Sclerostin antibody prevents particle-induced implant loosening by stimulating bone formation and inhibiting bone resorption in a rat model

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2012-12, Vol.64 (12), p.4012-4020
• Main Authors: Liu, Shuo, Virdi, Amarjit S., Sena, Kotaro, Sumner, Dale R.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - immunology; Antibodies - pharmacology; Antibodies - therapeutic use; Biological and medical sciences; Bone Morphogenetic Proteins - immunology; Bone Resorption - physiopathology; Bone Resorption - prevention & control; Bones; Diseases of the osteoarticular system; Femur - diagnostic imaging; Femur - physiology; Femur - surgery; Fundamental and applied biological sciences. Psychology; Genetic Markers - immunology; Male; Medical sciences; Models, Animal; Osteogenesis - drug effects; Osteogenesis - physiology; Polyethylene - adverse effects; Prostheses and Implants; Prosthesis Failure - etiology; Rats; Rats, Sprague-Dawley; Rodents; Signal Transduction - physiology; Skeleton and joints; Titanium; Tomography, X-Ray Computed; Vertebrates: osteoarticular system, musculoskeletal system; Wnt Proteins - physiology
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• DOI: 10.1002/art.37697

Objective To assess the ability of sclerostin antibody therapy to blunt the negative effects of polyethylene particles on implant fixation and peri‐implant bone structure in a rat implant fixation model. Methods Thirty‐six adult male rats received intramedullary titanium implants; 12 rats received vehicle injections only (control), and 24 rats received intraarticular injections of lipopolysaccharide‐doped polyethylene particles. Twelve of the rats that received particles also received sclerostin antibody treatment. The 3 groups of rats were maintained for 12 weeks in a pathogen‐free environment, at which time mechanical, micro–computed tomography, and dynamic and static histomorphometry end points were assessed. Results Sclerostin antibody treatment completely blocked the negative effect of the lipopolysaccharide‐doped polyethylene particles on implant fixation and peri‐implant bone volume by increasing the bone formation rate and depressing bone resorption. Conclusion Anabolic agents targeting the Wnt signaling pathway are a promising new alternative for the prevention of periprosthetic osteolysis and aseptic loosening.