Multiple studies have shown that ectopic bone forms when bone morphogenic proteins (for example BMP-2 and BMP-7) and a collagen matrix are surgically placed in a rat model either orthotopically or heterotopically. Bone begins to form by the 14 day, and is at it maximum calcified state by the 21st day. The purpose of this study is to observe and quantify the effect of distraction osteogenesis on the ectopic bone. First, a preliminary procedure was performed by surgically placing a titanium cage into the back of a rat just caudal to the thoracic vertebrae. The anterior corners were sutured to the spinotrapezius muscle for stabilization. The titanium cage containing rhBMP-2 in a collagen carrier was allowed to form bone for 21 days. It was then retrieved and prepared with TRAP stain to observe osteoclast activity. A high osteoclast activity would have indicated that the concentration of BMP-2 might be to high, and the same test would be repeated with a lower concentration. According to Dr. Andresen, various concentrations of BMP-2 had no significant effect on bone formation when used as a bone graft. Once a dose and concentration was established for the optimal bone growth all further studies were done at that concentration. The specimens were evaluated grossly and histologically for comparison. The dose was given by Medtronics to be 1.4ml of rhBMP-2 per sponge. Between one and one and a half sponges were used per rat. The concentration that formed the most bone was 0.3mg/ml, when compared to 0.1 mg/ml. The second phase of the experiment evaluated the effects of expansion by using a distractor like those used in clinical distraction osteogenesis. Instead of removing the cage at 21 days, the forming bone was cut with a 15 blade at day 14 between the two cages attached to the distractor. It was then allowed to "heal" for 1 day, after which expansion began. The rate of expansion was 2/3mm per day for 7 days. A 7 day latency period followed expansion before removal and examination of the expanded bone. The bone continued to form beyond 21 days in both types of cages (i.e. distraction and non-expansion). Specimens obtained for evaluation with CT, histology, and grossly.

LLU Discipline





Graduate Studies

First Advisor

Philip Boyne

Second Advisor

Raymond Hall

Third Advisor

Leroy Leggitt

Fourth Advisor

Kenneth Wright

Degree Name

Master of Science (MS)

Degree Level


Year Degree Awarded


Date (Title Page)




Library of Congress/MESH Subject Headings

Osteogenesis, Distraction; Bone Morphogenetic Proteins; Ossification, Heterotopic



Page Count

x; 50

Digital Format


Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.


Loma Linda University Electronic Theses and Dissertations

Collection Website



Loma Linda University. Del E. Webb Memorial Library. University Archives