scholarly journals Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses

2011 ◽  
Vol 209 (1) ◽  
pp. 21-32 ◽  
Author(s):  
William F Powell ◽  
Kevin J Barry ◽  
Irena Tulum ◽  
Tatsuya Kobayashi ◽  
Stephen E Harris ◽  
...  
Keyword(s):  
Volume Fraction ◽  
Bone Structure ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Blood Calcium ◽  
Low Calcium Diet ◽  
Exon 1 ◽  
Skeletal Homeostasis ◽  
Pthrp Receptor

Parathyroid hormone (PTH) is a major physiologic regulator of calcium, phosphorous, and skeletal homeostasis. Cells of the osteoblastic lineage are key targets of PTH action in bone, and recent evidence suggests that osteocytes might be important in the anabolic effects of PTH. To understand the role of PTH signaling through the PTH/PTHrP receptors (PPR) in osteocytes and to determine the role(s) of these cells in mediating the effects of the hormone, we have generated mice in which PPR expression is specifically ablated in osteocytes. Transgenic mice in which the 10 kb-Dmp1 promoter drives a tamoxifen-inducible Cre-recombinase were mated with animals in which exon 1 of PPR is flanked by lox-P sites. In these animals, osteocyte-selective PPR knockout (Ocy-PPRcKO mice) could be induced by administration of tamoxifen. Histological analysis revealed a reduction in trabecular bone and mild osteopenia in Ocy-PPRcKO mice. Reduction of trabeculae number and thickness was also detected by micro-computed tomography analysis whereas bone volume fraction (BV/TV%) was unchanged. These findings were associated with an increase in Sost and sclerostin expression. When Ocy-PPRcKO mice were subjected to a low-calcium diet to induce secondary hyperparathyroidism, their blood calcium levels were significantly lower than littermate controls. Moreover, PTH was unable to suppress Sost and sclerostin expression in the Ocy-PPRcKO animals, suggesting an important role of PTH signaling in osteocytes for proper bone remodeling and calcium homeostasis.

Prediction of Mechanical Properties of the Cancellous Bone of the Mandibular Condyle

2003 ◽  
Vol 82 (10) ◽  
pp. 819-823 ◽  
Author(s):  
L.J. van Ruijven ◽  
E.B.W. Giesen ◽  
M. Farella ◽  
T.M.G.J. van Eijden
Keyword(s):  
Mechanical Properties ◽  
Cancellous Bone ◽  
Volume Fraction ◽  
Bone Structure ◽  
Structural Parameters ◽  
Mandibular Condyle ◽  
Element Model ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Apparent Stiffness

The mechanical properties of cancellous bone depend on the bone structure. The present study examined the extent to which the apparent stiffness of the cancellous bone of the human mandibular condyle can be predicted from its structure. Two models were compared. The first, a structure model, used structural parameters such as bone volume fraction and anisotropy to estimate the apparent stiffness. The second was a finite element model (FEM) of the cancellous bone. The bone structure was characterized by micro-computed tomography. The calculated stiffnesses of 24 bone samples were compared with measured stiffnesses. Both models could predict 89% of the variation in the measured stiffnesses. From the stiffness approximated by FEM in combination with the measured stiffness, the stiffness of the bone tissue was estimated to be 11.1 ± 3.2 GPa. It was concluded that both models could predict the stiffness of cancellous bone with adequate accuracy.

scholarly journals Structural strength of cancellous specimens from bovine femur under cyclic compression

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1562 ◽  
Author(s):  
Kaori Endo ◽  
Satoshi Yamada ◽  
Masahiro Todoh ◽  
Masahiko Takahata ◽  
Norimasa Iwasaki ◽  
...  
Keyword(s):  
Elastic Modulus ◽  
Yield Stress ◽  
Bone Strength ◽  
Cancellous Bone ◽  
Structural Model ◽  
Volume Fraction ◽  
Bone Structure ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Structural Deterioration

The incidence of osteoporotic fractures was estimated as nine million worldwide in 2000, with particular occurrence at the proximity of joints rich in cancellous bone. Although most of these fractures spontaneously heal, some fractures progressively collapse during the early post-fracture period. Prediction of bone fragility during progressive collapse following initial fracture is clinically important. However, the mechanism of collapse, especially the gradual loss of the height in the cancellous bone region, is not clearly proved. The strength of cancellous bone after yield stress is difficult to predict since structural and mechanical strength cannot be determineda priori. The purpose of this study was to identify whether the baseline structure and volume of cancellous bone contributed to the change in cancellous bone strength under cyclic loading. A total of fifteen cubic cancellous bone specimens were obtained from two 2-year-old bovines and divided into three groups by collection regions: femoral head, neck, and proximal metaphysis. Structural indices of each 5-mm cubic specimen were determined using micro-computed tomography. Specimens were then subjected to five cycles of uniaxial compressive loading at 0.05 mm/min with initial 20 N loading, 0.3 mm displacement, and then unloading to 0.2 mm with 0.1 mm displacement for five successive cycles. Elastic modulus and yield stress of cancellous bone decreased exponentially during five loading cycles. The decrease ratio of yield stress from baseline to fifth cycle was strongly correlated with bone volume fraction (BV/TV,r= 0.96,p< 0.01) and structural model index (SMI,r= − 0.81,p< 0.01). The decrease ratio of elastic modulus from baseline to fifth cycle was also correlated with BV/TV (r= 0.80,p< 0.01) and SMI (r= − 0.78,p< 0.01). These data indicate that structural deterioration of cancellous bone is associated with bone strength after yield stress. This study suggests that baseline cancellous bone structure estimated from adjacent non-fractured bone contributes to the cancellous bone strength during collapse.

scholarly journals Pancreas deficiency modifies bone development in the ovine fetus near term

2021 ◽  
Author(s):  
Stuart A Lanham ◽  
Dominique Blache ◽  
Richard Oc Oreffo ◽  
Abigail L Fowden ◽  
Alison J Forhead
Keyword(s):  
Mechanical Strength ◽  
Volume Fraction ◽  
Bone Structure ◽  
Plasma Concentrations ◽  
In Utero ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Fetal Sheep ◽  
Trabecular Thickness ◽  
Near Term

Hormones have an important role in the regulation of fetal growth and development, especially in response to nutrient availability in utero. Using micro-computed tomography and an electromagnetic 3-point bend test, this study examined the effect of pancreas removal at 0.8 fraction of gestation on the developing bone structure and mechanical strength in fetal sheep. When fetuses were studied at 10 and 25 days after surgery, pancreatectomy caused hypoinsulinaemia, hyperglycaemia and growth retardation which was associated with low plasma concentrations of leptin and a marker of osteoclast activity and collagen degradation. In pancreatectomised fetuses compared to control fetuses, limb lengths were shorter and trabecular bone in the metatarsi showed greater bone volume fraction, trabecular thickness, degree of anisotropy and porosity, and lower fractional bone surface area and trabecular spacing. Mechanical strength testing showed that pancreas deficiency was associated with increased stiffness and a greater maximal weight load at fracture in a subset of fetuses studied near term. Overall, pancreas deficiency in utero slowed growth of the fetal skeleton and adapted the developing bone to generate a more compact and connected structure. Maintenance of bone strength in growth-retarded limbs is especially important in a precocial species in preparation for skeletal loading and locomotion at birth.

scholarly journals Trabecular bone patterning in the hominoid distal femur

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5156 ◽  
Author(s):  
Leoni Georgiou ◽  
Tracy L. Kivell ◽  
Dieter H. Pahr ◽  
Matthew M. Skinner
Keyword(s):  
Trabecular Bone ◽  
Distal Femur ◽  
Volume Fraction ◽  
Reaction Force ◽  
Intraspecific Variability ◽  
Trabecular Structure ◽  
Trabecular Architecture ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Distal Epiphysis

BackgroundIn addition to external bone shape and cortical bone thickness and distribution, the distribution and orientation of internal trabecular bone across individuals and species has yielded important functional information on how bone adapts in response to load. In particular, trabecular bone analysis has played a key role in studies of human and nonhuman primate locomotion and has shown that species with different locomotor repertoires display distinct trabecular architecture in various regions of the skeleton. In this study, we analyse trabecular structure throughout the distal femur of extant hominoids and test for differences due to locomotor loading regime.MethodsMicro-computed tomography scans ofHomo sapiens(n= 11),Pan troglodytes(n= 18),Gorilla gorilla(n= 14) andPongosp. (n= 7) were used to investigate trabecular structure throughout the distal epiphysis of the femur. We predicted that bone volume fraction (BV/TV) in the medial and lateral condyles inHomowould be distally concentrated and more anisotropic due to a habitual extended knee posture at the point of peak ground reaction force during bipedal locomotion, whereas great apes would show more posteriorly concentrated BV/TV and greater isotropy due to a flexed knee posture and more variable hindlimb use during locomotion.ResultsResults indicate some significant differences between taxa, with the most prominent being higher BV/TV in the posterosuperior region of the condyles inPanand higher BV/TV and anisotropy in the posteroinferior region inHomo. Furthermore, trabecular number, spacing and thickness differ significantly, mainly separatingGorillafrom the other apes.DiscussionThe trabecular architecture of the distal femur holds a functional signal linked to habitual behaviour; however, there was more similarity across taxa and greater intraspecific variability than expected. Specifically, there was a large degree of overlap in trabecular structure across the sample, andHomowas not as distinct as predicted. Nonetheless, this study offers a comparative sample of trabecular structure in the hominoid distal femur and can contribute to future studies of locomotion in extinct taxa.

Bone and muscle development in three inbred female mouse strains

2021 ◽  
Author(s):  
Ursula Föger-Samwald ◽  
Maria Papageorgiou ◽  
Katharina Wahl-Figlash ◽  
Katharina Kerschan-Schindl ◽  
Peter Pietschmann
Keyword(s):  
Trabecular Bone ◽  
Muscle Development ◽  
Bone Growth ◽  
Volume Fraction ◽  
Bone Structure ◽  
Bone Development ◽  
Mouse Strains ◽  
Structural Reorganization ◽  
Bone Volume Fraction ◽  
Trabecular Thickness

AbstractMuscle force is thought to be one of the main determinants of bone development. Hence, peak muscle growth is expected to precede peak bone growth. In this study, we investigated muscle and bone development in female C57BL/6 J, DBA/2JRj, and C3H/HeOuJ mice. Femoral cortical and trabecular bone structure and the weights of selected muscles were assessed at the ages of 8, 16, and 24 weeks. Muscle mass increased from 8 to 24 weeks in all 3 strains, suggesting peak muscle development at 24 weeks or later. Bone volume fraction, trabecular number, and connectivity density of the femur decreased or remained unchanged, whereas trabecular density and trabecular thickness largely increased. These results suggest a peak in trabecular bone accrual at 8 weeks or earlier followed by further increases in density and structural reorganization of trabeculae. Cortical density, cortical thickness, and cortical cross sectional area increased over time, suggesting a peak in cortical bone accrual at 24 weeks or later. In conclusion, our data provide evidence that growth of muscle lags behind trabecular bone accrual.

scholarly journals Structure-Function Relationships of the Vertebral Endplate

2021 ◽  
Author(s):  
Yuanqiao Wu ◽  
Elise Feng-i Morgan ◽  
Johnfredy Loaiza ◽  
Rohin Banerji ◽  
Olivia Rose Blouin
Keyword(s):  
Mechanical Properties ◽  
Mechanical Behavior ◽  
Yield Stress ◽  
Volume Fraction ◽  
Level Density ◽  
Micro Computed Tomography ◽  
Vertebral Endplate ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Apparent Stiffness

Background: Although deformation and fracture of the vertebral endplate have been implicated in spinal conditions such as vertebral fracture and disc degeneration, few biomechanical studies of this structure are available. The goal of this study was to quantify the mechanical behavior of the vertebral endplate. Methods: Eight-five rectangular specimens were dissected from the superior and/or inferior central endplates of human lumbar spine segments L1-L4. Micro-computed tomography (μCT) imaging, four-point-bend testing, and ashing were performed to quantify the apparent elastic modulus and yield stress (modulus and yield stress, respectively, of the porous vertebral endplate), tissue yield stress (yield stress of the tissue of the vertebral endplate, excluding pores), ultimate strain, fracture strain, bone volume fraction (BV/TV), bone mineral density (BMD), and various measures of tissue density and composition (tissue mineral density, ash fraction, and ash density). Regression was used to assess the dependence of mechanical properties on density and composition. Results: Wide variations in elastic and failure properties, and in density and tissue composition, were observed. BMD and BV/TV were good predictors of many of the apparent-level mechanical properties, including modulus, yield stress, and in the case of the inferior vertebral endplate, failure strains. Similar values of the mechanical properties were noted between superior and inferior vertebral endplates. In contrast to the dependence of apparent stiffness and strength on BMD and BV/TV, none of the mechanical properties depended on any of the tissue-level density measurements. Conclusion: The dependence of many of the mechanical properties of the vertebral endplate on BV/TV and BMD suggests possibilities for non-invasive assessment of how this region of the spine behaves during habitual and injurious loading. Further study of the non-mineral components of the endplate tissue is required to understand how the composition of this tissue may influence the overall mechanical behavior of the vertebral endplate.

scholarly journals Quantifying Subresolution 3D Morphology of Bone with Clinical Computed Tomography

2019 ◽  
Vol 48 (2) ◽  
pp. 595-605 ◽  
Author(s):  
S. S. Karhula ◽  
M. A. J. Finnilä ◽  
S. J. O. Rytky ◽  
D. M. Cooper ◽  
J. Thevenot ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Statistical Model ◽  
Trabecular Bone ◽  
Volume Fraction ◽  
Ex Vivo ◽  
Bone Volume ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Model Combining ◽  
Occurrence Matrix

Abstract The aim of this study was to quantify sub-resolution trabecular bone morphometrics, which are also related to osteoarthritis (OA), from clinical resolution cone beam computed tomography (CBCT). Samples (n = 53) were harvested from human tibiae (N = 4) and femora (N = 7). Grey-level co-occurrence matrix (GLCM) texture and histogram-based parameters were calculated from CBCT imaged trabecular bone data, and compared with the morphometric parameters quantified from micro-computed tomography. As a reference for OA severity, histological sections were subjected to OARSI histopathological grading. GLCM and histogram parameters were correlated to bone morphometrics and OARSI individually. Furthermore, a statistical model of combined GLCM/histogram parameters was generated to estimate the bone morphometrics. Several individual histogram and GLCM parameters had strong associations with various bone morphometrics (|r| > 0.7). The most prominent correlation was observed between the histogram mean and bone volume fraction (r = 0.907). The statistical model combining GLCM and histogram-parameters resulted in even better association with bone volume fraction determined from CBCT data (adjusted R2 change = 0.047). Histopathology showed mainly moderate associations with bone morphometrics (|r| > 0.4). In conclusion, we demonstrated that GLCM- and histogram-based parameters from CBCT imaged trabecular bone (ex vivo) are associated with sub-resolution morphometrics. Our results suggest that sub-resolution morphometrics can be estimated from clinical CBCT images, associations becoming even stronger when combining histogram and GLCM-based parameters.

Effects of Active Vitamin D or FGF23 Antibody on Hyp Mice Dentoalveolar Tissues

2021 ◽  
pp. 002203452110110
Author(s):  
E.J. Lira dos Santos ◽  
M.B. Chavez ◽  
M.H. Tan ◽  
F.F. Mohamed ◽  
T.N. Kolli ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Volume Fraction ◽  
Fibroblast Growth Factor 23 ◽  
Neutralizing Antibody ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Treatment Regimens ◽  
New Therapeutic Approaches ◽  
Phex Gene

Mutations in the PHEX gene lead to X-linked hypophosphatemia (XLH), a form of inherited rickets featuring elevated fibroblast growth factor 23 (FGF23), reduced 1,25-dihydroxyvitamin D (1,25D), and hypophosphatemia. Hyp mutant mice replicate the XLH phenotype, including dentin, alveolar bone, and cementum defects. We aimed to compare effects of 1,25D versus FGF23-neutralizing antibody (FGF23Ab) monotherapies on Hyp mouse dentoalveolar mineralization. Male Hyp mice, either injected subcutaneously with daily 1,25D or thrice weekly with FGF23 blocking antibody from 2 to 35 d postnatal, were compared to wild-type (WT) controls and untreated Hyp mice. Mandibles were analyzed by high-resolution micro–computed tomography (micro-CT), histology, and immunohistochemistry. Both interventions maintained normocalcemia, increased serum phosphate levels, and improved dentoalveolar mineralization in treated versus untreated Hyp mice. 1,25D increased crown dentin volume and thickness and root dentin/cementum volume, whereas FGF23Ab effects were limited to crown dentin volume. 1,25D increased bone volume fraction, bone mineral density, and tissue mineral density in Hyp mice, whereas FGF23Ab failed to significantly affect these alveolar bone parameters. Neither treatment fully attenuated dentin and bone defects to WT levels, and pulp volumes remained elevated regardless of treatment. Both treatments reduced predentin thickness and improved periodontal ligament organization, while 1,25D promoted a more profound improvement in acellular cementum thickness. Altered cell densities and lacunocanalicular properties of alveolar and mandibular bone osteocytes and cementocytes in Hyp mice were partially corrected by either treatment. Neither treatment normalized the altered distributions of bone sialoprotein and osteopontin in Hyp mouse alveolar bone. Moderate improvements from both 1,25D and FGF23Ab treatment regimens support further studies and collection of oral health data from subjects receiving a newly approved anti-FGF23 therapy. The inability of either treatment to fully correct Hyp mouse dentin and bone prompts further experiments into underlying pathological mechanisms to identify new therapeutic approaches.

scholarly journals Contemporary clinical isolates of Staphylococcus aureus from pediatric osteomyelitis patients display unique characteristics in a mouse model of hematogenous osteomyelitis

2021 ◽  
Author(s):  
Philip M Roper ◽  
Kara R Eichelberger ◽  
Linda Cox ◽  
Luke O’Connor ◽  
Christine Shao ◽  
...  
Keyword(s):  
Septic Arthritis ◽  
Volume Fraction ◽  
Direct Injection ◽  
Clinical Isolates ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Musculoskeletal Infection ◽  
Joint Infections ◽  
Hematogenous Osteomyelitis ◽  
Direct Inoculation

Osteomyelitis can result from the direct inoculation of pathogens into bone during injury or surgery, or from spread via the bloodstream, a condition called hematogenous osteomyelitis (HOM). HOM disproportionally affects children, and more than half of cases are caused by Staphylococcus (S.) aureus . Laboratory models of osteomyelitis mostly utilize direct injection of bacteria into the bone or the implantation of foreign material, and therefore do not directly interrogate the pathogenesis of pediatric hematogenous osteomyelitis. In this study, we inoculated mice intravenously and characterized resultant musculoskeletal infections using two strains isolated from adults (USA300-LAC and NRS384) and five new methicillin-resistant S. aureus isolates from pediatric osteomyelitis patients. All strains were capable of creating stable infections over five weeks, although the incidence varied. Micro-computed tomography (microCT) analysis demonstrated decreases in trabecular bone volume fraction but little effect on bone cortices. Histologic assessment revealed differences in the precise focus of musculoskeletal infection, with varying mixtures of bone-centered osteomyelitis and joint-centered septic arthritis. Whole genome sequencing of three new isolates demonstrated distinct strains, two within the USA300 lineage and one USA100 isolate. Interestingly, this USA100 isolate showed a distinct predilection for septic arthritis, compared to the other isolates tested, including NRS384 and LAC, which more frequently led to osteomyelitis or mixed bone and joint infections. Collectively, these data outline the feasibility of using pediatric osteomyelitis clinical isolates to study the pathogenesis of HOM in murine models and lay the groundwork for future studies investigating strain-dependent differences in musculoskeletal infection.

Contributions of Trabecular Rods of Various Orientations in Determining the Elastic Properties of Human Vertebral Trabecular Bone

2007 ◽  
Author(s):  
Xiaowei S. Liu ◽  
X. Henry Zhang ◽  
Paul Sajda ◽  
Punam K. Saha ◽  
Felix W. Wehrli ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Trabecular Bone ◽  
Elastic Properties ◽  
Volume Fraction ◽  
Three Dimensional ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Human Trabecular Bone ◽  
Vertebral Trabecular Bone ◽  
Age Related

Osteoporosis is an age-related disease characterized by low bone mass and architectural deterioration. Other than bone volume fraction (BV/TV), microarchitecture of trabecular bone, such as trabecular type (rods or plates), connectivity, and orientation of the trabecular network is also believed to be important in governing the mechanical properties of trabecular bone. A recent study [1] showed that the microarchitecture alone affects elastic moduli of trabecular bone and, further, that trabecular plates make a far greater contribution than rods. In human vertebral trabecular bone, the roles of transverse vs. vertical rods in conferring mechanical properties of trabecular bone have been debated [2, 3]. It has been suggested that the role of transverse trabecular rod is critical in determining elastic modulus of vertebral trabecular bone. However, without explicit classifications of trabecular type, or orientation assessment at an individual trabecula level, it is not possible yet to test this hypothesis in human trabecular bone samples despite the development of three-dimensional (3D) micro computed tomography (μCT) and μCT based finite element (FE) models of human trabecular bone. With the newly developed technique of complete volumetric decomposition and individual trabecula based orientation analyses [4], now it is possible to quantitatively examine the contributions of trabecular rods of various orientations in the elastic properties of vertebral trabecular bone.

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