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Background: Osteoporosis is one of the most commonly occurring bone diseases characterized by decrease in bone mass and increase bone resorption leading to fractures, severe pain and deformities. Glucocorticoid-induced osteoporosis results from long-term and high dose use. Lycopene is an unsaturated carotenoid that gives tomatoes and other fruits their red color. It was reported that it is a natural antioxidant and was associated with the prevention of many chronic diseases and cancers. Aim of Study: This work was performed to study the possible protective effect of lycopene against glucocorticoidinduced osteoporosis in adult male albino rat. Material and Methods: 40 adult male albino rats were used that divided equally into four main groups: Group I (control group) was subdivided equally into two subgroups (I-A & I-B), Group II received lycopene orally 30mg/kg once daily for 8 weeks, Group III received prednisolone orally 20mg/kg once daily for 8 weeks, Group IV concomitantly received lycopene and prednisolone orally once daily at the same previous doses for 8 weeks. At the end of experiment, femur heads of all animals were obtained and processed for histological study and stained with Hematoxylin & eosin, Mallory Trichrome and for scanning electron microscope study. Results: Light microscopic examination revealed structural changes in femur head of Group III in the form of discontinuous thin trabeculae of cancellous bone with apparent faintly stained matrix with multiple pores inside trabeculae associated with minor fractures, wide bone marrow spaces were seen between trabeculae containing abundant clear areas, the endosteal surface showed irregular eroded surface. Regarding Mallory stained sections; they showed decrease collagen fibers contents with their irregular distribution in bone matrix. Scanning electron microscopic specimens showed discontinuous thin and blind ended cancellous bone trabeculae containing some areas of decreased electron density with multiple pores and minor fractures inside them. Wide bone marrow spaces were seen between trabeculae lined with irregular eroded endosteal surface; which revealed the evident of prednisolone induced osteoporosis. Group IV specimens revealed partial preservation

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