Bone density, microstructure, and bone quality are all contributors of bone strength. Within bone quality, any changes to the inorganic (mineral) or organic (protein) components of bone’s extracellular matrix can lead to alterations in bone’s mechanical behavior. Further, microscale damage can accumulate within the extracellular matrix that also leads to deteriorations in bone mechanics. In this work, we consider several clinically relevant alterations to bone quality to understand how altered bone quality affects bone’s biomechanical behavior. To pursue this goal, we will 1) determine whether altered inorganic matrix detrimentally affects bone mechanical properties using an in vitro incubation that simulates skeletal fluorosis, 2) determine whether altered organic matrix detrimentally affects bone mechanical properties and whether bone mechanical properties in an in vitro incubation that simulates type 2 diabetes can be improved by treatment with [a] vitamin B and [b] metformin, and 3) determine how microdamage and altered organic matrix affects fracture in type 2 diabetic vs non-diabetic bone. Our findings show that changes to bone quality can significantly alter the mechanical properties of bone.