Microscopic tissue damage can occur in bone as a result of an isolated overload leading to reduces bone strength under subsequent loads. In addition, microscopic tissue damage is believed to stimulate bone resorption and bone loss. Microscopic tissue damage in bone is most commonly measured in two-dimensional sections using stereology techniques. Stereology techniques are accurate but can have limited precision. Previous studies have presented guidelines for adequate sampling of naturally occurring microcracks in cortical bone, but such guidelines have not been presented for cancellous bone and have not addressed other forms of microscopic tissue damage (i.e. diffuse damage). Here a statistical model is presented that can be used to design studies in which microscopic tissue damage in cancellous bone is a key study outcome.