Effects of anti-resorptive treatment on the material properties of individual canine trabeculae in cyclic tensile tests

Abstract

Osteoporosis is defined as a decrease of bone mass and strength, as well as an increase in fracture risk. It is conventionally treated with antiresorptive drugs, such as bisphosphonates (BPs) and selective estrogen receptor modulators (SERMs). Although both drug types successfully decrease the risk of bone fractures, their effect on bone mass and strength is different. For instance, BP treatment causes an increase of bone mass, stiffness and strength of whole bones, whereas SERM treatment causes only small (4%) increases of bone mass, but increased bone toughness. Such improved mechanical behavior of whole bones can be potentially related to the bone mass, bone structure or material changes. While bone mass and architecture have already been investigated previously, little is known about the mechanical behavior at the tissue/material level, especially of trabecular bone. As such, the goal of the work presented here was to fill this gap by performing cyclic tensile tests in a wet, close to physiologic environment of individual trabeculae retrieved from the vertebrae of beagle dogs treated with alendronate (a BP), raloxifene (a SERM) or without treatments. Identification of material properties was performed with a previously developed rheological model and of mechanical properties via fitting of envelope curves. Additionally, tissue mineral density (TMD) and microdamage formation were analyzed. Alendronate treatment resulted in a higher trabecular tissue stiffness and strength, associated with higher levels of TMD. In contrast, raloxifene treatment caused a higher trabecular toughness, pre-dominantly in the post-yield region. Microdamage formation during testing was not affected by either anti-resorptive treatment regimens. These findings highlight that the improved mechanical behavior of whole bones after anti-resorptive treatment is at least partly caused by improved material properties, with different mechanisms for alendronate and raloxifene. This study further shows the power of performing a mechanical characterization of trabecular bone at the level of individual trabeculae for better understanding of clinically relevant mechanical behavior of bone.

Keywords: Anti-resorptive treatment; Cyclic test; Individual trabeculae; Material properties; Microdamage.