Estrogen Deprivation and Diet-Induced Obesity Result in Alterations in Bone and Cartilage Content in the Murine Hip
Authors: Kelly Meghan , Loiselle Alayna , Zuscik Michael , Giordano Brian D. 
Published: July 2017

Objectives: Arthroscopic treatment of femoroacetabular impingement (FAI) has been shown to result in significant improvement in pain and function. However, female gender and obesity have been linked to poor patient reported outcomes following surgery. Despite this, there remains a paucity of literature examining the effect of estrogen deprivation and obesity on the pathomorphology of the hip joint. Thus, the aim of this study was to examine the effect of estrogen deprivation and diet -induced obesity on articular cartilage and bone content in the femoral head in a murine model. Methods: Female C57Bl/6J mice underwent ovariectomy (OVX) or sham (SHA) procedure at 16 weeks of age. At 20 weeks of age mice were placed on either a high fat diet (HFD, 60% kcal fat) or low fat diet (LFD, 10% kcal fat) for 12 weeks. Mice placed on a high fat diet (both OVX and SHA) exhibited significant weight gain and increased plasma concentrations of fasting glucose and leptin. At the time of sacrifice, one hip was disarticulated and the femur was cleaned of soft tissue attachments. The femur was then placed in 10% formalin for microCT and histological assessment. The femurs were embedded in paraffin and underwent Safranin O/Fast green staining. Histomorphometric analysis was performed utilizing Osteomeasure analysis software and quantification of cortical and trabecular bone within the femoral head utilized Amira 3D software platform. Two-way ANOVA with a Bonferroni post-hoc analysis was used to detect significant differences due to diet or ovariectomy with differences considered significant at p<0.05. Results: Ovariectomy resulted in a small but significant loss (-14%) in cortical bone volume within the femoral head (p=0.0469) while high fat diet resulted in a similar loss (-15%) in femoral head cortical volume (p=0.007, interaction effect p=0.0913). In addition, ovariectomy resulted in a loss of trabecular bone volume within the femoral head (-10%, p=0.0178); however there was no effect of high fat diet on trabecular bone content (p=0.645). Histomorphometric assessment demonstrated that ovariectomy resulted in a 15% loss in total hip cartilage area (p=0.0117) and this was accompanied by a 15% loss in mineralized cartilage area (p=0.0101) without a loss in unmineralized cartilage (p=0.849). Similar effects were not observed in response to a high fat diet. Conclusion: This is the first study to demonstrate characteristic histomorphometric changes within the murine hip due to estrogen deprivation and obesity. Mice that have either undergone ovariectomy or have been placed on a high fat diet demonstrate a loss of cortical bone volume within the femoral head, however these effects do not appear to be additive. Furthermore, while estrogen deprivation induces a loss of trabecular bone, total cartilage and mineralized cartilage, a similar effect is not seen in response to a high fat diet. These findings suggest that the mechanisms by which estrogen deprivation and obesity elicit changes in bone and cartilage content may be different. Furthermore, these effects, specifically within the femoral head, may be a causative factor for poorer patient reported outcomes following hip arthoscopy in women and obese patients.