Systemic oxidative stress in old rats is associated with both osteoporosis and cognitive impairment.

Aging is associated both with an increase in memory loss and with comorbidities such as Osteoporosis, which could be causatively linked. In the present study, a deleterious effect on bone is demonstrated for the first time in a model of aged rats with impaired memory. We show that bone marrow progenitor cells obtained from rats with memory deficit have a decrease in their osteogenic capacity, and an increase both in their osteoclastogenic profile and adipogenic capacity, when compared to aged rats with preserved memory. Rats with impaired (versus preserved) memory also show alterations in long-bone micro-architecture (decreased trabecular bone and osteocyte density, increased TRAP-positive osteoclasts), lower bone quality (decreased trabecular bone mineral content and density) and an increase in bone marrow adiposity. Interestingly, the development of bone alterations and memory deficit in old rats is associated with significantly higher levels of serum oxidative stress (versus unaffected aged rats). In conclusion, we have found for the first time in an aged rat model, a relationship between alterations in bone quality and memory impairment, with increased systemic oxidative stress as a possible unifying mechanism.