|Aronson, James - UAMS|
|Gao, G - UAMS|
|Shen, X - UAMS|
|Mclaren, S - UAMS|
|Skinner, R - UAMS|
|Lumpkin, Jr, C - UAMS|
Submitted to: Journal of Orthopaedic Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 30, 2000
Publication Date: N/A
Interpretive Summary: Distraction Osteogenesis (DO) is a procedure that can be used to lengthen and straighten human bones. We have developed an animal model that provides an excellent opportunity to study in a very short period of time how bone cells really behave and to learn the mechanisms by which new bone is formed. This is important in learning how to develop new ways to strengthen bone and to prevent bone loss under conditions such as aging. In this study, we examined new bone formation in young and old rats to determine if this rat model could be used to study bone formation during aging. If this model mimicked the human situation, we would predict that less new bone would be formed in older than younger rats in the same time period and there might be other obvious differences. The results confirmed that the older rats had new bone formation similar to that predicted in older people and these data suggest that this model is good for future studies of bone repair in the elderly.
Technical Abstract: The effect of age on bone formation in the limb lengthening model of distraction osteogenesis (DO) was investigated in two studies using Sprague-Dawley (SD) rats from two colonies at various ages (CAMM: 9 vs. 24 months, Harlan : 4 vs. 24 months). External fixators were placed on the right tibiae of 30 male SD rats (20 CAMM, 10 Harlan) and mid-diaphseal osteotomies were performed. Distraction was performed at 0.2 mm bid for 20 days (CAMM) or 14 days (Harlan). The experimental (DO) and control (contra-lateral)tibiae were removed for high-resolution radiography and decalcified histology. Videomicroscopy was used to quantitate radiodensity, histology (matrix type) and relative areas of cell proliferation, which was identified by proliferating cell nuclear antigen (PCNA) immunochemistry. Both studies demonstrated an age-related decrease in the percent mineralized bone (radiodensity) in the distraction gap (CAMM 9 vs. 24 months: 68% vs. 51%, P<0.003; Harlan 4 vs. 24 months: 95% vs. 36%, P<0.001) and no significant colony or distraction time-specific difference was seen between the two colonies of 24-month-old rats. Histology was performed on the Harlan rats. The DO gaps in the 24-month-old rats demonstrated less endosteal new bone compared to the 4-month-old rats (P<0.01), but equivalent periosteal new bone. In 4-month-old rats, PCNA-immunostained cells were oganized along the primary matrix front (where the first deposition of osteoid occurs) extending across both periosteal and endosteal surfaces. In 24-month-old rats, PCNA+ cells were organized in zones along the periosteal new bone fronts only and irregularly scattered throughout the endosteal gap within a fibrovascular non-ossifying matrix. These results indicate that 24-month-old rats have a relative deficit in endosteal bone formation which may not be related to cell proliferation but rather to cell organization. This model relfects the clinical situation where radiographic findings in older patients demonstrate significant delays in mineralization during DO. We believe this model of DO in aged rats presents unique in vivo opportunities to test hypotheses concerning (1) the effects of aging on bone repair, (2) the effects of pharmacological agents on bone repair in a geriatric setting, and (3) to study the mechanism underlying DO.