Table 1.

PDE5 inhibitors and skeleton effect

	Medication	Intervention	Skeletal changes	Other findings
Alp et al.59	Tadalafil​ Vardenfail​ Udenafil (10 mg/kg/d, OG), 2 mon	OVX (8 mon-old rats)	BMD↑ tadalafil and vardenafil (+12%) udenafil (+14%) P1NP↑ CTX↓
Huyut et al.60	Avanafil​ Zaprinast​ (10mg/kg/d, OG), 1mon	Dexamethasone (120ug/kg) (8 mon-old rat)	BMD↑ avanafil (+8%) and zaprinast (+2%)
Pal et al.55	Sildenafil (6 mg/kg/d) Vardenafil (2.5 mg/kg/d), OG, 6 wks	OVX (5 mon-old Balb/c mice)	BMD↑ sildenafil and vardenafil (L5,+45%) BV/TV↑, MS/BS↑, MAR↑, BFR↑ P1NP ↑, CTX ↔	VEGF and VEGFR2 expression ↑ In-vivo vascularization (FITC) ↑
Kim et al.15	Tadalafil (2 mg/kg/d) and vardenafil (10 mg/kg/d) OG, 6 wks	No intervention 4 mon-old C57Bl.6J mice	BMD↑ tadalafil (L4–6, 7%), vardenafil (~2%) BV/TV↑, MS/BS↑, MAR↑, BFR↑ and N.Oc/BS ↓, Cfu-Ob ↑ and ACP5+ OC ↓	Negative CNS-mediated effect
Histing et al.61	Sildenafil (5mg/kg/d), OG, 5wks	Femur fracture	Fracture healing (Radiologic and histologic finding)↑ Improved bending stiffness ↑	VEGF/CYR61 expression in callus ↑
Togral et al.63	Tadalafil (1mg/kg/d) Sildenafil (5mg/kg/d), OG, 6wks	Femur fracture	Fracture healing (Radiologic and histologic finding)↑	In-vivo vascularization (FITC) ↑
Cakir-Ozkan et al.62	Sildenafil (10mg/kg/d), OG, 4wks	Mandibular fracture	Fracture healing (Radiologic and histologic finding)↑	BMP2 and Col1 expression ↑ in callus
Dincel64	Sildenafil (10mg/kg/d), OG, 2 wks	Femur fracture	Fracture healing (Radiologic and histologic finding)↑

OG, oral gavage; MS/BS, mineralized surface/bone surface; MAR, mineral apposition rate; BFR, bone formation rate; IVIS: in vivo imaging system; FITC, fluorescein isothiocyanate-dextran