bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zoledronate Prevents the Development of Absolute Osteopenia Following Ovariectomy in Adult Rhesus Monkeys
Authors: Binkley Neil , Kimmel Donald , Bruner Julia , Haffa Arlene , Davidowitz Bradley , Meng Cliff , Schaffer Victoria , Green Jonathan 
Published: April 2006

Abstract
This study assessed effects of the bisphosphonate zoledronate (ZLN) on bone density and biochemical markers of bone turnover in ovariectomized (OVX) adult female rhesus monkeys. Forty monkeys were randomly assigned to one control or four OVX groups. The control and one OVX group received saline, and the other three OVX groups received ZLN (0.5, 2.5, or 12.5 μg/kg) by a single weekly subcutaneous injection for 69 weeks. Bone mass of the total body (TB), lumbar spine (LS), distal and central radius (dual-energy X-ray absorptiometry), and skeletal turnover markers were measured at baseline and at 13, 26, 39, 52, and 69 weeks of treatment. Increased skeletal turnover and decreased bone mass (LS and TB) were demonstrable by 13 weeks post-OVX. Maximal bone loss (7–8%) at these sites occurred by 39 weeks after OVX and persisted for the study duration. Long-term ZLN treatment was well tolerated and prevented increased skeletal turnover and bone loss in a dose-dependent fashion. Progressive turnover suppression was not observed with any ZLN dose. In conclusion, after OVX, adult rhesus monkeys develop persistent increased bone turnover and absolute osteopenia of the LS and TB, making them an outstanding model of skeletal behavior in perimenopausal women. These OVX-related skeletal changes are dose-dependently blocked by ZLN.
Changes in Bone Turnover Induced by Aerobic and Anaerobic Exercise in Young Males
Authors: Woitge Henning W. , Friedmann Birgit , Suttner Stefan , Farahmand Iris , Müller Martin , Schmidt-Gayk Heinrich , Baertsch Peter , Ziegler Reinhard , Seibel Markus J. 
Published: April 2006

Abstract
Physical activity is considered an important factor in attaining bone mass. However, the mechanisms by which exercise affects bone metabolism are not completely understood. The present study was performed to investigate the effects of aerobic and anaerobic exercise on bone turnover. Twenty healthy young males (aged 20–29 years) were followed through an 8-week program of aerobic (n = 10) and anaerobic training (n = 10). Ten age-matched individuals served as controls. Serum bone-specific alkaline phosphatase (BAP), serum osteocalcin (OC), and urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd) were determined as indices of bone metabolism. After 4 weeks of aerobic training, serum BAP and OC (p &lt; 0.01), and urinary Pyd (p &lt; 0.001) and Dpd (p &lt; 0.01) were significantly reduced. After 8 weeks, BAP and OC levels had returned to baseline values, whereas the urinary cross-link excretion remained low. In the anaerobic training group, elevated levels of BAP (p &lt; 0.05 vs. week 4), OC (p &lt; 0.05 vs. week 4), and Pyd (p &lt; 0.01 vs. week 0) were observed after 8 weeks of exercise. Changes in urinary Pyd and Dpd (week 0 vs. week 8) were positively correlated with changes in the mean power level in the Wingate test, a parameter of the anaerobic performance capacity (r = 0.50 and r = 0.55, p &lt; 0.01, respectively). In the controls, no significant changes in biochemical markers were observed. We conclude that aerobic and anaerobic training excert different effects on bone metabolism. While aerobic training led to changes compatible with reduced bone resorption activity, anaerobic training seems to result in an overall accelerated bone turnover. Therefore, the impact of physical activity on bone turnover may depend on the kind of exercise performed.
Homologous Up-Regulation of Vitamin D Receptors Is Tissue Specific in the Rat
Authors: Gensure Robert C. , Antrobus Steve D. , Fox John , Okwueze Martina , Talton Stephanie Y. , Walters Marian R. 
Published: April 2006

Abstract
1,25-dihydroxyvitamin D3 (1,25(OH)2D3) receptors (VDR) are expressed in multiple tissues within the body. VDR levels are increased by 1,25(OH)2D3 in intestine and kidney and in numerous cell models. The ability of 1,25(OH)2D3 to affect VDR levels in other target tissues in vivo was studied by assessing VDR levels by the3H-1,25(OH)2D3 binding assay under varied physiological conditions in the rat. When compared with vitamin D–deficient (−D) controls, rats raised on a normal vitamin D–sufficient (+D) diet showed elevated VDR levels in kidney (391 ± 53 vs. 913 ± 76 fmol/g of tissue; p &lt; 0.05), but not in testis, heart, or lung. Up-regulation of the VDR also occurred in kidney of +D rats 1 day after a single 100-ng dose of 1,25(OH)2D3 (454 ± 43 vs. 746 ± 113 fmol/mg of DNA; p &lt; 0.05), but no changes were seen in intestine, testis, or lung. Because 1,25(OH)2D3-induced hypercalcemia may independently affect VDR regulation, 1,25(OH)2D3 was infused into −D rats, and normocalcemia was maintained by reduced dietary calcium intake. In this model, the renal VDR was again up-regulated (446 ± 115 vs. 778 ± 58 fmol/mg of DNA; p &lt; 0.05), but VDR levels in testis and lung were unaffected. Scatchard analysis and tests of 1,25(OH)2D3 dose (1–100 ng/day for 7 days) and temporal (100 ng/day for 1–7 days) responsiveness further supported the tissue-specific nature of the homologous VDR regulation. Assay of VDR levels by l-1-tosylamido-2-phenylethyl chloromethyl ketone–3H-1,25(OH)2D3 exchange assay ruled out differences in endogenous 1,25(OH)2D3 occupancy as the basis for the observed differences in VDR regulation. Finally, coidentity of the VDR-like sites in kidney versus testis was confirmed by competitive binding analysis comparing their relative affinities for 25(OH)D3 versus 1,25(OH)2D3 (30.5 ± 6.4 vs. 35.6 ± 3.6 in kidney and testis, respectively) and by immunoblot analysis using a highly specific monoclonal anti-rat VDR antibody. Thus, under a wide variety of experimental conditions, homologous up-regulation of the VDR occurs in the rat kidney in vivo, but not in several other target tissues which do not regulate plasma calcium homeostasis. Moreover, this differential VDR regulation did not result from secondary changes in plasma calcium, from differential 1,25(OH)2D3 responsiveness in the various tissues, nor from differences in endogenous 1,25(OH)2D3 occupancy of the VDR. These studies thus establish that, in contrast to observations in vitro, the widely described phenomenon of homologous VDR up-regulation in kidney and intestine is not a universal property of 1,25(OH)2D3 target tissues in vivo in the rat.
Morphometric X-Ray Absorptiometry: Reference Data for Vertebral Dimensions
Authors: Mrs. Rea J. A. , Steiger P. , Blake G. M. , Potts E. , Smith I. G. , Fogelman I. 
Published: April 2006

Abstract
Vertebral fractures are a common and important consequence of osteoporosis and are often identified via morphometric analysis of conventional lateral spine radiographs (morphometric radiography or MRX). A new method of performing vertebral morphometry using images acquired on dual-energy X-ray absorptiometry (DXA) scanners (morphometric X-ray absorptiometry or MXA) has recently been developed. In this study, we derive reference data for vertebral heights and height ratios using MXA scans as the data source and compare the results with previously published MRX studies. One thousand and nineteen Caucasian women (mean age 63 years, range 33–86) were recruited. An MXA scan, covering 13 vertebrae from L4 to T4, was acquired for each subject on one of four DXA systems located at three centers in the U.K. Analysis of variance found statistically significant but relatively small differences among centers, machines, and scan modes, and therefore data were pooled for reference range calculations. Three vertebral heights (anterior, mid, and posterior) were measured and four ratios (wedge, mid-wedge, and two crush) calculated. These data sets were trimmed using an iterative algorithm to remove extreme values assumed to represent deformed vertebrae, then mean and SD values were calculated using the remaining data. When the data were split by age, a small but statistically significant decrease in vertebral height between the sixth and eighth decades was found, but this was not replicated for the vertebral height ratios. Marked differences were observed between MXA data and MRX, but were comparable to those between different MRX studies. These may result from differences in image quality and point placement protocols, population differences, differences in radiographic technique, and differences in the derivation of a group of “normal” vertebrae. This study suggests that reference data of vertebral dimensions should be specific to the technique which uses those data as a reference, i.e., MXA.
Calcium Supplementation Suppresses Bone Turnover During Weight Reduction in Postmenopausal Women
Authors: Ricci Trina A. , Chowdhury Hasina A. , Heymsfield Steven B. , Stahl Theodore , Pierson Richard N. , Shapses Sue A. 
Published: April 2006

Abstract
Bone mobilization, lowering of bone mineral density (BMD), and osteoporotic fractures are recognized in postmenopausal women with weight loss. Because a high-calcium intake suppresses bone loss in peri- and postmenopausal women, the present randomized, double-blind, placebo-controlled study was designed to test the hypothesis that calcium supplementation prevents net bone mobilization and consequent bone mineral loss during voluntary weight reduction in obese postmenopausal women. Subjects were placed on a moderate energy-restricted diet and either calcium supplementation (1 g/day) or placebo for 6 months. Body weight, bone turnover markers (pyridinium cross-links), osteocalcin, and parathyroid hormone (PTH) were measured at treatment weeks 1–5, 7, 10, 13, 16, 20, and 25. Total body BMD, insulin-like growth factor, 25-hydroxyvitamin D, and sex hormone binding globulin (SHBG) were measured at baseline and week 25. The calcium supplemented (n = 15; age 60.9 ± 9.4 years, body mass index [BMI] 33.2 ± 4.6 kg/m2) and placebo (n = 16; age 55.8 ± 8.3 years, BMI 32.9 ± 4.5 kg/m2) groups lost similar amounts of weight over the study interval (10.2 ± 5.3% vs. 10.0 ± 5.2%) and both groups increased SHBG (p &lt; 0.001). There was a statistical effect of calcium supplementation during weight loss to suppress pyridinium cross-links, osteocalcin, and PTH (p &lt; 0.05, &lt; 0.01, and &lt; 0.05, respectively). Loss of BMD tended to be greater in the placebo group by 1.4% (p &lt; 0.08) after weight loss. One gram per day calcium supplementation normalizes the increased calcium–PTH axis activity and the elevated bone turnover rate observed during moderate voluntary energy restriction in postmenopausal women.
Risk Factors for Hip Fracture in White Men: The NHANES I Epidemiologic Follow-up Study
Authors: Mussolino Michael E. , Looker Anne C. , Madans Jennifer H. , Langlois Jean A. , Orwoll Eric S. 
Published: April 2006

Abstract
This prospective population-based study assessed predictors of hip fracture risk in white men. Participants were members of the Epidemiologic Follow-up Study cohort of the First National Health and Nutrition Examination Survey, a nationally representative sample of noninstitutionalized civilians who were followed for a maximum of 22 years. A cohort of 2879 white men (2249 in the nutrition and weight-loss subsample, 1437 in the bone density subsample) aged 45–74 years at baseline (1971–1975) were observed through 1992. Ninety-four percent of the original cohort were successfully traced. Hospital records and death certificates were used to identify a total of 71 hip fracture cases (61 in the nutrition and weight-loss subsample, 26 in the bone-density subsample). Among the factors evaluated were age at baseline, previous fractures other than hip, body mass index, smoking status, alcohol consumption, nonrecreational physical activity, weight loss from maximum, calcium intake, number of calories, protein consumption, chronic disease prevalence, and phalangeal bone density. The risk adjusted relative risk (RR) of hip fracture was significantly associated with presence of one or more chronic conditions (RR = 1.91, 95% confidence interval [CI] = 1.19–3.06), weight loss from maximum ≥ 10% (RR = 2.27, 95% CI 1.13–4.59), and 1 SD change in phalangeal bone density (RR = 1.73, 95% CI 1.11–2.68). No other variables were significantly related to hip fracture risk. Although based on a small number of cases, this is one of the first prospective studies to relate weight loss and bone density to hip fracture risk in men.
Bone Morphogenetic Proteins and bFGF Exert Opposing Regulatory Effects on PTHrP Expression and Inorganic Pyrophosphate Elaboration in Immortalized Murine Endochondral Hypertrophic Chondrocytes (MCT Cells)
Authors: Terkeltaub Robert A. , Johnson Kristen , Rohnow David , Goomer Randy , Burton Doug , Deftos Leonard J. 
Published: April 2006

Abstract
A fundamental question in endochondral development is why the expression of parathyroid hormone–related protein (PTHrP), which inhibits chondrocyte maturation and mineralization, becomes attenuated at the stage of chondrocyte hypertrophy. To address this question, we used clonal, phenotypically stable SV40-immortalized murine endochondral chondrocytes that express a growth-arrested hypertrophic phenotype in culture (MCT cells). Addition of individual cytokines to the medium of MCT cells revealed that bone morphogenetic protein (BMP)-6, which commits chondrocytes to hypertrophy, markedly inhibited PTHrP production. This activity was shared by three other osteogenic bone morphogenetic proteins (BMP-2, BMP-4, and BMP-7) and by transforming growth factor β (TGF-β), which all inhibited the level of PTHrP mRNA. In contrast, basic fibroblast growth factor (bFGF), an inhibitor of chondrocyte maturation to hypertrophy, induced PTHrP in MCT cells and antagonized the effects of BMP-2, BMP-4, BMP-6, and BMP-7 and TGF-β on PTHrP expression. Opposing effects of bFGF and BMPs also were exerted on the elaboration of inorganic pyrophosphatase (PPi), which regulates the ability of hypertrophic chondrocytes to mineralize the matrix. Specifically, BMP-2 and BMP-4, but not BMP-6 and BMP-7, shared the ability of TGF-β to induce PPi release, and this activity was inhibited by bFGF in MCT cells. Our results suggest that effects on PTHrP expression could contribute to the ability of BMP-6 to promote chondrocyte maturation. BMPs and bFGF exert opposing effects on more than one function in immortalized hypertrophic chondrocytes. Thus, the normal decrease in bFGF responsiveness that accompanies chondrocyte hypertrophy may function in part by removing the potential for bFGF to induce PTHrP expression and to oppose the effects of BMPs. MCT cells may be useful in further understanding the mechanisms regulating the differentiation and function of hypertrophic chondrocytes.
A Third-Generation Bisphosphonate, YM175, Inhibits Osteoclast Formation in Murine Cocultures by Inhibiting Proliferation of Precursor Cells via Supporting Cell-Dependent Mechanisms
Authors: Nishikawa Miyuki , Yamamoto Michiko , Murakami Takehiko , Akatsu Takuhiko , Kugai Nobuo , Nagata Naokazu 
Published: April 2006

Abstract
The theory that bisphosphonates inhibit osteoclast formation through their effects on osteoblastic cells remains controversial. To confirm the inhibitory effect of bisphosphonates on osteoclast formation and gain some insights into the underlying mechanisms, we examined the effect of disodium dihydrogen (cycloheptylamino)-methylenebisphosphonate monohydrate (YM175) on osteoclast-like multinucleated cell (OCL) formation in various mouse coculture systems. When different origins of osteoclast precursors (bone marrow, spleen, or nonspecific esterase-positive cells) were cocultured with the same supporting cells (calvarial osteoblasts), YM175 inhibited OCL formation similarly in all cultures. When the same osteoclast precursors (spleen cells) were cocultured with supporting cells of different origin, the results were variable. YM175 inhibited OCL formation almost completely in cocultures with calvarial osteoblasts or osteoblastic cell line KS4, while it did not, or only slightly, inhibit OCL formation in cocultures with stromal cell lines, ST2 or MC3T3-G2/PA6. Temporal addition of YM175 in cocultures of spleen cells with osteoblastic cells revealed that YM175 was effective when it was present at an early phase of the culture period. Consistent with this observation, YM175 in the presence of osteoblastic cells inhibited proliferation of preosteoclastic cells, but did not inhibit the fusion of mononuclear prefusion osteoclasts. In conclusion, the inhibitory effect of YM175 on OCL formation was confirmed in various murine coculture systems, but the effect was dependent on the types of bone-derived cells supporting osteoclastogenesis. The findings suggest that YM175 inhibits osteoclastogenesis by inhibiting the proliferation of osteoclast precursors through its action on supporting cells of osteoblast lineage rather than acting directly on osteoclast precursors.
Expression of Bone Matrix Proteins mRNA During Distraction Osteogenesis
Authors: Sato Motohiko , Yasui Natsuo , Nakase Takanobu , Kawahata Hirohisa , Sugimoto Mizuo , Hirota Seiichi , Kitamura Yukihiko , Nomura Shintaro , Ochi Takahiro 
Published: April 2006

Abstract
Distraction osteogenesis is a recently advanced principle of bone lengthening in which a bone separated by osteotomy is subjected to slow progressive distraction using an external fixation device. Appropriate mechanical tension-stress is believed not to break the callus but rather to stimulate osteogenesis. To study the molecular features of this process, the expression and localization of the mRNAs encoding osteopontin (OPN), osteocalcin (OC), matrix Gla protein (MGP), osteonectin (ON), and collagen type I and II during distraction osteogenesis were examined by in situ hybridization and Northern blot analysis. The process can be divided into three distinct phases: the lag phase for 7 days between osteotomy and the beginning of distraction, the distraction phase for 21 days, and the consolidation phase for several weeks. The histologic and molecular events taking place during the lag phase were similar to those observed in fracture healing. The osteotomy site was surrounded by external callus consisting of hyaline cartilage. As distraction started at the rate of 0.25 mm/12 h, the cartilaginous callus was elongated, deformed, and eventually separated into proximal and distal segments. The chondrocytes were stretched along the tension vector and became fibroblast-like in shape. Although morphologically these cells were distinguishable from osteogenic cells, they expressed OPN, OC, and alkaline phosphatase mRNAs. As distraction advanced, the cartilaginous callus was progressively replaced by bony callus by endochondral ossification and thereafter new bone was formed directly by intramembranous ossification. OPN mRNA was detected in preosteoblasts and osteoblasts at the boundary between fibrous tissue and new bone. ON, MGP, and OC mRNAs appeared early in the differentiation stage. The variety of cell types expressing mRNA encoding bone matrix proteins in distraction osteogenesis was much greater than that detected in the embryonic bone formation and fracture healing process. Moreover, the levels of OPN, ON, MGP, and OC mRNA expression markedly increased during the distraction phase. These results suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins.
TNF-α Increases Expression of IL-6 and ICAM-1 Genes Through Activation of NF-κB in Osteoblast-like ROS17/2.8 Cells
Authors: Kurokouchi Kazutoshi , Kambe Fukushi , Yasukawa Kou , Izumi Ryutaro , Ishiguro Naoki , Iwata Hisashi , Seo Hisao 
Published: April 2006

Abstract
Tumor necrosis factor-α (TNF-α) plays a key role in inflammatory diseases such as rheumatoid arthritis and in postmenopausal osteoporosis. In various tissues, TNF-α action is mediated by a transcription factor, nuclear factor-kappa B (NF-κB). However, little is known about how TNF-α exerts its action in osteoblasts. We thus examined the effect of TNF-α on the activation of NF-κB in rat osteoblast-like osteosarcoma cells (ROS17/2.8). Electrophoretic mobility shift assay revealed that the activation of the p50-p65 heterodimer NF-κB was induced by TNF-α as early as 15 minutes followed by a persistent activation for 48 h. When the binding activity of NF-κB in cytosol was examined using detergents that dissociate NF-κB from an inhibitory protein IκB, it decreased during the initial 30 minutes and then increased to the unstimulated level. Northern blot analysis revealed a marked increase in the mRNA levels of p105, a precursor of p50, 6 h after TNF-α and a gradual increase in p65 mRNA levels during the initial 1 h. Significant increase in both mRNA levels continued until 24 h after TNF-α. These results suggest that the rapid activation of NF-κB by TNF-α is mainly due to the nuclear translocation of NF-κB pre-existing in cytosol, and that the subsequent increase in the expression of p50 and p65 may result in the persistent activation of NF-κB during TNF-α stimulation. TNF-α also increased the mRNA levels of interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1). An antioxidant, N-acetyl-L-cysteine, significantly attenuated the TNF-α–dependent increase in these mRNAs, and simultaneously reduced the activation of NF-κB by TNF-α, indicating that NF-κB mediates the TNF-α–dependent expression of IL-6 and ICAM-1 in ROS17/2.8 cells. These results suggest that the activation of NF-κB by TNF-α may play an important role in the production of cytokines and cell adhesion molecules from osteoblasts, leading to the promotion of bone resorption and inflammation.
Effects of Exercise on Bone Mineral Density in Mature Osteopenic Rats
Authors: Iwamoto Jun , Takeda Tsuyoshi , Ichimura Shoichi 
Published: April 2006

Abstract
Dual-energy X-ray absorptiometry (DXA) was used to examine the effects of quantitative application of treadmill running exercise on bone mineral density (BMD) of the tibia and the fourth and fifth lumbar (L4 + L5) vertebrae in mature osteopenic rats. Twenty 37-week-old rats with bone loss, resulting from feeding a relatively low calcium diet for 14 weeks after ovariectomy at the age of 23 weeks, were divided into four groups of five rats each according to the intensity and duration of the exercise: 12 m/minute, 1 h/day in group EX1; 18 m/minute, 1 h/day in group EX2; 12 m/minute, 2 h/day in group EX3; and sedentary control in group CON. With a standard calcium diet, the exercise was performed 5 days a week for 12 weeks, and the BMD of both the right tibia and the L4 + L5 vertebrae was measured using DXA at weeks 0, 4, 8, and 12. At the end of 12 weeks of exercise, the right femur and the L5 vertebra were dissected and the mechanical strength was measured using a three-point bending test and a compression test, respectively. After 12 weeks of exercise, a significant increase in the tibial BMD was observed in only group EX1 compared with that in group CON (p = 0.0039, by two-way analysis of variance). However, any significant increase in the L4 + L5 vertebral BMD was not observed in any exercise groups compared with that in the control group. While a maximum breaking force of the femoral shaft in group EX1 was significantly greater than that in group CON (p &lt; 0.05, by Mann-Whitney's U-test), that in groups EX2 and EX3 did not significantly differ from that in group CON. However, there was no significant difference in a maximum breaking force of the L5 vertebral body among all the exercise and control groups. These results indicated that the beneficial effects of treadmill running exercise under a standard calcium diet were recognized only in the weight-bearing bones of the mature osteopenic rats resulting from estrogen deficiency and inadequate calcium intake only when an optimal level of exercise was applied.