Understanding basic multicellular unit activity in cortical bone through 3D morphological analysis: New methods to define zones of the remodeling space.

The activity of basic multicellular units (BMU) in cortical bone is classically described as a sequential order of events- resorption, reversal and formation. This simplified portrayal of the remodeling process is pervasive despite the reported variability in remodeling space morphology. These variations may reflect meaningful nuances in BMU activity but methods to quantify 3D remodeling space morphology within the context of the cellular activity are currently lacking. This study developed new techniques to define zones of BMU activity based on the 3D morphology of remodeling spaces in rabbit cortical bone and integrated morphological data with the BMU longitudinal erosion rate (LER) to elucidate the spatial-temporal coordination of BMUs and estimate mineral apposition rate (MAR). The tibiae of New Zealand white rabbits (n = 5) were imaged in vivo using synchrotron radiation and two weeks later ex vivo with desktop microCT. The in vivo and ex vivo datasets were co-registered, and 27 remodeling spaces were identified at both timepoints. A radial profile representing the 3D morphology was the platform for partitioning the remodeling spaces into resorption, reversal and formation zones. Manual, automated and semi-automated partitioning approaches were compared, and the zone-segmentations were used to calculate the length, change in radius and slope of each zone. The manual approach most accurately defined the zones of idealized remodeling spaces with known dimensions (relative error = 0.9-9.2 %) while the semi-automated method reliably defined the zones in rabbit remodeling spaces (ICC = 0.85-1.00). Combining LER and the manually derived zone dimensions indicated that a BMU passes through a cross-section in approximately 18.8 days with resorption, reversal and formation taking 4.1, 2.2, and 12.5 days, respectively. MAR estimated by the 3D analysis was not significantly different than that determined with classic histomorphometry (p = 0.48). These techniques have the potential to assess dynamic parameters of bone resorption and formation, eliminate the need for fluorochrome labeling and provide a more comprehensive perspective of the remodeling process.