The role of sympathetic control in bone vasculature: insights from spinal cord injury

J Bone Miner Res. 2024 Dec 23:zjae204. doi: 10.1093/jbmr/zjae204. Online ahead of print.

Abstract

Bone vasculature is richly innervated by an extensive network of sympathetic nerves. However, our understanding of bone blood flow regulation and its contribution to human bone health is limited. Here, we further our previous findings by characterizing bone vascular responses in the absence of sympathetic control - studying individuals with spinal cord injury (SCI), a population with known peripheral sympathetic disruption. We assessed tibial vascular responses to isometric handgrip exercise (IHE) in individuals with SCI (n = 12) and controls (n = 12). When sustained to fatigue, IHE increases perfusion pressure and sympathetic vasoconstriction in the non-active tissues of the legs. During IHE, we measured blood pressure, whole leg blood velocity via ultrasound, and tibial perfusion (as hemoglobin content) via near-infrared spectroscopy. Controls demonstrated active sympathetic vasoconstriction in the whole leg (i.e., increased vascular resistance, arterial pressure/leg blood velocity) and tibia (i.e., decreased hemoglobin). In contrast, SCI individuals demonstrated modest whole leg vasoconstriction with lesser increases in vascular resistance than controls (P<.04). Tibial vasculature evidenced absent or blunted vasoconstriction compared to controls (P<.01), indicated by increasing tibial hemoglobin until plateauing at higher pressure levels. This suggests that, in the absence of sympathetic control, tibial vascular response may involve other regulatory mechanisms like myogenic vasoconstriction. Lastly, we leveraged existent whole-body Dual Energy X-ray Absorptiometry scans in a subgroup of nine individuals with SCI and we found a strong relationship between leg bone mineral density (BMD) and tibial hemoglobin at end of IHE (r2 = 0.67, P<.01). Our findings indicate that in the absence of sympathetic mechanisms, myogenic control may play a compensatory role in regulating blood flow, though to a lesser extent in bone compared to muscle. The close relationship between lesser declines in bone blood content and higher BMD underscores the link between blood flow and bone health.

Keywords: Bone blood flow; Isometric handgrip exercise; Myogenic vasoconstriction; Near infrared spectroscopy; Spinal cord injury; Sympathetic control.

Plain language summary

The bone vasculature is regulated by nerves that control blood flow, which are vital for maintaining bone health. However, our understanding of how these nerves regulate flow in bone is extremely limited, especially in humans. In this work we examined how bone vasculature responds without nerve control by studying people with spinal cord injuries (SCI), who have control mechanisms disrupted. We measured blood flow response in the shin bone during handgrip exercise in 12 people with SCI and 12 uninjured people. This exercise increases blood pressure and nerve-induced constriction in the legs. We used ultrasound to measure leg blood flow and a light-based technique to measure shin blood flow. In uninjured people, nerve activity reduced blood flow in the shin, but in those with SCI there was almost no constriction in the shin. This suggests that other mechanisms might regulate blood flow when nerve control is absent. Additionally, we found a strong link between higher blood content in the shin at the end of exercise and better bone density in the SCI participants. Our findings indicate that blood flow is important for maintaining bone health.