bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pretreatment with low doses of norethindrone potentiates the osteogenic effects of fluoride on human osteosarcoma cells
Authors: Takada Junichi , Baylink David J. , Lau William K.-H. 
Published: February 2010

Abstract
We recently reported that picomolar doses of norethindrone (NET), a synthetic analog of 19-nortestosterone, significantly stimulated human TE85 osteosarcoma cell proliferation, differentiation, and activity in vitro. In the present study, we investigated the possibility that NET interacts with another osteogenic agent, i.e., fluoride, to stimulate human TE85 osteosarcoma cell proliferation, differentiation, and activities. Bone cell proliferation was measured by the stimulation in [3H]thymidine incorporation. Differentiation was monitored by the increase in alkaline phosphatase-specific activity. Osteoblastic activity was assessed by the stimulations in collagen synthesis and in osteocalcin secretion (in the presence of 1 nM 1,25-dihydroxyvitamin D3). When the human TE85 cells were incubated with mitogenic doses of NET and fluoride concurrently, the stimulatory effects of the two agents on these parameters exhibited no significant interaction. The enhancing effect of NET on the osteogenic effect of fluoride was not due to a shift of the fluoride dose response curve. Pretreatment with NET for 24 h followed by a treatment with a mitogenic dose (i.e., 100 μM) of fluoride for an additional 24 h significantly and synergistically potentiated the effects of fluoride on the [3H]thymidine incorporation, alkaline phosphatase-specific activity, collagen synthesis, and osteocalcin secretion, compared with those with the subsequent vehicle (0.05% ethanol) treatments. In contrast, pretreatment with fluoride for 24 h before the addition of NET for 24 h did not produce significant synergistic stimulations in the test parameters. Pretreatment of TE85 cells with the same doses of dihydrotestosterone or progesterone prior to treatment with fluoride under the same conditions did not induce synergistic potentiation of fluoride in [3H]thymidine incorporation, suggesting that the synergistic interaction with fluoride is probably not a common property of anabolic sex steroids. In summary, we found that: (1) the osteogenic effects of fluoride and NET were additive when cells were treated with both agents concurrently; (2) a 24-h pretreatment with picomolar doses of NET potentiated the osteogenic actions of fluoride in human TE85 osteosarcoma cells; and (3) pretreatment with NET produced a subsequent fluoride response that was synergistic. In conclusion, these findings led us to speculate that the osteogenic actions of NET and fluoride act through different mechanisms, and that NET at low doses has a permissive effect on the osteogenic effects of fluoride, and as such NET may be used in concert with fluoride to increase osteoblast proliferation, differentiation, and activity.
Evidence for interrupted bone resorption in human iliac cancellous bone
Authors: Croucher P.I. , Gilks W.R. , Compston J.E. 
Published: February 2010

Abstract
Bone resorption and formation are coupled both in time and space and may occur simultaneously in the same remodeling unit. A number of studies have shown that the formative phase of the remodeling sequence may undergo temporary interruptions prior to completion and it is possible that bone resorption may be subject to similar interruptions. We have investigated this hypothesis by studying the distribution of eroded depth in resorption cavities in human cancellous bone. Eroded depth was assessed in iliac crest cancellous bone from 41 normal healthy subjects using a cubic spline curve fitting technique. The distribution of mean eroded depths was skewed to the right. Comparison of the observed distribution with an expected distribution, which was calculated from previously published data and assumes resorption begins rapidly and slows as it approaches completion, showed a significantly greater proportion of shallower cavities than expected (p &lt; 0.0001). Similarly, comparison of observed and uniform distributions, which assumes a constant rate of resorption throughout the erosion period, also showed a significantly greater proportion of smaller cavities (p &lt; 0.01). In subjects aged less than 39 years, there were fewer small cavities than in those aged 40-59 years. In addition, there was some evidence that females of 40-59 years had a proportionately greater number of smaller cavities than males; however, there were no differences in other age groups. Our results demonstrate a significantly greater proportion of smaller resorption cavities than would be expected from current models of bone remodeling and are consistent with the hypothesis that resorption undergoes temporary interruptions and/or permanent arrest during the process of bone remodeling. (J Bone Miner Res 1995;10:1537-1543)
Assessment of the skeletal status by peripheral quantitative computed tomography of the forearm: Short-term precision in vivo and comparison to dual X-ray absorptiometry
Authors: Grampp Stephan , Lang Philipp , Jergas Michael , Glüer Claus C. , Mathur Ashwini , Engelke Klaus , Genant Harry K. 
Published: February 2010

Abstract
In order to assess precision of peripheral quantitative computed tomography (pQCT), duplicate bone mineral density (BMD) measurements at the radius were performed in 20 healthy premenopausal, 20 healthy postmenopausal, and 20 osteoporotic postmenopausal women using a Stratec XCT-960 system. The short-term reproducibility in vivo for the total, trabecular, and cortical regions of interest (ROI) was expressed as the absolute precision error (standard deviation, SD) and as the relative precision error (SD/mean x 100, or coefficient of variation, CV, in %). Reproducibility in vivo was good in all volunteers but was influenced by the study group and the ROI. The precision error for trabecular BMD was 3 mg/cm3, or about 1.6%. This is large relative to the aging decrease of 0.22%/year, or to the difference (12 mg/cm3 or 7%) between osteoporotic women and postmenopausal controls. In order to compare pQCT to dual X-ray absorptiometry (DXA) at the forearm and at the lumbar spine (L1–L4), 40 premenopausal healthy controls, 40 postmenopausal healthy controls, and 35 postmenopausal osteoporotic women were assessed. DXA measurements performed at the ultradistal, middistal, 1/3, and total ROI of the radius showed only moderate correlations between r = 0.38–0.75, r = 0.27–0.64, and r = 0.38–0.53 for the comparison versus pQCT total BMD, versus pQCT trabecular BMD, and versus pQCT cortical BMD, respectively. Correlations of DXA at the lumbar spine and pQCT were between r = 0.18 and 0.44. DXA at radius and spine was able to discriminate between postmenopausal controls and osteoporotic women (p = 0.001–0.004), but BMD measurements by pQCT did not show this ability (p = 0.15–0.52). However, two nonstandard pQCT parameters, namely the surface area of the cortical bone and the cortical BMC were factors that discriminated well between these two groups (p = 0.002, p = 0.005, respectively). These pQCT parameters also yielded the highest relative annual changes in pre- and postmenopausal control subjects. The measurement of cortical bone in the distal radius proved to be a good predictor of vertebral fracture status and was a good indicator of age-related skeletal change. Our data emphasize the importance of cortical measurements when using pQCT of the radius to assess osteoporosis.
Bone density determinants in elderly women: A twin study
Authors: Dr. Flicker Leon , Hopper John L. , Rodgers Lisa , Kaymakci Bahtiyar , Green Robyn M. , Wark John D. 
Published: February 2010

Abstract
This cross-sectional twin study examined the influence of constitutional, lifestyle, and genetic factors on bone mineral density (BMD) in elderly women. BMD, at the lumbar spine, femoral neck, Ward's triangle, total hip, and total forearm, total body bone mineral content (BMC), and lean mass and fat mass were measured using dual energy X-ray absorptiometry in 69 volunteer female twin pairs (37 monozygotic [MZ], 32 dizygotic [DZ]) aged 60–89 years. Height and weight were measured. Medical history and lifetime tobacco and alcohol use were determined by questionnaire. In terms of within-pair differences, lean mass was independently associated with BMD at all sites. In contrast, fat mass was not associated with BMD at any site once allowance had been made for lean mass. Lifetime tobacco use was independently associated with BMD at the lumbar spine, total hip, and forearm. Total body BMC was independently predicted by lean mass, fat mass, tobacco use, and alcohol consumption. Age and the above independently predictive body composition and lifestyle factors accounted for 20–33% of variation in BMD. After allowing for these covariates, MZ and DZ correlations were consistent with about 75% of residual variation in BMD at the nonforearm sites being determined by genetic factors. For total body BMC, the covariates explained 75% of total variation, and genetic factors 76% of the residual variation. Therefore, at the proximal femur and lumbar spine, after taking into account the relation of BMD with lean mass and smoking, genetic factors appear to play a substantial role in explaining variation in BMD in elderly women.
Enhanced expression of type I receptors for bone morphogenetic proteins during bone formation
Authors: Ishidou Yasuhiro , Kitajima Isao , Obama Hiroya , Maruyama Ikuro , Murata Fusayoshi , Imamura Takeshi , Yamada Naoshi , Ten Duke Peter , Miyazono Kohei , Sakou Takashi 
Published: February 2010

Abstract
Type I receptors for bone morphogenetic proteins (BMPs), i.e., BMPR-IA and BMPR-IB, are transmembrane serine/threonine kinases, that bind osteogenic protein-1 (OP-1, also termed BMP-7) and BMP-4. Using antibodies specific to BMPR-IA and -IB, we have studied the expression of BMP type I receptors in the bone formation process during embryonic development and fracture healing. In the mouse embryo, both BMPR-IA and -IB were expressed in condensing mesenchymal cells at 13.5 days post coitum (p.c.). At 15.5 days p.c., expression of BMPR-IB, but not of BMPR-IA, was observed in the cells in perichondrium of developing cartilage. At 17.5 and 19.5 days p.c., expression of both receptors was observed in chondrocytes and in osteoblasts. In normal rat adult bone, expression of BMPR-IA, but not of BMPR-IB, was observed in osteoblasts in the periosteum. Three days after the femoral fracture, expression of BMPR-IA and -IB was up-regulated in cells at the proliferating osteogenic layer of the periosteum. On day 7, both receptors were found in fibroblast-like spindle cells and chondrocytes in the endochondral ossification sites, and osteoblasts in the newly formed trabecular bone. Expression of BMPR-IA was higher than that of BMPR-IB in osteogenic layer on day 3 and in osteoblasts in the trabecular bone on day 7. On day 14, expression of BMP type I receptors was observed at similar sites, albeit with lower expression levels than were observed on day 7. The present data suggest that expression of BMP type I receptors is up-regulated during bone formation, and that they may play important roles in bone morphogenesis.
Human osteoclasts, not osteoblasts, deposit osteopontin onto resorption surfaces: An in vitro and ex vivo study of remodeling bone
Authors: Dr. Dodds Robert A. , Connor Janice R. , James Ian E. , Lee Rykaczewski Elizabeth , Appelbaum Edward , Dul Edward , Gowen Maxine 
Published: February 2010

Abstract
Osteopontin is a phosphorylated glycoprotein believed to be secreted by osteoblasts and deposited into the bone matrix to facilitate osteoclast adhesion or to initiate osteoid mineralization. Previously we have presented contradictory evidence that osteoclasts express osteopontin mRNA in human remodeling bone. The aim of this study was to ascertain whether osteoclasts synthesize and deposit osteopontin in resorption lacunae. We characterized expression of osteopontin mRNA and protein expression in both intramembranous and endochondral ossification, as well as remodeling bone, in the human osteophyte. Osteopontin mRNA was expressed in osteoclasts with tartrate-resistant acid phosphatase (TRAP) positivity within resorption lacunae. The osteoclasts and immediate resorption surfaces also expressed osteopontin. However, osteopontin mRNA and protein were weak (transient) or undetectable in osteoblasts at adjacent bone formation sites; no osteopontin expression was observed in the osteoid, although occasional reactivity was observed in osteocytes and the mineral-osteoid interface. In contrast, osteopontin was highly expressed in the osteoblasts and matrix of woven bone during intramembranous and endochondral ossification. The matrix expression correlated with mineralization; however, in some instances osteopontin deposition was observed prior to mineralization. Similarly, osteopontin expression was evident in cartilage matrix, solely at foci of mineralization. Chondroclasts expressed osteopontin mRNA and protein; the surfaces of resorbed calcified cartilage also expressed osteopontin. Abnormal, unmineralized matrices apparently lacked deposited osteopontin, but were nevertheless resorbed by osteoclasts; the osteoclasts and resorbed surfaces expressed no osteopontin protein. That osteoclasts are responsible for the deposition of osteopontin was confirmed in vitro, whereby resorption pits in whale dentine and bovine bone slices, produced by isolated human osteoclasts, contained deposited osteopontin. Osteopontin may facilitate the adhesion (or detachment) of the osteoclast to the bone surface. Alternatively, the possibility that osteopontin may act as a postresorptive signal to recruit osteoblasts, or to polarize and direct the mineralization of the formed osteoid, is discussed.
Cell proliferation of human fibroblasts and osteoblasts in osteogenesis imperfecta: Influence of age
Authors: Fedarko N.S. , D'Avis P. , Frazier C.R. , Burrill M.J. , Fergusson V. , Tayback M. , Sponseller P.D. , Shapiro J.R. 
Published: February 2010

Abstract
Clinical studies indicate that as a group, osteogenesis imperfecta (OI) subjects are shorter than age- and sex-matched controls. Not only somatic growth, but also cellular growth appears to be impaired, and these may be related to defects in extracellular matrix common to this disorder. We have investigated the growth characteristics of dermal fibroblasts and trabecular osteoblasts isolated from patients with OI and control subjects of various ages. Cell growth curves and cell doubling times were determined by measuring cell number using crystal violet dye binding. Growth curves were modeled by a modified logistic function, the three parameters of which are markers for biologically relevant growth parameters: the plateau value or upper asymptote, which reflects the maximum cell density upon confluence; the maximal growth rate (μm); and the lag time. Both normal human fibroblasts and osteoblasts showed an age-dependent decrease in μm. Normal fibroblasts exhibited no age-dependence to their upper asymptote or lag time. Fibroblasts derived from patients with OI did not have significantly different upper asymptote values, μm, or lag times when compared with normal fibroblasts. Normal osteoblasts had a decrease in upper asymptote, decrease in μm, but a relatively constant lag time with increasing age. In contrast, OI osteoblast μm was decreased relative to that of normal subjects. For osteoblasts from OI patients, decreased μm appeared unrelated to the age of the subject, whereas OI fibroblasts did exhibit an age-dependent decrease in μm. The percentage of collagenase-digestible protein (a measure of collagen synthesis) produced by normal human fibroblasts correlated well with μm. Treating normal human osteoblasts with the proline analogue 3,4-dehydroproline, which destabilizes collagen triple helix formation and alters collagen synthesis, secretion, and turnover, also decreased μm. A dose response to varying concentrations of 3,4-dehydroproline was observed for normal human bone cell μm. These data suggest a link between type I collagen synthesis and cellular proliferation.
Intact parathyroid hormone levels are not elevated in glucocorticoid-treated subjects
Authors: Paz-Pacheco Elizabeth , El-Hajj Fuleihan Ghada , Leboff Meryl S. 
Published: February 2010

Abstract
To assess whether chronic glucocorticoid therapy results in a compensatory increase in parathyroid hormone (PTH), we measured intact PTH levels and other indices of mineral metabolism in 13 postmenopausal glucocorticoid-treated women and 16 normal age-matched controls. The glucocorticoid-treated women received a mean prednisone dose of 15.8 ± 3.1 mg/day for 12.9 ± 3.1 years. A linear regression analysis between intact PTH levels and a wide range of prednisone doses in these 13 glucocorticoid-treated women and 26 additional male and female subjects receiving chronic glucocorticoid therapy for a variety of rheumatic and pulmonary disorders (n = 39) was also performed. Intact PTH levels using the sensitive immunoradiometric assay (IRMA, Nichols Institute, San Juan Capistrano, CA) were comparable in the glucocorticoid-treated and normal control women (35.3 ± 4.4 vs 31.3 ± 3.2 ng/l, respectively) as were the total calcium concentrations (9.67 ± 0.12 vs 9.52 ± 0.11 mg/dl). In the glucocorticoid-treated women, the 25-hydroxyvitamin D levels, measured by competitive protein assay were similar to those of the control subjects (29.2 ± 2.8 vs 29.1 ± 2.3 ng/ml), and no patient was treated with vitamin D in excess of 400 IU daily. In the combined 39 male and female patients, there were also no significant regression relationships between daily prednisone dose and intact PTH levels. Thus, secondary hyperparathyroidism does not accompany chronic oral glucocorticoid therapy in women on low to moderate doses of oral glucocorticoids. The lack of an elevation in intact PTH levels in the presence of chronic glucocorticoid therapy may represent an increased sensitivity of bone to PTH, or an alteration in the relationship between calcium and PTH, or both.
Inhibition of antigen-presenting cell function by alendronate in vitro
Authors: Sansoni Paolo , Passeri Giovanni , Fagnoni Francesco , Mohagheghpour Nahid , Snelli Gianluca , Brianti Vincenzo , Dr. Engleman Edgar G. 
Published: February 2010

Abstract
Bisphosphonates are potent inhibitors of bone resorption in vivo and are emerging as important and widely used drugs for the treatment of a variety of abnormal bone resorptive processes. In the current study we investigated the in vitro effects of 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate), a recently developed, extremely potent bisphosphonate, on the immune functions of human peripheral blood mononuclear cells (PBMCs). PBMC proliferation induced by lectins, alloantigens, and a nominal antigen (tetanus toxoid) was inhibited in a dose-dependent manner by alendronate. Pretreatment of monocytes, but not T cells, with the compound at concentrations ranging from 10−4 to 10−8 M was inhibitory, indicating that alendronate acts selectively on antigen-presenting cells (APCs). Alendronate did not affect the viability of monocytes or T cells or the expression of cell surface molecules known to play critical roles in antigen presentation. Alendronate exhibited dose-dependent inhibition of the production of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) by activated monocytes. The inhibitory effect of 10−6 M alendronate on PBMC proliferation was reversed by 10 U/ml recombinant rIL-1β, whereas other cytokines such as IL-6, TNF-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF) had no effect. Thus, alendronate acts on monocytes to inhibit their antigen-presenting/accessory cell functions through a mechanism that can be overcome by exogenous IL-1. The inhibitory effect of this agent on cytokine production may contribute to its inhibitory effect on bone resorption.
Effects of physical training on bone adaptation in three zones of the rat tibia
Authors: Dr. Bourrin Sandrine , Palle Sabine , Pupier René , Vico Laurence , Alexandre Christian 
Published: February 2010

Abstract
This study has been conducted to examine the effects of physical exercise on the bone trabecular network and the cellular adaptations in three different areas of a single bone, the tibia. Male Wistar rats (9 weeks old) were treadmill-trained for 0, 3, 4, or 5 weeks at 60% of their measured maximal O2 consumption (VO2max). Histomorphometric analysis of the proximal tibia of running and age-matched control groups was performed in the epiphyseal trabecular bone, in the primary spongiosa and in the secondary spongiosa. Dynamic and static bone cell activities and serum calcium and phosphorus levels were measured. VO2max increased significantly by 18.4% after 5 weeks of training. In the epiphysis, a 9% increase in bone volume, associated with more numerous trabeculae (8%) was detected the third week of training. In primary spongiosa a significant increase (6.7%) in newly formed trabeculae was found. In secondary spongiosa bone volume increased significantly by 26.2% the fifth week of exercise and was associated with thicker trabeculae. The number of osteoclast profiles was significantly depressed. Osteoid surfaces and bone formation rate increased significantly in weeks 3 to 5. Serum calcium levels were found to be significantly decreased in weeks 3 and 4. There was no change in osteoid thickness or mineral apposition rate. These results suggest 1) a rapid increase in osteoblastic recruitment without change of the cell activity in response to moderate exercise; 2) a decreased bone resorption associated with a marked increase in bone formation from the third week of training; 3) adaptation of the trabecular network to exercise that seems to be bone-site-dependent, suggesting a cell sensitivity to training-engendered strain distribution within the bone or to strain-related local factors.