Osteoporosis is one of the most common chronic bone diseases, involving the progressive loss of bone density with age and sex hormone deficiency. Although osteoporosis is more common in women than men, several risk factors such as alcoholism, inflammatory diseases, and hormonal disorders increase the incidence of secondary osteoporosis in men. In order to prevent and treat osteoporosis, studies on the molecular mechanism of osteoporosis and efficacies of new drugs have been performed using an ovariectomy or orchiectomy-induced osteoporosis model or a naturally aged SAMP6 model. However, these methods are time-consuming and thus extremely costly. Our study shows that TH mice may constitute an effective osteoporosis model as it displays early onset of osteoporosis and male-specific osteoporotic phenotype secondary to hyperglycemia. Moreover, testosterone injection increased BMD in orchiectomized TH mice, and treatment with alendronate restored BMD and BMC values of TH mice to the levels of age-matched B6 mice. Therefore, we propose that TH mice could be a useful animal model of secondary osteoporosisfor the development of novel therapeutics that prevent or treat bone loss and bone destruction in metabolic bone diseases. Microglia,Bulleyaconi-cine-A the resident macrophages of the central nervous system parenchyma, are exquisitely sensitive to pathological tissue alterations, altering their morphology and phenotype to adopt a so-called activated state and perform immunological functions in response to pathophysiological brain insults. A wealth of data now demonstrate that the microglia have very diverse effector functions, in line with macrophage populations in other organs. Mounting evidences also indicate that microglial activation contributes to neuronal damage in several neurodegenerative diseases including Alzheimer’s disease, prion diseases, Parkinson’s disease, multiple sclerosis, and Huntington’s disease. In prion diseases and other neurodegenerative disorders, microglia can become overactivated and release ROS, NO, and cytokines, which might cause vascular damage in addition to neurodegeneration. Pattern recognition receptors expressed on the microglial surface, including Toll-like receptors and scavenger receptors seem to associate physically to form a receptor complex, which is one of the primary, common pathways through which diverse toxin signals are transduced into ROS production in microglia. Scavenger receptor CD36 is a cell surface protein that is differentially regulated in microglia through development and in response to disease,Benzoylmesaconine and is known to be involved in microgliamediated immune response in the central nervous system. The role of CD36 in the amyloid-beta -induced microglial activation in Alzheimer’s disease has been extensively investigated, but there has been no report so far of its role in prion diseases. Neurotoxic prion protein fragment 106–126 possesses similar physicochemical and pathological properties to PrPSc, in that it forms amyloid fibrils with high b-sheet content, shows partial proteinase K resistance, and is neurotoxic in vitro. Therefore, PrP106–126 is commonly used as a model for the investigation of PrPSc neurotoxicity. In the present study, we investigated the role of the class B scavenger receptor CD36 in the activation of murine microglia induced by PrP106–126. The results of this study suggest that CD36 participates in PrP106–126-induced microglial activation by mediating iNOS, and pro-inflammatory cytokines up-regulation through the activation of Src tyrosine kinases. Microglia activation involves multiple pathways that result in morphological changes, proliferation and release of bioactive substances that play an important role in the onset and progression of neurodegenerative diseases such as Alzheimer’s disease and prion diseases.