Osteoporosis following ovariectomy has been suggested to modulate bone response to polyethylene wear debris. In this work, we evaluate the influence of estrogen deficiency on experimental particle-induced osteolysis. Polyethylene (PE) particles were implanted onto the calvaria of wild-type (WT), sham-ovariectomized (OVX), OVX mice and OVX mice supplemented with estrogen (OVX+E2) (12 mice per group). Sham-implanted mice served as internal controls. After 14 days, seven skulls per group were analyzed with a high-resolution micro-computed tomography (CT) and by histomorphometry, and for tartrate-specific alkaline phosphatase. Five calvariae per group were cultured for the assay of IL-1, IL-6, TNF- and RANKL secretion using quantitative ELISA. The expression of RANKL and OPG mRNA were evaluated using real-time PCR. As assessed by CT and by histomorphometry, PE particles induced an extensive bone resorption and an intense inflammatory reaction in WT, sham-OVX and OVX+E2 mice. In OVX mice group, these features appeared considerably attenuated. In WT, sham-OVX and OVX+E2 mice, PE particles induced an increase in serum IL-6, in TNF-and RANKL local concentrations, and resulted in a two-fold increase in RANKL/OPG mRNA ratio. Conversely, these parameters remained unchanged in OVX mice after PE implantation. The combination of two well-known bone resorptive mechanisms ultimately attenuated osteolytic response, suggesting a protective effect of estrogen deficiency on particle-induced osteolysis. This paradoxical phenomenon was associated with a downregulation of pro-resorptive cytokines. It is hypothesized that excessive inflammatory response was controlled, illustrated by the absence of increase of serum IL-6 in OVX mice after PE implantation.

Introduction

Osteoporosis is a metabolic disease of the bone responsible for a loss of bone resistance and an increase in fracture risk. World Health Organization (WHO) estimations are about 6.3 millions of femoral neck fractures in the world by 2050. These estimations make osteoporosis a real problem in term of public health.

Knowledge in biological tissues mechanical behaviour and its evolution with age are important for the design of diagnosis and therapeutic tools. From the mechanical aspect, bone resistance is dependent on bone density, bone architecture and bone tissue quality. If the importance of bone density and bone architecture has been well explored, the bone tissue quality still remains unstudied because of the lack of biomechanical tools suitable for testing bone at this microscopic dimension.

Therefore the goal of this study is to estimate the osteoporotic cancellous bone tissue mechanical behaviour at its microscopic scale, using an approach coupling mechanical assays and digital reconstruction.