Bone Loss following Spinal Cord Injury in a Rat Model

Abstract

The current study was undertaken to follow the time course of bone loss in the proximal tibia of rats over several weeks following thoracic contusion spinal cord injury (SCI) of varying severity. It was hypothesized that bone loss would be more pronounced in the more severely injured animals, and that hindlimb weight bearing would help prevent bone loss. Twenty-six female Sprague-Dawley rats (200-225 g, 6-7 weeks old) received standard thoracic (T9) injuries at energies of 6.25, 12.5, 25, or 50 g-cm. The rats were scored weekly for hindlimb function during locomotion. At 0, 2 or 3, and 8 weeks, high-resolution micro-CT images of each right tibia were obtained. Mechanical indentation testing was done to measure the compressive strength of the cancellous bone structure. The 6.25 g-cm group showed near normal locomotion, the 12.5 and 25 g-cm groups showed the ability to frequently or occasionally generate weight-supported plantar steps, respectively, and the 50 g-cm group showed only movement without weight-supported plantar stepping. The 6.25, 12.5 and 25 g-cm groups remained at the same level of bone volume fraction (cancBV/TV=0.24±0.07), while the 50 g-cm group experienced severe bone loss (67%), resulting in significantly lower (p<0.05) bone volume fraction (cancBV/TV=0.11±0.05) at 8 weeks. Proximal tibia cancellous bone strength was reduced by approximately 50% in these severely injured rats. Instead of a linear proportionality between injury severity and bone loss, there appears to be a distinct functional threshold, marked by occasional weight-supported stepping, above which bone loss does not occur.

Testosterone Dose Dependently Prevents Bone and Muscle Loss in Rodents after Spinal Cord Injury

“…23,24 In this regard, severe contusion SCI produces progressive hindlimb bone loss in female rodents, reaching a level of *67% cancellous bone loss and *20% cortical bone loss 8 weeks after injury. 21 Interestingly, within 21 days of SCI we observed a magnitude of hindlimb cancellous bone loss that exceeded that of other severe contusion SCI models 21 and was similar to that of the long-term ( > 6 month) transection SCI model. 20 Our SCI model differed from previous rodent contusion and transection SCI bone loss models in that we used male rats (previous studies used females) that were of a significantly older age at time of injury (14 weeks in our study vs. 6-9 weeks in previous studies).…”

“…20,33,34 This bone loss is characterized by large reductions in cancellous bone mass within the first few years after SCI with cortical bone loss persisting for > 10 years. 3 Similarly, the severe cancellous bone loss that we and others 20,21,35 observed after SCI appears to have resulted from a combination of increased bone resorption, as indicated by an increased osteoclast surface, and reduced bone formation, as indicated by reduced cancellous MAR and BFR/BS. Interestingly, no changes in circulating osteocalcin or C-telopeptide (markers of whole body bone formation and resorption, respectively) were observed after SCI, which is somewhat inconsistent with previous reports indicating increased circulating markers of bone resorption occur in male and female rodents after spinal cord transection.…”

“…20,21,35 Of these, spinal cord transection induces the most severe bone loss, 20 which exceeds that resulting from ovariectomy, 17 sciatic neuroectomy, 19 or hindlimb immobilization. 18 Within 3 weeks of spinal cord transection, large cancellous bone deficits are observable, and these deficits are slightly worsened over the subsequent 6 months, ultimately reaching 70-80% cancellous bone loss that is characterized by a 60-80% loss of trabecular number/thickness and > four-fold increase in trabecular separation.…”

“…18,19 In particular, severe cancellous bone deficits are present within 21 days of SCI in several rodent models. 20,21 In this regard, we are unaware of any study that has examined whether testosterone administration prevents the SCI-induced bone loss that occurs rapidly after injury.…”

Insights on the paleoepidemiology of ancient tuberculosis from the structural analysis of postcranial remains from the Ligurian Neolithic (northwestern Italy)

“…It can therefore be excluded that TB resulted in complete immobilization for several years. However, compared to immobilization due to spinal cord injuries, a decrease in physical activity in adulthood leads to more of a decrease in trabecular and bone mineral density than cortical area thickness or a change in mechanical properties (Tervo et al, 2009;Kontulainen et al, 2001;Nordström and Nordström, 2011;Voor et al, 2012). Therefore, results for AQ1 could be consistent with either a rapid course of the disease, or a period of metabolic disturbance and reduced activity, which could have endured for a few years before death.…”