Date of Award

6-2014

Degree Name

MS in Biomedical Engineering

Department

Biomedical and General Engineering

Advisor

Scott Hazelwood

Abstract

The purpose of this study is to characterize the compact-bone remodeling response to an ovariectomy model of human postmenopausal osteoporosis. Animal models are a beneficial practice allowing for the evaluation of the effectiveness of medical therapies and devices on diseases. The ovine model was chosen for this study due to its large size, similar bone remodeling to humans, and cost effectiveness. The main obstacle to overcome with the use of the ovine model was the lack of natural menopause experienced by this species. To overcome this, it was necessary to perform an ovariectomy to create estrogen depletion and artificially induce menopause in the sheep. The use of OVX (ovariectomized) sheep has been widely accepted as a model for the loss of bone mass. Effects of bone loss first appear around 3 months post-ovariectomy, however the effect of the bone loss at the 3 month time point as well as its effect on different anatomical positions within the bone have not been thoroughly studied. 16 skeletally mature Columbia-Rambouillet cross ewes were used for this portion of the study. The group of 16 was divided into 2 groups, one underwent an ovariectomy procedure and the other group underwent a sham surgery to put them through the same surgical stress as the test group. 3 months post surgery the ewes were sacrificed and had their right and left radii and ulna removed. The left radial-ulna bone was then divided into 6 anatomical locations: craniolateral, cranial, craniomedial, caudolateral, caudal, and caudomedial. With the bone divided into different anatomical sectors, microradiographs were fabricated to allow for further analysis of the bone samples. Using the microradiographs histomorphometric measurements were taken to quantify the bone remodeling occurring; the measurements taken were the bone volume to tissue volume, fraction of remodeled tissue and material, the millimeter (mm) of cement line per square mm of bone tissue and material, osteons per field, and the mean osteon area. Densitometry analysis was also performed using the microradiographs using image analysis and the use of an aluminum step wedge on each microradiograph as a key. Once all of the data was collected a 2-way repeated measures ANOVA statistical analysis was performed on the histomorphometry and densitometry data to evaluate the possible differences seen due to treatment, anatomical sector, and possible interaction of both. For the histomorphometry portion there was a significant variation seen between the caudal sectors of bone in the OVX vs control sheep in both the fraction of remodeled material and the mean osteonal area. There was also a significant variation seen between the caudomedial sectors of bone in the OVX vs control sheep for the average osteons per field. For the densitometry analysis it was found that the OVX sheep had significantly lower bone density than the control sheep. This study shows that there are significant changes seen even after only 3 months with depleted estrogen levels and that differences can be seen based on the anatomical sector of the bone. With this information it will be important to take this into consideration when creating future studies using the ovariectomized ewe as an animal model for postmenopausal osteoporosis study.

Share

COinS