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 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.

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 Insulin Receptor Deletion in S100a4-lineage cells accelerates age-related bone loss

2018 ◽  
Author(s):  
Valentina Studentsova ◽  
Emma Knapp ◽  
Alayna E. Loiselle
Keyword(s):  
Insulin Receptor ◽  
Volume Fraction ◽  
Bone Cells ◽  
Torsional Rigidity ◽  
Bone Volume ◽  
Type I ◽  
Bone Homeostasis ◽  
Skeletal Health ◽  
Bone Volume Fraction ◽  
Age Related

AbstractType I and Type II Diabetes dramatically impair skeletal health. Altered Insulin Receptor (IR) signaling is a common feature of both diseases, and insulin has potent bone anabolic functions. Several previous studies have demonstrated that loss of IR in bone cells results in disrupted bone homeostasis during early post-natal growth. Here we have deleted IR in S100a4-lineage cells (IRcKOS100a4) and assessed the effects on bone homeostasis at both young (15 weeks) and older adult (48 weeks) mice. S100a4-cre has previously been shown to target the perichondrium during bone development, and here we show that S100a4 is expressed by adult trabecular and cortical bone cells, and that S100a4-Cre effectively targets adult bone, resulting in efficient deletion of IR. Deletion of IR in S100a4-lineage cells does effect initial bone acquisition or homeostasis with no changes in cortical, trabecular or mechanical properties at 15-weeks of age, relative to wild type (WT) littermates. However, by 48-weeks of age, IRcKOS100a4 mice display substantial declines in trabecular bone volume, bone volume fraction and torsional rigidity, relative to age-matched WT controls. This work establishes the utility of using S100a4-cre to target bone and demonstrates that IR in S100a4-lineage cells is required for maintenance of bone homeostasis in adult mice.

scholarly journals Effects of Bisphosphonate Administration on Cleft Bone Graft in a Rat Model

2017 ◽  
Vol 54 (6) ◽  
pp. 687-698 ◽  
Author(s):  
Nicole Cheng ◽  
Juyoung Park ◽  
Jeffrey Olson ◽  
Taewoo Kwon ◽  
Deborah Lee ◽  
...  
Keyword(s):  
Bone Graft ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Volume Fraction ◽  
Bone Grafts ◽  
Saline Group ◽  
Bone Volume ◽  
Systemic Administration ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Volume Fraction

Objective Bone grafts in patients with cleft lip and palate can undergo a significant amount of resorption. The aim of this study was to investigate the effects of bisphosphonates (BPs) on the success of bone grafts in rats. Design Thirty-five female 15-week-old Fischer F344 Inbred rats were divided into the following experimental groups, each receiving bone grafts to repair an intraoral CSD: (1) Graft/saline: systemic administration of saline and (2) systemic administration of zoledronic acid immediately following surgery (graft/BP/T0), (3) 1 week postoperatively (graft/BP/T1), and (4) 3 weeks postoperatively (graft/BP/T2). As an additional control, the defect was left empty without bone graft. Main Outcome Measures Microcomputed tomography and histologic analyses were performed in addition to evaluation of osteoclasts through tartrate-resistant acid phosphatase staining. Results Bone volume fraction (bone volume/tissue volume) for the delayed BP treatment groups (graft/BP/T1 = 45.4% ± 8.8%; graft/BP/T2 = 46.1% ± 12.4%) were significantly greater than that for the graft/saline group (31.0% ± 7.9%) and the graft/BP/T0 (27.6% ± 5.9%) 6 weeks postoperatively ( P < .05). Hematoxylin and eosin staining confirmed an evident increase in bone volume and fusion of defect margins with existing palatal bone in the graft/BP/T1 and graft/BP/T2 groups. The graft/BP/T0 group showed the lowest bone volume with signs of acute inflammation. Conclusions Delayed BP administration following cleft bone graft surgery led to significant increase in bone volume and integration compared with saline controls. However, BP injection immediately after the surgery did not enhance bone volume, and rather, may negatively affect bone graft incorporation.

scholarly journals Bone health in spacefaring rodents and primates: systematic review and meta-analysis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jingyan Fu ◽  
Matthew Goldsmith ◽  
Sequoia D. Crooks ◽  
Sean F. Condon ◽  
Martin Morris ◽  
...  
Keyword(s):  
Bone Formation ◽  
Trabecular Bone ◽  
Bone Health ◽  
Volume Fraction ◽  
Meta Analysis ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Bone Volume Fraction ◽  
Percentage Difference ◽  
Induced Changes

AbstractAnimals in space exploration studies serve both as a model for human physiology and as a means to understand the physiological effects of microgravity. To quantify the microgravity-induced changes to bone health in animals, we systematically searched Medline, Embase, Web of Science, BIOSIS, and NASA Technical reports. We selected 40 papers focusing on the bone health of 95 rats, 61 mice, and 9 rhesus monkeys from 22 space missions. The percentage difference from ground control in rodents was –24.1% [Confidence interval: −43.4, −4.9] for trabecular bone volume fraction and –5.9% [−8.0, −3.8] for the cortical area. In primates, trabecular bone volume fraction was lower by –25.2% [−35.6, −14.7] in spaceflight animals compared to GC. Bone formation indices in rodent trabecular and cortical bone were significantly lower in microgravity. In contrast, osteoclast numbers were not affected in rats and were variably affected in mice. Thus, microgravity induces bone deficits in rodents and primates likely through the suppression of bone formation.

scholarly journals Biaxial Normal Strength Behavior in the Axial-Transverse Plane for Human Trabecular Bone—Effects of Bone Volume Fraction, Microarchitecture, and Anisotropy

2013 ◽  
Vol 135 (12) ◽  
Author(s):  
Arnav Sanyal ◽  
Tony M. Keaveny
Keyword(s):  
Trabecular Bone ◽  
Volume Fraction ◽  
Elastic Anisotropy ◽  
Bone Volume ◽  
Transverse Plane ◽  
Mechanical Anisotropy ◽  
Bone Volume Fraction ◽  
Human Trabecular Bone ◽  
Strength Behavior ◽  
Normal Strength

The biaxial failure behavior of the human trabecular bone, which has potential relevance both for fall and gait loading conditions, is not well understood, particularly for low-density bone, which can display considerable mechanical anisotropy. Addressing this issue, we investigated the biaxial normal strength behavior and the underlying failure mechanisms for human trabecular bone displaying a wide range of bone volume fraction (0.06–0.34) and elastic anisotropy. Micro-computed tomography (CT)-based nonlinear finite element analysis was used to simulate biaxial failure in 15 specimens (5 mm cubes), spanning the complete biaxial normal stress failure space in the axial-transverse plane. The specimens, treated as approximately transversely isotropic, were loaded in the principal material orientation. We found that the biaxial stress yield surface was well characterized by the superposition of two ellipses—one each for yield failure in the longitudinal and transverse loading directions—and the size, shape, and orientation of which depended on bone volume fraction and elastic anisotropy. However, when normalized by the uniaxial tensile and compressive strengths in the longitudinal and transverse directions, all of which depended on bone volume fraction, microarchitecture, and mechanical anisotropy, the resulting normalized biaxial strength behavior was well described by a single pair of (longitudinal and transverse) ellipses, with little interspecimen variation. Taken together, these results indicate that the role of bone volume fraction, microarchitecture, and mechanical anisotropy is mostly accounted for in determining the uniaxial strength behavior and the effect of these parameters on the axial-transverse biaxial normal strength behavior per se is minor.

Architectural changes of trabecular bone caused by the remodeling process

2005 ◽  
Vol 874 ◽  
Author(s):  
Richard Weinkamer ◽  
Markus A. Hartmann ◽  
Yves Brechet ◽  
Peter Fratzl
Keyword(s):  
Trabecular Bone ◽  
Feedback Loop ◽  
Mechanical Response ◽  
Volume Fraction ◽  
Bone Volume ◽  
Bone Architecture ◽  
Mechanical Problem ◽  
Bone Volume Fraction ◽  
Obvious Effect ◽  
Trabecular Bone Architecture

AbstractUsing a stochastic lattice model we have studied the architectural changes of trabecular bone occurring while the structure is remodeled. Our model considers the mechanical feedback loop, which control the remodeling process. A fast algorithm was employed to solve approximately the mechanical problem. A general feature of the model is that a networklike structure emerges, which further coarsens while the bone volume fraction remains unchanged. Decreasing the mechanical response of the system by either lowering the external load or the internal mechano-sensitivity leads not only to a reduction of the bone volume fraction, but results in topological changes of the trabecular bone architecture, where the loss of horizontal trabeculae is the most obvious effect.

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