Dual energy X-ray absorptiometry (DEXA) measures bone density which may be only one of several elements responsible for biomechanical competence. It has been suggested in the literature that bone strength is multi-factorial and may depend not only on bone density but also on bone marrow quality. 1H MRS of human vertebra has been used to quantify both fat content and bone density measurement. It is believed that an animal study will allow a more precise and systematic correlation between a) bone fat content and age and b) bone fat content and experimentally induced bone involution / osteoporosis. Therefore an animal model will allow to confirm experiences and insights obtained in the human study. It is hypothesized: (I) that increased marrow fat content, as seen with aging and with certain pathologic bone conditions, i.e. osteoporosis, can affect bone strength and that lipid-water ratio (LWR), fat fraction (FF) or per cent fat fraction (%FF) can quantify bone fat content; (II) that susceptibility changes due to the trabecular bone loss cause line width (LW) narrowing. The goal of this proposal is to use an animal model (rat tibia) to acquire both LWR and LW as an objective method to evaluate age related bone changes and predict bone weakening. To achieve the goal we have the following research design. 1) Specific Aim #1: To determine age dependence of LWR and LW. In group A, twelve healthy female rats, 3 animals in the age categories of 3, 12 , 21, 30 months, will be submitted to hindleg tibial NM and 1HMRS on nine occasions. The first measurements are obtained after one week of acclimatization. This will be followed by measurements at monthly intervals, for a total of 8 followup examinations. LWR and LW functions will be determined and correlated to the age of the animals. Both LWR and LW data will be tabulated in 1-month increments and analyzed using the linear regression method and polynomial fit respectively. 2) Specific Aim #2: To determine the dependence of LWR and LW on bone involution / osteoporosis in tibiae of partially immobilized, back-suspended rats. In group B, twelve female Wistar rats will be used. There will be three animals in each age category (3, 12, 21, and 30 months). These animals will be submitted to hindleg tibial NM and 1HMRS after a period of back-suspension. The period of back suspension will be 3 weeks. Each animal of group B will first undergo MRI and 1H MRS after one week of acclimatization. The animals will then be back-suspended for three weeks and scanned at 7,14 and 21 days of back suspension. This experimental protocol will be used for all four age groups (3,12, 21, 30 months of age). Both LWR and LW will be measured versus the degree of inactivity. Each subset of data (totals 3 subsets) will be tabulated and be analyzed against the corresponding age normal rats (group A) using two-tailed Student t-test method. P < 0.05 is considered significant.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
1R03AG019854-01
Application #
6400115
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Carrington, Jill L
Project Start
2001-08-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2003-07-31
Support Year
1
Fiscal Year
2001
Total Cost
$75,392
Indirect Cost
Name
Georgetown University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057