Therapeutic Effect of Strontium Ranelate on Bone in Chemotherapy-Induced Osteopenic Rats via Increased Bone Volume and Reduced Bone Loss

Abstract

The purpose of this study was to determine whether treatment with strontium ranelate (SrR) can restore bone mass and strength at a skeletal site with established osteopenia in chemotherapy-induced rats. Forty-five Sprague-Dawley male rats were randomly assigned to three study groups (n = 15 rats per group): normal rats (control group), osteopenic rats (chemo group), and osteopenic rats with SrR (chemo-SrR group). We chose a male rat model that mimicked a clinical setting by weekly intravenous injection of cyclophosphamide at 20 mg/kg. The control and chemo groups were maintained without treatment, and the chemo-SrR group was intragastrically administered strontium ranelate at a dosage of 900 mg/kg/day. All animals were fed a standard laboratory diet, and blood samples were collected for biochemical analysis. After 12 weeks of treatment, micro-CT, biomechanical testing, and histomorphometry were examined. In addition, bone samples were obtained to evaluate the content of mineral substances in bones. SrR treatment of chemo rats significantly increased tibial trabecular bone volume, trabecular thickness, and BV/TV. Serum levels of the bone formation marker alkaline phosphatase (ALP) in the SrR group were significantly higher than those in the chemo animals, which was accompanied by an increase in the bone mineral content, bone calcium and phosphate, as well as reduced serum Ca and P concentrations. The serum level of tartrate-resistant acid phosphatase (TRAP) in the SrR treatment group showed no obvious changes. Histomorphological analyses revealed that chemotherapy resulted in decreased osteoclast number, which may be due to the inhibition of bone turnover. However, SrR treatment enhanced the number of osteoblasts while restoring bone mass and improving bone strength in chemo rats. Therefore, the results of this study indicate that SrR treatment has a positive effect on bone in chemotherapy-induced osteoporosis.

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