Table 2

Targeting the subchondral bone microenvironment for the treatment of osteoarthritis (OA)

Therapeutic strategy	Agents	Effects	References
Restoring abnormal subchondral bone remodelling	Bisphosphonate, osteoprotegerin, cathepsin K inhibitor, strontium ranelate	Relieve pain, improve joint structure, and reduce bone and cartilage degradation markers	96–101
	Calcitonin	Prevent bone pathology development and promote chondrocyte anabolism	102 103
	TGF-β1 inhibitor	Reform subchondral bone remodelling and inhibit subchondral angiogenesis	60
Blocking the bridge—subchondral type H vessels	Bevacizumab	Attenuate subchondral angiogenesis	50
Blocking the bridge—subchondral type H vessels	Halofuginone	Restore coupled bone remodelling and alleviate type H vessel formation by inhibiting TGF-β1 signalling	105
Ameliorating OA-related pain by modulating the subchondral bone microenvironment	Tanezumab	Reduce pain and improve joint function by binding NGF specifically	111 112
	SB366791, APETx2	Improve acidic subchondral bone microenvironment and acid-induced pain by inhibiting TRPV1 and ASIC3, respectively	110 115
	COX2 inhibitor, Na_v1.8 inhibitor, EP4 receptor inhibitor	Blunt nociceptive signals in subchondral sensory neurons	11 113 114