Teriparatide Topical Delivery Supports Osseointegration in Ovariectomized Rats Receiving Cafeteria Diet and Bisphosphonate: An In Vivo Experimental Study
Ana Cláudia Ervolino da Silva, Fábio Roberto de Souza Batista, Jaqueline Suemi Hassumi, Naara Gabriela Monteiro, Marina Santos Fernandes, Luana Marotta Reis Vasconcellos, Gabriel Mulinari‐Santos, Reinhard Gruber, Paulo Noronha Lisboa‐Filho, Roberta OkamotoABSTRACT
Background
Postmenopausal osteoporosis associated with cafeteria diet and bisphosphonate therapy may impair peri‐implant bone repair. Therefore, strategies to enhance osseointegration are needed.
Aim
This study investigated whether teriparatide‐coated implant surfaces enhance osseointegration in a rodent model of estrogen deficiency (OVX) and cafeteria diet (CD) treated with risedronate (RIS).
Material and Methods
In the in vitro phase, titanium discs coated with 10 or 40 ng of teriparatide were evaluated by in vitro bioassays, and drug adsorption was confirmed by UV–Vis spectroscopy. As both loading amounts produced similar biological responses, 10 ng was selected for the in vivo phase. In the in vivo phase, 48 rats were randomly assigned to SHAM (sham‐operated control), OVX/CD (ovariectomized with cafeteria diet), or OVX/CD/RIS (ovariectomized with cafeteria diet and risedronate) groups. Titanium implants either coated with teriparatide using a layer‐by‐layer topical drug delivery system or left non‐coated were placed bilaterally in the maxilla. Rats were euthanized after 28 days. Osseointegration was evaluated by removal torque testing, micro computed tomography, fluorescence microscopy, and RT‐qPCR analysis.
Results
In the cell culture experiment, both teriparatide amounts successfully promoted mineralized nodule formation in vitro and UV–Vis spectroscopy confirmed drug adsorption. In vivo, teriparatide significantly increased removal torque across all groups, with the greatest increase in OVX/CD/RIS. Teriparatide also increased peri‐implant bone volume in OVX/CD and OVX/CD/RIS, confirmed by micro computed tomography and fluorescence microscopy. RT‐qPCR also confirmed upregulation of osteogenic and angiogenic markers.
Conclusion
Topical teriparatide delivery improves peri‐implant bone repair under estrogen deficiency, cafeteria diet, and bisphosphonate therapy.