marker of bone and cartilage collagen degradation, along with serum osteocalcin and urinary hydroxyproline, in 36 elderly women with vertebral osteoporosis who had a simultaneous iliac crest biopsy. Urinary pyridinoline crosslinks, but not hydroxyproline, correlated significantly with histologic resorption, assessed by the osteoclast surface (r = 0.35, p &lt; 0.05 for Pyr; r = 0.46, p &lt; 0.01 for D-Pyr). In addition, Pyr and D-Pyr were correlated with the bone formation rate as well as serum osteocalcin, with correlation coefficients ranging from 0.69 to 0.80, p &lt; 0.0001. These data indicate that Pyr and D-Pyr are sensitive markers of bone turnover in elderly women with vertebral osteoporosis. The poor correlation between the level of urinary collagen crosslinks and histological assessment of bone resorption indicates the low sensitivity of iliac crest histomorphometry in the measurement of resorption rate of the skeleton.
Application of reflected light microscopy to identify and quantitate resorption by isolated osteoclasts
Authors: Walsh C.A. , Beresford J.N. , Birch M.A. , Boothroyd B. , Gallagher J.A. 
Published: February 2010

Abstract
A simple technique has been developed to identify the resorption lacunae excavated by avian osteoclasts in vitro. Briefly, devitalized bovine bone wafers, with cells in situ, are fixed, stained with toluidine blue, and then examined by reflected light microscopy. Resorption pits are clearly visible using a x 10 objective, even when the resorbed areas are covered by a confluent layer of cells. The technique can be used to quantify the plan area, depth, and volume of the excavations. Depth and volume are assessed using the x 50 objective lens. This technique has been used to investigate the effects of retinyl acetate and EHDP on bone resorption.
Evidence for nonrenal synthesis of 1,25-dihydroxyvitamin d in patients with inflammatory arthritis
Authors: Dr. Mawer Barbara E. , Hayes Michael E. , Still Pamela E. , Davies Michael , Lumb Geoffrey A. , Palit Jayanta , Holt Lennox P.J. 
Published: February 2010

Abstract
The extrarenal synthesis of 1,25-dihydroxyvitamin D [1,25-(OH)2D] is a characteristic of activated macrophages and has been demonstrated to occur in vitro in synovial fluid macrophages from patients with inflammatory arthritis. To examine whether such synthesis occurs in vivo, 19 patients with rheumatoid arthritis, 5 patient controls, and 5 healthy controls received a challenge oral dose of 250 μg 25-hydroxyvitamin D3 (25-OHD3) and the serum 1,25-(OH)2D3 response was measured. The median rise in serum 1,25-(OH)2D3 was significantly greater (22 pg/ml) in the rheumatoid patients compared to either of the control groups (8 pg/ ml), although the increase in precursor 25-OHD3 was similar in all groups. The serum 1,25-(OH)2D concentration did not rise above the normal upper limit in any of the control subjects but exceeded the normal range in 8 of the rheumatoid patients. Extrarenal 1,25-(OH)2D synthesis is substrate dependent, unlike renal 1α-hydroxylation, which is homeostatically controlled. Excessive 1,25-(OH)2D3 synthesis in the rheumatoid group on raising the 25-OHD3 concentration is indicative of nonrenal production of the hormonal metabolite. Further evidence for substrate-dependent extrarenal synthesis came from measurements of 25-OHD and 1,25-(OH)2D in paired serum and synovial fluid samples from 19 patients with inflammatory arthritis, including 15 with rheumatoid arthritis. Synovial fluid 1,25-(OH)2D was usually present at a lower concentration than serum 1,25-(OH)2D, with which it was strongly correlated (Kendall's R = 0.46, P &lt; 0.001). Synovial fluid 1,25-(OH)2D was also correlated with synovial fluid 25-OHD (R = 0.55, P &lt; 0.001), but serum 1,25-(OH)2D and 25-OHD were not related. At high synovial fluid 25-OHD concentrations the 1,25-(OH)2D level in synovial fluid exceeded that in serum, suggesting local synthesis of 1,25-(OH)2D within the synovium. Distribution of vitamin D metabolites between serum and synovial fluid could not be explained by the relevant concentrations of vitamin D binding protein. Together these results provide strong evidence for nonrenal synthesis of 1,25-(OH)2D in patients with inflammatory arthritis. The extent of synovial synthesis of 1,25-(OH)2D may be governed both by the severity of the inflammatory disease and by drug treatment. Such synthesis may be significant in the immunoregulatory system in the affected joint and may prove to have relevance to the development of periarticular osteoporosis in rheumatoid arthritis.
A histomorphometric study of cortical bone activity during increased weight-bearing exercise
Authors: Raab Diane M. , Crenshaw Thomas D. , Kimmel Donald B. , Smith Everett L. 
Published: February 2010

Abstract
To quantify cortical bone response to weight-bearing exercise, bone size, mineral content, and formation were measured at the femoral midshaft in swine. Bone formation was measured histomorphometrically on the periosteal, endosteal, and osteonal surfaces. Sedentary adult crossbred sows (3 years, 229 kg) were randomly assigned to basal (B, n = 6), control (C, n = 7), or trained (T, n = 7) groups. The basal and control groups did not exercise and were killed initially (B) or after 20 weeks (C). The trained group walked on a treadmill 20 minutes/day at 5 km/h and 5% grade, 5 days/week for 20 weeks. Bone length, area, or fat-free dry weight was not different with time (B versus C) or with training (C versus T). Periosteal modeling was stimulated by walking. Periosteal formation surface and mineral apposition rate (MAR) were greater in trained than control femora. No effects of walking were measured on the endosteal surface. Intracortical remodeling was not affected by walking. The number of labeled osteons (22.4 cm−2) was not different among groups, but osteonal MAR was greater in trained (1.18 μm/day) than control (0.96 μ/day) femora. Walking for 20 weeks in the previously sedentary sows was not a sufficient stimulus to create differences in gross measures of bone size or mineral content but did increase periosteal and intracortical MAR. The primary effect of increased exercise appeared to be osteoblast activation.