Expression And Significance Of Serum Sclerostin During The Iron Accumulation Osteoporotic Fracture Healing In Rabbits

Objective: Iron accumulation osteoporotic fracture rabbit models were established to investigate the expression and significance of serum sclerostin during the healing of iron accumulation osteoporotic fracture in current investigation.Iron accumulation conditions were established by treating animals with iron sucrose.Our study was aimed to provide a theoretical basis for the treatment of iron accumulation osteoporotic fracture by inhibiting serum sclerostin,and develop a new animal method for iron accumulation condition osteoporosis.Methods: 40 five-month old female New Zealand rabbits were randomly divided into three groups: Control group(10 rabbits);ovariectomized group(OVX,10 rabbits);and model group(iron sucrose 20mg/kg,20 rabbits),respectively.The bilateral ovaries of OVX and model group were removed,while those of the control were not.The level of serum ferritin,P1 NP,CTX and the lumbar bone mineral density(BMD)were measured before and 4,8,12,16,20 and 24 weeks after the ovariectomy.After 24 weeks,Iron accumulation models of model group were randomly divided into two groups: non-fracture group(10 rabbits)and fracture group(10 rabbits).Left distal radius fractures were caused by operation of fracture group,while rabbits in the non-fracture group were not.The level of serum ferritin,P1 NP,CTX and sclerostin were determined before and 1,3,7,14,21,and 28 days after the operation,respectively.The score of callus formation were evaluated by X-Rays 1,3,7,14,21,and 28 days after operation,respectively.Results:(1)Iron accumulation rabbits model can be induced by injecting iron sucrose with no adverse reaction or death.(2)Compared with control group,serum ferritin in the model group was significantly increased at 8,12,16,20 and 24-week(P<0.05).(3)Compared with control group,P1 NP,CTX in the model group and OVX were significantly increased at 12,16,20 and 24-week(P<0.05),while P1 NP and CTX in the model group were significantly higher than those in the OVX at 20 and 24-week(P<0.05).(4)The decreased percentage of lumbar BMD in the model group and OVX were 33.40% and 25.92%(P<0.05).(5)Compared with SHAM group,the serum sclerostin in fracture group was significantly decreased at 1,3,7,14,21 and 28-day(P<0.05),and the change of level was related to fracture.(6)All process of callus formation in fracture group were accompanied with the decline of serum sclerostin(P<0.05),which reached the lowest value(34.72ng/ml)14 days after fracture.Serum sclerostin negatively correlated with the score of callus formation(r=-0.746,P<0.05).(7)The changes of serum sclerostin and CTX were in the trend of decline in the fracture group,while P1 NP was increased.No correlation was found between serum sclerostin and serum ferritin.Conclusion:(1)Iron accumulation osteoporosis rabbit model can be successfully established by injecting iron sucrose combined with ovariectomy.(2)The decline of serum sclerostin were initiated in the early stage of iron accumulation osteoporotic fracture healing,and the condition of lower serum sclerostin level companied with all the fracture healing process.(3)The down-regulation of serum sclerostin was suggested to promote fracture healing.