Dataset Information

Long-term treatment with odanacatib maintains normal trabecular biomechanical properties in ovariectomized adult monkeys as demonstrated by micro-CT-based finite element analysis.

ABSTRACT: The cathepsin K inhibitor odanacatib (ODN) is a potent and reversible inhibitor of osteoclastic resorption activity. This drug is currently under development for the treatment of postmenopausal osteoporosis. Previously, we described data on the treatment efficacy of ODN in a preclinical estrogen-deficient model of an ovariectomized (OVX) rhesus monkey using HR-pQCT based finite element analysis (FEA) in vivo estimates of bone strength on the distal radius. To support the bone safety profile of ODN, we report ex vivo data on the apparent and hard tissue biomechanical properties of the trabecular bone of vertebrae of animals after 20 months of dosing in three treatment groups: Vehicle (VEH), ODN (2 mg/kg/day), and ALN (30 ?g/kg/week). Biomechanical axial compression tests were performed on cylindrical trabecular samples cored out of the third lumbar vertebra of each animal at the end of the study. The biomechanical test results demonstrated that a normal (positive correlation between bone mineral density and bone strength) apparent material property relationship was maintained in the lumbar spine of ODN and ALN treated non-human primates (NHP). Trabecular bone hard tissue Young's modulus value was estimated using experimentally measured stiffness combined with FEA. The FEA and experimental results demonstrated that ODN treatment for 20 months maintained normal trabecular bone material hard tissue properties in the OVX-monkeys and was comparable to ALN.

SUBMITTER: Cabal A

PROVIDER: S-EPMC5365313 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Long-term treatment with odanacatib maintains normal trabecular biomechanical properties in ovariectomized adult monkeys as demonstrated by micro-CT-based finite element analysis.

Cabal Antonio A Williams Donald S DS Jayakar Richa Y RY Zhang Jingru J Sardesai Swanand S Duong Le T LT

Bone reports 20170107

The cathepsin K inhibitor odanacatib (ODN) is a potent and reversible inhibitor of osteoclastic resorption activity. This drug is currently under development for the treatment of postmenopausal osteoporosis. Previously, we described data on the treatment efficacy of ODN in a preclinical estrogen-deficient model of an ovariectomized (OVX) rhesus monkey using HR-pQCT based finite element analysis (FEA) in vivo estimates of bone strength on the distal radius. To support the bone safety profile of O ...[more]

PMID: 28377978

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Project description:BackgroundIn the follow-up after internal fixation of thoracolumbar fractures, the imaging of some patients shows "crater-like" collapse of the superior endplate of the injured vertebra, with variable collapse area and depth, even involving the anterior edge of the vertebral body. Though many papers had described the phenomenon, but nearly no one did biomechanical research about this. So we did this research in a creative way by using finite element model.MethodsA healthy male volunteer was selected. The 64-slice thin-section spiral computed tomography images at the level of T11-L3 were collected. Data were imported into Mimics 15.0 medical image processing software to establish three-dimensional finite element skeletal models of T11 to L3 containing only three-dimensional surface elements without entities. The model was assigned values and verified. Then the pedicle screw-rod system was added to this model, and five models containing the screw-rod system with different defect sizes as well as five models that simulated the removal of the screw-rod system were derived at the same time (the defect volume was 1/5, 2/5, 3/5, 4/5, or 5/5 of the anterior vertebral column, respectively). Biomechanical analysis was then performed on this basis.ResultsAfter the removal of the internal fixator, as defect volume increased, the stress difference between the 4/5 defect group and the 5/5 defect group had the greatest magnitude of combined stress under the seven working conditions. When the volume of the collapse defect reached 4/5 of the anterior column of the vertebral body, the concentration of stress increased significantly, suggesting that the risk of continued compression or even refracture of the injured vertebra increased if the internal fixator was removed at that time.ConclusionsWhen the volume of the defect in the superior endplate of the injured vertebra reaches 4/5 of the anterior column, the removal of the internal fixator should be carefully considered to avoid refracture of the anterior column of the injured vertebra.

Project description:Background/objectivesTo compare the biomechanical characteristics of maxillary molar distalization with clear aligners in conjunction with three types of miniscrew anchorage.Materials/methodsThree-dimensional (3D) finite element models of maxillary molar distalization with clear aligners and three types of miniscrew anchorage were established, including (A) control group, (B) direct buccal miniscrew anchorage group, (C) direct palatal miniscrew anchorage group, and (D) indirect buccal miniscrew anchorage group. The 3D displacement of maxillary teeth and the principal stress (maximum tensile and compressive stress) on the root and periodontal ligament (PDL) during molar distalization were recorded.ResultsThe tooth displacement pattern during maxillary molar distalization in the four groups showed similarities, including labial tipping of anterior teeth, mesial and buccal tipping of premolars, and distal and buccal tipping of molars, but with varying magnitudes. Group C exhibited the greatest molar distalization, with the first molar achieving 0.1334 mm of crown distalization. Group D demonstrated a notable buccal crown movement (0.0682 mm) and intrusion (0.0316 mm) of the first premolar. Compared to Groups A and B, Groups C and D showed less labial crown tipping of the central incisor. Group B showed the greatest amount of maxillary incisor intrusion (central incisor: 0.0145 mm, lateral incisor: 0.0094 mm). Moreover, Groups C and D displayed significantly lower levels of compressive and tensile stress in the roots and PDL of the maxillary central and lateral incisors.LimitationMolar distalization is a dynamic process involving sequential tooth movement stages; however, our research primarily examined the tooth movement patterns in the initial aligner.Conclusions/implicationsThe use of miniscrew anchorage, especially direct palatal miniscrew anchorage, may enhance the treatment efficacy of maxillary molar distalization with clear aligners, leading to increased molar distalization, reduced mesial movement of premolars, and minimized labial tipping of anterior teeth.

Dataset Information

Long-term treatment with odanacatib maintains normal trabecular biomechanical properties in ovariectomized adult monkeys as demonstrated by micro-CT-based finite element analysis.

Publications

Long-term treatment with odanacatib maintains normal trabecular biomechanical properties in ovariectomized adult monkeys as demonstrated by micro-CT-based finite element analysis.

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