The net amount of bone lost during aging is determined by the difference between the amount of bone removed from the endocortical, trabecular and intracortical components of its endosteal (inner) envelope and formed beneath its periosteal (outer) envelope. Endosteal bone loss is determined by the remodeling rate (number of basic multicellular units, BMUs) and the negative balance (the difference between the volumes of bone resorbed and formed in each BMU). Bone loss already occurs in young adult women and men and is probably due to a decline in the volume of bone formed in each BMU. The rate of loss is slow because the remodeling rate is low in young adulthood. Bone loss accelerates in women at menopause because remodeling intensity increases and BMU balance becomes more negative as estrogen deficiency reduces osteoblast lifespan and increases osteoclast lifespan. The high remodeling rate also reduces the mineral content of bone tissue. The negative BMU balance results in trabecular thinning, disappearance and loss of connectivity, cortical thinning and increased intracortical porosity. These changes compromise the material and structural properties of bone while concurrent age-related subperiosteal bone formation increases the cross-sectional area (CSA) of bone partly offsetting endosteal bone loss and the loss of structural and material strength. Thus, treatments aimed at reducing the progression of bone fragility, and reversing it, should reduce activation frequency and so reduce the number of remodeling sites, reduce osteoclastic resorption in the BMU, and so reduce the volume of bone resorbed on each of the three components of the endosteal surface thereby reducing the progression of trabecular thinning, loss of connectivity, cortical thinning and porosity. If treatment also increases periosteal bone formation, the CSA of the whole bone and its cortical area will increase. If treatment also increases endosteal bone formation in the BMU, bone balance will be less negative, especially if resorption depth is reduced. This may produce thickening of trabeculae provided activation frequency is not too low. If treatment can increase de novo bone formation at quiescent endosteal surfaces, this will increase cortical and trabecular thickness, and reduce intracortical porosity. In this way, drugs directed at both the resorptive and formative aspects of remodeling, and bone modeling may (i) increase compressive and bending strength of cortical bone by increasing the diameter of the whole bone, its CSA and the distance the cortical mass is placed from the neutral long bone axis;​ (ii) maintain or increase peak compressive stress and peak strain in trabecular bone, preventing microcracks and buckling;​ and (iii) increase the material density of bone tissue, an effect that probably should not be permitted to reach a level which reduces resistance to microdamage accumulation and progression (toughness).