Optimization of Peri-Implant Bone Repair in Estrogen-Deficient Rats on a Cafeteria Diet: The Combined Effects of Systemic Risedronate and Genistein-Functionalized Implants

Abstract

Estrogen deficiency, coupled with a cafeteria diet (CD), can impair peri-implant bone repair, posing a significant challenge to implant success in affected individuals. Thus, it is crucial to explore strategies for implant functionalization and systemic treatments that could alleviate these bone alterations. This study aimed to assess peri-implant bone repair in ovariectomized (OVX) rats subjected to a CD, with a focus on implants functionalized with genistein (GEN), compared to conventional implants (CONV), and the effects of systemic treatment with risedronate sodium (RIS). In total, thirty-six female rats were assigned to three groups: rats with estrogen (SHAM), rats with estrogen deficiency and CD (OVX-CD), rats with estrogen deficiency, CD, and systemic RIS treatment (OVX-CD-RIS). All rats underwent bilateral extraction of the first upper molars followed by implant installation. Each group was further subdivided based on implant type: conventional implants (CONV) or GEN-functionalized implants, resulting in six subgroups (<i>n</i> = 6). The study employed several analyses, including reverse torque testing, microcomputed tomography (Micro-CT), epifluorescence microscopy, and molecular assays. The main result demonstrated that the OVX-CD-RIS/GEN subgroup exhibited significantly higher reverse torque values, indicating stronger implant stability. Micro-CT scans revealed a greater bone volume in the OVX-CD-RIS/GEN subgroup compared to other subgroups. Epifluorescence microscopy also demonstrated an increased mineral apposition rate in both the OVX-CD/GEN and OVX-CD-RIS/GEN subgroups. Molecular analysis indicated elevated expression levels of osteocalcin, alkaline phosphatase, and vascular endothelial growth factor in the OVX-CD-RIS/GEN subgroup. In conclusion, the combined treatment of systemic RIS and GEN-functionalized implants significantly enhanced peri-implant bone repair, offering a promising strategy to improve implant outcomes in postmenopausal women with metabolic syndrome.