Inflammaging and Bone Loss in a Rat Model of Spinal Cord Injury

A moderate spinal contusion injury in rats alters bone turnover both below and above the level of injury with sex-based differences apparent in long-term recovery

“…Bone loss below the level of injury is expected given the reduced loading of the lower limbs after SCI; however, animal studies have demonstrated that SCI-induced bone loss is greater than bone loss in other models of disuse, including hindlimb immobilization ( Liu et al, 2008 ) or sciatic neurectomy ( Jiang et al, 2006 ). Additionally, previous work from our group has shown lower trabecular bone volume and altered bone turnover at the proximal tibia following a moderate spinal contusion injury, despite weeks to months of regained weightbearing and locomotor function ( Metzger et al, 2018 ; Metzger et al, 2022 ). These pre-clinical studies clearly demonstrate that bone loss is different and greater than can be explained solely by disuse-related factors, including reduced mechanical loads, and decreased or absent contraction of skeletal muscles.…”

“…Animals from this study are a subset of rats previously described ( Metzger et al, 2022 ). Proximal tibia, proximal humerus, 4th lumbar vertebra from eight different sets of spinal cord injured and age-matched sham rodents were examined: young male and female and adult male and female at both 30 days and 180 days post injury (n = 6–8/group).…”

“…Rats were given a moderate spinal contusion (T11-T12) or a sham injury. The moderate contusion injury was produced by applying an impact force (150 kdynes with a 1 s dwell time) onto the T11-T12 spinal tissue with an Infinite Horizon (IH) spinal cord impactor (PSI, Fairfax Station, VA, USA), as previously described ( Metzger et al, 2022 ). Sham rats were treated identically to the SCI rats with the same laminectomy, but the impact force was not applied to the spinal cord tissue and the contusion injury was not produced.…”

“…Clinical studies suggest that SCI-related factors that could contribute to bone loss include a pro-inflammatory state ( Wang et al, 2007 ; Gibson et al, 2008 ; Davies et al, 2007 ; Hayes et al, 2002 ) and alterations in endocrine factors ( Bauman et al, 2006 ; Sullivan et al, 2017 ; Boehl et al, 2022 ). Animal models have also demonstrated systemic inflammation ( Metzger et al, 2022 ; Maldonado-Bouchard et al, 2016 ) and hormonal changes following SCI ( Otzel et al, 2019 ; Hubscher et al, 2006 ; del Rivero and Bethea, 2016 ). Any systemic factor contributing to SCI-induced bone loss would be expected to have effects on skeletal sites above the injury.…”

“…Previously, we assessed bone structural parameters and bone turnover in the sublesional tibia after a moderate contusion injury at sub-chronic and chronic timepoints in male and female rats at two different ages ( Metzger et al, 2022 ). Even at the chronic timepoint, months after resumption of regular weightbearing, SCI rats in most groups had lasting decrements in tibial trabecular microarchitecture compared to age-matched controls.…”