Ischemic stroke reduces bone perfusion and alters osteovascular structure

Abstract

Stroke patients lose bone mass and experience fracture at an elevated rate. Although functional intraosseous vasculature is necessary for skeletal maintenance, the effect of stroke on osteovasculature is unknown. In this study we characterized changes to osteovascular perfusion, structure, and composition following mild-to-moderate stroke severity in mice, both with and without exercise therapy. Twelve-week-old male mice (n = 27) received either an ischemic stroke (middle cerebral artery occlusion) or sham procedure, followed by a four-week recovery with either moderate daily treadmill or sedentary activity. Intraosseous perfusion, measured weekly in the proximal tibial metaphysis with laser Doppler flowmetry, was reduced for two weeks in the stroke group relative to the sham group. After four weeks, osteovascular structure was assessed in the distal femoral metaphysis with contrast-enhanced computed tomography. Increased osteovascular volume and branching, decreased number of smaller vessels (6–22 μm), and increased number of larger vessels (>66 μm) were observed in the stroke groups compared to sham groups, which may be a compensatory response to early perfusion deficits. Although moderate exercise mitigated the impact of stroke on osteovascular perfusion and volume, it tended to reduce the amount of osteogenic type H vasculature quantified with immunofluorescence microscopy and, exacerbated by stroke effects, produced fewer vessels in close proximity to bone and thus may have detrimental effects on bone remodeling during early stroke recovery. Since results were similar in both limbs, the effects of ischemic stroke on osteovascular perfusion and structure were primarily systemic, rather than resulting from paresis or disuse, providing new insight for future studies on the pathogenesis and treatment of skeletal fragility in stroke patients.