ePoster #312 - ISHA Annual Scientific Meeting 2016

Estrogen Deprivation Reduces Articular Cartilage and Subchondral Bone Content in the Murine Hip

Meghan Kelly, MD, PhD, Rochester, NY UNITED STATES
Alayna Loiselle, PhD, Rochester, NY UNITED STATES
Michael Zusick, PhD, Rochester, NY UNITED STATES
Brian D. Giordano, MD, Rochester, NY UNITED STATES

University of Rochester Centre for Musculoskeletal Research, Rochester, New York, UNITED STATES

FDA Status Not Applicable

Summary: Female mice subject to ovariectomy demonstrate reduced cortical volume and femoral head articular cartilage and subchondral bone loss. Addition of a high fat diet resulted in a further reduction of cortical bone volume without significant effects on articular cartilage or subchondral bone content.

Abstract:
Introduction: Arthroscopic treatment of femoroacetabular impingement (FAI) has been shown to result in significant improvement in pain and function. However, some patients may not experience satisfactory clinical improvement following surgery. Various demographic and clinical factors have been linked to a poorer patient reported outcome (PRO). In particular, female gender has been shown to represent an independent risk factor for compromised outcomes following hip arthroscopy. Furthermore, increasing age and obesity may represent additional risk factors that predict poorer outcomes. Although clinical outcome studies reflect known risk factors, there remains a paucity of literature examining the effect of estrogen deprivation and obesity on the pathomorphology of the hip joint. Purpose: The primary aim of this study was to examine the effect of estrogen deprivation and high fat diet on articular cartilage and subchondral bone within the femoral head in a murine model. Methods: Female C57Bl6 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. At the time of sacrifice, the bilateral hips were disarticulated and femurs were cleaned of soft tissue attachments. The left femur was immediately placed in formalin for microCT and histological assessment and the right femur was placed in saline soaked gauze for biomechanical testing. Two-way ANOVA with a Bonforroni post-hoc analysis was used to detect significant differences due to diet or ovariectomy with differences considered significant at p<0.05. Results: Mice placed on a high fat diet (both OVX and SHA) exhibited significant weight gain and elevated plasma concentrations of fasting glucose and leptin. MicroCT analysis of femoral specimens demonstrated reduced cortical bone in ovariectomized mice (p<0.0001). This effect was noted to be augmented in mice also placed on a high fat diet (interaction effect p=0.0015). The proximal femur underwent histomorphometric assessment and demonstrated that ovariectomy resulted in a 20% loss in total hip cartilage area (p=0.022) and trended towards a loss of mineralized cartilage area (p=0.10). There was no additional effect of the high fat diet on cartilage loss. A 20% increase in unmineralized cartrilage was observed in mice that underwent either ovariectomy procedure or a high fat diet, however this increase was not observed in animals that had undergone both high fat diet and ovariectomy. Finally, ovariectomy was found to result in a 25% loss of subchondral bone area within the femoral head (p=0.023) without a difference in total femoral head area. High fat diet did not alter subchondral bone content Conclusions: This is the first study to demonstrate characteristic histomorphometric changes within the murine hip due to estrogen deprivation and high fat diet. Mice that have undergone ovariectomy demonstrate a loss of cortical bone volume and this was amplified in animals placed on a high fat diet. Furthermore, ovariectomy, but not high fat diet, resulted in loss of articular cartilage and subchondral bone within the murine hip.