Osteoporosis is associated with systemic bone loss, leading to a significant deterioration of bone microarchitecture and an increased fracture risk. Although recent studies have shown that the distribution of bone mineral becomes more heterogeneous because of estrogen deficiency in animal models of osteoporosis, it is not known whether osteoporosis alters mineral distribution in human bone. Type 2 diabetes mellitus (T2DM) can also increase bone fracture risk and is associated with impaired bone cell function, compromised collagen structure, and reduced mechanical properties. However, it is not known whether alterations in mineral distribution arise in diabetic (DB) patients' bone. In this study, we quantify mineral content distribution and tissue microarchitecture (by ¿CT) and mechanical properties (by compression testing) of cancellous bone from femoral heads of osteoporotic (OP; n = 10), DB (n = 7), and osteoarthritic (OA; n = 7) patients. We report that though OP cancellous bone has significantly deteriorated compressive mechanical properties and significantly compromised microarchitecture compared with OA controls, there is also a significant increase in the mean mineral content. Moreover, the heterogeneity of the mineral content in OP bone is significantly higher than controls (+25%) and is explained by a significant increase in bone volume at high mineral levels. We propose that these mineral alterations act to exacerbate the already reduced bone quality caused by reduced cancellous bone volume during osteoporosis. We show for the first time that cancellous bone mineralization is significantly more heterogeneous (+26%) in patients presenting with T2DM compared with OA (non-DB) controls, and that this heterogeneity is characterized by a significant increase in bone volume at low mineral levels. Despite these mineralization changes, bone microarchitecture and mechanical properties are not significantly different between OA groups with and without T2DM. Nonetheless, the observed alterations in mineral heterogeneity may play an important tissue-level role in bone fragility associated with OP and DB bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.