Supplementary Material for: Tranexamic Acid Protects Ovary and Testis Functions and Ameliorates Osteoporosis in Mice

<b><i>Introduction:</i></b> In a rapidly aging society, the number of people suffering from osteoporosis keeps increasing. However, effective prevention strategies for osteoporosis are not yet currently available. <b><i>Objective:</i></b> In this study, we examined the ameliorative effects of tranexamic acid on osteoporosis in 24-month-old mice. <b><i>Methods:</i></b> During the study period, mice were orally administered tranexamic acid 3 times per week. <b><i>Results:</i></b> Bone mineral density, which is a parameter of osteoporosis, was improved following tranexamic acid administration. In addition, female mice evidenced a stronger phenotypic improvement than male mice. In female mice treated with tranexamic acid, ovary abnormalities were reduced. Furthermore, the levels of transforming growth factor-β, hyaluronic acid, CD44, reactive oxygen species, and apoptosis, as well as the number of infiltrated neutrophils and macrophages in the ovary were lower than those in the control or solvent-administered mice. In addition, 17β-estradiol levels in blood increased when compared with the control or solvent-treated mice. In addition, administration of tranexamic acid to 24-month-old male mice decreased the level of apoptosis in the testis. However, the levels of 17β-estradiol and testosterone in blood increased compared with the control or solvent-administered mice. <b><i>Conclusions:</i></b> The use of tranexamic acid had an ameliorative effect on osteoporosis, possibly by protecting ovaries and testes.