The Effects Of ADFR Scheme With Analogue Of C-terminal Pentapeptide Of Osteogenic Growth Peptide And Diphosphonate On Bone Metabolism In Ovariectomized Rats

Objective To study the effects of ADFR scheme with an analogue of osteogenic growth peptide C-terminal pentapeptide-H13D and diphosphonate on bone mineral density(BMD)and histomorphometry in ovariectomized rats,and investigate the relationships between these indexes.Methods Sixty-five female virgin Sprague—Dawley rats,three months old,were randomized by the stratified weight method into the following seven groups:ADFR of H13D-Alen-free groups including three groups such as ADFR1,ADFR2 and ADFR3,NADFR group,ALEN group,ovariectomized group(OVX)and Shamed-operated group(SHAM).All groups except SHAM were Performed bilateral ovariectomized operation.From the 15th day of operation,the rats of SHAM and OVX groups were injected subcutaneously with phosphate buffered saline(PBS)while the rats of ALEN group with alendronate 5ug/kg and the rats of NADFR group with both alendronate 5ug/kg and H13D 10nmol/kg per day for 12 weeks,the rats of ADFR groups were injected subcutaneously with H13D 10nmol/kg per day at the first several days,with alendronate 5ug/kg per day at the second several days,with an intermittent several days,then repeat.The administering modes in the three groups of ADFR were 5-5-5(day),10-10-5(day)and 14-14-7(day)respectively.12 weeks after treatment all rats were sacrificed,the BMD of femora and lumbar vertebra,the morphological and dynamic parameters for bone histomorphometry were measured.The relationship between BMD,histormorphometry in the respective group were investigated.These data were analyzed by SPSS13.0 software with analysis of variance and correlation.Results 1.Compared with group SHAM,decreased uterine wet weight and atrophyic endometrium and Similar histologic appearance and weight of kidney and liver in OVX,ADFR1,ADFR2,ADFR3,NADFR and ALEN groups were noticed.2.A high-turnover osteoporosis(OP)was evidenced in OVX group by decreased BMD, decreased trabecular volume,impaired trabecular connectivity,increased double-label bone surface and bone formation rate.The BMD,trabecular volume and connectivity were restored by alendronate which exceeded those in SHAM group,whereas dynamic parameters showed bone activation frequency and bone formation rate were significantly inhibited.Combination of alendronate and H13D could maintenance the bone activation frequency when improving bone mass and bone strength in NADFR group and ADFR groups.In comparison with group NADFR,there was an increased trend of bone activation frequency and bone formation rate in ADFR1 group.There existed superiorities in BMD and histomorphomety parameters in ADFR1 group as compared with the other two ADFR groups.Conclusions The bone loss in OVX rats could be prevented by combination of the analogues of osteogenic growth peptide C-terminal penta-peptide(H13D)and alendronate with different modes such as ADFR and NADFR.There existed superiorities in BMD and histomorphomety parameters in ADFR1 group as compared with the other two ADFR groups.The histologic appearance and weight of uterus,kidney and liver were unaffected by H13D and alendronate treatment.