Table 1.

The effects of the skeletal and systemic diseases on bone vasculature functioning

Skeletal or systemic disease	The effects of a disease on bone vasculature and bone functioning in humans or laboratory animals
Avascular necrosis of the femoral head (ANFH)	Decreased neovascularization caused by low number of endothelial progenitor cells (EPCs), their diminished capacity to migrate and increased senescence in humans [56] Blood flow interruption caused by damage of the endothelial cell membrane, in some circumstances combined with an increased susceptibility of an individual to blood clot formation [55] Ischemic injury, necrotic death of the osteocytes, the collapse of articular surface and the eventual onset of osteoarthritis [55, 56]
Postmenopausal osteoporosis	Decrease in blood vessel volume and expression of angiogenesis-related HIF-1α, HIF-2α, and VEGF proteins in ovariectomized mice, suggesting that estrogen deficiency-induced bone loss is accompanied by a decrease in number of bone marrow-localized blood vessels [60]
Diabetes mellitus	Microangiopathy accompanying DM causes vasoconstriction and impairs blood flow within the long bones of ZDF rats [63] Decreased blood vessel supply, especially within bone marrow, may further lead to osteopenia, usually observed in chronic T2DM-affected long bones [63] Advanced glycation end products (AGEs), produced in diabetes mellitus, may also disrupt bone vasculature [68]
Atherosclerosis	Oxidized lipids produced during atherosclerotic plaque formation within bone blood vessels negatively affect bone mass by increasing anti-osteoblastogenic inflammatory cytokines and decreasing pro-osteoblastogenic Wnt ligands in ApoE-knockout, high-fat-diet-fed mice [70]