bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteogenic response to marrow aspiration: Increased serum osteocalcin and alkaline phosphatase in human bone marrow donors
Authors: Foldes Josef , Statter Michael , Menczel Jacob , Naparstek Ella , Prof. Bab Itai 
Published: February 2010

Abstract
It has been shown recently in experimental animals that regeneration of bone marrow after ablation is associated with enhanced osteogenic growth factor activity and a systemic increase in bone formation. To assess the possible occurrence of a similar phenomenon in humans, serum markers of bone formation, osteocalcin and alkaline phosphatase, were measured in marrow donors before the aspiration of large amounts of iliac marrow and 1 day to 5 weeks thereafter. Both osteocalcin and alkaline phosphatase showed significant increases, with peak values 1–3 and 2–4 weeks postaspiration, respectively. The absolute maximal increase in osteocalcin was significantly higher in adolescent and child donors than in adults. When evaluated together with studies on systemic changes during fracture healing and marrow regeneration, these findings suggest that marrow aspiration in humans evokes a systemic osteogenic response.
Perspectives: Methodologic issues in evaluating risk factors for osteoporotic fractures
Authors: Ross Philip D. , Wasnich Richard D. , Davis James W. , Vogel John M. , Heilbrun Lance K. 
Published: February 2010

Abstract
Techniques for measuring bone mineral content (BMC) were developed for the purpose of providing an objective and noninvasive indication of bone strength (or lack thereof) and fracture risk, to the extent that strength relates to bone mass. As such, BMC measurements could help to (1) identify those who are most likely to experience nonviolent fractures in the future and who would therefore benefit most from preventive measures, (2) improve their treatment compliance, and (3) monitor the efficacy of treatments intended to reduce bone loss. All these potential uses require that the measurement provide an indication of fracture risk (probability of fractures).
During the past 10–15 years there have been conflicting reports regarding the association of reduced BMC with nonviolent fractures. Some authors have criticized the usefulness of BMC measurements, whereas others have questioned the value of one or more techniques. However, the epidemiology of osteoporosis has only recently been subjected to rigorous study. The use of appropriate statistical methods for relating fracture risk to bone mass may be no more widely practiced in osteoporosis epidemiology today than it was for studying risk factors (e.g., blood pressure) in cardiovascular epidemiology during the 1960s.
The intent of this article is to explore three areas that may have contributed to controversy in the study of bone mass and fracture occurrence: (1) perspective of the investigators, (2) study design, and (3) analytic methodology. Although the focus of this paper is on bone mass, these considerations are equally applicable to some investigations of other risk factors for osteoporotic fractures (e.g., bone architecture, bone turnover and loss rate, or biochemical markers of bone loss).
The effect of cross-gender hormonal treatment on bone metabolism in male-to-female transsexuals
Authors: Dr. Lips P. , Asscheman H. , Uitewaal P. , Netelenbos J.C. , Gooren L. 
Published: February 2010

Abstract
A deficiency of sex hormones leads in both sexes to increased bone loss, and hormonal substitution can prevent this. The effect of the change of hormonal environment on bone metabolism in transsexuals is unknown. Transilial bone biopsies were obtained from 23 male-to-female transsexuals (mean age ± SD, 38.0 ± 11.7 years) after estrogen (ethinylestradiol, 100 μg/day) and antiandrogen treatment (cyproterone acetate, 100 mg/day) for 8–41 months. Histomorphometric data were compared with those from 11 healthy men (39.6 ± 9.4 years). There was no difference in bone volume, bone surface, or trabecular thickness between transsexuals and controls. Eroded surface and osteoclast number were not different between the groups. The osteoid volume, surface, and thickness were significantly lower in the transsexuals than in the controls. The mineral apposition rate and adjusted apposition rate were normal, but mineralizing surface and bone formation rate were suppressed in the transsexuals compared with data reported from the literature. The results indicate that antiandrogen and estrogen treatment in male-to-female transsexuals may suppress bone turnover and is not associated with bone loss.
Calibration and standardization of bone mineral densitometers
Authors: Kelly T.L. , Slovik D.M. , Neer Robert M. 
Published: February 2010

Abstract
Measurements of bone mineral density (BMD) by four 153Gd and two x-ray bone densitometers were compared utilizing spine phantoms that simulated the human lumbar spine. The six instruments provided BMD values that differed by as much as 16%, due to differences as large as 8% in bone mineral content and as large as 7% in bone area. Instrument calibration curves, determined by measuring thin, medium, and thick hydroxyapatite blocks, were linear (r = 0.99) but had different (p &lt; 0.0001) slopes and intercepts.
Serial measurements of spine and total body phantoms were employed to evaluate the long-term stability of 153Gd bone densitometry. These measurements of spine phantom BMD increased 1.0–2.6% (p &lt; 0.0001) following a software change, and measurements of total body bone density increased 4–6% after 153Gd source replacement. The changes occurred at a time when serial measurements of cylindrical calibration standards were stable, indicating that such simple standards are unable to detect and correct for changes in instrumental response. We conclude that investigators, manufacturers, and government regulatory agencies must develop and implement the following: (1) effective calibration procedures that would assure comparability among instruments, and (2) appropriate quality control phantoms that would allow the confident interpretation of serial patient measurements.
The evolution of osteomalacia in the rat with acute aluminum toxicity
Authors: Rodriguez Mariano , Felsenfeld Arnold J. , Llach Francisco 
Published: February 2010

Abstract
Aluminum toxicity is the presumed cause of aluminum-associated osteomalacia. In animal models, osteomalacia has been produced after a prolonged course of aluminum. In the present study, rats with renal failure received 20 mg intraperitoneal aluminum during a 2 day period. This model allows sequential observations in the development of osteomalacia. Rats were sacrificed and studied 5, 12, 25, and 40 days after aluminum administration. No differences were observed in serum calcium, phosphorus, or creatinine as a consequence of aluminum administration. Compared with control rats, parathyroid hormone was decreased at 12 and 25 days. A direct correlation was present between plasma and bone aluminum at 12 days (r = 0.92, p &lt; 0.01), 25 days (r = 0.85, p &lt; 0.005), and 40 days (r = 0.88, p &lt; 0.001) but not 5 days after aluminum administration. Plasma aluminum peaked at 5 days (727 ± 89 μg/liter, mean ± SEM) and bone aluminum at 40 days (273 ± 40 μg/g). Aluminum had profound effect on bone histology. At 5 days there was a decrease in osteoblast surface and osteoid surface; at 12 days osteoblast surface and osteoid surface returned to normal but osteoclast surface decreased. Subsequently there was a progressive increase in osteoid surface and osteoid volume. Bone formation rate measured at 12, 25, and 40 days was decreased at these intervals.
In conclusion, (1) high plasma aluminum may be directly toxic to the osteoblast; (2) progressive osteoid accumulation is secondary to matrix (osteoid) deposition, which exceeds the depressed bone formation rate; (3) the progressive decrease in plasma aluminum and increase in bone aluminum suggest that bone has a high affinity for aluminum but may have a relatively slow rate of uptake at any given time; (4) aluminum may directly decrease parathyroid hormone; (5) the correlation between plasma and bone aluminum suggest an exchange is present; and (6) aluminum toxicity may independently affect the osteoblast and bone mineralization.
Cigarette smoking, obesity, and bone mass
Authors: Slemenda Charles W. , Hui Siu L. , Longcope Christopher , Johnston C. Conrad 
Published: February 2010

Abstract
This study was designed to assess the effects of smoking on bone mass and bone loss and to ascertain whether these effects are independent of effects on adiposity and hormone concentrations.
A total of 84 healthy, peri- and postmenopausal women were studied prospectively over 3½2 years. Heavy smokers had significantly (p &lt; 0.05) lower radial and vertebral bone mineral content than light or nonsmokers (who did not differ from each other). In regression models, which contained measurements of obesity, pack-years smoking remained a significant predictor of bone mass. However, there were no detectable effects of smoking on rates of bone loss at any site.
Smokers appear to be at greater risk of osteoporosis due to their lower bone mass. However, this reduced bone mass is already present around the time of menopause, and rates of bone loss during this period do not appear to be influenced by smoking. Furthermore, we have previously shown in this population that menopausal serum estrogen concentrations (which determine rates of bone loss) do not differ between the smokers and nonsmokers. Further studies of larger groups are required to determine whether small differences in bone loss may exist, since the power to detect such differences was not ideal in this study.
Application of an in vitro model and a clinical protocol in the assessment of the potency of a new bisphosphonate
Authors: Papapoulos Socrates E. , Hoekman Klaas , Löwik Clemens W.G.M. , Vermeij Pieter , Bijvoet Olav L.M. 
Published: February 2010

Abstract
The development of new bisphosphonates for clinical use requires congruence between the results of basic and clinical investigations. We have previously shown that this can be achieved with the use of an in vitro coculture mouse metacarpal resorption system sensitive to the activation of osteoclast precursors together with a clinical protocol in which the rate of decrease in urinary hydroxyproline excess with bisphosphonate treatment is assessed in patients with Paget's disease. In these studies bisphosphonates of known potencies were used. In the present study we have evaluated these approaches prospectively in the assessment of the antiresorptive potency of the new bisphosphonate (3-dimethylamino-1-hydroxypropylidene)-1,1-bisphosphonate (dimethyl-APD). A total of 42 patients with Paget's disease of bone received dimethyl-APD in doses predicted from the in vitro system. A total of 24 patients received the bisphosphonate intravenously (2, 4, and 8 mg/day) in groups of 8 patients each and 18 orally (100, 200, and 400 mg/day) in groups of 6 patients each for 10 days. Dimethyl-APD therapy was highly effective in inhibiting bone resorption. Urinary hydroxyproline excretion reached 30.9 ± 5.6, 17.1 ± 3.1, and 2.1 ± 5.3% of initial excess after 10 days treatment with intravenous dimethyl-APD, 2, 4, and 8 mg/day, and 37.4 ± 18, 10.4 ± 8.5, and 13 ± 4.1% with oral therapy, 100, 200, and 400 mg/day, respectively. Comparison of the antiresorptive potency of dimethyl-APD with that of APD showed that the former is roughly five times more potent, as predicted in the in vitro study. These results demonstrate the predictive power of the coculture mouse metacarpal resorption assay and the use of a standardized protocol in Paget's disease for the introduction of new bisphosphonates into clinical practice. Full treatment efficacy in a simple and convenient way can be achieved with oral dimethyl- APD, which can be considered representative of third-generation bisphosphonates.
Relationship between interleukin-1 and prostaglandins in resorbing neonatal calvaria
Authors: Dr. Garrett I. Ross , Mundy Gregory R. 
Published: February 2010

Abstract
The relationship between the cytokine interleukin-1 and prostaglandins in resorbing bone cultures is very confusing. In some reports, the effects of interleukin-1 are described as prostaglandin dependent, but in some they appear prostaglandin independent. Recent data suggest that events occurring during the preculture period may be important for understanding later effects of any factor on bone resorption in neonatal mouse calvaria. In this study, we examined neonatal mouse calvaria morphologically for indices of resorption to determine the importance of this preculture period to their subsequent response to interleukin-1. Our results show that after a preculture period of 24 h in control media, osteoclast numbers and resorption areas are markedly enhanced. The numbers of osteoclasts fall when the calvaria are transferred to fresh control media for the following 72 h. This increase in osteoclast formation was inhibited by the addition of indomethacin (10−6 M) during the preincubation period. When interleukin-1 was added to bones after the preincubation period, osteoclast numbers present at this time were maintained and indomethacin had no effect on this response. Furthermore, the inhibitory effect of indomethacin on osteoclast formation during the preculture period could be reversed by adding prostaglandins of the E series in low concentrations together with indomethacin. The effects of interleukin-1 did not appear to be related to osteoclast precursor proliferation, since hydroxyurea (which inhibits DNA synthesis in these cultures) had no effect on the response of calvarin to interleukin-1. These results indicate that prostaglandin production by mouse calvaria increases osteoclast numbers during the preincubation period. The effects of interleukin-1 were not dependent on prostaglandin synthesis, and this factor may stimulate bone resorption by acting at later stages in osteoclast formation and activation in these bones.
The effect of tartrate on bone cell acid phosphatase activity: A quantitative cytochemical study
Authors: Webber D. , Dr. Braidman I. P. , Robertson W. R. , Anderson D. C. 
Published: February 2010

Abstract
Tartrate-resistant acid phosphatase activity (TRAPase) is widely used as a cytochemical marker to distinguish osteoclasts from macrophages and other related cell types. The degree of tartrate resistance, however, may depend on which reaction methods, tissues, or species are used. To investigate this further, we have measured the amount of cytochemical reaction product by microdensitometry. We compared osteoclast acid phosphatase (APase) activity in fresh frozen sections of neonatal rat calvaria using two different reaction methods; one is commonly employed for qualitative histochemistry and includes α naphthyl phosphate as substrate, simultaneous coupling to the chromagen Fast Garnet, and a 30-minute reaction time (method A). The other may be used to measure enzyme reaction rates in cells in situ and employs conditions suitable for initial velocity kinetics, namely naphthol-ASBI phosphate as substrate, post coupling to Fast Garnet, and a 2-minute reaction time. Although enzyme reaction rates differed greatly between the two methods, significant inhibition of APase activity by tartrate was observed in calvarial osteoclasts (69% and 59% with methods A and B, respectively), osteoblasts, and spleen macrophages. Using method B, mouse calvarial osteoclasts had similar APase activity to that seen in the rat. Tartrate produced little inhibition in these mouse cells, in contrast to the observations made with rat tissue, but murine spleen macrophages were significantly tartrate sensitive (40% inhibition with tartrate). On this basis, conclusions regarding the cell specificity of TRAPase should be treated cautiously.
Organization of osteoclast microfilaments during the attachment to bone surface in vitro
Authors: Lakkakorpi Päivi , Tuukkanen Juha , Hentunen Teuvo , Järvelin Kaisa , Väänänen Kalervo 
Published: February 2010

Abstract
Rat and chicken osteoclasts were cultured on bone slices, where they showed active resorption with resorption lacunae, which cold be seen by toluidine blue staining or with a scanning electron microscope. Osteoclast microfilaments, F-actin, vinculin, and talin were studied by immunofluorescence. In attached osteoclasts, vinculin appeared as a double circle in the periphery of the cell, and the most intense F-actin staining was located between these vinculin zones. Some chicken osteoclasts showed also intense F-actin staining throughout the center of the cell. Talin appeared in a similar double circle to vinculin. This kind of distribution of microfilaments was always associated with resorption lacunae, and F-actin, vinculin, and talin zones correspond roughly to the edge of lacunae. Osteoclasts showing a diffuse staining pattern were not associated with a resorption pit. The results suggest that this specific microfilament arrangement is located at the attachment zone of the osteoclast and is obligatory for the attachment and resorption. However, this arrangement of microfilaments is quite different from the one that has been previously described in osteoclasts cultured on glass.
Rapid, simple identification of individual osteoblastic cells and their specific products by cell blotting assay
Authors: Murray Elsa , Martin Estralita , Burton Douglas , Deftos Leonard J. 
Published: February 2010

Abstract
Biochemical and molecular biological studies of osteoblastic cell function and hormonal regulation are frequently confounded by the inherent cellular heterogeneity and phenotypic instability of existing in vitro and in vivo model systems. A new technique (derived from Western blotting or antibody-based detection of protein molecules bound to nitrocellulose paper) is described for identification of individual cells which synthesize osteoblast-specific gene products (bone Gla-protein, type I collagen, and alkaline phosphatase) or produce cAMP in response to parathyroid hormone (PTH) or isoproterenol. Dispersed primary neonatal rat calvariae or osteogenic sarcoma cells were “plated” on Immobilon-P (a hydrophobic transfer membrane with very high protein-binding capacity) for 30 minutes to several hours, followed by agonist treatment, formalin fixation, hematoxylin staining, and immunostaining with a battery of antibodies specific for osteoblastic products. Individual cells and their secretory zones were visualized by light microscopy and counted. Treatment with PTH with or without isoproterenol resulted in increases in the percentages of osteoblastic cells elaborating cAMP, as well as the intensity of immunostaining, but had no effects on MCF-7 cells, a nonosteoblastic breast carcinoma control line. The percentage of cells within each primary osteoblastic cell population isolated or rat osteogenic sarcoma cell clone (G2 or C12) that elaborated bone-specific proteins or that generated cAMP in response to PTH varied with time and the individual cellular preparation, reconfirming the cellular heterogeneity of these systems. This method, in conjunction with techniques such as in vitro hybridization, should prove useful in characterizing discrete osteoblastic bone cell subpopulations and in clarifying mechanisms of hormonal regulation by local and systemic agents.
Bone remodeling in predialysis chronic renal failure: How does the choice of index for mineralizing surface influence the interpretation?
Authors: Dr. Dahl Eilif , Nordal Knut P. , Aksnes Lage , Halse Johan 
Published: February 2010

Abstract
To study how calculating bone dynamics with different indices of mineralizing surface (MS) may influence the interpretation of bone remodeling in chronic renal failure (CRF) and to discuss which of three often used indices may be closest to the true MS, we compared bone histomorphometry in predialysis patients with moderate (se-creatinine &lt; 400 μmol/liter) and advanced CRF. All were double-labeled with tetracycline and had no stainable bone aluminum. Bone dynamics were calculated with MS = double-labeled (dLS) + single-labeled surface (sLS), MS = dLS + sLS/2, and MS = dLS. As sLS was twice that of dLS in both groups and the label interval was only 10 days, most single labels were probably double labels, but unseparable due to wide and unsharp labels resulting from high rather than low bone turnover. Bone volume was the same in both groups, while osteoid and resorption indices, sLS, and bone formation rate (with MS = dLS + sLS) were increased in advanced CRF. dLS + sLS is higher than the true MS, but more representative for MS than dLS + sLS/2, with the true value between these two indices. Bone resorption, osteoid formation, and mineralization remain in balance even in advanced CRF. Osteomalacia is hardly the consequence of CRF alone.
WR-2721 reduces bone loss after hindlimb tenotomy in rats
Authors: Shaker Joseph L. , Fallon Michael D. , Goldfarb Stanley , Farber Joshua , Attie Maurice F. 
Published: February 2010

Abstract
WR-2721 is a thiophosphate analog of cysteamine that produces hypocalcemia in vivo. Previous studies suggest that WR-2721 produces hypocalcemia by independent inhibitory effects on parathyroid hormone (PTH) secretion, osteoclastic bone resorption, and tubular reabsorption of calcium. We sought to determine if WR-2721 would decrease bone loss in an animal model of disuse osteoporosis produced by unilateral knee tenotomy in the rat. Tenotomy significantly increased osteoclast number in tibias on the side of the procedure compared with tibias on the opposite side which had not undergone the procedure at 3 and 14 days. Femoral weight of tenotomized limbs were also reduced significantly compared with the contralateral limb at 3 and 14 days. WR-2721 treatment (240 mg/kg daily) prevented 26% of the loss of femoral dry weight and 29% of the loss of femoral ashed weight produced 14 days after tenotomy. In addition, WR-2721 treated (240 mg/kg daily) animals had fewer osteoclasts in tenotomized tibias than control animals at 3 days (6.6 ± 0.7/mm versus 10.3 ± 0.9/mm, p &lt; 0.02) and at 14 days (5.8 ± 0.3/mm versus 8.7 ± 0.4/mm, p &lt; 0.02). These data suggest that WR-2721 decreases bone loss in this model by decreasing osteoclastic bone resorption.
Inhibition of bone resorption by α-difluoromethylornithine may not be mediated by polyamine depletion
Authors: Dr. Lucas Rita C. , Seidenfeld Jerome , Krieger Nancy S. , Stern Paula H. 
Published: February 2010

AbstractWe have examined the effect of α-difluoromethylornithine (DFMO) on bone polyamine content and parathyroid hormone (PTH)- and calcitriol-stimulated bone resorption in cultures of neonatal mouse calvaria. Polyamine content in bone homogenates was determined by reverse-phase paired-ion HPLC. Treatment with 5 mM DFMO for 48 h reduced putrescine from 0.4 nmol/bone to nondetectable levels, slightly decreased spermidine, and did not affect spermine. Bone resorption elicited by 48 h of treatment with PTH or calcitriol was inhibited by concentrations of DFMO ≥ 5 mM added 48 h prior to hormone. This observation supported the concept that polyamines may play a role in bone resorption. However, other observations cast uncertainty on this conclusion. Measurement of calvarial polyamine content at 2 h intervals revealed no increase in endogenous polyamines for up to 10.5 h after calcitriol addition. Although addition of putrescine restored bone polyamine content, exogenous polyamines failed to reverse the inhibitory effects of DFMO on calcitriol-stimulated resorption. These results suggest that a mechanism other than depletion of polyamines could be contributing to the inhibitory effect of DFMO on resorption.