Towards novel measurements of remodeling activity in cortical bone: implications for osteoporosis and related pharmaceutical treatments.

Bone remodelling is performed by basic multicellular units (BMUs) that resorb and subsequently form discrete packets of bone tissue. Normally, the resorption and formation phases of BMU activity are tightly coupled spatially and temporally to promote relatively stable bone mass and bone quality. However, dysfunctional remodelling can lead to bone loss and is the underlying cause of osteoporosis. This review surveys how BMU activity is altered in postmenopausal, disuse and glucocorticoid-induced osteoporosis as well as the impact of anabolic and anti-resorptive pharmaceutical treatments. The dysfunctional remodelling observed during disease and following medical intervention bares many testable hypotheses regarding the regulation of BMU activity and may provide novel insights that challenge existing paradigms of remodelling dynamics, particularly the poorly understood BMU coupling mechanisms. Most bone remodelling research has focused on trabecular bone and 2D analyses, as technical challenges limit the direct assessment of BMU activity in cortical bone. Recent advances in imaging technology present an opportunity to investigate cortical bone remodelling in vivo. This review discusses innovative experimental methods, such as 3D and 4D (i.e. time- lapsed) evaluation of BMU morphology and trajectory, that may be leveraged to improve the understanding of the spatio-temporal coordination of BMUs in cortical bone.