Lrp5 A241T High‐Bone‐Mass Mutation Enhances Implant Osseointegration: An Experimental Murine Study

Objectives This study aimed to assess the effect of the low‐density lipoprotein receptor‐related protein 5 (Lrp5) A241T gain‐of‐function mutation, which induces a high‐bone‐mass phenotype, on implant osseointegration in a murine model. Methods Heterozygous Lrp5 A241T mutant ( Lrp5 A/+ ) and wild‐type (WT) littermate male mice on a C57BL/6J background were used. Micro‐computed tomography (micro‐CT) was performed to assess tibial trabecular bone architecture. Sandblasted and acid‐etched (SLA) titanium implants were surgically inserted into the proximal tibiae, and samples were harvested after 4 weeks for micro‐CT and histological analysis. Primary osteoblasts were seeded onto SLA titanium sheets and induced for osteogenesis for 7 days. Osteogenic marker expression was assessed by quantitative real‐time polymerase chain reaction and western blotting. Results The Lrp5 A/+ group exhibited significantly improved trabecular bone architecture compared to WT controls. At 4 weeks post‐implantation, micro‐CT revealed greater peri‐implant bone formation in the Lrp5 A/+ group, while hard tissue sections showed increased bone area and bone‐implant contact. HE and Masson staining further confirmed greater new bone formation. After 7 days of in vitro osteogenic induction, Lrp5, Runx2, and Sp7 were significantly upregulated in the Lrp5 A/+ group. Conclusions The Lrp5 A241T mutation significantly enhanced implant osseointegration in a transgenic murine model.