Skeletal mass and architecture are regulated to meet the physical and metabolic demands placed upon the skeleton. This is accomplished through the actions of bone-resorbing osteoclasts, bone-forming osteoblasts, and the matrix-bound, mechanosensitive osteocytes. These cells are regulated to a great extent by one another. The challenge is determining how this regulatory cross-talk changes with age and in disease states to cause imbalances in bone formation and resorption. Of particular interest in our lab is the role estrogen receptors play in modulating the actions of all three bone cell populations. Unique genetic models and novel in vitro bone cell culture systems provide insights into the role of mechanical stimuli, estrogen, and its receptors in regulating bone mass.