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.