Abstract: OBJECTIVE:To investigate serum bone biomarkers in rats with intrauterine growth restriction(IUGR)in order to determine the effects of puerarin on bone metabolism.METHODS:A rat model of IUGR was induced using a low protein diet during pregnancy.The offspring were given puerarin or an identical volume of saline via subcutaneous abdominal injection.All rats were studied at 1,3,and 8 weeks of age.Serum biomarkers of bone formation,including insulin-like growth factor-1(IGF-1),bone-specific alkaline phosphatase(BALP),osteocalcin(OC),osteoprotegerin(OPG),receptor-activator of nuclear factor-κB ligand(RANKL),as well as blood levels of calcium and phosphorus were measured.RESULTS:Serum BALP,OPG,IGF-1,and OC levels,as well as the OPG/RANKL ratio,were lower in the IUGR group compared with the control group at 1week of age(P=0.024,0.011,0.014,0.004,and0.002,respectively).At 3 weeks of age,the serum BALP and OC levels were higher in the protein-re-stricted group compared with the control group(P=0.003 and 0.001,respectively).A comparison between the IUGR plus puerarin intervention group and the IUGR group revealed differences in the levels of BALP and IGF-1 at 3 weeks of age(P=0.008 and 0.003,respectively).In addition,serum OPG and OC levels and the OPG/RANKL ratio were higher at 8 weeks of age(P=0.044,0.007,and0.016,respectively).No differences in serum calcium and phosphorus levels were observed among the three groups.CONCLUSION:Our study demonstrates that the bone microenvironment of the fetus can be altered by a low protein maternal diet and that puerarin can reverse these effects.These results indicate that the nutritional environment plays an important role in early skeletal development and that the bone turnover of IUGR rats can be altered by puerarin treatment.

Key words: Puerarin, Fetal growth retardation, Os teogenesis, Bone biomarker