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New York City Research Initiative

Research Projects at the State University of New York at Stony Brook

Go to projects in: 2009 | 2008 | 2007 | 2006 | 2005 | 2004

The State University of New York at Stony Brook — 2009

The Effect of Simulated Microgravity on Bone Quantity and Quality in the Mid-Diaphysis of the Mouse Femur
Team Members

Principle Investigator (PI):
Stefan Judex

Mentor:
Shikha Gupta, Graduate Student

Researchers:
Lisa Tan, High School Student

Final Research Presentation
Summary

Abstract: This study investigated the effect of frequency and duration of periods of hindlimb unloading (HLU) on bone loss in the femoral mid-diaphysis of the mouse. Bone quantity and quality was tested in terms of morphological indices such as mineral density, cortical thickness, and endosteal area. A hindlimb suspension device was used to test the effect of mechanical unloading on this specific region of the mouse femur which simulated zero-gravity conditions in space that cause bone loss in astronauts. Four groups of mice from a heterogeneous generation of BALB/cByJ x C3H/HeJ were studied, each differing in the length and regularity of periods of hindlimb suspension. It was found that after 1 week of HLU there was little difference between baseline and after suspension animals. However, it was noted that there was a significant difference in cortical thickness between males and females. This disparity remained constant before and after loss of weight-bearing on the femur. In males from the group suspended for 4 weeks, a relatively substantial increase was noted in the mineral density of the compact bone. Results were inconclusive in proving whether multiple short exposures to HLU were less detrimental to cortical bone than a single long exposure. From these results, it was concluded that the overall insignificant difference between the morphological parameters of the baseline and after suspension animals from all groups could be due to properties of the mid-diaphysis that make it less sensitive to mechanical unloading. However, the relatively greater changes in the endosteal area and cortical thickness in the 4 week group could indicate that changes in bone quantity and quality can be delineated in terms of these parameters.

The State University of New York at Stony Brook — 2008

Defining Bone Quality as an Assessment of Bone Strength of an Astronaut
Team Members

Principle Investigator (PI):
Dr. Stefan Judex

Co-Principle Investigator (Co-PI):
Dr. Steven Tommasini

Researchers:
Svetlana Lublinsky, Graduate Student
Ashley Titan, SHARP Apprentice

Final Research Presentation
Summary

Background Information:

The skeleton has evolved to allow efficient locomotion and support the body [1]. Bones are made up of two kinds of tissue: Trabecular bone is highly porous with low density and high surface area [2]. Cortical Bone is the very dense outer shell [2]. The strength of bone is based its quantity, shape, thickness, and composition. It is important to note that it is essential to understand both bone quantity and quality when defining bone strength. Due to gravitational differences the human skeleton does not need the same amount of strength in outer space as on Earth. In previous studies it has been shown that both cortical and trabecular bone mineral loss results from long-duration spaceflight. Some bone specimens lost up to twice the amount of mineral content compared to there earthly counterparts [3].

Existing bone strength diagnostic methods are unreliable. Susceptibility to bone fracture is currently measured by Bone Mineral Density (BMD). This parameter accounts for < 40% of variation in trabecular bone strength [4].

The goal o f this study is to determine more accurate ways to analyze and define bone strength. It is proposed that the strength and quality of the bone's matrix will be significantly influenced by both the chemical and structural composition.

The State University of New York at Stony Brook — 2007

Interactions of Musculoskeletal Tissues During Disuse
Team Members

Principle Investigator (PI):
Dr. Stefan Judex

Team Members:
Engin Ozcivici, Graduate Student
Christopher Gambino, High School Student

Final Research Presentation
Summary

Bone loss is an increasing problem that affects all demographics. This loss occurs when a load bearing bone is not used for a prolonged periods of time. Such an example of disuse would be an astronaut on a mission or a sick person undergoing bed rest. Currently, methods are being developed to help prevent this loss as it poses a serious problem to long duration space missions or critically ill patients. Ways of recovering bone mass such as running or lifting weights will not work for these people due to a zero-g environment or they would be already too weak to do such activities. The experimental methods focus on various speeds and magnitudes of vibrations which can induce strain even in a zero-g environment or on a weakened patient. Some of these methods have been rather successful in increasing overall bone mass but the amount it affects bones sections relative to each other is largely unexamined. To induce disuse in mice a hind limb suspension apparatus is utilized. This lift's the mice's tail upsing no pressure to be exerted on the rear limbs. The mice still maintain mobility via their front limbs. To examine the effects a VivaCT scanner is employed. This generates images of the bone cross-sections while not harming the mouse. These images can later be reconstructed into a 3D model.

The State University of New York at Stony Brook — 2006

Tissue's Response to Mechanical Stimuli
Team Members

Principle Investigator (PI):
Dr. Stefan Judex

Researchers:
Russell Garman, Graduate Student
Engin Ozcivici, Graduate Student
Shiyun Xu

Christopher Gambino, SHARP Apprentice

Final Research Presentation
Summary

Results:

+ During the 1-3 week period bone volume decreased an average of 1%.
+ During the 3-6 week period bone volume increased an average of 4%
+ During weeks 1-3 the muscle volume decreased and average of 10%
+ During Weeks 4-6 muscle mass volume increased 7%

The bone seemed to be more responsive to mechanical loading (walking) than unloading (immobilized).
The reverse of this is true for the muscle.

The distribution of loss/gain rather than being grouped around one value suggests that there is a controlling factor that was spread through the genetically heterogeneous population.

The State University of New York at Stony Brook — 2005

Combining Genetic, Molecular, and Biomechanical Approaches to Elucidate how Bone Regulates its Quantity and Quality (and How Mechanical Stimuli May Perturb this Regulation)
Team Members

Principle Investigator (PI):
Dr. Stefan Judex

Researchers:
Maria Squire, NASA GSRP

Russell Garman, Graduate Student
Liqin Xie, Graduate Student
Engin Ozcivici, Graduate Student
Amy Brazin, SHARP Apprentice

Final Research Presentation
Summary

My research focuses on how organ systems, such as the skeleton, respond to altered functional demand. Specifically, my lab has been interested in combining genetic, molecular, and biomechanical approaches to elucidate how bone regulates its quantity and quality and how mechanical stimuli may perturb this regulation. An improved understanding of how external signals are translated into a biological response require the rigorous integration of engineering with biology, from the genome to the molecular, cellular, and tissue level. This understanding will, ultimately, lead to the design of pharmacological and non-pharmacological (e.g., mechanical or nutritional) interventions that will enhance tissue strength in young adults and prevent the loss of tissue quantity and quality during osteoporosis, aging, or space flight.  To this end, genetic (e.g., QTL) and molecular (e.g., RT-PCR, immunocytochemistry, or microarrays) assays are used to relate specific loci on chromosomes and the expression level of corresponding genes to traits at the level of the tissue.  These traits are rigorously defined by their chemical, morphological, and mechanical properties by cutting edge technology such as MRI, high resolution computed tomographic imaging, in situ infrared spectroscopy, or finite element modeling.

The State University of New York at Stony Brook — 2004

The Genetic Basis of the Loss of Musculo-Skeletal Tissue during Weightlessness: Towards the Identification of Individuals that are at Greatest Risk
Team Members

Principle Investigator (PI):
Dr. Stefan Judex

Researchers:
Maria Squire, Graduate Student
Xin Lei, Graduate Student
Russell Garman, Graduate Student
Liqin Xie, Graduate Student
Amy Brazin,SHARPApprentice

Final Research Presentation
Summary

The National Research Council's Space Studies Board has stated that a principal physiologic hurdle to man's extended presence in space is the osteopenia and sarcopenia which parallels reduced gravity. The extent of the loss is extremely high, approaching a decrease in bone mineral density (BMD) in the lower appendicular skeleton at a rate of 1.6% per month and reducing maximal voluntary contractions of some muscle groups at a rate of 5% per month. Interestingly, the amount of bone (and muscle) loss between individual astronauts is highly variable with some astronauts losing large amounts of tissue while others are largely unaffected. This large individual variability, which has also been observed during bedrest and immobilization studies on Earth, may be accounted for, at least to a large extent, by genetic variations which may give rise to a differential mechanosensitivity of the musculoskeleton. We have collected preliminary data demonstrating that genetically distinct inbred strains of mice also demonstrate a distinct sensitivity to conditions of simulated weightlessness; while as much as 60% of trabecular bone is lost in the hindlimbs of BALB/cByJ mice within 3 weeks of disuse, the same conditions leave trabecular bone quantity and quality nearly unchanged in C3H/HeJ mice. In this proposal, we aim to elucidate this genetic basis of the sensitivity of the musculo-skeleton to the loss of appropriate mechanical signals by identifying the quantitative trait loci (QTL) responsible for the difference exhibited between these two strains of inbred mice. The identification of QTL (and ultimately the responsible genes) may be used as both a critical diagnostic sensor for the identification of astronauts that are in greatest need of pharmacologic and/or biomechanical countermeasures in space and as a discovery tool of novel drug targets against the loss of musculo-skeletal tissue.

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