AUTHORS
Dr. Corinne Metzger, Dr. Josephina Rau, Mr. Alexander Stefanov, Ms. Rose M Joseph, Dr. Heather C Allaway, Dr. Matthew R. Allen, and Dr. Michelle A Hook
ABSTRACT
Spinal cord injury (SCI) results in significant loss of sublesional bone, adding to the comorbidity of SCI with an increased risk of fracture and post-fracture complications. Unfortunately, the effect of SCI on skeletal health is also likely to rise as the average age of SCI has increased and there are well-known negative effects of age on bone. To date, however, the impact of age and age-associated inflammation (inflammaging) on skeletal health after SCI remains largely unknown. To address this, we compared bone parameters in young (3 month) and middle-aged (9 month) male and female rats with a moderate thoracic contusion injury, to age and sex matched sham-operated controls. Skeletal parameters, locomotor function and serum cytokine levels were assessed at both subchronic (30 days) and chronic (180 days) time points post injury. We hypothesized that SCI would lead to a dramatic loss of bone immediately after injury in all SCI-groups, with inflammaging leading to greater loss in middle-aged SCI rats. We also predicted that while younger rats may re-establish bone properties in more chronic phases of SCI, middle-aged rats would not. Supporting these hypothesis, trabecular bone volume was significantly lower in male and young female SCI rats early after injury. Contrary to our hypothesis, however, there was greater loss of trabecular bone volume, relative to age-matched shams, in young compared to middle-aged SCI rats with no effects of SCI on trabecular bone volume in middle-aged female rats. Moreover, despite recovery of weight-supported locomotor activity, bone loss persisted into the chronic phase of injury for the young rats. Bone formation rates were lower in young male SCI rats, regardless of the time since injury, while both young and middle-aged female SCI rats had lower bone formation in the subchronic but not chronic phase of SCI. In middle-aged rats, SCI-induced higher osteoclast surfaces, which also persisted into the chronic phase of SCI in middle-aged females. Neither age nor SCI-induced increases in inflammation seemed to be associated with bone loss. In fact, SCI had more dramatic and persistent effects on bone in male rats, while aging and SCI elevated serum cytokines only in female rats. Overall, this study demonstrates SCI-induced loss of bone and altered bone turnover in male and female rats that persists into the chronic phase post-injury. The sex and age dependent variations in bone turnover and serum cytokines, however, underscore the need to further explore both mechanisms and potential therapeutics in multiple demographics.