The Key Role of the Blood Supply to Bone

Abstract

The importance of the vascular supply for bone is well-known to orthopaedists but is still rather overlooked within the wider field of skeletal research. Blood supplies oxygen, nutrients and regulatory factors to tissues, as well as removing metabolic waste products such as carbon dioxide and acid. Bone receives up to about 10% of cardiac output, and this blood supply permits a much higher degree of cellularity, remodelling and repair than is possible in cartilage, which is avascular. The blood supply to bone is delivered to the endosteal cavity by nutrient arteries, then flows through marrow sinusoids before exiting via numerous small vessels that ramify through the cortex. The marrow cavity affords a range of vascular niches that are thought to regulate the growth and differentiation of hematopoietic and stromal cells, in part via gradients of oxygen tension. The quality of vascular supply to bone tends to decline with age and may be compromised in common pathological settings, including diabetes, anaemias, chronic airway diseases and immobility, as well as by tumours. Reductions in vascular supply are associated with bone loss. This may be due in part to the direct effects of hypoxia, which blocks osteoblast function and bone formation but causes reciprocal increases in osteoclastogenesis and bone resorption. Common regulatory factors such as parathyroid hormone or nitrates, both of which are potent vasodilators, might exert their osteogenic effects on bone via the vasculature. These observations suggest that the bone vasculature will be a fruitful area for future research.

Keywords: hypoxia; osteoblast; osteoclast; oxygen; skeleton; vasculature.

Figure 1

Schematic diagram showing general arrangement of the vascular supply to healthy adult bone. The main blood supply is derived from one or more nutrient arteries, which penetrate to the medulla and connect to the smaller periosteal arterial supply to enable perfusion of cortical bone. The arterial branches drain into arterio-venous sinuses in the medulla that support hematopoietic and stromal cells. Blood exits the medullary cavity via multiple small veins that penetrate the cortex. Thus, perfusion is predominantly centrifugal, at least in young adult bone.

Figure 2

Bone vasculature. A: Light micrograph showing a thin-walled blood vessel (white arrows) penetrating lamellar cortical bone of adult human phalanx; longitudinal section, image width 1.5 mm. B: Transverse section of human phalanx (ground with carbon black) showing Haversian systems with central blood vessel canals; image width 2 mm. C: MicroCT scan of a sagittal section (2-D) of adult mouse tibia infused ex vivo with a radiopaque contrast agent showing the main medullary vessel (highlighted in red);image width 3.5 mm. D: 3-D rendering of the vascular network and sinuses of the same tibia, rescanned by microCT after decalcifying the bone.

Figure 3

Schematic diagram summarising the key effects of oxygen on bone cell function. Osteoblast function (proliferation, differentiation and collagen production) are inhibited in hypoxia; osteoblasts enter a quiescent state. In contrast, hypoxia stimulates the formation of osteoclasts from mononuclear precursor cells (in the presence of RANKL and M-CSF), resulting in increased bone resorption. The negative impact of hypoxia is exacerbated by the accompanying acidosis, which blocks matrix mineralisation and stimulates mature osteoclasts to resorb.