Table 1.

Relative factor in HO caused by S-TBI.

Factors		Main function
Osteogenic factors	BMP	Promotes differentiation of osteoblast and bone induction [33], [34]
	Thrombin	Promotes the proliferation and inhibits the apoptosis of osteoblastic cells [35]
	TGF-β1	Adjusts the proliferation and differentiation of bone cells [36], [37]
	VEGF	Induces angiogenesis and neurogenesis, and thereby promotes the healing of fractures and formation of new bone [38]
Neuropeptide and hormones	CGRP	Improves blood supply of the damaged area and accelerate fracture healing [39], [40]
	Substance P	Intensifies inflammatory response and promotes osteogenesis [41], [42]
	Leptin	Regulates the bone formation [43]
	Melatonin	Promotes the proliferation of normal bone cells and human osteoblast [44]
Change of blood–brain barrier permeability		Osteogenic macromolecules within the central nervous system release from the damaged brain tissue [30], [45]
Mechanical ventilation		Changes the electrolyte and acid–base balance in the body [46]
Coma and immobilisation		Result in inadequate supply of local blood and oxygen
Inflammation		Some inflammatory factors may promote bone formation [47], [48]

BMP = bone morphogenetic protein; CGRP = calcitonin gene-related protein; TGF-β1 = transforming growth factor β1; VEGF = vascular endothelial growth factor.