scholarly journals Gender-Specific Changes in Bone Turnover and Skeletal Architecture in Igfbp-2-Null Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2051-2061 ◽  
Author(s):  
V. E. DeMambro ◽  
D. R. Clemmons ◽  
L. G. Horton ◽  
M. L. Bouxsein ◽  
T. L. Wood ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Volume Fraction ◽  
Fold Increase ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Volume Fraction ◽  
Independent Manner ◽  
Insulin Resistant ◽  
Tensin Homolog ◽  
Igf I

IGF-binding protein-2 (IGFBP-2) is a 36-kDa protein that binds to the IGFs with high affinity. To determine its role in bone turnover, we compared Igfbp2−/− mice with Igfbp2+/+ colony controls. Igfbp2−/− males had shorter femurs and were heavier than controls but were not insulin resistant. Serum IGF-I levels in Igfbp2−/− mice were 10% higher than Igfbp2+/+ controls at 8 wk of age; in males, this was accompanied by a 3-fold increase in hepatic Igfbp3 and Igfbp5 mRNA transcripts compared with Igfbp2+/+ controls. The skeletal phenotype of the Igfbp2−/− mice was gender and compartment specific; Igfbp2−/− females had increased cortical thickness with a greater periosteal circumference compared with controls, whereas male Igfbp2−/− males had reduced cortical bone area and a 20% reduction in the trabecular bone volume fraction due to thinner trabeculae than Igfbp2+/+ controls. Serum osteocalcin levels were reduced by nearly 40% in Igfbp2−/− males, and in vitro, both CFU-ALP+ preosteoblasts, and tartrate-resistant acid phosphatase-positive osteoclasts were significantly less abundant than in Igfbp2+/+ male mice. Histomorphometry confirmed fewer osteoblasts and osteoclasts per bone perimeter and reduced bone formation in the Igfbp2−/− males. Lysates from both osteoblasts and osteoclasts in the Igfbp2−/− males had phosphatase and tensin homolog (PTEN) levels that were significantly higher than Igfbp2+/+ controls and were suppressed by addition of exogenous IGFBP-2. In summary, there are gender- and compartment-specific changes in Igfbp2−/− mice. IGFBP-2 may regulate bone turnover in both an IGF-I-dependent and -independent manner.

Estimation of an early meaningful time point of bone parameter changes in application to an osteoporotic rat model with in vivo microcomputed tomography measurements

2012 ◽  
Vol 46 (3) ◽  
pp. 237-244 ◽  
Author(s):  
Annekathrin Martina Keiler ◽  
Oliver Zierau ◽  
Günter Vollmer ◽  
Dieter Scharnweber ◽  
Ricardo Bernhardt
Keyword(s):  
Bone Turnover ◽  
Volume Fraction ◽  
Expression Profiles ◽  
Lumbar Vertebrae ◽  
Microcomputed Tomography ◽  
Bone Volume ◽  
Marker Genes ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Bone Volume Fraction

The commonly used preclinical animal model of postmenopausal osteoporosis is the mature ovariectomized rat, whereby cessation of ovarian oestrogen production consequently results in bone volume reduction. The study aim was to precisely define the time course of structural changes resulting from ovariectomy and thereby reduce the time animals have to be treated to judge the effects of osteoporosis treatment. For this purpose, we assessed architectural changes by microcomputed tomography ( μCT) during 10 weeks following ovariectomy or sham surgery at two-week intervals. Moreover, the trabecular microarchitecture of the lumbar vertebrae was assessed after necropsy. Besides this, serum biomarkers of bone turnover were determined. These data were in a new approach additionally correlated to femur mRNA expression profiles. We selected the osteoblast marker genes osteocalcin and type I collagen as well as the two osteoclast marker genes cathepsin k and tartrate-resistant acid phosphatase 5. The gene expression analysis suggested an activation of osteoblasts as well as octeoclasts. The significantly induced serum levels of osteocalcin and collagen degradation fragments also revealed this higher rate of bone turnover. Our results indicate that as soon as four weeks after ovariectomy the bone volume fraction exhibited a decline of 30% and 50% of the connectivity density. In addition, significant decreases of trabecular number and thickness as well as of the bone volume fraction were only observed in vertebrae of ovariectomized animals. Interestingly, changes of trabecular morphology were also found in the sham animals as a consequence of senescence.

scholarly journals Pharmacodynamics of Trovafloxacin and Levofloxacin against Bacteroides fragilis in an In Vitro Pharmacodynamic Model

2002 ◽  
Vol 46 (1) ◽  
pp. 203-210 ◽  
Author(s):  
M. L. Peterson ◽  
L. B. Hovde ◽  
D. H. Wright ◽  
G. H. Brown ◽  
A. D. Hoang ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Bacteroides Fragilis ◽  
Fold Increase ◽  
Independent Manner ◽  
Time Curve ◽  
Resistant Strains ◽  
Vitro Model ◽  
Kill Curve ◽  
Selection Of

ABSTRACT An in vitro pharmacodynamic investigation was conducted to explore whether the area under the concentration time curve from 0 to 24 h (AUC0–24)/MIC ratio could predict fluoroquinolone performance against Bacteroides fragilis. An in vitro model was used to generate kill curves for trovafloxacin (TVA) and levofloxacin (LVX) at AUC0–24/MIC ratios of 1 to 406 against three strains of B. fragilis (ATCC 25285, ATCC 23745, and clinical isolate M97-117). TVA and LVX were bolused prior to the start of experiments to achieve the corresponding AUC0–24/MIC ratio. Experiments were performed in duplicate over 24 h and in an anaerobic environment. Analyses of antimicrobial performance were conducted by comparing the rates of bacterial kill (K) using nonlinear regression analysis with 95% confidence intervals. Statistical significance was defined as a lack of overlap in the 95% confidence limits generated from the slope of each kill curve. For both TVA and LVX, K was maximized once an AUC0–24/MIC ratio of ≥40 was achieved and was not further increased despite a 10-fold increase in AUC0–24/MIC from approximately 40 to 400 against all three strains of B. fragilis. No significant differences were found in K between AUC0–24/MIC ratios of approximately 40 to 200. In experiments where AUC0–24/MIC ratios that were ≥ 5 and ≤ 44 were conducted, 64% demonstrated regrowth at 24 h. Resistant strains were selected in 50% of those experiments, demonstrating regrowth, which resulted in increased MICs of two- to 16-fold for both TVA and LVX. Regrowth did not occur, nor were resistant strains selected in any studies with an AUC/MIC that was > 44. Our findings suggest that fluoroquinolones provide antibacterial effects against B. fragilis in a concentration-independent manner associated with an AUC0–24/MIC ratio of ≥40. Also, the potential for the selection of resistant strains of B. fragilis may increase with an AUC0–24/MIC ratio of ≤44.

scholarly journals The effect of PPARγ inhibition on bone marrow adipose tissue and bone in C3H/HeJ mice

2019 ◽  
Vol 316 (1) ◽  
pp. E96-E105 ◽  
Author(s):  
Kerensa M. Beekman ◽  
Annegreet G. Veldhuis-Vlug ◽  
Albert van der Veen ◽  
Martin den Heijer ◽  
Mario Maas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Bone Turnover ◽  
Volume Fraction ◽  
Structural Parameters ◽  
Bone Volume ◽  
Peroxisome Proliferator ◽  
Bone Volume Fraction ◽  
Bone Marrow Adipose Tissue ◽  
Marrow Adipose Tissue

Bone marrow adipose tissue (BMAT) increases after menopause, and increased BMAT is associated with osteoporosis and prevalent vertebral fractures. Peroxisome proliferator-activated receptor-γ (PPARγ) activation promotes adipogenesis and inhibits osteoblastogenesis; therefore, PPARγ is a potential contributor to the postmenopausal increase in BMAT and decrease in bone mass. The aim of this study is to determine if PPARγ inhibition can prevent ovariectomy-induced BMAT increase and bone loss in C3H/HeJ mice. Fourteen-week-old female C3H/HeJ mice ( n = 40) were allocated to four intervention groups: sham surgery (Sham) or ovariectomy (OVX; isoflurane anesthesia) with either vehicle (Veh) or PPARγ antagonist administration (GW9662; 1 mg·kg−1·day−1, daily intraperitoneal injections) for 3 wk. We measured BMAT volume, adipocyte size, adipocyte number. and bone structural parameters in the proximal metaphysis of the tibia using polyoxometalate-based contrast enhanced-nanocomputed topogaphy. Bone turnover was measured in the contralateral tibia using histomorphometry. The effects of surgery and treatment were analyzed by two-way ANOVA. OVX increased the BMAT volume fraction (Sham + Veh: 2.9 ± 2.7% vs. OVX + Veh: 8.1 ± 5.0%: P < 0.001), average adipocyte diameter (Sham + Veh: 19.3 ± 2.6 μm vs. OVX + Veh: 23.1 ± 3.4 μm: P = 0.001), and adipocyte number (Sham + Veh: 584 ± 337cells/μm3 vs. OVX + Veh: 824 ± 113cells/μm3: P = 0.03), while OVX decreased bone volume fraction (Sham + Veh: 15.5 ± 2.8% vs. OVX + Veh: 7.7 ± 1.9%; P < 0.001). GW9662 had no effect on BMAT, bone structural parameters, or bone turnover. In conclusion, ovariectomy increased BMAT and decreased bone volume in C3H/HeJ mice. The PPARγ antagonist GW9662 had no effect on BMAT or bone volume in C3H/HeJ mice, suggesting that BMAT accumulation is regulated independently of PPARγ in C3H/HeJ mice.

scholarly journals Raloxifene administration enhances retention in an orthodontic relapse model

2020 ◽  
Vol 42 (4) ◽  
pp. 371-377
Author(s):  
Niloufar Azami ◽  
Po-Jung Chen ◽  
Shivam Mehta ◽  
Zana Kalajzic ◽  
Eliane H Dutra ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Volume Fraction ◽  
Orthodontic Tooth Movement ◽  
Bone Volume ◽  
Resin Cement ◽  
Control Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Volume Fraction ◽  
Tissue Density

Abstract Background and objectives Orthodontic relapse is a physiologic process that involves remodelling of the alveolar bone and principle periodontal ligament fibres. Raloxifene is an Food and Drug Administration (FDA)-approved selective oestrogen receptor modulator that inhibits systemic bone loss. In our study, we examined the effects of Raloxifene on alveolar bone modelling and orthodontic relapse in a rodent model. Materials and methods The efficacy of raloxifene was evaluated in 15-week-old male Wistar rats, 8 in each group (Control, Raloxifene, Raloxifene + 7-day relapse, Raloxifene + 14-day relapse) for a total of 42 days. All animals had 14 days of orthodontic tooth movement with a closed nickel–titanium coil spring tied from incisors to right first molar applying 5–8 gm of force. On the day of appliance removal, impression was taken with silicon material and the distance between first molar and second molar was filled with light-cured adhesive resin cement for retention phase. Raloxifene Retention, Raloxifene Retention + 7D, Raloxifene Retention + 14D groups received 14 daily doses of raloxifene (2.0 mg/kg/day) subcutaneously after orthodontic tooth movement during retention. After 14 days of retention, the retainer was removed and right first molar was allowed to relapse for a period of 14 days. Raloxifene injection continued for the Raloxifene + 14-day relapse group during relapse phase too. Control group received saline injections during retention. Animals were euthanized by CO2 inhalation. The outcome measure included percentage of relapse, bone volume fraction, tissue density, and histology analysis using tartrate-resistant acid phosphatase staining and determining receptor activator of nuclear factor-кB-ligand (RANKL) and osteoprotegerin expression. Results Raloxifene Retention + 14D group had significantly less (P &lt; 0.05) orthodontic relapse when compared with other groups. There was a significant increase (P &lt; 0.05) in bone volume fraction and tissue density in the Raloxifene Retention + 14D group when compared with other groups. Similarly, there was significant decrease in number of osteoclasts and RANKL expression in Raloxifene Retention + 14D group when compared with Raloxifene Retention + 7D group (P &lt; 0.05). Conclusion Raloxifene could decrease post-orthodontic treatment relapse by decreasing bone resorption and indirectly enhancing bone formation.

scholarly journals Voxel size dependency, reproducibility and sensitivity of an in vivo bone loading estimation algorithm

2016 ◽  
Vol 13 (114) ◽  
pp. 20150991 ◽  
Author(s):  
Patrik Christen ◽  
Friederike A. Schulte ◽  
Alexander Zwahlen ◽  
Bert van Rietbergen ◽  
Stephanie Boutroy ◽  
...  
Keyword(s):  
Volume Fraction ◽  
Estimation Algorithm ◽  
Bone Volume ◽  
Micro Ct ◽  
Bone Volume Fraction ◽  
Voxel Size ◽  
Size Dependency ◽  
Bone Loading

A bone loading estimation algorithm was previously developed that provides in vivo loading conditions required for in vivo bone remodelling simulations. The algorithm derives a bone's loading history from its microstructure as assessed by high-resolution (HR) computed tomography (CT). This reverse engineering approach showed accurate and realistic results based on micro-CT and HR-peripheral quantitative CT images. However, its voxel size dependency, reproducibility and sensitivity still need to be investigated, which is the purpose of this study. Voxel size dependency was tested on cadaveric distal radii with micro-CT images scanned at 25 µm and downscaled to 50, 61, 75, 82, 100, 125 and 150 µm. Reproducibility was calculated with repeated in vitro as well as in vivo HR-pQCT measurements at 82 µm. Sensitivity was defined using HR-pQCT images from women with fracture versus non-fracture, and low versus high bone volume fraction, expecting similar and different loading histories, respectively. Our results indicate that the algorithm is voxel size independent within an average (maximum) error of 8.2% (32.9%) at 61 µm, but that the dependency increases considerably at voxel sizes bigger than 82 µm. In vitro and in vivo reproducibility are up to 4.5% and 10.2%, respectively, which is comparable to other in vitro studies and slightly higher than in other in vivo studies. Subjects with different bone volume fraction were clearly distinguished but not subjects with and without fracture. This is in agreement with bone adapting to customary loading but not to fall loads. We conclude that the in vivo bone loading estimation algorithm provides reproducible, sensitive and fairly voxel size independent results at up to 82 µm, but that smaller voxel sizes would be advantageous.

scholarly journals Effect of cyclical forces on the periodontal ligament and alveolar bone remodeling during orthodontic tooth movement

2013 ◽  
Vol 84 (2) ◽  
pp. 297-303 ◽  
Author(s):  
Zana Kalajzic ◽  
Elizabeth Blake Peluso ◽  
Achint Utreja ◽  
Nathaniel Dyment ◽  
Jun Nihara ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Periodontal Ligament ◽  
Structural Integrity ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Volume Fraction ◽  
Tartrate Resistant Acid Phosphatase ◽  
Vibratory Stimulus ◽  
Bone Volume Fraction ◽  
Alveolar Bone Remodeling

ABSTRACT Objective: To investigate the effect of externally applied cyclical (vibratory) forces on the rate of tooth movement, the structural integrity of the periodontal ligament, and alveolar bone remodeling. Methods: Twenty-six female Sprague-Dawley rats (7 weeks old) were divided into four groups: CTRL (unloaded), VBO (molars receiving a vibratory stimulus only), TMO (molars receiving an orthodontic spring only), and TMO+VB (molars receiving an orthodontic spring and the additional vibratory stimulus). In TMO and TMO+VB groups, the rat first molars were moved mesially for 2 weeks using Nickel-Titanium coil spring delivering 25 g of force. In VBO and TMO+VB groups, cyclical forces at 0.4 N and 30 Hz were applied occlusally twice a week for 10 minutes. Microfocus X-ray computed tomography analysis and tooth movement measurements were performed on the dissected rat maxillae. Tartrate-resistant acid phosphatase staining and collagen fiber assessment were performed on histological sections. Results: Cyclical forces significantly inhibited the amount of tooth movement. Histological analysis showed marked disorganization of the collagen fibril structure of the periodontal ligament during tooth movement. Tooth movement caused a significant increase in osteoclast parameters on the compression side of alveolar bone and a significant decrease in bone volume fraction in the molar region compared to controls. Conclusions: Tooth movement was significantly inhibited by application of cyclical forces.

scholarly journals The Ginsenoside Exhibits Antiosteoporosis Effects in Ketogenic-Diet-Induced Osteoporosis via Rebalancing Bone Turnover

2021 ◽  
Vol 11 ◽  
Author(s):  
Qi Liu ◽  
Jian Zhou ◽  
Zhou Yang ◽  
Chuhai Xie ◽  
Yan Huang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Ketogenic Diet ◽  
Cancellous Bone ◽  
Volume Fraction ◽  
Cathepsin K ◽  
Tartrate Resistant Acid Phosphatase ◽  
Protective Effects ◽  
Bone Volume Fraction ◽  
Ppar Γ ◽  
Ginsenoside Rb2

Ginsenoside is widely used in China for therapeutic and healthcare practice. Ginsenoside-Rb2 shows the antiosteoporosis effects in ovariectomized rodents. However, the protective effects on osteoporosis induced by ketogenic diet (KD) remain unknown. Therefore, this study aimed at evaluating the effects of ginsenoside-Rb2 on KD-induced osteoporosis. Thirty mice were randomly divided into three groups: sham, KD, and KD + Rb2. Bone microstructures, biomechanical properties, concentrations of serum bone alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase (TRACP), and protein expression of osteocalcin (OCN), peroxisome proliferation-activated receptor γ (PPAR-γ), cathepsin K, and TRAP were evaluated after a 12-week intervention. The results show that KD induced significant bone loss and biomechanical impairment. Ginsenoside-Rb2 attenuated significant bone loss and maintained biomechanics in cancellous bone. The bone volume fraction increased from 2.3 to 6.0% in the KD + Rb2 group than that in the KD group. Meanwhile, ginsenoside-Rb2 effectively maintained biomechanical strengths in cancellous bone, increased serum BALP and decreased TRACP, and upregulated OCN and downregulated TRAP, PPAR-γ, and cathepsin K in the KD mice. This study demonstrated that ginsenoside-Rb2 retards bone loss and maintains biomechanics with KD. The underlying mechanism might be that ginsenoside-Rb2 inhibits bone resorption process and induces osteogenic differentiation, providing evidence for ginsenoside as being an alternative option for osteoporosis induced by KD.

scholarly journals Early-Onset Type 2 Diabetes Impairs Skeletal Acquisition in the Male TALLYHO/JngJ Mouse

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3806-3816 ◽  
Author(s):  
M. J. Devlin ◽  
M. Van Vliet ◽  
K. Motyl ◽  
L. Karim ◽  
D. J. Brooks ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Bone Mass ◽  
Early Onset ◽  
Volume Fraction ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Skeletal Acquisition

Abstract Type 2 diabetes (T2D) incidence in adolescents is rising and may interfere with peak bone mass acquisition. We tested the effects of early-onset T2D on bone mass, microarchitecture, and strength in the TALLYHO/JngJ mouse, which develops T2D by 8 weeks of age. We assessed metabolism and skeletal acquisition in male TALLYHO/JngJ and SWR/J controls (n = 8–10/group) from 4 weeks to 8 and 17 weeks of age. Tallyho mice were obese; had an approximately 2-fold higher leptin and percentage body fat; and had lower bone mineral density vs SWR at all time points (P &lt; .03 for all). Tallyho had severe deficits in distal femur trabecular bone volume fraction (−54%), trabecular number (−27%), and connectivity density (−82%) (P &lt; .01 for all). Bone formation was higher in Tallyho mice at 8 weeks but lower by 17 weeks of age vs SWR despite similar numbers of osteoblasts. Bone marrow adiposity was 7- to 50-fold higher in Tallyho vs SWR. In vitro, primary bone marrow stromal cell differentiation into osteoblast and adipocyte lineages was similar in SWR and Tallyho, suggesting skeletal deficits were not due to intrinsic defects in Tallyho bone-forming cells. These data suggest the Tallyho mouse might be a useful model to study the skeletal effects of adolescent T2D.

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