Is osteoporosis a matter of over-adaptation?

The stiffness and strength of cancellous bone depends on the amount of bone mineral (BMD) and on the three-dimensional distribution of the mineral (architecture). The relationship between mechanical properties and architecture, excluding confounding effects due to BMD can be studied using computer models of cancellous bone. It was shown that adaptation to mechanical deformation energy leads to an architecture which is an optimal or semi-optimal configuration with respect to maximal stiffness and minimal mass. Thus, the stiffness of the cancellous bone relative to the amount of bone (the bone density) can be considered as an optimality criterion. Based on these findings we assumed that the status of osteoporosis - or better fracture risk - could be related to how close this optimality criterion was met. In other words, we assumed that a higher fracture risk is simply related to a less optimal structure. This was tested for cancellous bone samples taken from post mortem vertebral bodies from two groups of subjects: one group with high fracture incidence during their lives and one group of "healthy" controls. It was found that the specimen from the high fracture incidence group had an architecture leading to a slightly stiffer structure relative to the BMD value. The conclusion is therefore that vertebral bone specimen from subjects with high fracture incidence are better optimized which was contradictory to what we expected. This finding indicates that bone specimen from the "healthy" control subjects had bone matrix at locations which are relatively unloaded. This tissue can be considered as not mechanically efficient or functional. A possible explanation of the present findings is that bone from subjects with increased fracture incidence is better adapted to mechanical stress, because it needs all bone material to carry the load. This stronger adaptation might be related to a compromised safety factor against bone loss, or diminished intrinsic matrix properties (e.g., microdamage).