Objective: To observe the therapeutic effect and mechanism of lactoferrin on glucocorticoid-induced osteoporosis (GIOP) in rats. Methods: Sixty female SPF Wistar rats were randomly divided into control group

model group

low-dose lactoferrin group

medium-dose group

high-dose group and alendronate group. Dexamethasone sodium phosphate injection was intramuscularly injected to establish GIOP model rats. After the molding being completed

drug intervention was given to them by gavage. The bone morphology and bone mineral density (BMD) were detected by radiological examinations. The levels of procollagen type 1 amino-terminal propeptide (P1NP)

bone alkaline phosphatase (bALP)

osteocalcin (OC)

β-crosslaps (β-CTX)

insulin like growth factor-1 (IGF-1)

IGF binding protein-3 (IGFBP-3)

IGFBP-4

and IGFBP-5 in serum were detected by enzyme linked immunosorbent assay (ELISA). Western blot was used to detect the expression of IGF-1 receptor (IGF-1R) and phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) signal-related proteins in femoral tissue. Results: Compared with control group

the BMD value of rats in the model group was decreased (P=0.000) and bone morphology was destroyed. The serum levels of P1NP

bALP

OC

β-CTX

IGF-1

IGFBP-3

IGFBP-4 and IGFBP-5 were increased significantly (P=0.000). There was no significant difference in the protein expression of IGF-1R

p-PI3K/PI3K

p-Akt/Akt

and p-mTOR in femoral tissue (P>0.05). Compared with those of model group

the BMD (P=0.030

P=0.008) and bone morphology of rats in middle and high-dose of lactoferrin groups increased; serum levels of P1NP (P=0.009

P=0.000)

bALP (P=0.002

P=0.000)

OC (P=0.007

P=0.000) and β-CTX (P=0.020

P=0.009) decreased; serum levels of IGF-1 (P=0.007

P=0.003)

IGFBP-3 (P=0.030

P=0.007)

IGFBP-4 (P=0.020

P=0.009)

and IGFBP-5 (P=0.040

P=0.008) increased dose-dependently; the protein expression of IGF-1R (P=0.020

P=0.006)

p-PI3K/PI3K (P=0.040

P=0.005)

p-Akt/Akt (P=0.003

P=0.007) and p-mTOR (P=0.010

P=0.000) was significantly up-regulated in middle and high-dose lactoferrin groups in femoral tissues. Conclusion: Lactoferrin can improve the bone metabolism of GIOP in rats

and it is related to the regulation of IGFBP and IGF-1-mediated PI3K/mTOR signal activation. Lactoferrin has potential anti-osteoporosis activity.