All factors influencing the material composition and structure of bone do so through the final common cellular pathways of modeling and remodeling. During growth, modeling, the formation of new bone in different locations without prior bone resorption, deposits matrix upon the periosteum, enlarging the cross-sectional area of bone. Concurrently, endocortical resorption excavates the medullary canal while remodeling, the resorption and deposition of bone in the same location, assembles cortical osteons, each with their central Haversian canal. The Haversian canals and the connecting Volkmann canals form an intracortical canal network that occupies 30% of the total cortical volume. The remaining 70% is mineralized bone matrix volume. Around midlife, in women, remodeling balance becomes negative; less bone is deposited than it is resorbed by each bone’s basic multicellular units (BMUs), and remodeling rate increases; there are more BMUs removing bone upon its intracortical, endocortical, and trabecular surfaces. Canals enlarge and coalesce creating giant pores. Remodeling upon trabeculae removes them, whereas intracortical and endocortical remodeling cavitates and fragments the cortex. Bone loss becomes almost entirely cortical as trabeculae disappear. Remodeling removes more bone from a diminishing total mineralized bone matrix volume so that by old age, total mineralized bone matrix volume is halved; 70% of all bone loss is cortical because 80% of the skeleton is cortical; 30% of the bone loss arises from the 20% of the skeleton that is trabecular. Of all fractures occurring, 80% are nonvertebral and 20% are vertebral. The notion of osteoporosis as a disease of trabecular bone loss and vertebral fractures needs to be revised.