bluuebunny/crossref_metadata_2025_split huggingface dataset:
Additive effect of treadmill exercise and 17β-estradiol replacement on prevention of tibial bone loss in adult ovariectomized rat
Authors: Yeh James K. , Liu Chung C. , Aloia John F. 
Published: February 2010

Abstract
The effects of 17β-estradiol (E2) and treadmill exercise on tibial bone mass, tibial uptake of 45Ca, and proximal tibia osteoblast and osteoclast cell number were determined in adult ovariectomized rats. Female rats aged 10 months were ovariectomized and divided into five groups: (1) sham-operated; (2) ovariectomized; (3) ovariectomized, given 10 μg E2 biweekly; (4) ovariectomized, trained to exercise on a treadmill daily; and (5) ovariectomized, given E2 and exercised. E2 and/or exercise interventions were started 2 months following surgery and continued for 4 months. The calcium content of the tibial metaphysis and diaphysis and the proximal cancellous bone (BV/TV) were lower in the ovariectomized than in the sham-operated controls 6 months after ovariectomy. This lower bone content was associated with a greater bone uptake of 45Ca and a greater number of osteoblasts and osteoclasts in the proximal tibia compared to the control rats. The meta-physeal calcium content was higher and the 45Ca uptake and osteoblast and osteoclast number were lower in the E2-treated rats than in the nontreated rats. In the exercised group, higher diaphyseal calcium content and proximal cancellous bone were associated with lower bone resorption parameters without a significant effect on bone formation. This study demonstrates that E2 primarily influences tibial cancellous bone of the ovariectomized rat and a positive adaptation to exercise occurs in both cancellous and cortical bone. Under estrogen deficiency, E2 replacement suppresses increased bone formation and resorption; exercise suppresses mainly bone resorption. The effects of E2 replacement and exercise training are independent and additive.
Precision of dual-energy x-ray absorptiometry: Development of quality control rules and their application in longitudinal studies
Authors: Orwoll Eric S. , Oviatt Shelia K. , Biddle Julie A. 
Published: February 2010

Abstract
In research settings, longitudinal measurements of bone mineral density have become an integral part of the assessment of patients with metabolic skeletal disorders. To adequately utilize longitudinal measures, confidence in the long-term precision of the measurement technique must be very high. Dual-energy x-ray absorptiometry (DXA) has become commonly utilized in this context, and to better understand its long-term precision and to develop quality assurance protocols for its use, we examined the performance of eight DXA machines over a 3 year period. Anthropomorphic spine phantoms were measured frequently on each machine during the period of observation, and precision was estimated from the consistency of these determinations. Overall precision was excellent (mean longitudinal coefficient of variation, 0.4%). Nevertheless, by using a series of objective quality control criteria, small alterations in the performance of each machine were identified (mean number of changes, 4.6 in 3 years; mean magnitude, 0.0039 g/cm2, or 0.4%). The cumulative effects of those changes were sufficient to cause a significant (albeit minor) change in the regression slopes (phantom mineral density versus time) of most machines. The same quality control rules were also used to quantitate the magnitude of change and to adjust retrospectively machine performance during the period of observation, such that alterations were minimal and regression slopes were not significantly different from zero. Although the precision of DXA is excellent, alterations in machine function must be anticipated during longitudinal use. The development of quality control protocols provides the means to detect change objectively and to adjust for alterations in performance during the course of longitudinal evaluations.
Cytoplasmic pH influences cytoplasmic calcium in MC3T3-E1 osteoblast cells
Authors: Lin H.-S. , Hughes-Fulford M. , Kumegawa M. , Pitts A.C. , Snowdowne Kenneth W. 
Published: February 2010

Abstract
We found that the cytoplasmic concentration of calcium (Cai) of MC3T3-E1 osteoblasts was influenced by the type of pH buffer we used in the perfusing medium, suggesting that intracellular pH (pHi) might influence Cai. To study this effect, the Cai and pHi were monitored as we applied various experimental conditions known to change pHi. Exposure to NH4Cl caused a transient increase in both pHi and Cai without a change in extracellular pH (pHo). Decreasing pHo and pHi by lowering the bicarbonate concentration of the medium decreased Cai, and increasing pHi by the removal of 5% CO2 increased Cai. Clamping pHi to known values with 10 μM nigericin, a potassium proton ionophore, also influenced Cai: acid pHi lowered Cai, whereas alkaline pHi increased it. The rise in Cai appears to be very sensitive to the extracellular concentration of calcium, suggesting the existence of a pH-sensitive calcium influx mechanism. We conclude that physiologic changes in pH could modulate Cai by controlling the influx of calcium ions and could change the time course of the Cai transient associated with hormonal activation.
TGF-β1 induces bone closure of skull defects: Temporal dynamics of bone formation in defects exposed to rhTGF-β1
Authors: Beck L. Steven , Amento Edward P. , Xu Yvette , Deguzman Leo , Lee Wyne P. , Nguyen Tue , Gillett Nancy A. 
Published: February 2010

Abstract
The temporal dynamics of bone repair in a skull defect in rabbits was examined to characterize the in vivo cellular events occurring following a single local application of recombinant human TGF-β1 (rhTGF-β1). Rabbits received vehicle or 0.4, 1, 2, or 5 μg rhTGF-β1 applied to 12 mm defects at the time of surgery. The defect sites were subsequently evaluated by radiography and qualitative and quantitative histology at time points ranging from 1 to 180 days. Based on radiographic assessment, the defect area decreased rapidly in a dose-dependent manner through 35 days after surgery in the rhTGF-β1-treated groups. Minimal closure occurred in sites administered vehicle control at all time points examined. Sites treated with rhTGF-β1 were characterized histologically by an increase in parameters of active bone formation through 49 days, including percentage osteoid surface, percentage osteoblast/total surface, and an increase in the trabecular bone volume. Bone resorption parameters were increased at 16 and 49 days with histologic evidence of remodeling from woven to lamellar bone. By 70 days, no differences were observed among the groups for parameters of either bone formation or resorption. Bone formation rate was not altered with rhTGF-β1 treatment at any time point. These results indicate that exogenously applied rhTGF-β1 stimulated the recruitment and proliferation of osteoblasts at the defect site, resulting in a rapid deposition of bony matrix, with normal remodeling processes occurring thereafter. This study supports the hypothesis that TGF-β1 is a potent osteoinductive growth factor in vivo and may have potential application as a therapeutic aid to nonhealing bony defects.
Bone and mineral metabolism in the androgen-resistant (testicular feminized) male rat
Authors: Dr. Vanderschueren D. , van Herck E. , Suiker A.M.H. , Visser W.J. , Schot L.P.C. , Chung K. , Lucas R.S. , Einhorn T.A. , Bouillon R. 
Published: February 2010

Abstract
Androgens have important effects on bone in vivo, possibly by direct activation of the androgen receptors in osteoblasts. To test this hypothesis, calcium homeostasis, bone mass, and bone turnover were evaluated in mature (4-month-old) androgen-resistant (testicular feminized, TFM) male rats. Data were compared with data from both female and male littermates of the same age and strain. Compared to normal males, TFM had similar serum testosterone, twofold higher estradiol and estrone, and sixfold higher androstenedione concentrations. Compared to normal females, TFM rats showed lower estradiol but also elevated concentrations of androstenedione and estrone. Despite similar free 1,25-(OH)2D3 concentrations, both TFM and male rats maintained higher serum calcium and phosphate concentrations than their female littermates. Serum IGF-I concentrations in TFM rats were decreased compared to male rats (-12%) or female rats (-27%). Serum osteocalcin concentrations, however, were twofold higher in TFM rats than in females but not significantly different from males. Femoral length, diameter, and cortical thickness were intermediate between those of males and females. The cancellous bone density of the femur and cancellous bone volume of the proximal metaphysis of the tibia, however, were not significantly different between groups. The ash weight of the tibia was also not significantly different, and the ash weight of the four distal lumbar vertebrae ranged between male and female values. Bone mechanical properties as measured by torsional strength and energy absorption of the femur were lower in TFM than in females but not different from males. Osteoblast surfaces, osteoid, and osteoclast surfaces in the proximal tibial metaphysis of TFM rats were in the female range and lower than in males. Bone formation and mineral apposition rates measured at the same site were intermediate between male and female rates. Bone formation rates were significantly higher in male than in female rats. We conclude that the absence of functional androgen receptors results in a decrease in radial and longitudinal bone growth and in a decrease in serum IGF-I concentrations. TFM rats, however, have a cancellous bone volume and density similar to those of their normal male and female littermates. Bone turnover at the cancellous level is not increased compared to normal males. Cancellous bone volume in androgen resistance, in contrast to androgen deficiency, is probably maintained by a modest increase in serum estrogen concentrations.
Stimulation of interleukin-6 production by either calcitonin gene-related peptide or parathyroid hormone in two phenotypically distinct bone marrow-derived murine stromal cell lines
Authors: Sakagami Y. , Girasole G. , Yu X.-P. , Boswell H.S. , Manolagas Stavros C. 
Published: February 2010

Abstract
It was recently shown that interleukin-6 (IL-6) is produced by bone and bone marrow-derived stromal cells and that it plays an important role in osteoclast development. Here we examined whether parathyroid hormone (PTH), calcitonin (CT), or the calcitonin gene-related peptide (CGRP) influence IL-6 production by two murine bone marrow-derived stromal cell lines: the preadipocyte-like stromal cell line +/+ LDA11 and the fibroendothelial stromal cell line MBA 13.2. We found that CGRP (but not PTH or CT) exerted a dose-dependent increase in cAMP and IL-6 production in the +/+ LDA11 cells. In addition, CGRP had an inhibiting effect on the proliferation of this stromal cell line. CGRP, however, did not affect cAMP or IL-6 in the rat osteogenic sarcoma cell line UMR-106-06, which exhibits CT receptors, whereas CT stimulated both cAMP and IL-6 by the UMR-106-01 cells. In contrast to the specificity of the IL-6 response of the +/+ LDA11 cells to CGRP, IL-6 production by the MBA 13.2 stromal cells was stimulated by PTH whereas CGRP or CT had no effect. These data suggest that bone marrow-derived stromal cells express receptors for either CGRP or PTH in a phenotype-specific manner and that, acting via these receptors, CGRP and PTH stimulate IL-6 production by stromal cells. In addition, the evidence for specific receptors for the neuropeptide CGRP in bone marrow stromal cells and an effect of CGRP on IL-6 raises the possibility for a role of cytokines in a putative interplay between neuronal stimuli and bone.
Prevalence of vertebral fracture in women and the relationship with bone density and symptoms: The chingford study
Authors: Dr. Spector Tim D. , Mccloskey Eugene V. , Doyle David V. , Kanis John A. 
Published: February 2010

Abstract
A population survey was performed to estimate the prevalence of vertebral fractures in women aged 45–69 and to determine their relationship to bone density and symptoms. Subjects were 1035 women aged 45–69 (mean 55.4 years, response rate 77%) from the age-sex register of a large 11,000-person general practice in Chingford, London. Thoracic and lumbar spine x-rays were read by a semiautomated quantitative method. Vertebral fractures were diagnosed using a variety of morphometric methods, including a new method we recently developed and the published methods of Melton and Eastell. These methods all detect abnormal ratios between anterior, central, or posterior vertebral height and between observed posterior vertebral height and values predicted from the posterior height of adjacent vertebrae. Bone mineral density (BMD) of lumbar spine L1–4 and neck of femur was measured by dual-energy x-ray absorptiometry (DXA). Using our method, 147, 14.2% (95% CI 12.0–16.2%) of the 1035 women, had minor fractures (at least two vertebral ratios 2–2.99 SD below the mean) and 20, 1.9% (95% CI 1.2–3.0%) of the total, had severe fractures (at least two ratios more than 3 SD below the mean). In the 147 women with minor fractures, bone density of the spine was not significantly lower than in the other 868 women, and reported back pain or loss of height was no more common. Women with multiple minor fractures did have lower bone density, by 0.4 SD. In the 20 women with severe fracture, bone density was significantly lower, by 0.6 SD. Loss of height was more common, but back pain was not. Using the method of Melton the prevalence of deformity was 10.2% and, for the Eastell 3 and 4 SD method, 9.7 and 1.3%, respectively, which is similar to published data from the Rochester population. Minor vertebral deformities are common in postmenopausal women, but they are not usually associated with pain, loss of height, or (unless multiple) reduced bone density. This suggests that they may not be of clinical or pathologic importance. Severe deformities associated with low bone density are rare in U.K. women under the age of 70.
Estrogen does not restore bone lost after ovariectomy in the rat
Authors: Abe T. , Chow J.W.M. , Lean J.M. , Chambers T.J. 
Published: February 2010

Abstract
We recently found that 17β-estradiol (E2) not only suppresses bone resorption but also stimulates bone formation in the cancellous bone of female rats. This raises the possibility that E2 treatment might restore the bone lost after ovariectomy in the rat. To test this, 13-week-old rats were ovariectomized (ox). After a further 13 weeks the animals were injected with E2 (4 mg or 40 μg/kg daily), human calcitonin (hCT) (3 IU/kg daily), (3-amino-1-hydroxypropylidene)-1-bisphosphonate (AHPrBP) (0.3 mg/kg twice per week), or a combination of E2 with hCT or AHPrBP, for 8 weeks. The bone volume at the tibial metaphysis of ox animals was approximately 40% of that of sham-operated controls at the end of the experiment. Although the bone volume of ox rats treated with E2 and/or hCT or AHPrBP was slightly higher than that of untreated ox rats, the increase was not significant. Neither E2 alone nor a combination of E2 with hCT or AHPrBP was associated with a higher bone volume than hCT or AHPrBP alone, suggesting no effect of E2 beyond that of inhibition of bone resorption. Histodynamic indices of bone formation were increased in untreated ox rats compared to controls but suppressed in E2-treated, hCT-treated, and AHPrBP-treated animals. These results emphasize the similar responses of rat and human bone, both of which not only show bone loss with estrogen deficiency, preventable by estrogen administration, but also show an inability of estrogen to restore bone lost as a result of estrogen deficiency.
Stable murine chondrogenic cell lines derived from c-fos-induced cartilage tumors
Authors: Dr. Wang Zhao-Qi , Grigoriadis Agamemnon E. , Wagner Erwin F. 
Published: February 2010

Abstract
This study describes the detailed characterization of four murine chondrogenic cell lines (wT2-1, wT2–7, wT2–8, and wT2–9) that were isolated from a cartilage tumor induced by the protooncogene c-fos in chimeric mice. All cell lines are clonal and display a fibroblastic morphology with a doubling time of 1–2 days. Northern blot analysis demonstrated that in addition to expressing high levels of exogenous c-fos, all clones express varying levels of the cartilage marker gene type II collagen in addition to type I collagen. The clones also expressed high levels of the AP-1 genes c-jun and fra-1. The doubling times of these clones did not change over a period of 14 months in culture. Most importantly, however, expression of type II collagen was maintained in all cell lines for 8 months in culture, and two cell lines maintained type II collagen expression when analyzed after 14 months. Interestingly, type I collagen expression was lost after long-term culture. Following injection into syngeneic and nude mice, all cell lines formed tumors containing areas with the morphologic appearance of hyaline cartilage, indicating that these cell lines are chondrogenic. Thus, these stable murine chondrogenic cell lines provide a useful tool for studying the transcriptional control of cartilage-specific gene expression, as well as the growth control of chondrogenic cells.
Effects of combined prostaglandin and alendronate treatment on the histomorphometry and biomechanical properties of bone in ovariectomized rats
Authors: Lauritzen D.B. , Balena R. , Shea M. , Seedor J.G. , Markatos A. , Le H.M. , Toolan B.C. , Myers E.R. , Rodan G.A. , Hayes W.C. 
Published: February 2010

Abstract
Prostaglandin E2 (PGE2) has been shown to stimulate both bone resorption and formation in experimental animals, leading to augmentation of trabecular and cortical bone. The amino bisphosphonate alendronate (ALN) is a potent inhibitor of bone resorption. The objectives of this study were to examine if PGE2 stimulation of bone formation was dependent on bone resorption and if the bone accrued as a result of PGE2 treatment contributed to bone strength. The 48 female Sprague-Dawley rats were assigned to six groups as follows: five groups (8/group) were ovariectomized at the age of 6 months. One group was sacrificed 2 months later to establish baseline conditions, and four groups were treated for 25 days with (1) vehicle, (2) PGE2 at 3 mg/kg/day, (3) ALN sc at 0.8 μg/kg/day, and (4) PGE2 + ALN at the respective doses. The sixth group served as nonovariectomized untreated controls. Histomorphometric analysis of 6–10 μm thick tibial sections after in vivo fluorochrome double labeling showed that treatment with PGE2 alone increased endo-cortical mineral apposition rate and bone formation rate, stimulated production of bone trabeculae in the marrow cavity, and increased cortical porosity. Combined ALN + PGE2 treatment prevented the resorption induced by PGE2 but not the stimulation of bone formation on endocortical and periosteal surfaces and resulted in a significant increase in cortical thickness. Consistent with these observations, the femoral midshaft tested to failure in three-point bending showed a significant increase in strength in the PGE2 + ALN group (181 ± 15 N) compared to time 0 controls (145 ± 23 N) or to the ovariectomized vehicle-treated group (141 ± 28 N). Similarly, there was a statistically significant increase in femoral midshaft stiffness. There was also a statistically significant increase in the ash content of bones from animals treated with PGE2 + ALN relative to vehicle-treated animals. No statistically significant differences among groups were observed in femoral neck or vertebral strength or stiffness. These findings show that PGE2 stimulation of bone formation is not blocked by inhibition of bone resorption and that combined treatment with PGE2 and the bone resorption inhibitor ALN increased the mechanical strength of ovariectomized rat femoral shaft compared to nonovariectomized animals.
Urinary hydroxypyridinium crosslinks of collagen as markers of bone resorption and estrogen efficacy in postmenopausal osteoporosis
Authors: Seibel M.J. , Cosman F. , Shen V. , Gordon S. , Dempster D.W. , Ratcliffe A. , Lindsay R. 
Published: February 2010

Abstract
Estrogen deficiency-induced bone loss has been associated with accelerated bone turnover. Levels of some biochemical markers, such as serum osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), and urinary hydroxyproline (OHP), have been shown to be related to the rate of bone turnover. They may therefore be useful in identifying the individual at risk for osteoporosis and monitoring the efficacy of the treatment. Two recently discovered markers, urinary pyridinoline (PYD) and deoxypyridinoline (DPD), are apparently directly related to bone matrix degradation and may be more accurate markers of bone resorption than OHP or TRAP. To evaluate the effects of menopause, osteoporosis, and estrogen replacement on the excretion of these new markers, we measured the levels of PYD and DPD and other biochemical markers of bone turnover in four groups of women, premenopausal healthy (PRE), postmenopausal healthy (POST), postmenopausal osteoporotic (UTO), and postmenopausal osteoporotic with estrogen treatment (ETO). Significant increases in PYD, DPD, BGP, TRAP, and OHP were found in POST and UTO groups compared with PRE. These increases were blunted by estrogen treatment when the levels of each of the markers returned to PRE levels. When comparing POST and UTO groups, significant increases were observed in UTO only for PYD, DPD, and urinary calcium but not for OHP, BGP, or TRAP. With subgroups matched for age and years from menopause, only DPD discriminated between POST and UTO. Indices of bone formation co-varied with markers of bone resorption in the total population. Although this held true in PRE and ETO groups, the bone resorption markers were not well correlated with bone formation markers in POST or UTO groups when they were analyzed individually. None of the markers correlated with bone mineral density measurements. Our results suggest that (1) urinary pyridinium crosslinks are significantly elevated after menopause, and estrogen replacement reverses the increase in osteoporotic patients; (2) DPD may be the most discriminating marker of bone turnover; and (3) the lack of correlation between bone resorption and formation markers found in estrogen-deficient groups indicates the possibility of an imbalance in bone remodeling.