Purpose: To evaluate age- and gender-related mechanical properties and bone mineral density (BMD) of the proximal humerus at different levels and regions. Materials and Methods: Mechanical indentation testing, DXA, QCT, pQCT and the radiogrammetry (Cortical Index, CI) were carried out in 70 freshly harvested humeri from 46 human cadavers (23 females, 23-males; median age 70.5 years). Results: In the female group, a high correlation between age and BMD was found (p = 0.62 to -0.70, p <0.01) with statistically significant differences between specimens of patients 69 years or younger, and 70 years or older (p < 0.05). In the group of female specimens of age 70 years or older, BMD values were found to be significantly lower compared to their male counterparts (p < 0.05). Regardless of the specimen's age, the highest BMD and bone strenght were found in the proximal aspect and in the medial and dorsal regions of the proximal humerus. Conclusion: These findings provide an insight into the fracture mechanism of the proximal humerus and should be the basis for designing structure-oriented implants with improved implant-bone stability in osteoporotic patients.