A novel murine model of orthopaedic wear-debris associated osteolysis

Objective: To develop a mouse model of bone resorption to quantitatively evaluate wear-debris induced osteolysis. Methods: Air pouches were established on the back of BALB/c mice, followed by the surgical introduction of a section of femur or calvaria from a syngeneic mouse donor. One group of bone-implanted pouches was stimulated with ultra-high molecular weight polyethylene (UHMWPE) debris, and the remaining bone-implanted pouches received saline alone as controls. The tissues were harvested at 2, 7, and 14 days after bone implantation for molecular and histological analyses. Results: Marked inflammatory responses (thicker membrane and increased cellular infiltration) were observed in UHMWPE-stimulated pouches, compared with the saline control. Intensive tartrate-resistant acid phosphatase (TRAP) staining was identified in the UHMWPE-stimulated pouches, especially at the attachment site of inflammatory tissue with implanted bone, where active osteolysis occurred. Image analysis showed that the bone collagen loss was closely related to the amount of UHMWPE within the tissue, and was most prevalent at the contact site of bone with inflammatory tissue. UHMWPE stimulation also significantly increased the release of free calcium into the pouch fluids. Conclusion: This model demonstrates a sensitive, rapid, and reproducible method for studying wear-debris induced osteolysis seen in patients with aseptic loosening.