Odanacatib Coating Supports Osseointegration of Implants: A Preclinical Study

Abstract

INTRODUCTION: Odanacatib (ODN), a cathepsin K inhibitor, is a drug that reduces bone resorption while preserving bone formation. ODN was initially developed for the treatment of postmenopausal osteoporosis, but further development as a systemic medication has been discontinued. Here, we propose ODN as a topical treatment, the coating of dental implants, to achieve an anabolic shift of early osseointegration. MATERIAL AND METHODS: To this aim, we have coated double acid etching titanium implants (SLA) with and without ODN dispersed in a simulated body fluid (SBF). The implants were inserted into the tibia of 72 male Wistar rats and osseointegration was studied on Days 15 and 40. Biomechanical testing, micro-computed microtomography, and histomorphometric analyses were performed. RESULTS: Biomechanical testing reveals that after 15 days of healing, removal torque increased from 2.5 Ncm (1.5-4.4) to 3.9 Ncm (1.7-7.6) when comparing SBF alone with SBF containing ODN, respectively (p = 0.017). Consistently, micro-computed microtomography indicated that local bone volume increased from 24.4% (13.86-32.45) to 32.8% (19.7-39.4), respectively (p = 0.003). The same was true for presumed bone-to-implant contact, which was 34.38% (27.0-50.0) and 43.33% (31.6-54.2), respectively (p = 0.035). Histomorphometric analyses confirmed that the new bone area per total area increased from 34.78% (18.9-43.7) to 41.10% (23.5-54.0), respectively (p = 0.102). This trend proceeds after 40 days of osseointegration. DISCUSSION: These findings suggest that topical delivery of a cathepsin K inhibitor can support the early osseointegration phase in an ectopic rodent implantation model.