Osteopenia in a Mouse Model of Spinal Cord Injury: Effects of Age, Sex and Motor Function.

Abstract

Simple SummaryIn the first two years following spinal cord injury, people lose up to 50% of bone below the injury. This injury-induced bone loss significantly affects rehabilitation and leaves people vulnerable to fractures and post-fracture complications, including lung and urinary tract infections, blood clots in the veins, and depression. Unfortunately, little is known about the factors driving this bone loss. In fact, even though we know that injury, age, and sex independently increase bone loss, there have been no studies looking at the cumulative effects of these variables. People with spinal injury are aging, and the age at which injuries occur is increasing. It is essential to know whether these factors together will further compromise bone. To examine this, we assessed bone loss in young and old, male and female mice after spinal injury. As expected, we found that aging alone decreased motor activity and bone volume. Spinal injury also reduced bone volume, but it did not worsen the effects of age. Instead, injury effects appeared related to reduced rearing activity. The data suggest that although partial weight-bearing does not reduce bone loss after spinal cord injury, therapies that put full weight on the legs may be clinically effective.After spinal cord injury (SCI), 80% of individuals are diagnosed with osteopenia or osteoporosis. The dramatic loss of bone after SCI increases the potential for fractures 100-fold, with post-fracture complications occurring in 54% of cases. With the age of new SCI injuries increasing, we hypothesized that a SCI-induced reduction in weight bearing could further exacerbate age-induced bone loss. To test this, young (2–3 months) and old (20–30 months) male and female mice were given a moderate spinal contusion injury (T9–T10), and recovery was assessed for 28 days (BMS, rearing counts, distance traveled). Tibial trabecular bone volume was measured after 28 days with ex vivo microCT. While BMS scores did not differ across groups, older subjects travelled less in the open field and there was a decrease in rearing with age and SCI. As expected, aging decreased trabecular bone volume and cortical thickness in both old male and female mice. SCI alone also reduced trabecular bone volume in young mice, but did not have an additional effect beyond the age-dependent decrease in trabecular and cortical bone volume seen in both sexes. Interestingly, both rearing and total activity correlated with decreased bone volume. These data underscore the importance of load and use on bone mass. While partial weight-bearing does not stabilize/reverse bone loss in humans, our data suggest that therapies that simulate complete loading may be effective after SCI.