An In Silico Model for the Prediction of Changes in Mineral Density in Cortical Bone Remodeling

2019 ◽  
Vol 142 (1) ◽  
Author(s):  
Rafael R. Mattazio ◽  
Pedro Y. Noritomi ◽  
Zilda C. Silveira
Keyword(s):  
Parathyroid Hormone ◽  
Cortical Bone ◽  
Bone Remodeling ◽  
In Silico ◽  
Vigorous Physical Activity ◽  
Bone Matrix ◽  
Numerical Error ◽  
Mineral Density ◽  
In Silico Model ◽  
Proposed Model

Abstract An in silico model for the estimation of volumetric bone mineral density (vBMD) changes at a cortical bone site subjected to mechanobiological bone remodeling is proposed in this manuscript. Mechanisms of cell differentiation, receptor–ligand binding, mechanical signaling, and resorption or deposition of bone matrix were considered, therefore providing a comprehensive description of mechanobiological bone remodeling in the bone microenvironment and enabling the analysis of temporal evolution of disease or therapy scenarios. The proposed model is composed by five modules, namely, bone cells populations, mechanobiology, volume fractions and porosity, mineral density, and structural stiffness. The model is an extension of other models found in the literature because equations for the obtaining of cortical vBMD and the binding of parathyroid hormone (PTH) to parathyroid hormone 1 receptor are included. The proposed model showed a satisfactory agreement with the solutions of other in silico models found in the literature. Simulations of walking and running exercise routines were performed for the evaluation of model capability regarding the control of the numerical error and prediction of vBMD. The computational method used to solve the case study controlled the relative numerical error by less than 1 × 10−7 for approximately 1.7 × 106 time steps. The predicted values correlate with the concept of increasing BMD by vigorous physical activity; however, they contrast with the specific effect of physical activities on cortical vBMD.

scholarly journals Effects of Parathyroid Hormone, Alendronate and Odanacatib on the mineralisation process in intracortical and endocortical Haversian bone of ovariectomized rabbits

2018 ◽  
Author(s):  
Christina Vrahnas ◽  
Pascal R Buenzli ◽  
Thomas A Pearson ◽  
Brenda L Pennypacker ◽  
Mark J Tobin ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Cortical Bone ◽  
Bone Strength ◽  
Bone Matrix ◽  
Cathepsin K ◽  
Bone Composition ◽  
Carbonate Substitution ◽  
Matrix Maturation

AbstractAlthough cortical bone strength depends on optimal bone composition, the influences of standard therapeutic agents for osteoporosis on bone mineral accrual in cortical bone are not understood. This study compared effects on cortical bone composition of two current therapeutic approaches for osteoporosis: the anti-resorptive bisphosphonate alendronate (ALN), and anabolic intermittent parathyroid hormone (PTH). The experimental anti-resorptive cathepsin K inhibitor, odanacatib (ODN) which inhibits resorption without inhibiting bone formation, was also tested.To determine effects of these agents on Haversian remodeling and mineral accrual, we compared ALN (100μg/kg/2xweek), PTH(1-34) (15μg/kg, 5x/week) and ODN (7.5μM/day) administered for 10 months commencing 6 months after ovariectomy (OVX) in skeletally mature rabbits by histomorphometry. We used synchrotron-based Fourier-transform infrared microspectroscopy (sFTIRM), coupled to fluorochrome labelling, to measure maturation of the cortical matrix in situ at both endocortical and intracortical sites of bone formation.PTH and ODN, but not ALN, treatment increased bone toughness, and PTH treatment stimulated bone formation, not only on endocortical and periosteal bone, but also in intracortical pores. In Sham and OVX rabbits, normal matrix maturation was observed at both endocortical and intracortical sites including: mineral accrual (increasing mineral:matrix), carbonate substitution (carbonate:mineral) and collagen molecular compaction (amide I:II) in situ in endocortical and intracortical bone. ALN treatment reduced bone formation on these surfaces. In ALN-treated bone, while intracortical bone matured normally, endocortical bone did not show a significant increase in mineral:matrix. ODN treatment resulted in slower mineral accrual and limited carbonate substitution. While PTH-treatment did not modify matrix maturation in endocortical bone, the initial stages of mineral accrual were slower in intracortical bone.In conclusion, these three classes of therapy have differing effects on both bone formation, and the process of bone matrix maturation. ALN suppresses bone formation, and the normal process of matrix maturation in endocortical bone. ODN does not suppress bone formation, but limits mineral accrual. PTH stimulates bone formation, and the matrix formed matures normally in endocortical bone. The ability of PTH treatment to stimulate bone formation in intracortical bone may provide a novel additional mechanism by which PTH increases bone strength.

scholarly journals Raman spectroscopy reveals age- and sex-related differences in cortical bone from people with osteoarthritis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Michel K. Nieuwoudt ◽  
Rayomand Shahlori ◽  
Dorit Naot ◽  
Rhea Patel ◽  
Hannah Holtkamp ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Cortical Bone ◽  
Volume Fraction ◽  
Bone Matrix ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Male And Female ◽  
Health Lifestyle ◽  
Age Related ◽  
Age And Sex

Abstract Bone strength in human cortical bone is determined by the composition and structure of both the mineral and collagen matrices and influenced by factors such as age, gender, health, lifestyle and genetic factors. Age-related changes in the bone matrix are known to result in loss of mechanical strength and increased fragility. In this study we show how Raman spectroscopy, with its exquisite sensitivity to the molecular structure of bone, reveals new insights into age- and sex-related differences. Raman analysis of 18 samples of cortical hip bone obtained from people aged between 47–82 years with osteoarthritis (OA) found subtle changes in the lipid and collagen secondary structure, and the carbonate (CO32−) and phosphate (PO43−) mineral ratios in the bone matrix. Significant differences were observed between older and younger bones, and between older female and older male bones; no significant differences were observed between younger male and female bones. Older female bones presented the lowest mineral to matrix ratios (MMR) and highest CO32−/PO43− ratios, and relative to lipid/collagen –CH2 deformation modes at 1450 cm−1 they had lowest overall mineral content, higher collagen cross linking and lipid content but lower levels of α-helix collagen structures than older male and younger male and female bones. These observations provided further insight on bone composition changes observed in the bone volume fraction (BV/TV) for the older female bones from microCT measurements on the same samples, while tissue mineral density (TMD) measurements had shown no significant differences between the samples.

scholarly journals The calcium-sensing receptor complements parathyroid hormone-induced bone turnover in discrete skeletal compartments in mice

2012 ◽  
Vol 302 (7) ◽  
pp. E841-E851 ◽  
Author(s):  
Yingben Xue ◽  
Yongjun Xiao ◽  
Jingning Liu ◽  
Andrew C. Karaplis ◽  
Martin R. Pollak ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Turnover ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Bone Mineral ◽  
Bone Volume ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

Although the calcium-sensing receptor (CaSR) and parathyroid hormone (PTH) may each exert skeletal effects, it is uncertain how CaSR and PTH interact at the level of bone in primary hyperparathyroidism (PHPT). Therefore, we simulated PHPT with 2 wk of continuous PTH infusion in adult mice with deletion of the PTH gene ( Pth−/− mice) and with deletion of both PTH and CaSR genes ( Pth−/−- Casr −/− mice) and compared skeletal phenotypes. PTH infusion in Pth−/− mice increased cortical bone turnover, augmented cortical porosity, and reduced cortical bone volume, femoral bone mineral density (BMD), and bone mineral content (BMC); these effects were markedly attenuated in PTH-infused Pth−/−- Casr−/− mice. In the absence of CaSR, the PTH-stimulated expression of receptor activator of nuclear factor-κB ligand and tartrate-resistant acid phosphatase and PTH-stimulated osteoclastogenesis was also reduced. In trabecular bone, PTH-induced increases in bone turnover, trabecular bone volume, and trabecular number were lower in Pth−/−- Casr−/− mice than in Pth−/− mice. PTH-stimulated genetic markers of osteoblast activity were also lower. These results are consistent with a role for CaSR in modulating both PTH-induced bone resorption and PTH-induced bone formation in discrete skeletal compartments.

scholarly journals Distinctive anabolic roles of 1,25-dihydroxyvitamin D3 and parathyroid hormone in teeth and mandible versus long bones

2009 ◽  
Vol 203 (2) ◽  
pp. 203-213 ◽  
Author(s):  
Hong Liu ◽  
Jian Guo ◽  
Lin Wang ◽  
Ning Chen ◽  
Andrew Karaplis ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Secondary Hyperparathyroidism ◽  
Alveolar Bone ◽  
Bone Matrix ◽  
Long Bones ◽  
Wild Type ◽  
Mineral Density ◽  
Dihydroxyvitamin D3 ◽  
Reparative Dentin

To assess the roles of 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) in hard tissue formation in oro-facial tissues, we examined the effect of either 1,25(OH)2D or PTH deficiency on dentin and dental alveolar bone formation and mineralization in the mandibles, and osteoblastic bone formation in long bones of 1α-hydroxylase knockout (1α(OH)ase−/−) mice. Compared with wild-type mice, the mineral density was decreased in the teeth and mandibles, and unmineralized dentin (predentin and biglycan immunopositive dentin) and unmineralized bone matrix in the dental alveolar bone were increased in 1α(OH)ase−/− mice. The dental volume, reparative dentin volume, and dentin sialoprotein immunopositive areas were reduced in 1α(OH)ase−/− mice. The cortical thickness, dental alveolar bone volume, and osteoblast number were all decreased significantly in the mandibles; in contrast, the osteoblast number and surface were increased in the trabecular bone of the tibiae in 1α(OH)ase−/− mice consistent with their secondary hyperparathyroidism. The expression of PTH receptor and IGF1 was reduced slightly in mandibles, but enhanced significantly in the long bones in the 1α(OH)ase−/− mice. To control for the role of secondary hyperparathyroidism, we also examined teeth and mandibles in 6-week-old PTH−/− mice. In these animals, dental and bone volumes in mandibles were not altered when compared with their wild-type littermates. These results suggest that 1,25(OH)2D3 plays an anabolic role in both dentin and dental alveolar bone as it does in long bones, whereas PTH acts predominantly in long bones rather than mandibular bone.

scholarly journals Metabolic activities affect femur and lumbar vertebrae remodeling, and anti-resorptive risedronate disturbs femoral cortical bone remodeling

2021 ◽  
Vol 53 (1) ◽  
pp. 103-114
Author(s):  
Mi Yeong Kim ◽  
Kyunghee Lee ◽  
Hong-In Shin ◽  
Kyung-Jae Lee ◽  
Daewon Jeong
Keyword(s):  
Cortical Bone ◽  
Bone Remodeling ◽  
Subcutaneous Administration ◽  
Lumbar Vertebrae ◽  
Bone Resorption Marker ◽  
Type I ◽  
Mineral Density ◽  
C3h Mice ◽  
Cortical Bone Remodeling ◽  
Metabolic Activities

AbstractMetabolic activities are closely correlated with bone remodeling and long-term anti-resorptive bisphosphonate treatment frequently causes atypical femoral fractures through unclear mechanisms. To explore whether metabolic alterations affect bone remodeling in femurs and lumbar vertebrae and whether anti-osteoporotic bisphosphonates perturb their reconstruction, we studied three mouse strains with different fat and lean body masses (BALB/c, C57BL6, and C3H mice). These mice displayed variable physical activity, food and drink intake, energy expenditure, and respiratory quotients. Following intraperitoneal calcein injection, double calcein labeling of the femoral diaphysis, as well as serum levels of the bone-formation marker procollagen type-I N-terminal propeptide and the bone-resorption marker C-terminal telopeptide of type-I collagen, revealed increased bone turnover in mice in the following order: C3H > BALB/c ≥ C57BL6 mice. In addition, bone reconstitution in femurs was distinct from that in lumbar vertebrae in both healthy control and estrogen-deficient osteoporotic mice with metabolic perturbation, particularly in terms of femoral trabecular and cortical bone remodeling in CH3 mice. Interestingly, subcutaneous administration of bisphosphonate risedronate to C3H mice with normal femoral bone density led to enlarged femoral cortical bones with a low bone mineral density, resulting in bone fragility; however, this phenomenon was not observed in mice with ovariectomy-induced femoral cortical bone loss. Together, these results suggest that diverse metabolic activities support various forms of bone remodeling and that femur remodeling differs from lumbar vertebra remodeling. Moreover, our findings imply that the adverse effect of bisphosphonate agents on femoral cortical bone remodeling should be considered when prescribing them to osteoporotic patients.

May polymorphisms of DHFR, CBS and MTHFR genes modulate metabolic and bone remodeling parameters associated with reduced bone mineral density?

2018 ◽  
Author(s):  
Joana Freitas ◽  
Carla Carvalho ◽  
Carolina Ribeiro ◽  
David Sarmento ◽  
Barbosa Ana Paula ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Mineral Density
Sign in / Sign up

Export Citation Format

Share Document