Preparation And Feasibility Study Of Zoledronic Acid-Loaded Bone Cement

ObjectiveGiant cell tumor of bone is a common primary bone tumor. It is about4-5%of allprimary bone tumors,15%of benign bone tumors. Its incidence rate is different betweenEastern and Western countries, significantly higher in the Eastern countries. Theprevalence rate of of women is higher than the men’s. Giant cell tumor of bone haspotential malignancy, strong invasiveness，and high local recurrence rate. In order toreduce the recurrence rate, we usually use an adjuvant measure. Several methods havebeen proposed, such as phenol. liquid nitrogen high-speed burring cryotherapy andPMMA.But It can not determine if these measures can significantly reduce the recurrencerate. Bisphosphonates is a synthetic analogue of pyrophosphate,It is the most importantdrugs which is used in the clinical treatment of the disease which own osteoclast-mediatedbone resorption characteristics. It is widely used in a variety of malignant tumors of bonemetastases, cancer-induced hypercalcemia, osteoporosis, Paget’s bone disease and otherdiseases. Studies have shown that bisphosphonates can reduce the recurrence rate of giantcell. Tumor of bone. It is used mainly by oral and Intravenous infusion. There are manyadverse reactions. The local delivery is an ideal choice. Zoledronic acid is thethird-generation of bisphosphonates. It has many advantages suach as low dosesHighefficacy and so on. The bone cement is a good carrier of multiple drugs. To confirmzoledronic acid-loaded bone cement’S safety and effectiveness required biomechanicaltesting tand elution studies of drug delivery system. In this paper,we preliminarily evaluatethe feasibility of zoledronic acid bone cement and to determine the suitable amountofzoledronic acid in the bone cement. In order to use it to treat giant cell tumor of bone inthe future.Methods1.Study of biomeehanicsSamples of compression strength，bending strength, bending modulus were prepared with bone cements added0mg.or0.5mg、or1.0mg、or2.0mg、or4.0mg zoledronic acid in40gbone cement powders respectively. Compression strength，bending strength and bendingmodulus of bone cements were examinated by RGT-10A tester before elution and afterelution for4weeks.2.Elution experimentsProgram OneSamples lixiviated were prepared with bone cement added0mg.or0.5mg、or1.0mg、or2.0mg、or4.0mg zoledronic acid in40g bone cement powders respectively. One sampleof each group was dipped into50ml0.9%physiologieal saline and lixiviated for4weeks.5ml leaching liquor of eaeh group was collected at l、2、3、4、5、6、7、9、11、14、17、21、28d，and concentrations of zoledronic acid were detected by high-pressure liquidchromatography-ultraviolet spectrometry. zoledronic acid’s release percent of total amountand it’s reasing velocity of each group were determined at different time points.Program TwoCompared with the program one,we added0mg.or0.5mg、or1.0mg、or2.0mg、or4.0mgzoledronic acid in1.0g bone cement powders respectively.and used the detection methods.Program ThreeCompared with the program two,we changed the brand of bone cement,and used thesame methods like program two.Results1There are no effects on bending strength and bending modulus when0.5mg、or1.0mg、or2.0mg、or4.0mg zoledronic acid added in40g bone cement powders. There aresignificant effect on compression strength.2We failed to detect the zoledronic acid in last three programs.Conclusions1Static mechanical properties of bone cement in all groups accorded to standards ofISO5833(2002) for acrylic bone cement.Less than4.0mg zoledronic acid added in40gbone cement powders didn’t decrease compressive strength、flexural(modulus) strengthbefore elution and after elution for4weeks.2The methods that added the zoledronic acid into bone cement directly to prepare thezoledronic acid loaded bone cement is unacceptable.