Margret Khoushi
Pronouns: she/her
Research Mentor(s): Hsiao Hsin Sung
Co-Presenter: Pirela, Carlos
Research Mentor School/College/Department: Orthopaedic Research Lab (ORL) / Dentistry
Presentation Date: April 20
Presentation Type: Poster
Session: Session 3 – 1:40pm – 2:30 pm
Room: League Ballroom
Authors: Margret Khoushi, Anuj Amin, Carlos Pirela, Hsiao Sung, Kenneth Kozloff
Presenter: 107
Abstract
Introduction: Osteogenesis Imperfecta (OI) is a congenital low-bone mass disorder that causes a higher rate of long bone fractures and craniofacial hard tissue disturbances. Sclerostin antibody is a novel anabolic treatment for OI patients. Previous studies show SclAb induces an increase of bone mass in long bones. We aim to assess if similar SclAb responses were to be observed in the craniofacial bone by using an implant mouse model. Methods: 3-month-old WT and Brtl/+ mice under general anesthesia underwent bilateral maxillary and tibial titanium implant placements. Concomitantly with implant placement and randomly, mice received subcutaneous SclAb (SclAb VI, Amgen and UCB) treatment or vehicle injection (PBS) at 25 mg/kg, 2X/week, for 5 weeks. Maxillary and tibial implant samples were embedded in polymethyl methacrylate, sectioned with diamond blade (Isomet), grinded and polished prior to the Scanning electron microscopy (SEM) for peri-implant bone formation assessment. MicroCT (Xradia) imaging assessed the bone implant contact (BIC). Also to determine the effectiveness of Sclerostin antibody is commensurate with our previous data, femoral and tibial BMD, trabecular thickness and number, and cortical thickness were assessed. TRAP staining assessed the peri-implant osteoclastic activity. Statistical analysis was tested with two-tailed unpaired Student’s t-test p<0.05 considered as statistically significant. Results: SEM images show that Xradia uCT images (Zeiss) have minimal images, which do not obscure our ability to visualize and 3D quantify the bone in direct contact with the implant. Untreated Brtl/+ mice have a substantially reduced BIC in the maxilla (3,72%) compared to WT (20.58%). SclAb increased BIC, being more accentuated in the Brtl/+ group (20,20%, p<0.001) than WT (p=23,79%, 0.129). The peri-implant BV/TV is more substantially impaired in the maxilla than the tibia in untreated Brtl/+ (22,99%, 39.8%) compared to WT (39,6%, 50.1%). SclAb is able to significantly rescue this deficit in BV/TV in Brtl/+ in the maxilla (44.03%, p=0.003), but only slightly in the tibia (51.8%, p=0.58). Osteoclastic activity is visualized mainly in the peri-implant bone of the untreated-Brtl/+ mice. Tibial peri-implant is more robust compared with maxilla in both genotypes. Our findings suggest distinct biologic differences between anatomic sites and higher response to SclAb in the Brtl/+ maxilla. Our findings suggest that dental implant studies should be performed in maxilla/mandible animal models and not in long bones. We conclude that SclAb is able to enhance the peri-implant osseointegration , therefore it could be a promising clinical solution for OI and other osteopenic patients. Presentation link
Biomedical Sciences, Interdisciplinary
