Mechanisms of bone blood flow regulation in humans

Bone is a highly vascularized tissue. However, despite the importance of appropriate circulation for bone health, regulation of bone blood flow remains poorly understood. Invasive animal studies suggest that sympathetic activity plays an important role in bone flow control. However, it remains unknown if bone vasculature evidences robust vasoconstriction in response to sympathoexcitatory stimuli. Here, we characterized bone blood flow in young healthy individuals [n = 13, (four females)] in response to isometric handgrip exercise (IHE) and cold pressor test (CPT). These provide a strong stimulus for active vasoconstriction in the inactive muscle, and perhaps also in the bone. During sustained IHE to fatigue and CPT, we measured blood pressure, whole leg blood flow, and tibial perfusion using near-infrared spectroscopy. Tibia perfusion was determined as oxy- and deoxyhemoglobin. For both stimuli, tibial metabolism remained constant (i.e., no change in deoxyhemoglobin) and thus tibial arterial perfusion was represented by oxyhemoglobin. During IHE, oxyhemoglobin declined (beginning -0.20 ± 1.04 μM; end -1.13 ± 3.71 μM, both P < 0.01) slower than whole leg blood flow (beginning -0.85 ± 1.02 cm/s; end -2.72 ± 1.64 cm/s, both P < 0.01). However, during CPT, both oxyhemoglobin (beginning -0.46 ± 1.43 μM; end -0.60 ± 1.59 μM, both P < 0.01) and whole leg blood flow (beginning -1.52 ± 1.63 cm/s; end -0.69 ± 1.51 cm/s, both P < 0.01) declined with a similar timecourse, even though the magnitudes of decline were smaller than during IHE. These responses are likely due to the different timecourses of sympathetically mediated vasoconstriction in bone and muscle. These results indicate that sympathetic innervation of the bone vasculature serves a functional role in the control of flow in young healthy individuals.NEW & NOTEWORTHY The current study is the first one to noninvasively investigate control of bone blood perfusion in vivo in humans, on a moment-by-moment basis. Our results indicate that tibial bone vasculature demonstrates active vasoconstriction in response to sympathoexcitatory stimuli in young healthy individuals. Compared with whole leg vasculature, bone vasoconstrictor response seems to be smaller, delayed, and more variable.