bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of spine bone mineral density in ovariectomized rats using DXA
Authors: Yamauchi Hideki , Kushida Kazuhiro , Yamazaki Kaoru , Inoue Tetsuo 
Published: February 2010

Abstract
Measurements of lumbar spine (L1–L6) bone mineral density (BMD) and bone mineral content (BMC) of Wistar rats were obtained by dual energy X-ray absorptiometry (DXA) (QDR-1000W, Hologic Inc., Waltham, MA) to estimate reproducibility and investigate age-related changes. In addition we evaluated the accuracy of the technique in female rats. The coefficients of variation (CV) for spine BMD measurements were found to range from 0.73–1.04 in vivo and from 0.36–1.56 in vitro. The in vitro measurements were performed in a 3 cm deep water bath to stimulate an equivalent tissue thickness. Spine BMC, measured in vivo and in vitro correlated closely with the subsequently determined ash weights (r2 = 0.87 and 0.97, respectively). We examined age-related spine BMD by DXA. A relatively constant increase in spine BMD was observed from 6 weeks to 22 weeks; spine BMD remained stable between 22 and 58 weeks. No peak was observed in spine BMD. To evaluate the effect of estrogen deficiency on animals of different ages, we measured spine BMD weekly in female rats subjected to ovariectomy (OVX) or sham operation at 8 and 23 weeks of age. The spine BMDs in each OVX rat were significantly lower than that of the controls. In the 23-week-old rats, bone loss was quite rapid for the first 3 weeks of observation and stable afterward. The BMD of 8-week-old OVX rats increased with body size. We conclude that DXA allows the observation of age-related changes in the spine BMD of rats with great precision. The data we have gathered using this method should prove useful for the assessment of experimental models of osteoporosis in rats.
Growth hormone stimulates bone formation and strength of cortical bone in aged rats
Authors: Andreassen Troels T. , Jørgensen Peter H. , Oxlund Hans , Flyvbjerg Allan , Ørskov Hans 
Published: February 2010

Abstract
The influence of growth hormone on bone formation, mechanical strength, and composition has been investigated in femur middiaphyseal cortical bone from 2-year-old male rats. The rats were given biosynthetic human growth hormone (bhGH) at 2.7 mg/kg/day in two daily injections for 20, 40, or 80 days, and all animals were killed 80 days after the start of bhGH administration. Control animals were given saline. All animals were labeled with tetracycline on days 41 and 69. Only in the bhGH-80-day group was subperiosteal tetracycline double labeling seen all around the femur diaphysis, and this pattern was found in all animals of the group. Double labeling subperiosteally at the posteromedial aspect was found in all animals of the experiment, but compared with the control group, a 400% and an 800% increase in mineral apposition rate was seen in the bhGH-40-day and bhGH-80-day groups, respectively. Light microscopy and polarization microscopy showed that this newly deposited bone was organized in the same concentric lammellae and had the same direction of the collagen fibers when compared with the surrounding bone formed before the start of bhGH injections. The cortical bone cross-sectional area was increased in the bhGH-40-day and bhGH-80-day groups. At the endosteum, scattered labeling was found in animals from all groups, and no differences in medullary cross-sectional areas were seen. The mechanical analysis revealed an increased mechanical strength of the whole diaphyseal bone after bhGH administration. When the data were corrected for dimensions of the diaphyseal bone, no differences in intrinsic mechanical properties of the bone tissue were found. No differences in apparent density of dry defatted bone, ash, and collagen were seen, whereas apparent density of dry defatted bone minus ash was decreased in all groups given bhGH. Correspondingly, a slight increase in ash concentrations of the bhGH-injected animals was seen. bhGH administration also increased the body weight, muscle mass, and total serum IGF-I and thyroxine concentrations. (
Validation of accuracy and precision of dual energy X-ray absorptiometry for infants
Authors: Koo Winston W. K. , Massom Larry R. , Walters Jocelyn 
Published: February 2010

Abstract
There is limited information on the validity of bone mineral content measurement by dual energy X-ray absorptiometry (DXA BMC) for use in subjects with low body mass. We evaluated the accuracy and precision of DXA in piglets (body weight 886–5526 g, median 2096 g). Stepwise multiple regression analyses showed that ash weight is the major determinant of DXA BMC (adjusted r2 = 0.98, RMS residual = 3.61 g). The intercept was not significantly different from zero. DXA BMC measurements of other piglets under various clinical situations showed no significant effect from the use of cotton blanket, diaper, or positioning (prone, supine, lateral). In vivo replication of DXA BMC measurements of infants at a postnatal age of from 1–350 days showed a slope of 0.99 and high correlation coefficient (r2 = 0.99, RMS residual = 3.59 g). The intercept was not significantly different from zero, and the average coefficient of variation of duplicate DXA BMC in infants was 2.8%. We conclude that DXA BMC reliably but proportionately underestimates ash weight and is a highly precise method for measuring bone mineral status in young pediatric subjects.
Calvarial and limb bone cells in organ and monolayer culture do not show the same early responses to dynamic mechanical strain
Authors: Rawlinson Simon C. F. , Mosley John R. , Suswillo Rosemary F. L. , Pitsillides Andrew A. , Lanyon Lance E. 
Published: February 2010

Abstract
Responses to mechanical strain in calvaria and limb bone organ cultures were compared by measuring cellular glucose 6-phosphate dehydrogenase (G6PD) activity in situ and prostaglandin release. Normal functional strains were recorded in the ulnae (1000 μϵ) and calvarium (30 μϵ) in vivo in 110 g rats. Organ cultures of ulnae and calvaria from similar animals were loaded to produce dynamic strains (600 cycles, 1 Hz) of 1000 μϵ in the ulna, and 100 or 1000 μϵ in calvaria. In ulnae, both PGE2 and PGI2 were released and resident osteocytes and osteoblasts showed increased G6PD activity. Neither response was seen in calvaria. However, exogenous PGI2 (10−5−10−9 M) stimulated G6PD activity in osteocytes and osteoblasts in organ cultures of both calvaria and ulnae. In ulnar cells the response was linear, in calvarial cells it was biphasic with maximum activity at 10−7 M. Osteoblasts derived from ulnae and cultured on plastic plates subjected to dynamic strain (600 cycles, 1 Hz, 4000 μϵ) showed increased G6PD activity. There was no such response in similarly treated calvarial-derived cells. Calvarial bone cells differ from those of the ulna in that they do not respond to physiological strains in their locality with increased prostanoid release or G6PD activity either in situ or when seeded onto dynamically strained plastic plates. Cells from both sites in organ culture show increased G6PD activity in response to exogenous PGI2, but their dose: Responses differ in shape. These differences may reflect the extent to which functional loading influences bone architecture in these two sites.
Factors contributing to skeletal health of postmenopausal Mexican-American women
Authors: Villa Marie Luz , Marcus Robert , Delay Romelia Ramírez , Kelsey Jennifer L. 
Published: February 2010

Abstract
Incidence rates of hip fracture are lower in Hispanic (HC) than non-Hispanic Caucasians (NHC). To investigate factors that may affect skeletal health of Hispanics, we recruited 152 healthy community-dwelling Mexican-American Caucasian women into a 4-year longitudinal study that evaluates bone mass, nutritional status, muscle strength, mobility, falls, and other factors that may contribute to fracture risk. Results from the baseline component of the study are reported herein. Average bone mineral densities (BMD) evaluated by dual-energy X-ray absorptiometry (DXA) in this study group did not differ from BMDs in healthy, NHC women of similar age. Hip axis length (HAL), however, was significantly shorter than that reported for nonosteoporotic NHC. Factors independently associated with greater BMD and BMC at certain skeletal sites were lean body mass, fat mass, acculturation, years of estrogen use, sun exposure, hip adductor strength, grip strength, erythrocyte folate, and serum glucose concentrations. Factors independently associated with lower BMD and BMC at certain skeletal sites were age, parity, and vertebral deformities (all p &lt; 0.05). Thus, the decreased risk of hip fracture in HC compared with NHC does not appear to be due to high bone mass. However, other factors such as HAL and body composition may play a role in maintenance of skeletal integrity.
Effects of differentiation and transforming growth factor β1 on PTH/PTHrP receptor mRNA levels in MC3T3-E1 cells
Authors: Mccauley Laurie K. , Koh Amy J. , Beecher Christopher A. , Cui Yingqi , Decker James D. , Franceschi Renny T. 
Published: February 2010

Abstract
TGFβ has opposing effects on osteoblasts which are thought to be differentiation stage dependent; however, little is known concerning the effects of TGFβ on osteoblastic characteristics at different stages of maturation. The purpose of this study was to characterize the pattern of mRNA expression for the PTH/PTHrP receptor during normal osteoblastic differentiation in vitro, and evaluate the effects of TGFβ1 on PTH/PTHrP receptor and osteocalcin (OCN) steady-state mRNA at different stages of osteoblastic differentiation. MC3T3-E1 preosteoblasts were plated at low density and induced to differentiate with ascorbic acid and β-glycerophosphate. The first group served as a vehicle control and the remaining five groups received a single 48 h TGFβ1 (3.0 ng/ml)-pulse staggered on a weekly basis for 30 days. Cell cultures were harvested weekly and evaluated for: steady-state PTH/PTHrP receptor and OCN mRNA levels via northern analysis, calcium and phosphorous levels, bone nodules via Von Kossa staining, alkaline phosphatase enzyme levels, and hydroxyproline levels. Group 1 (control) samples followed a normal pattern of proliferation, extracellular matrix deposition, and mineralization. PTH/PTHrP receptor and OCN mRNA expression increased 8-fold and 10-fold respectively, over the collection periods. When TGFβ1 was administered during the first 48 h period (group 2) while cells were rapidly proliferating, there was a persistent inhibition of PTH/PTHrP receptor expression and a striking reduction in OCN mRNA expression at all time points. There was also a down-regulation of PTH/PTHrP receptor and OCN expression when TGFβ1 was administered later during osteoblast differentiation (groups 3–6); however, these effects were not persistent. In addition there was a total lack of bone nodule formation in group two cultures, whereas groups 3–6 had increasing bone nodule formation because the TGFβ1 was administered later in the culture period. These studies indicate that expression of the PTH/PTHrP receptor increases with osteoblastic differentiation and suggest that TGFβ1 inhibits osteoblastic maturation with more persistent effects found in less differentiated osteoblastic cells.
Droloxifene prevents ovariectomy-induced bone loss in tibiae and femora of aged female rats: A dual-energy X-ray absorptiometric and histomorphometric study
Authors: Chen Hong Ka , Ke Hua Zhu , Jee Webster S. S. , Ma Yan Fei , Pirie Christine M. , Simmons Hollis A. , Thompson David D. 
Published: February 2010

Abstract
Our previous studies indicated that droloxifene (DRO), a tissue-specific estrogen antagonist/agonist, prevented bone loss without causing uterine hypertrophy in growing ovariectomized (OVX) rats. Using dual-energy X-ray absorptiometry (DXA) and bone histomorphometry, the current study compared the efficacy of DRO to 17β-estradiol (E2) in preventing OVX-induced bone loss in tibiae and femora of 19-month-old rats to determine whether DRO had similar skeletal effects as E2 in aged female rats. Sprague-Dawley female rats were OVX or sham-operated (sham) at 19 months of age. The sham-operated rats were treated with vehicle (oral), while the OVX rats were treated with vehicle (oral), E2 at 30 μg/kg/day (sc), or DRO at 2.5, 5, or 10 mg/kg/day (oral) for 8 weeks. Bone mineral density (BMD) of whole femora (WF), distal femoral metaphyses (DFM), femoral shafts (FS), and proximal femora (PF) was determined using DXA. Static and dynamic cancellous bone histomorphometric analyses were performed in double-labeled undecalcified longitudinal sections from proximal tibial metaphyses. Ovariectomy for 8 weeks significantly reduced the BMD of WF, DFM, FS, and PF (from −6 to −15%). Treatment with E2 completely prevented the decreases in BMD of WF and DFM and had no significant effects in BMD of FS and PF in aged OVX rats. The decrease in BMD of DFM induced by OVX was prevented by treatment with DRO at all dose levels. In addition, DRO at 10 mg/kg/day prevented OVX-induced decreases in BMD of WF, FS, and PF. Furthermore, proximal tibial cancellous bone histomorphometric results showed that OVX significantly decreased the trabecular bone volume by 34% and increased the activation frequency by 104% while it nonsignificantly increased other indices including percent eroded perimeter, mineral apposition rate, and bone formation rate per bone volume compared with sham-operated controls. Treatment with E2 or DRO at all dose levels completely prevented the OVX-induced decreases in trabecular bone volume and increases in bone turnover, indicating that DRO is an estrogen agonist in bone in aged OVX rats. Together with the previous findings that DRO inhibited body weight gain, reduced total serum cholesterol, and had no effect on uterine weight, we conclude that DRO is as efficacious as E2 in preventing OVX-induced bone loss and inhibiting bone turnover but without estrogenic uterine effects in aged OVX rats. These data suggest that DRO may be superior to E2 for the treatment of postmenopausal and senile osteoporoses.
Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass in healthy premenopausal women
Authors: Garnero Patrick , Borel Olivier , Sornay-Rendu Elizabeth , Dr. Delmas Pierre D. 
Published: February 2010

Abstract
Bone mineral density (BMD) is under strong genetic control. Polymorphisms at the vitamin D receptor (VDR) gene have been recently suggested to account for up to 75% of this genetic effect. We analyzed these polymorphisms, i.e., that of BsmI, TaqI, and ApaI restriction enzymes by PCR of the DNA in 189 healthy premenopausal women aged 31 to 57 years. For the BsmI polymorphism they were 17% BB homozygotes, 51% Bb heterozygotes, and 32% bb homozygotes, genotype frequencies that are very similar to those previously reported in other Caucasian populations of north European ancestry. Women in the three genotypes for any of the three polymorphisms were matched for age and did not differ in body weight, height, physical activity, nor smoking habits. We found no relationship between the genotype for any of the three polymorphisms nor bone formation and resorption rate assessed by five specific biochemical markers of bone turnover nor with BMD measured at the spine, proximal femur, forearm, and whole body by dual-energy X-ray absorptiometry (DXA). We concluded that these polymorphisms are not predictive of bone turnover nor BMD in a sample of healthy premenopausal women drawn from the French population.
Triiodothyronine potentiates the stimulatory effects of interleukin-1β on bone resorption and medium interleukin-6 content in fetal rat limb bone cultures
Authors: Tarjan Gabor , Dr. Stern Paula H. 
Published: February 2010

Abstract
It has been demonstrated that thyroid hormones stimulate osteoclasts indirectly and that this effect is mediated by products of other cell types present in bone. To determine if interleukin-6 (IL-6) could be a mediator of thyroid hormone action, we investigated the effect of 3,5,3′-triiodothyronine (T3) on bone resorption (45Ca release) and on the IL-6 concentration in medium from cultured 19-day-old fetal rat limb bones. T3 alone increased 45Ca release significantly only at a fairly high concentration (10−6 M) under the conditions used. T3 alone, over a 10−11–10−6 M concentration range, failed to elicit a detectable effect on the medium IL-6 content. However, T3 potentiated the stimulatory effect of interleukin-1β (IL-1β) on IL-6 production in a dose-dependent manner. T3, 10−8 M, also significantly increased IL-1β-stimulated calcium release. Inhibition of IL-1β with 1 μM interleukin-1 receptor antagonist (IL-Ira) abrogated the potentiating effects of T3 on IL-1β-stimulated IL-6 production and blocked the combined effect of T3 and IL-1β on 45Ca release. One micromolar indomethacin significantly, but not completely, inhibited the effect of IL-1β, as well as the combined effect of IL-1β and T3 on resorption and IL-6 production, indicating the involvement of prostaglandins in these actions. Consistent with this, 1 μM prostaglandin E1 (PGE1) significantly increased both the IL-6 production and the calcium release. By potentiating the effect of IL-1β, T3 increased bone resorption at much lower concentrations. We therefore speculate that the enhancement of IL-1β effects may be a biologically relevant mechanism of thyroid hormone action on bone.
The potential role of fibroblasts in periprosthetic osteolysis: Fibroblast response to titanium particles
Authors: Yao Jianling , Dr. Glant Tibor T. , Lark Michael W. , Mikecz Katalin , Jacobs Joshua J. , Hutchinson Nancy I. , Hoerrner Lori A. , Kuettner Klaus E. , Galante Jorge O. 
Published: February 2010

Abstract
Periprosthetic osteolysis with or without aseptic loosening is a major clinical problem in total hip arthroplasty. While the macrophage response to prosthetic wear debris and its role in periprosthetic osteolysis has been extensively studied, information regarding other cell types (fibroblasts, osteoblasts) is limited. This study explored the response of fibroblasts to particulate wear debris. Fibroblasts isolated from interfacial membranes of patients with failed total hip replacements and normal synovial tissue, when challenged with small-sized (&lt;3 μm) titanium (Ti) particles, responded with significantly enhanced expressions of collagenase, stromelysin and, to a much lesser extent, their tissue inhibitor of metalloproteinases (TIMP). These “regulated” expressions at both mRNA and protein levels were correlated with the size and composition of particles. De novo protein synthesis was required for the regulation of these mRNAs. A similar effect could be induced by the treatment of the cells with particle-free conditioned medium from Ti particle-stimulated fibroblasts. Furthermore, this conditioned medium significantly suppressed the mRNA levels of procollagen α1(I) and α1(III) in osteoblast-like MG-63 cells. It is concluded that fibroblasts stimulated with certain particle debris may play an important role in periprosthetic osteolysis by releasing bone-resorbing metalloproteinases and mediator(s) which resulted in suppressed collagen synthesis in osteoblasts.
Intermittent treatment with human parathyroid hormone (hPTH[1-34]) increased trabecular bone volume but not connectivity in osteopenic rats
Authors: Dr. Lane Nancy E. , Thompson J.M. , Strewler Gordon J. , Kinney J.H. 
Published: February 2010

Abstract
Previous studies have determined that intermittent parathyroid hormone (PTH) therapy increases bone mass and improves biomechanical strength in osteopenic animal models. The purpose of this investigation was to determine if intermittent human parathyroid hormone (hPTH[1–34]) therapy increased trabecular bone volume and connectivity in a rat model of established osteopenia using three-dimensional (3D) ex vivo in situ morphometry by X-ray tomographic methods (XTM). Six-month-old retired Sprague-Dawley breeder rats were used. Thirty animals were ovariectomized (OVX) and six were Sham operated. On day 56, post-OVX, a prePTH-treatment OVX group was sacrificed. The remaining OVX animals were randomized into four groups of six animals each, given injections 5 out of every 7 days for 28 days of either vehicle or hPTH(1-34) at 4, 40, or 400 μg/kg of body weight (BW)/day and were sacrificed on day 84 post-OVX. At sacrifice, the left proximal tibias were harvested for XTM scans. hPTH(1-34) at medium and high doses significantly increased trabecular bone volume and trabecular thickness compared with ovariectomized animals treated with vehicle (p &lt; 0.05). The trabecular bone volume was equal to or greater than the Sham-operated animals in both hPTH(1–34) 40 and 400 μg/kg of BW treatment groups. Trabecular bone connectivity decreased by nearly 50% compared to the Sham-operated group at day 84 post-OVX and did not increase with any of the hPTH(1-34) treatments. Intermittent hPTH(1-34) treatment in osteopenic OVX rats increased trabecular bone volume to control levels or higher by thickening existing trabecule. Human PTH(1–34) did not re-establish connectivity when therapy was started after 50% of the trabecular connectivity was lost. We hypothesize that to re-establish trabecular connectivity, a therapeutic intervention would have to be given before a significant distance between trabeculae has developed. Further studies will need to be done to refute or confirm our hypothesis.
Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo
Authors: Hughes David E. , Wright Kenneth R. , Uy Harry L. , Sasaki Akira , Yoneda Toshiyuki , Roodman David G. , Mundy Gregory R. , Dr. Boyce Brendan F. 
Published: February 2010

Abstract
Bisphosphonates inhibit bone resorption and are therapeutically effective in diseases of increased bone turnover, such as Paget's disease and hypercalcemia of malignancy. The mechanisms by which they act remain unclear. Proposed mechanisms include inhibition of osteoclast formation from precursors and inhibitory or toxic effects on mature osteoclasts. We have developed a new in vitro model to study osteoclast survival and in this paper present in vitro and in vivo evidence that may explain both the observed reduction in osteoclast numbers and in bone resorption by mature osteoclasts, namely that bisphosphonates induce programmed cell death (apoptosis). Three bisphosphonates (risedronate, pamidronate, and clodronate) caused a 4- to 24-fold increase in the proportion of osteoclasts showing the characteristic morphology of apoptosis in vitro. This observation was confirmed in vivo in normal mice, in mice with increased bone resorption, and in nude mice with osteolytic cancer metastases, with similar-fold increases to those observed in vitro. Of the three compounds, risedronate, the most potent inhibitor of bone resorption in vivo, was the strongest inducer of osteoclast apoptosis in vitro. Osteoclast apoptosis may therefore be a major mechanism whereby bisphosphonates reduce osteoclast numbers and activity, and induction of apoptosis could be a therapeutic goal for new antiosteoclast drugs.