Cortical Bone Porosity in Rabbit Models of Osteoporosis

Abstract

Cortical bone porosity is intimately linked with remodeling, is of growing clinical interest, and is increasingly accessible by imaging. Thus, the potential of animal models of osteoporosis (OP) to provide a platform for studying how porosity develops and responds to interventions is tremendous. To date, rabbit models of OP have largely focused on trabecular microarchitecture or bone density; some such as ovariectomy (OVX) have uncertain efficacy and cortical porosity has not been extensively reported. Our primary objective was to characterize tibial cortical porosity in rabbit-based models of OP, including OVX, glucocorticoids (GC), and OVX + GC relative to controls (SHAM). We sought to: (i) test the hypothesis that intracortical remodeling is elevated in these models; (ii) contrast cortical remodeling and porosity in these models with that induced by parathyroid hormone (1-34; PTH); and (iii) contrast trabecular morphology in the proximal tibia across all groups. Evidence that an increase in cortical porosity occurred in all groups was observed, although this was the least robust for GC. Histomorphometric measures supported the hypothesis that remodeling rate was elevated in all groups and also revealed evidence of uncoupling of bone resorption and formation in the GC and OVX + GC groups. For trabecular bone, a pattern of loss was observed for OVX, GC, and OVX + GC groups, whereas the opposite was observed for PTH. Change in trabecular number best explained these patterns. Taken together, the findings indicated rabbit models provide a viable and varied platform for the study of OP and associated changes in cortical remodeling and porosity. Intriguingly, the evidence revealed differing effects on the cortical and trabecular envelopes for the PTH model.

Current and emerging histomorphometric and imaging techniques for assessingage‐at‐deathand cortical bone quality

“…Emerging collaborative SRμCT experiments performed at the CLS by Cooper's group and associated colleagues aim to address this limitation by combining rabbit animal models of bone remodeling with in vivo high‐resolution phase contrast imaging (Cooper, Harrison, Hiebert, & Andronowski, 2019; Hiebert et al, 2018). The authors have established that remodeling‐related resorption events can be visualized and subsequently tracked over imaging sessions (Cooper et al, 2019; Harrison et al, 2020). This advance has set the stage for the direct testing of hypotheses related to the steering of resorption events that initiate new osteon formation, and stimuli related to osteon morphology and dimensions.…”

Glucocorticoid‐induced dose‐related and site‐specific bone remodelling, microstructure, and mechanical changes in cancellous and cortical bones

“…In comparison to cancellous bone, cortical bone has two different bone remodelling patterns and more factors are likely to be involved in their regulation, so the importance of cortical bones is underestimated in most cases 31 . Some studies revealed that cortical bone undergoes a process of thinning cortical bone and increasing intracortical porosity 32 . In this study, the expanded pores were relatively common in the subendocortical region while cortical thickness remained stable.…”

Experimental Aqueous Alteration of Cortical Bone Microarchitecture Analyzed by Quantitative Micro-Computed Tomography

“…Within the composite structure of bone, collagen acts as a framework, whereas bioapatite crystals serve as reinforcement between the collagen helices (Zhu et al, 2008;Reznikov et al, 2018;Binkley et al, 2020;Lee et al, 2020). Apart from its structural role, bioapatite plays a crucial role in calcium homeostasis serving as important reservoir of Ca and PO 4 ions (Heaney, 2006;Rigo et al, 2012 and references cited therein). In addition, bone is pervaded by a system of canals filled with nerves and blood vessels.…”

“…On a structural level, bone porosity constitutes one of the most important parameters that can provide information about the diagenetic history of a given bone, in particular because differences in porosity are closely related to changes of organic and/or inorganic components of bone. Bone porosity has thus been the subject of investigation for a long time, especially in osteoporosis research (e.g., Bjørnerem, 2016 and references cited therein;Harrison et al, 2020), but also in archaeology Nielsen-Marsh and Hedges, 2000a;Nielsen-Marsh and Hedges, 2000b;Turner-Walker et al, 2002). Commonly used destructive techniques for determining bone porosity on the nano-and micrometer scale are water sorption analyses and mercury intrusion porosimetry, with the latter technique also being used to determine pore size distribution Nielsen-Marsh and Hedges, 1999).…”