Background: Osteoporosis (OP) is a disease characterized by decreased bone mass and is widely recognized as a major health problem. Flutamide is an androgen receptor blocker used in treatment of cancer prostate. Its prolonged use is usually associated with OP which is now treated by bisphosphonates. Aim: this work was designed to explore the potential benefit of forskolin (a cAMP/protein kinase A pathway stimulant) alone and in combination with alendronate on flutamide -induced osteoporosis in rats.
Subjects and methods: Forskolin 6 mg/kg/day orally was taken either singly or in combination with Alendronate 0.1mg/kg /day orally in rat model with osteoporosis which was induced by flutamide 15 mg/kg/day orally for 4 weeks (in a three-months case-controlled study, at clinical pharmacology department labs- Benha Faculty of Medicine- Benha University). The tested parameters include bone formation marker serum osteocalcin (OC), bone resorption markers as urinary hydroxyproline (HPO) and serum sclerostin (SOST) as well as bone histopathological and histomorphometric studies on femoral bone. Results: Flutamide produced full picture of OP manifested as significant rise in urinary HPO and serum SOST level with significant decreased in serum OC level as well as distortion of microscopic bone architecture with rarefaction of cortex and trabeculae of tested bone. Alendronate failed to induce significant improvement in histomorphometric parameters or bone formation marker. It only resulted in significant decrease of urinary HPO excretion. Forskolin significantly decreased urinary HPO excretion and serum SOST with significant increase in serum OC level. It produced marked improvement in both histopathologic and histomorphometric parameters. Moreover, Forskolin augmented the effect of alendronate. Conclusion: Forskolin is a promising agent in management of OP either singly or in combination with alendronate.
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