Purpose
The purpose of this study was to evaluate the efficacy and toxicity of a novel lanthanum compound, La(XT), in an ovariectomized (OVX) rat model of osteoporosis.
Methods
Twenty-four ovariectomized female Sprague Dawley rats were divided into 3 groups receiving a research diet with/without treatment compounds (alendronate: 3 mg/kg; La(XT) 100 mg/kg) for three months. At the time of sacrifice, the kidney, liver, brain, lung and spleen were collected for histological examination. The trabecular bone structure of the tibiae was evaluated using micro-CT and a three-point metaphyseal mechanical test was used to evaluate bone failure load and stiffness.
Results
No significant differences were noted in plasma levels of calcium, phosphorus, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) between the La(XT) treatment compared to the non-treated OVX group. Alendronate-treated animals (positive control) showed higher BV/TV, Tb.N and lower Tb.Th and Tb.Sp when compared to the non-treated OVX group. Mechanical analysis indicated that stiffness was higher in the alendronate (32.88%, p = 0.04) when compared to the non-treated OVX group. Failure load did not differ among the groups.
Conclusions
No kidney or liver toxicities of La(XT) treatments were found during the three-month study. The absence of liver and kidney toxicity with drug treatment for 3 months, as well as the increased trabecular bone stiffness are encouraging for the pursuit of further studies with La(XT) for a longer duration of time.
Spine models are typically developed from supine clinical imaging data, and hence clearly do not fully reflect postures that replicate subjects’ clinical symptoms. Our objectives were to develop a method to: (i) estimate the subject-specific sagittal curvature of the whole spine in different postures from limited imaging data, (ii) obtain muscle lines-of-action in different postures and analyze the effect of posture on muscle fascicle length, and (iii) correct for cosine between the magnetic resonance imaging (MRI) scan plane and dominant fiber line-of-action for muscle parameters (cross-sectional area (CSA) and position). The thoracic spines of six healthy volunteers were scanned in four postures (supine, standing, flexion, and sitting) in an upright MRI. Geometry of the sagittal spine was approximated with a circular spline. A pipeline was developed to estimate spine geometry in different postures and was validated. The lines-of-action for two muscles, erector spinae (ES) and transversospinalis (TS) were obtained for every posture and hence muscle fascicle lengths were computed. A correction factor based on published literature was then computed and applied to the muscle parameters. The maximum registration error between the estimated spine geometry and MRI data was small (average RMSE∼1.2%). The muscle fascicle length increased (up to 20%) in flexion when compared to erect postures. The correction factor reduced muscle parameters (∼5% for ES and ∼25% for TS) when compared to raw MRI data. The proposed pipeline is a preliminary step in subject-specific modeling. Direction cosines of muscles could be used while improving the inputs of spine models.
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