If bone is the answer, then what is the question?

In the 19th century, several scientists attempted to relate bone trabecular morphology to its mechanical, load-bearing function. It was suggested that bone architecture was an answer to requirements of optimal stress transfer , pairing maximal strength to minimal weight, according to particular mathe matical design rules. Using contemporary methods of analysis, stress transf er in bones was studied and compared with anatomical specimens, from which it was hypothesised that trabecular architecture is associated with stress trajectories. Others focused on the biological processes by which trabecula r architectures are formed and on the question of how bone could maintain t he relationship between external load and architecture in a variable functi onal environment. Wilhelm Roux introduced the principle of functional adapt ation as a self-organising process based in the tissues. Julius Wolff, anat omist and orthopaedic surgeon, entwined these 3 issues in his book The Law of Bone Remodeling (translation), which set the stage for biomechanical res earch goals in our day. 'Wolff's Law' is a question rather than a law, aski ng for the requirements of structural optimisation. In this article! based on finite element analysis (FEA) results of stress transfer in bones, it is argued that it was the wrong question, putting us on the wrong foot. The m aximal strength/minimal weight principle does not provide a rationale for a rchitectural formation or adaptation; the similarity between trabecular ori entation and stress trajectories is circumstantial, not causal. Based on co mputer simulations of bone remodelling as a regulatory process, governed by mechanical usage and orchestrated by osteocyte mechanosensitivity. it is s hown that Roux's paradigm, conversely, is a realistic proposition. Put in a quantitative regulatory context, it can predict both trabecular formation and adaptation. Hence, trabecular architecture is not an answer to Wolff's question, in the sense of this article's title. There are no mathematical o ptimisation rules for bone architecture; there is just a biological regulat ory process, producing a structure adapted to mechanical demands by the nat ure of its characteristics, adequate for evolutionary endurance. It is pred icted that computer simulation of this process can help us to unravel its s ecrets.