bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anabolic Effects of Human Biosynthetic Parathyroid Hormone Fragment (1–34), LY333334, on Remodeling and Mechanical Properties of Cortical Bone in Rabbits
Authors: Hirano Toru , Burr David B. , Turner Charles H. , Sato Masahiko , Cain Rick L. , Hock Janet M. 
Published: April 2006

Abstract
Intermittent administration of parathyroid hormone (PTH) has an anabolic effect in cancellous bone of osteoporotic humans. However, the effect of PTH on cortical bone with Haversian remodeling remains controversial. The aim of this study was to determine the effects of biosynthetic human PTH(1–34) on the histology and mechanical properties of cortical bone in rabbits, which exhibit Haversian remodeling. Mature New Zealand white rabbits were treated with once daily injections of vehicle, or PTH(1–34), LY333334, at 10 μg/kg/day or 40 μg/kg/day for 140 days. Body weight in rabbits treated with PTH did not change significantly over the experimental period. Serum calcium and phosphate were within the normal range, but a 1 mg/ml increase in serum calcium was observed in rabbits given the higher dose of PTH. Histomorphometry of cortical bone in the midshaft of the tibia showed significant increases in periosteal and endocortical bone formation in these rabbits. Intracortical bone remodeling in the tibia was activated and cortical porosity increased by PTH. Cross-sectional bone area and bone mass of the midshaft of the femur increased significantly after PTH treatment. Ultimate force, stiffness, and work to failure of the midshaft of the femur of rabbits given the 40 μg dose of PTH were significantly greater than those in the control group, whereas elastic modulus was significantly lower than that in the rabbits given the 10 μg dose of PTH, but not different from controls. In the third lumbar vertebra, PTH increased both formation and resorption without increasing cancellous bone volume. The increases in bone turnover and cortical porosity were accompanied by concurrent increases in bone at the periosteal and endocortical surfaces. The combination of these phenomena resulted in an enhancement of the ultimate stress, stiffness, and work to failure of the femur.
Effects of Continuous Infusion of PTH on Experimental Tooth Movement in Rats
Authors: Soma S. , Iwamoto M. , Higuchi Y. , Kurisu K. 
Published: April 2006

Abstract
Development of new methods for accelerating orthodontic tooth movement has been strongly desired for shortening of the treatment period. The rate of orthodontic tooth movement is dependent on the rate of bone resorption occurring in the compressed periodontium in the direction of orthodontic force applied to the tooth. In the present study, we examined the effects of continuous infusion of parathyroid hormone (PTH) on tooth movement. Male rats weighing 350–400 g were treated with subcutaneous infusion of vehicle or hPTH(1–84) at 1–10 μg/100 g of body weight/day. When the upper right first molar (M1) was moved mesially for 72 h by the insertion of an elastic band between the first and second molars, M1 movement was accelerated by PTH infusion at 10 μg. PTH infusion caused a 2- to 3-fold increase in the number of osteoclasts in the compressed periodontium of M1, indicating that such treatment accelerated tooth movement by enhancing bone resorptive activity induced in the compressed periodontium. When M1 was moved mesially by an orthodontic coil spring ligated between upper incisors and M1 for 12 days, PTH(1–84) infusion at 10 μg caused a 2-fold increase in the rate of M1 movement. PTH(1–34) infusion at 4 μg had an effect comparable to that of PTH(1–84). However, intermittent injection of PTH(1–34) did not accelerate M1 movement. PTH infusion for 13 days did not affect either bone mineral measurements or the serum calcium level. These findings suggest that continuous administration of PTH is applicable to accelerate orthodontic tooth movement.
The Proportion of Carboxylated to Total or Intact Osteocalcin in Serum Discriminates Warfarin-Treated Patients from Control Subjects
Authors: Obrant Karl J. , Käkönen Sanna-Maria , Astermark Jan , Lilja Hans , Lövgren Timo , Åkesson Kristina , Pettersson Kim 
Published: April 2006

Abstract
We assessed the serum concentration of γ-carboxylated osteocalcin (OC), total OC, and full-length OC in a clinical setting of 37 patients on continuous warfarin treatment (international normalized ratio 2.0–3.8). A comparison was done with the results from 30 untreated age-matched controls. Four monoclonal antibodies, previously generated and characterized as to their ability to recognize different human OC forms and fragments, were used in three two-site immunofluorometric assays. The warfarin-treated patients had significantly lower levels of carboxylated OC 4.9 ± 3.8 (± 1 SD) ng/ml compared with the controls 13.1 ± 9.7 (p &lt; 0.0001). There was no difference in the levels of total OC or full-length OC between the two groups of patients. A strong correlation was found between the serum concentration of carboxylated OC and total OC, both for the warfarin-treated patients (r = 0.98) and for the controls (r = 0.99). There was a distinct cut-off level at 0.80, in the quotient carboxylated OC/total OC, at which all warfarin-treated patients fell below and all controls above this level. Hence, the concentration or ratio of serum γ-carboxylated OC in clinical settings such as warfarin-treated patients could be measured using two-site immunoassays.
Longitudinal Study of Calcium Intake, Physical Activity, and Bone Mineral Content in Infants 6–18 Months of Age
Authors: Specker Bonny L. , Mulligan Lizanne , Ho Mona 
Published: April 2006

Abstract
Although increased physical activity early in life is recommended for optimizing bone health, no controlled trials on the effect of activity on bone mass accretion during periods of rapid growth have been reported. The purpose of this study was to determine whether infants randomized to a 1 year gross motor activity program had a greater bone mass accretion than infants randomized to a fine motor activity program. The gross motor program included activities that focused on loading the skeleton and were performed for 15–20 minutes/day, 5 days/week by study personnel. Infants (n = 72) were enrolled at 6 months of age, and total body bone mineral content (BMC), 3-day diet records, and activity levels were obtained at 6, 9, 12, 15, and 18 months. BMC was associated with weight, length, and bone area at all ages and correlated with earlier calcium intakes. Calcium intake appeared to modify the effect of gross motor activity on bone mass accretion; infants in both groups had similar bone accretion at moderately high calcium intakes, but at low calcium intakes infants in the gross motor program had less bone accretion than infants in the fine motor program. Compliant infants in the gross motor group had lower BMC at 18 months compared with noncompliant infants. These results indicate that BMC in infants is related to calcium intake, and we speculate that participation in a gross motor program during rapid bone growth may lead to reduced bone accretion in the presence of a moderate to moderately low calcium intake.
Dietary Calcium and Bone Density in Adolescent Girls and Young Women in Europe
Authors: Kardinaal A. F. M. , Ando S. , Charles P. , Charzewska J. , Rotily M. , Väänänen K. , Van erp-baart A. M. J. , Heikkinen J. , Thomsen J. , Maggiolini M. , Deloraine A. , Chabros E. , Juvin R. , Schaafsma G. 
Published: April 2006

Abstract
The objective of this study was to investigate the association between dietary calcium intake and radial bone density among young women, over the whole range of intake and at different levels of calcium intake. The study design was a cross-sectional, observational multicenter investigation in six European countries. One thousand one hundred and sixteen healthy Caucasian girls aged 11–15 years and 526 women aged 20–23 years participated, after having been selected from larger population samples to represent a large range in calcium intake. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at the ultradistal and middistal radius. Calcium intake was assessed with 3-day food records. Other potential determinants of BMD were measured by anthropometry or questionnaires. Mean calcium intake among the girls varied between 609 mg/day in Italy and 1267 mg/day in Finland; intakes for women were in a similar range. After adjustment for height, weight, and age at menarche for the women, and adjustment for age, height, weight, Tanner stage, and bone area for the girls, radial BMD at both sites did not significantly vary among quartiles of calcium intakes for both age groups. In multivariate linear regression, calcium was weakly positively associated with BMD at both sites in the girls (per 100 mg of calcium: β = 0.57 mg/cm2, p = 0.03 for middistal BMD and β = 0.56 mg/cm2, p = 0.01 for ultradistal BMD). For middistal BMD, the association was observed predominantly in premenarcheal girls. The associations were no longer statistically significant after full adjustment for all determinants of BMD, except again in pre-menarcheal girls. Radial BMD in the women was not associated with calcium intake, except after full adjustment for determinants of BMD, when ultradistal BMD became inversely associated with calcium intake (per 100 mg β = −1.02, p = 0.03); this finding was due to results in one of the countries and not found in other countries. There was no evidence for a different relation between calcium and BMD at different levels of intake; although there was a positive association at calcium intake levels &lt;600 mg/day, the interaction was not significant and there was no consistent trend over intake categories. These results do not support the hypothesis that dietary calcium is a determinant of peak BMD in European women, for a wide range of intake. This study does not provide evidence that Recommended Dietary Allowances for calcium should be increased.
Ovariectomized Murine Model of Postmenopausal Calcium Malabsorption
Authors: Kalu Dike N. , Chen Cang 
Published: April 2006

Abstract
Two experiments were carried out to examine whether the ovariectomized mouse is a potential in vivo model of intestinal calcium malabsorption as occurs in postmenopausal osteoporosis. In the first experiment, we compared the effects of ovariectomy and 17β-estradiol (E2) therapy on calcium absorption in C3H/HeJ (C3H) and C57BL/6J (C57BL) mice, which have high and low peak bone mass, respectively. For each strain of mice, three groups were studied: sham operated, ovariectomized, (OVX), and OVX + E2 (60 μg/kg of body weight [bw]/day). Therapy was continued for 35 days and calcium absorption measured. In the C3H mice, ovariectomy caused an increase in fecal calcium (17.6%), and a decrease in the amount (12.8%) and percentage (12.5%) of calcium absorbed. The decrease was prevented by E2 therapy, but the differences in the calcium absorption parameters among the groups were not statistically significant. In contrast, in the C57BL mice, ovariectomy caused a marked increase in fecal calcium (84.5%, p &lt; 0.01), and a marked decrease in the amount (55%, p &lt; 0.01) and percentage (34.8%, p &lt; 0.001) of calcium absorbed, and the decrease in the percentage of calcium absorbed was partially prevented by E2 therapy (p &lt; 0.05). In experiment 2, a dose-response study of the effects of E2 therapy on calcium absorption in OVX C57BL mice was carried out. Five groups of mice were studied: Group 1, sham operated; Group 2, OVX; Group 3, OVX + 60 μg of E2/kg of bw/day; Group 4, OVX + 120 μg of E2/kg of bw/day; Group 5, OVX + 240 μg of E2/kg of bw/day. Therapy was continued for 28 days and calcium absorption measured. Ovariectomy caused a marked increase in fecal calcium (50%, p &lt; 0.0001) and urinary calcium (31%, p &lt; 0.0001) and a marked decrease in calcium absorption (44.9%, p &lt; 0.0001), and these changes were prevented by E2 therapy. The highest level of calcium absorption (109%, p &lt; 0.0001, vs. OVX) was observed in the 120 μg of E2 group. Ovariectomy and E2 slightly increased plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) levels but there was no significant correlation between 1,25(OH)2D levels and calcium absorption. The findings in the C57BL mice suggest that estrogen is a physiological regulator of calcium absorption in this strain of mice. Furthermore, these findings share many characteristics with intestinal calcium malabsorption and its reversal by estrogen therapy in hypoestrogenic women. We propose that the OVX C57BL mice warrants further characterization as a potential animal model for investigating issues related to calcium malabsorption in postmenopausal women.
Changes in Bone Resorption During the Menstrual Cycle
Authors: Chiu Kit Mui , Ju Julia , Mayes Darrel , Bacchetti Peter , Weitz Steve , Arnaud Claude D. 
Published: April 2006

Abstract
To determine if the cyclic changes of female sex hormones during the menstrual cycle are related to changes in bone formation and resorption, we measured serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC) and bone resorption markers, serum and urine deoxypyridinoline (Dpyr), three times per week during one menstrual cycle in 20 healthy premenopausal women. Serum estradiol (E2) and progesterone (P) showed characteristic cyclic fluctuations. Serum Dpyr was higher during the follicular phase (FP) than in the luteal phase (p = 0.027). Serum BAP, OC, and urine Dpyr levels did not change substantially across the cycle. Serum Dpyr correlated negatively with serum E2 values measured 6 (p = 0.011) and 8 (p = 0.001) days earlier and with P measured concurrently (p = 0.033) 2 (p = 0.002), 4 (p = 0.003), and 6 (p = 0.014) days earlier. BAP correlated negatively with E2 measured 6 days earlier (p = 0.006). We found no statistically significant correlations of E2 or P with OC or urine Dpyr within women over their cycles. BAP was positively correlated with concurrent serum Dpyr (p = 0.015) during the menstrual cycle. Serum OC levels correlated inversely with age (rs = −0.48, p = 0.036). Women with higher mean urine Dpyr levels had higher mean serum OC levels (rs = 0.49, p = 0.033) and showed a trend toward lower hip bone mineral density (rs = −0.40, p = 0.078). We conclude that the low level of E2 and/or P observed during the FP of the normal menstrual cycle is associated with increased bone resorption. These relationships suggest that normal women experience monthly episodes of increased bone resorption from menarche to menopause.
Does Combining the Results from Multiple Bone Sites Measured by a New Quantitative Ultrasound Device Improve Discrimination of Hip Fracture?
Authors: Dr. Hans D. , Srivastav S. K. , Singal C. , Barkmann R. , Njeh C. F. , Kantorovich E. , Glüer C. C. , Genant H. K. 
Published: April 2006

Abstract
There is a growing interest in the use of quantitative ultrasound (QUS) measurements as an alternative to current radiation-based bone densitometry techniques for the noninvasive assessment of fracture risk. While most of the commercialized ultrasound devices measure only single predefined peripheral skeletal sites, the Omnisense prototype (Sunlight Ltd., Israel) can be used on multiple bones, including the spinous processes. In this study, we examined the ability of speed of sound measured at the calcaneus, distal third and ultradistal radius, proximal third phalanx, metacarpal, capitate, patella, and the posterior process of the thoracic spine to differentiate subjects with hip fractures from normal controls. Seventy-nine postmenopausal Caucasian Israeli women who had sustained an atraumatic fracture of the proximal femur within the last 6 months were recruited from the local population (mean age 80 ± 8.9 years). As controls, 295 postmenopausal Caucasian Israeli women without osteoporotic fractures were also included (mean age 70 ± 8.7 years). Discrimination of hip fractures with QUS at all ultrasound sites was highly statistically significant (p &lt; 0.01) (odds ratios [ORs] = 1.4–3.0; area under the ROC curve [AUC] 77–92%), except for the hand metacarpal. Distal radius and calcaneus measurements (ORs = 2.4 and 3.0) were the best discriminators of hip fracture patients from controls. Using a forward selective linear regression model, the discriminator values of combined assessment at two sites were investigated. There was moderate improvement in diagnostic value, but the best combination was the calcaneus with the distal radius, which improved the AUC by 3% and raised both the sensitivity and specificity to 94%. These data demonstrate the encouraging potential of improving discrimination of hip fracture by using multiple-site ultrasonic measurements.
Role of Osteopontin in Bone Remodeling Caused by Mechanical Stress
Authors: Terai Kunihiro , Takano-Yamamoto Teruko , Ohba Yasuo , Hiura Kenji , Sugimoto Mizuo , Sato Motohiko , Kawahata Hirohisa , Inaguma Naohiro , Kitamura Yukihiko , Nomura Shintaro 
Published: April 2006

Abstract
Changes in the number and proportion of osteopontin mRNA (Opn) expressing osteocytes and osteoclasts caused by the mechanical stress applied during experimental tooth movement were examined in the present study. Opn expression was detected in the osteocytes on the pressure side at the early stage, and gradually spread to those on the tension side and also to the osteoblasts and bone-lining cells in the alveolar bone. Only 3.3% of the osteocytes located on the pressure side expressed Opn in the interradicular septum of control rats; in contrast, the value was increased to 87.5% at 48 h after the initiation of tooth movement. These results indicate that these cells responded to mechanical stress loaded on the bone with expression of the osteopontin gene. Following the increased expression of Opn in these cells, a 17-fold greater number of osteoclasts compared with the control and numerous resorption pits were observed on the pressure side of the alveolar bone. Injection of arginine-glycine-aspartic acid-serine peptide but not that of arginine-glycine-glutamic acid-serine peptide strongly inhibited the increase in the number of osteoclasts. Furthermore, an in vitro migration assay demonstrated the chemotactic activity of osteopontin (OPN) on the precursor of osteoclasts. Our study strongly suggests that OPN is an important factor triggering bone remodeling caused by mechanical stress.
No Evidence for Mutations in the Calcium-Sensing Receptor Gene in Sporadic Parathyroid Adenomas
Authors: Cetani Filomena , Pinchera Aldo , Pardi Elena , Cianferotti Luisella , Vignali Edda , Picone Antonella , Miccoli Paolo , Viacava Paolo , Marcocci Claudio 
Published: April 2006

Abstract
Inactivating mutations of the calcium-sensing receptor gene (CaR) might explain abnormalities in the regulation of both parathyroid cell proliferation and parathyroid hormone secretion. In a previous study, using RNAse A protection assay, no mutations were identified in a series of parathyroid specimens from patients with primary and secondary hyperparathyroidism, but the analysis was incomplete, since part of exon 6 could not be analyzed. In the present study, we examined the presence of mutations in the CaR gene in 20 parathyroid adenomas using direct sequencing. The entire coding region of the CaR gene was successfully amplified by polymerase chain reaction and directly sequenced. This analysis did not identify CaR gene mutations in any tumors studied. A polymorphism that encoded a single amino acid change (Ala826Thr) was identified in 4 parathyroid adenomas and in 8 of 50 normal unrelated subjects. Loss of heterozygosity studies were also performed on adenomas using markers for the locus of the CaR gene on chromosome 3q. No allelic loss was demonstrated. In conclusion, our results extend previous observation and suggest that clonal somatic mutations of the CaR gene and allelic loss at the CaR locus on chromosome 3q do not play a major role in the pathogenesis of sporadic parathyroid tumors.
Matrix Vesicle Plasma Cell Membrane Glycoprotein-1 Regulates Mineralization by Murine Osteoblastic MC3T3 Cells
Authors: Johnson Kristen , Moffa Allison , Chen Ying , Pritzker Kenneth , Goding James , Terkeltaub Robert 
Published: April 2006

Abstract
A naturally occurring nonsense truncation mutation of the inorganic pyrophosphate (PPi)-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) PC-1 is associated with spinal and periarticular ligament hyperostosis and cartilage calcification in “tiptoe walking” (ttw) mice. Thus, we tested the hypothesis that PC-1 acts directly in the extracellular matrix to restrain mineralization. Cultured osteoblastic MC3T3 cells expressed PC-1 mRNA and produced hydroxyapatite deposits at 12–14 days. NTPPPH activity increased steadily over 14 days. Transforming growth factor-β and 1,25-dihydroxyvitamin D3 increased PC-1 and NTPPPH in matrix vesicles (MVs). Because PC-1/NTPPPH was regulated in mineralizing MC3T3 cells, we stably transfected or infected cells with recombinant adenovirus, in order to express 2- to 6-fold more PC-1. PC-1/NTPPPH and PPi content increased severalfold in MVs derived from cells transfected with PC-1. Furthermore, MC3T3 cells transfected with PC-1 deposited ∼80–90% less hydroxyapatite (by weight) than cells transfected with empty plasmid or enzymatically inactive PC-1. ATP-dependent45Ca precipitation by MVs from cells overexpressing active PC-1 was comparably diminished. Thus, regulation of PC-1 controls the PPi content and function of osteoblast-derived MVs and matrix hydroxyapatite deposition. PC-1 may provide a novel therapeutic target in certain disorders of bone mineralization.
Isolation and Characterization of MC3T3-E1 Preosteoblast Subclones with Distinct In Vitro and In Vivo Differentiation/Mineralization Potential
Authors: Wang Dian , Christensen Kurt , Chawla Kanwal , Xiao Guozhi , Krebsbach Paul H. , Dr. Franceschi Renny T. 
Published: April 2006

Abstract
A series of subclonal cell lines with high or low differentiation/mineralization potential after growth in the presence of ascorbic acid (AA) were derived from murine MC3T3-E1 cells. Subclones were characterized in terms of their ability to mineralize a collagenous extracellular matrix both in vitro and in vivo and express osteoblast-related genes. When compared with nonmineralizing cells, mineralizing subclones selectively expressed mRNAs for the osteoblast markers, bone sialoprotein (BSP), osteocalcin (OCN), and the parathyroid hormone (PTH)/parathyroid hormone-related protein (PTHrP) receptor. In contrast, alkaline phosphatase mRNA was present in certain nonmineralizing as well as mineralizing subclones, suggesting that its expression may be subject to different controls from other osteoblast markers. Only highly differentiating subclones exhibited strong AA-dependent induction of a transiently transfected OCN promoter-luciferase reporter gene, indicating that there was a good correlation between mRNA levels and transcriptional activity. Consistent with its postulated role in biomineralization, BSP as measured by Western blotting was only present in mineralizing subclones. After implantation into immunodeficient mice, highly differentiating subclones formed bone-like ossicles resembling woven bone, while poorly differentiating cells only produced fibrous tissue. Interestingly, subclones with both high and low differentiation potential produced similar amounts of collagen in culture and expressed comparable basal levels of mRNA encoding Osf2/Cbfa1, an osteoblast-related transcription factor. Although some strongly differentiating cells exhibited a modest AA-dependent up-regulation of Osf2/Cbfa1 mRNA, there was no clear relationship between levels of this message and induction of mRNAs for other differentiation markers. Thus, the mere presence of Osf2/Cbfa1 in a subclone was not sufficient for osteoblast differentiation. These subclones will be very useful for studying critical events in osteoblast differentiation and mineralization.