Thermoneutral Housing Did Not Impact the Combined Effects of External Loading and Raloxifene on Bone Morphology and Mechanical Properties in Growing Female Mice

Abstract

Raloxifene is an FDA-approved selective estrogen receptor modulator (SERM) that improves tissue quality by binding to collagen and increasing the bound water content in the bone matrix in a cell-independent manner. In this thesis, active tissue formation was induced by non-invasive external tibial loading in female mice and combined with raloxifene treatment to assess their combined effect on bone morphology and mechanical properties. Thermoregulation is an important factor that could have physiological consequences on research outcomes, and was introduced as an additional experimental factor in this study. We hypothesized that by removing the mild cold stress under which normal lab animals are housed, a metabolic boost would allow for further architectural and mechanical improvements as a result of the combination of tibial loading and raloxifene treatment. Ten week old female C57BL/6J mice were treated with raloxifene, underwent tibial loading to a strain level of 2050µε and were housed in thermoneutral conditions (32°C) for 6 weeks. We investigated bone morphology through microcomputed tomography (µCT) and mechanical properties via four-point bending and fracture toughness testing. Results indicated a combined improvement by external loading and raloxifene on geometry, particularly in the cancellous region of the bone, and also in bone mechanics leading to greater improvements than either treatment individually. Temperature did not have a robust impact on either bone architecture or mechanical integrity.