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Principal Investigator:
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Luis Cardoso Landa, Ph.D.
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Organization:
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Mount Sinai School of Medicine
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Project Ended:
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2005
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Studies from spaceflights have shown that due to weightlessness, astronauts may dramatically lose their bone mass, resulting in a significant increase in the risk of fracture. As a countermeasure, NSBRI Postdoctoral Fellow Dr. Luis Cardoso Landa will investigate the ability of ultrasound measurements to assess changes in bone integrity, tissue architecture and mechanical function. Using healthy and osteoporotic bone samples, both with and without therapeutic treatment, Cardoso Landa is evaluating ultrasound-derived structural parameters to distinguish global and directional changes as predictors of weakness in bone. He will then compare the ultrasound bone measuremensts against predictions made by the laboratory mathematical model.
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Principal Investigator:
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Luis Cardoso Landa, Ph.D.
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Organization:
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Mount Sinai School of Medicine
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Project Ended:
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2005
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Currently, the approach most widely used to examine bone loss is bone densitometry, which cannot show the microarchitectural aspects of cancellous bone that are key to the estimation of bones mechanical integrity. Recently, a novel architecture density-based approach for acoustic-wave propagation in a poroelastic media was developed. This approach provides the potential to use ultrasound measurements in bone to examine tissue architecture in addition to bone mass.
Initial studies show that this approach significantly improves prediction of mechanical properties of bovine and human cancellous bone when compared to density-based approaches. Better estimation of bone mechanical properties is expected to result in enhanced discrimination of osteoporotic and non-osteoporotic bone.
The aim of the present study is to investigate the ability of this microstructural-based approach to discriminate quantitatively the changes in density, microstructure and mechanical properties of bone in the real-world situations of a rapidly evolving osteoporosis (disuse), both with and without anti-resorptive treatment, and after recovery.
The present research builds on the ongoing NSBRI studies (Resorption Suppression and Bone Health in Disuse) conducted by my mentor, Dr. Mitchell Schaffler, at the Orthopaedics department of Mount Sinai School of Medicine. From these studies, canine cancellous bone samples were obtained and split into four groups: Immobilized (Im), Immobilized and treated with anti-resorptive therapy (ImTx), Non-immobilized control bones (Cn), and non-immobilized control bones treated with bisphononate (CnTx).
Ultrasound-wave velocities were measured in three anatomical directions (SI, ML and AP). The values of ultrasound velocities and the bone density were used to directly compute the directional anisotropic mechanical properties of cancellous bones in the four analyzed groups. In particular, from these measurements, it was found a noticeable change in mechanical properties when comparing control and immobilized cancellous bone samples. The group of bones immobilized and treated with anti-resorptive therapy has shown an intermediate level of mechanical properties when compared against the control and immobilized bone samples. These results were found in close agreement with previous results from Dr. Schafflers research project, which have shown that anti-resorptive treatment with bisphosphonate reduced bone loss in disuse but did not completely inhibit it.
Dr. Schaffler's data suggest that disuse osteoporosis differs from other osteoporoses in its sensitivity to anti-resorptive treatment. The results from the present project support this suggestion and demonstrate the ability of ultrasound procedure to assess differences between normal, disuse-induced osteoporotic and normal bone. Moreover, the data analysis for the three anatomical directions have shown that beside changes in bone density, the ratio of anisotropy in healthy bone is highly modified during disuse. However, this ratio of anisotropy can be preserved in disuse-induced osteoporotic bone when using the anti-resorptive therapy.
Observations of directional (anatomical) changes of bone loss undergoing disuse and treated with anti-resorptive therapy were effectively assessed through changes in mechanical properties from ultrasound measurements. Furthermore, mechanical properties obtained from ultrasound measurements were compared against mechanical properties computed from a poroelastic model using measurements from 3D images of the trabecular bone samples from microCT images. In particular, a high correlation was found between mechanical properties derived from ultrasound measurements and obtained from direct measurement of the microstructure in samples. Finally, using the poroelastic model, the directional information of the microstructure was extracted from each ultrasound measurement and compared to direct measurements from microCT images. The correlation between the bone density obtained from ultrasound and microCT images was moderated but highly improved when the bone density was directionally modulated with this structural information. The structural information derived from ultrasound measurements was then proved relevant to improving the assessment of mechanical properties when analyzing anisotropic cancellous bone.
The results obtained during the first year of the present project suggest that the ultrasound measurements and/or the use of the new poroelastic model can effectively distinguish directional and global changes in trabecular bone undergoing disuse and treated with anti-resorptive therapy. The effectiveness of the ultrasound measurements to determine anisotropic changes in mechanical properties of bone was demonstrated against direct analysis of 3D images obtained from microCT.
The aim of the proposed research for the coming year consist of determining microstructure and mechanical properties of bone that has been allowed to recover from long-term disuse (restoration of mechanical loading + bone anabolic agent). In these experiments, anisotropic mechanical and structural properties of cancellous bone will be analyzed from a newly initiated series of experiments (NSBRI grant, Bone recovery after bisphosphonate and PTH treatment of disuse osteoporosis BL00406) that examines recovery potential for disuse and bisphosphonate-treated bone once mechanical loading has been restored. Data suggest that once trabeculae are lost, recovery can only occur through thickening of the remaining trabeculae.
These studies will determine whether our acoustical-anisotropy approach remains a good predictor of anisotropic mechanical properties in restored as well as normal and osteoporotic bone. Anisotropic mechanical properties of bone in which recovery was augmented using a bone anabolic agent (PTH) will be also examined.
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Principal Investigator:
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Luis Cardoso Landa, Ph.D.
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Organization:
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Mount Sinai School of Medicine
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Project Ended:
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2005
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This research has the potential to improve the assessment of bone quality using ultrasound and thus the diagnostic of osteoporosis.
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