Reduced bone formation markers, and altered trabecular and cortical bone mineral densities of non-paretic femurs observed in rats with ischemic stroke: A randomized controlled pilot study

Abstract

Background: Immobility and neural damage likely contribute to accelerated bone loss after stroke, and subsequent heightened fracture risk in humans. Objective: To investigate the skeletal effect of middle cerebral artery occlusion (MCAo) stroke in rats and examine its utility as a model of human post-stroke bone loss. Methods: Twenty 15-week old spontaneously hypertensive male rats were randomized to MCAo or sham surgery controls. Primary outcome: group differences in trabecular bone volume fraction (BV/TV) measured by Micro-CT (10.5 micron istropic voxel size) at the ultra-distal femur of stroke affected left legs at day 28. Neurological impairments (stroke behavior and footfaults) and physical activity (cage monitoring) were assessed at baseline, and days 1 and 27. Serum bone turnover markers (formation: N-terminal propeptide of type 1 procollagen, PINP; resorption: C-terminal telopeptide of type 1 collagen, CTX) were assessed at baseline, and days 7 and 27. Results: No effect of stroke was observed on BV/TV or physical activity, but PINP decreased by -24.5% (IQR -34.1, -10.5, p = 0.046) at day 27. In controls, cortical bone volume (5.2%, IQR 3.2, 6.9) and total volume (6.4%, IQR 1.2, 7.6) were higher in right legs compared to left legs, but these side-to-side differences were not evident in stroke animals. Conclusion: MCAo may negatively affect bone formation. Further investigation of limb use and physical activity patterns after MCAo is required to determine the utility of this current model as a representation of human post-stroke bone loss.