In this paper, we review recent studies of the mechanism by which mechanical loading of bone is transduced into cellular signals of bone adaptation. Current biomechanical theory and in vivo as well as in vitro experiments agree that the three-dimensional network of osteocytes and bone-lining cells provides the cellular basis for mechanosensing in bone, leading to adaptive bone (re)modeling. They also agree that flow of interstitial fluid through the lacunar-canalicular porosity of bone, as a result of mechanical loading, most likely provides the stimulus for mechanosensing, and informs the bone cellular network about the adequacy of the existing bone structure. Important signaling molecules involved in in vivo adaptive bone formation, as well as in in vitro cellular response to fluid flow, are nitric oxide and prostaglandins. The expression of key enzymes for nitric oxide and prostaglandin production in bone cells is altered by fluid shear stress in vitro. Together, these studies have increased our understanding of the cell biology underlying Wolff's Law. This may lead to new strategies for combating disuse-related osteoporosis, and may also be of use in understanding and predicting the long-term integration of bone-replacing implants.
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