Interventional effect of ibandronate on osteoporosis in ovariectomized rats / 中国组织工程研究

ABSTRACT

BACKGROUND: Diphosphonate has a predominant therapeutic effect in the prevention and treatment of postmenopausal osteoporosis. Ibandronate, as a new-type diphosphonate preparation, is gradually becoming a study hotspot.OBJECTIVE: This study is to investigate the efficiency of ibandronate in interfering postmenopausal osteoposis by observing bone mass loss related indexes in ovariectomized rats, and made a comparison with nilestriol.DESIGN: A completely randomized grouping, and controlled animal experiment.SETTING: Study Room for Bone metabolism, Fudan University Medical College.MATERIALS Forty SD female rats, aged 10-12 months, were involved in this study. Ibandronate was provided by the State Key Laboratory of Jiangsu Institute of Atomic Medicine. Nilestriol was produced in the Shanghai 12th Pharmaceutical Factory.METHODS: This experiment was carried out in the Study Room for Bone Metabolism, Institute of Radiation Medicine,Shanghai Medical University between August 1996 and June 1998. The rats were divided into 4 groups by a lot, 10 rats in each sham-operation group, ovariectomized group, ovariectomized+ibandronate group and ovariectomized +nilestriol group. In the sham-operation group, only small pieces of adipose tissue around the ovary were resected from the rats.Three months after operation, each rat was intragastrically administrated with 1 mL normal saline; In the ovariectomized group, ovariectomized+ibandronate group and ovariectomized +nilestriol group, each rat was subjected to bilateral ovariectomy, and 3 months later, they were intragastrically administrated with normal saline, ibandronate water solution [0.5 mg/( kg·d)] and nilestriol suspension [1 mg/(kg· time)] respectively. Each rat in the latter three groups was administrated for 90 days, twice in the first week, and then once a week.MAIN OUTCOME MEASURES: Left femur was taken out, and its dry weight and ash weight were measured. Calcium content of bone was determined with an atomic absorption spectrophotometer, bone density of the whole body with a bone density apparatus, the bone density at the juncture of 1/2 right femoral bone length with a single photon bone density apparatus, and femoral anti-bending force was determined with a universal testing machine. Alkaline phosphatase were determined by dynamical method with an automatic biochemistry analyzer, urine calcium by EDTA titration method, urine creatinine by picric kinetic method, and urinary hydroxyproline by modified proline assay.Trabecular area was calculated.RESULTS: Forty rats were involved in the final analysis. ① Bone dry weight, bone ash weight and bone calcium content in the ovariectomized group were significantly lower than those in the other 3 groups, respectively (t =13.58-52.98, P ＜0.05). ② Femoral bone density and bone density of the whole body of rats in the ovariectomized group were significantly lower than those in the other 3 groups (t =3.31-5.61, P＜0.05), while anti-bending force was close between ovariectomized group and the other 3 groups (P＞0.05). ③ The ratio of urine calcium to urine creatinine was significantly lower in the ovariectomized+ibandronate group and ovariectomized +nilestriol group than in the ovariectomized group (t =4.04, 3.30, P＜0.05). No significant difference in the alkaline phosphatase and ratio of urinary hydroxyproline to urinary creatinine existed among the groups (P ＞ 0.05). ④Trabecular area of vertebrae in the ovariectomized group was significantly smaller than that in the other 3 groups (t =2.22,2.41,3.45,P ＜ 0.05), while the trabecular area of tibia in the ovariectomized group was only smaller than that in the ovariectomized +nilestriol group (t =2.45, P＜ 0.05).CONCLUSION: Osteoporosis apPears obviously in the SD rats 3 months after ovariectomy. Ibandronate has obviously inhibitory effects on the bone mass loss of rats with postmenopausal osteoposis, and it is equivalent to nilestriol in inhibitory effect.