A case for strain-induced fluid flow as a regulator of BMU-coupling and osteonal alignment.

Throughout life, human bone is renewed continuously in a tightly controlled sequence of resorption and formation. This process of bone remodeling is remarkable because it involves cells from different lineages, collaborating in so-called basic multicellular units (BMUs) within small spatial and temporal boundaries. Moreover, the newly formed (secondary) osteons are aligned to the dominant load direction and have a density related to its magnitude, thus creating a globally optimized mechanical structure. Although the existence of BMUs is amply described, the cellular mechanisms driving bone remodeling-particularly the alignment process-are poorly understood. In this study we present a theory that explains bone remodelling as a self-organizing process of mechanical adaptation. Osteocytes thereby act as sensors of strain-induced fluid flow. Physiological loading produces stasis of extracellular fluid in front of the cutting cone of a tunneling osteon, which will lead to osteocytic disuse and (continued) attraction of osteoclasts. However, around the resting zone and the closing cone, enhanced extracellular fluid flow occurs, which will activate osteocytes to recruit osteoblasts. Thus, cellular activity at a bone remodeling site is well related to local fluid flow patterns, which may explain the coordinated progression of a BMU.