To explore the effect of proton pump inhibitors (PPI) on the micro-structure of bone in older men. A retrospective study was conducted on data of patients over the age of 60 who were admitted to the Geriatric Department of Jiangsu People's Hospital from June 2018 to January 2019. Patients were divided into control group (taking PPI for less than 1 week, 50 cases) and PPI treatment group (taking PPI for more than 3 months, 30 cases).Biochemical indexes, bone mineral density (BMD)and trabecular bone score (TBS) were analyzed. Compared with control group, the weight and albumin level in the PPI treatment group were lower, and the thyrotropin level was higher (P<0.05).There was no statistical difference in the BMD of femur or lumbar vertebrae between the two groups (P>0.05), but the TBS of lumbar vertebrae in the PPI treatment group was significantly decreased (P<0.05).Correlation analysis found that TBS was positively correlated with alkaline phosphatase (ALP) (r=0.45, P=0.002) and body mass index (r=0.164, P=0.045), and negatively correlated with age (r=-0.291, P=0.025).Multiple linear regression model analysis showed that there was still a positive correlation between TBS and ALP (β=0.437, P=0.023).In the elderly men, the use of PPI for more than 3 months can significantly affect the bone micro-structure, and the bone micro-structure can better reflect the adverse effect of PPI on bone than BMD.