Bone shaft geometry adaptation to effects of estrogen deficiency, glucocorticoid therapy, rheumatoid arthritis and bisphosphonate. (a) Estrogen deficiency or usage of systemic glucocorticoids leads to enhanced osteoclastogenesis and thus endosteal resorption and cortical porosity. However, bone formation in these conditions is inhibited, resulting in a decreased periosteal bone apposition that insufficiently compensates for the endosteal resorption. Solid lines, present bone envelopes; dashed lines, past bone envelopes. (b) Under inflammatory conditions such as rheumatoid arthritis (RA) endosteal bone resorption is accelerated, leading to an increase of marrow cross-sectional area (CSA). Periosteal bone apposition seems to compensate the endosteal bone loss and leads to an increase in total and cortical shaft CSA, resulting in a maintained estimated compression and bending strength. (c) Preliminary data in RA patients indicate that bisphosphonate may inhibit periosteal bone apposition and does not always stop endosteal bone resorption. In these cases, the endosteal resorption cannot be compensated and the cortical thinning predisposes to fractures of long bone shaft.