Balanced Basic Multicellular Unit Activity in Cortical Bone of Ovariohysterectomized Rabbits.

Abstract

It is well documented that the activation frequency of basic multicellular units (BMUs) is increased following menopause, but it is unclear if a negative BMU balance also contributes to osteoporosis-related bone loss or how remodeling dynamics are altered to maintain or disrupt BMU balance. Time-lapsed imaging was used to track individual BMUs in cortical bone and investigate their spatio-temporal balance in a rabbit model of osteoporosis. The distal tibiae of female New Zealand White rabbits that received ovariohysterectomy (OVH) or SHAM surgery were scanned in vivo using synchrotron radiation micro-CT and two weeks later ex vivo using desktop micro-CT. Remodeling spaces were partitioned into resorption and formation zones based on their 3D morphology. BMU balance was assessed by the maximum radius, canal radius, wall thickness, and relative resorption and formation volumes. The longitudinal erosion rate and zone lengths were used to calculate the radial rate and duration of resorption and formation. Remodeling spaces were larger in OVH vs. SHAM rabbits; however, this augmented resorption was accompanied by increased formation such that OVH and SHAM BMUs were similarly balanced. Maintaining this balance was achieved by a 50% longer formation period in OVH vs. SHAM (21.0 vs 13.2days) as the radial infill rate was equivalent (OVH = 2.1 vs SHAM = 2.0μm/day). Radial erosion rate was faster in OVH (10.3 vs 8.6 μm/day), but resorption duration (OVH = 4.2 vs SHAM = 3.5days) and longitudinal erosion rate (OVH=41.3 vs SHAM = 40.1μm/day) were not different. This novel imaging pipeline demonstrated that the spatio-temporal dynamics of cortical BMUs are altered in this rabbit model of osteoporosis, but the collective changes in resorption and formation activity work in concert to maintain BMU balance. In contrast to the common perspective in the literature, this suggests that the elevated cortical porosity in osteoporosis is predominately due to increased activation of remodeling events rather than negative BMU balance.