Bone Abstracts

Bone is a tissue that continually adapts to changing external loading conditions (so-called modeling) and has the capacity for self-repair and renewal (remodeling). These processes construct and reconstruct the skeleton by the removal and formation of bone packets that mediate the size, architecture, mass, and consequently the bone’s strength, allow bones to perform their mechanical functions successfully over long periods of time. Both adaptation and self-repair are believed to be mediated by osteocytes, which acts as a mechano-strain sensor embedded within the bone tissue. Although bone is able to accommodate changes in loading circumstances during growth, the adaptive capacity seems to diminish with age, contributing to compromised material and structural properties. Either the skeleton’s ability to form new bone declines with increasing age or the appropriate stimulus required to form new bone in an aged skeleton is not perceived. The underlying mechanism(s) responsible for this alteration are largely unknown, although recently developed imaging methods are providing new insights. Until recently, bone formation and resorption were primarily measured using biochemical markers of bone turnover or histomorphometry. However, advances in computed tomography allow for following structural changes in cortical and trabecular bone of living animals and human patients in four dimensions, 3D space and over time. My research group and others has developed 3D time lapse tomography-based methods that allow the monitoring of bone formation and resorption as well as tracking surface modeling and remodeling processes in vivo in mice by using registered longitudinal tomography data. With these new methods, detailed information on biological processes can be provided, in addition to or instead of standard histomorphometry. The lecture reviews current knowledge about skeletal mechanobiology in animal disease models during bone growth and aging, and discusses how novel tomography-based imaging methods are providing insights.

Disclosure: Amgen provided me with Sclerostin neutralizing antibody. Novartis provided me with SOST KO mice.