| Objective: (1)To explore a new strontium compound with little toxicity and side effects, with considerable solubility, with upgrading bioavalibility and bone target, we designed the compound with improved organic principle. (2)We investigate the toxicity and physiological effects of the compound to ROS17/2.8 cells. (3)To ivestegate the therapeutical effects to the SD rat model of postmenopausal osteoporosis.Methords. (1)Improving the organic principle of strontium: Taking the etidronate as the organic principle of strontium, we combined the both and got a new compound—strontium etidronate. (2)In order to study the vitro bone-targeted characteristic, we did the hydroxylapatite absorption experiment. (3)We studied the cell morphology, typan blue exclude ecperiment, and MTT reduction assay experiment of ROS17/2.8 cells, with 10-5M～10-3M disodium etidronate, strontium chloride and strontium etidronate, to investigat the cell toxicity. (4)We studied the ALP activity, I collagen express of ROS17/2.8 cells, with 10-5M～10-3M disodium etidronate, strontium chloride and strontium etidronate, to investigat the cell physiological effects. (5)We studied the serum BGP and TRAP-5b of SD rats model of postmenopausal osteoporosis model at different times, to investegat the drug effects of bone metabolism involving disodium etidronate (80mg/Kg.day), strontium chloride (60mg/Kg.day) and strontium etidronate (50mg/Kg.day, 100mg/Kg.day and 150mg/Kg.day). (6)We studied the femoral and second lumbar vertebral BMD of SD rats model of postmenopausal osteoporosis model at different times, to investegat the drug effects of BMD involving disodium etidronate (80mg/Kg.day), strontium chloride (60mg/Kg.day) and strontium etidronate (50mg/Kg.day, 100mg/Kg.day and 150mg/Kg.day). (7)We studied the femoral and second lumbar vertebral biomechanical characteristics of SD rats model of postmenopausal osteoporosis model at different times, to investegat the drug effects of biomechanical characteristics involving disodium etidronate (80mg/Kg.day), strontium chloride (60mg/Kg.day) and strontium etidronate (50mg/Kg.day, 100mg/Kg.day and 150mg/Kg.day). (8)We studied the femoral and second lumbar vertebral histomorphology of SD rats model of postmenopausal osteoporosis model at different times, to investegat the drug effects of femoral and second lumbar vertebral histomorphology involving disodium etidronate (80mg/Kg.day), strontium chloride (60mg/Kg.day) and strontium etidronate (50mg/Kg.day, 100mg/Kg.day and 150mg/Kg.day).Rsults. (1)Condensed phosphorus trichloride with glacial acetic acid, then counteracted by NaOH, we could get disodium etidronate. Added strontium chloride into the solution of disodium etidronate, we got highly purified strontium etidronate. (2)In the vitro hydroxylapatite absorption experiment, we found the strontium iron in strontium etidronate showed obvious affinity with the hydroxylapatite. (3)In experiment, we didn't find the cell toxicity form 10-5M～10-3M strontium etidronate. We found strontium etidronate could evidently prompt the growth and proliferation of ROS 17/2.8 cells, and the effects was more obvious than strontium chloride. (4)In experiment, we found there was more colour of ALP and I collagen express in ROS17/2.8 cells cultivated with strontium chloride and strontium etidronate. The strontium chloride and strontium etidronate had more ability on improving ALP activity and I collagen express in ROS17/2.8 cells than disodium etidronate. (5)We didn't find the obvious changes of serum BGP level, after being treated with strontium etidronate (100mg/Kg.day) and strontium chloride (60mg/Kg.day), and it continually decrease in involving disodium etidronate (80mg/Kg.day) rats, but it continually decrease in involving strontium chloride (60mg/Kg.day)rats. We found the quickly decrease of serum TRAP-5b level, after being treated with disodium etidronate (80mg/Kg.day), it decrease gradually in strontium etidronate (100mg/Kg.day), and it showed little higher in strontium chloride (60mg/Kg.day) rats. We found there no obvious changes of serum BGP level, after being treated with strontium etidronate (50mg/Kg.day, and 100mg/Kg.day), but it increased gradually in strontium etidronate (150mg/Kg.day) rats, and show obviously different. Being treated with strontium etidronate (50mg/Kg.day, 100mg/Kg.day and 150mg/Kg.day), serum TRAP-5b level of all rats decrease apparently. (6)We found the second lumbar vertebral BMD increased gradually in the rats treated by disodium etidronate (80mg/Kg.day) and strontium etidronate (100mg/Kg.day), and there no obvious changes of those treated by strontium chloride (60mg/Kg.day), there no obvious changes on femoral BMD in all rats above. We ound the second lumbar vertebral BMD increased gradually in the rats treated by strontium etidronate (50mg/Kg.day, 100mg/Kg.day and 150mg/Kg.day), and the obvious increase on femoral BMD in the rats treated by strontium etidronate (150mg/Kg.day). (7)We found no obvious changes in femoral Max Load and Flexure at Max Load under three point bending test in rats treated by disodium etidronate (80mg/Kg.day), strontium chloride (60mg/Kg.day) and strontium etidronate (50mg/Kg.day, 100mg/Kg.day and 150mg/Kg.day). we found the apparently increase in second lumbar vertebral Max Load under compress test in rats treated by strontium etidronate (50mg/Kg.day, 100mg/Kg.day and 150mg/Kg.day), and Flexure at Max Load in rats treated by strontium etidronate (100mg/Kg.day and 150mg/Kg.day). (8)We found there obviously increased bone trabecular micro-crack, inhibition of both bone resorption and formation, and increase of bone trabecular on number and volume after 8～12 weeks treated by disodium etidronate (80mg/Kg.day). We also found there obviously increased bone trabecular micro-crack, activity of both bone resorption and formation, and no obvious increase of bone trabecular on number and volume after 8～12 weeks treated by strontium chloride (60mg/Kg.day). We found there no obviously increased bone trabecular micro-crack, inhibition of both bone resorption and activity of bone formation, and obvious increase of bone trabecular on number and volume after 8～12 weeks treated by strontium etidronate (100mg/Kg.), and these phenomemons also could be found in rats treated by strontium etidronate (50mg/Kg.day). We found above phenomemons were more obvious in 100mg/Kg.day and 150mg/Kg.day groups than 50mg/Kg.day group, and most micro-cracks had been repaired.Conclusions: (1) we could get highly purified strontium etidronate in lab. (2)The etidronate could improve strontium iron affinity with the hydroxylapatite. (3)10-5M～10-3M strontium etidronate shows no toxicity to ROS 17/2.8 cells. Strontium etidronate could evidently prompt the growth and proliferation of ROS17/2.8 cells. (4)Strontium etidronate could improve the ALP activity and I collagen express in ROS17/2.8 cells. (5)Strontium etidronate (100mg/Kg.day) shows no obvious effect on the serum BGP level, and decrease the serum TRAP-5b level. Strontium etidronate (50mg/Kg.day, 100mg/Kg.day and 150mg/Kg.day) could decrese serum TRAP-5b level of all rats apparently. (6)Strontiurn etidronate (100mg/Kg.day) could increase the second lumbar vertebral BMD in the osteoporosis rats, and prevent the decrease of femoral BMD. Strontium etidronate (50mg/Kg.day, 100mg/Kg.day andlS0mg/Kg.day), could obviously increase the lumbar vertebral BMD in osteoporosis rats. (7)Strontium etidronate (100mg/Kg.day) could improve the osteoporosis rats on femoral Max Load after 8 weeks. Strontium etidronate (100mg/Kg.day and 150mg/Kg.day) could improve the osteoporosis lumbar vertebral Max Load and the deformation ability under compress test. (8)Strontium etidronate (50mg/Kg.day, 100mg/Kg.day,and150mg/Kg) could increase the number and volume bone trabecular and repair activity, increase the bone mass, and the effect shows positive relation with the dose.
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