Regeneration of bone marrow after tibial ablation in immunocompromised rats is age dependent

Injuries to the marrow cavity result in rapid endosteal bone formation followed by remodeling and regeneration of the marrow. It is not known whether this process is affected by age, although marrow quality is markedly different in young and old animals. To test if marrow regeneration differs with age, we used a bone marrow ablation model that has been used to examine calcification, osteointegration of metal implants, and remodeling of bone graft substitutes. Marrow was ablated in the left tibia of seven immunocompromised rats (rNu/rNu) per time point. At 0, 7, 14, 21, 28, 35 and 42 days post-surgery, treated and contralateral tibias were harvested and fixed in buffered formalin. Both tibias were scanned using microCT and trabecular and cortical BVF calculated. Mid-sagittal histological sections of the treated limbs were stained with haematoxylin and eosin and BV/TV calculated. MicroCT and histomorphometry showed the greatest increase in bone formation was in young animals and was seen on day 7. Remodeling also occurred at an earlier time point in young rats. Bone formation peaked on day 7 in adult rats, but remodeling was slower than in young rats. Aged animals showed a delay in bone formation. Moreover, aged rats produced less primary bone than younger animals and remodeling was initiated later. These results show that response to injury in immunocompromised rats is reduced in aging and restoration of normal tissue quality is age-dependent.