ROLE OF BISPHOSPHONATES IN PROSTHODONTICS – A REVIEW.

ABSTRACT Bisphosphonates (BPs), particularly nitrogen-containing variants (N-BPs) such as zoledronate, alendronate, ibandronate, pamidronate, and risedronate, represent a promising class of bioactive agents for functionalizing implant surface coatings to enhance osseointegration in dental and orthopedic applications. These coatings enable localized drug delivery, directly inhibiting osteoclast-mediated bone resorption via disruption of the mevalonate pathway and farnesyl pyrophosphate synthase, while promoting osteoblast proliferation and differentiation through upregulation of osteogenic genes (e.g., BMP-2, Runx2) and pathways like ERK/JNK. Materials commonly employed include titanium dioxide nanotubes (TNTs), hydroxyapatite (HA), mesoporous silica, and organic polymers (e.g., chitosan, PLGA) for sustained release, achieved via methods such as physical adsorption, covalent grafting, or porous carrier encapsulation. Preclinical studies in sheep and ovariectomized rat models demonstrate superior early mechanical stability (e.g., higher removal torque at 10 days for zoledronate-coated implants) and increased bone-to-implant contact compared to uncoated controls, with no observed necrosis. However, benefits may be time-limited (diminishing by 28 days), and systemic BP use correlates with a 49.96% implant failure rate, mitigated by local coatings that avoid such risks. Challenges include dose-dependent cytotoxicity at high concentrations (>10^{-4} M) and limited long-term clinical data. Future directions emphasize hybrid multifunctional coatings integrating N-BPs with growth factors or antimicrobials for personalized, 3D-printed implants, potentially revolutionizing outcomes in osteoporotic patients. Keywords: Bisphosphonates; Nitrogen-containing bisphosphonates; Implant surface coatings; Osseointegration; Dental implants; Zoledronate; Osteoclast inhibition.