In a rat model of ligature-induced periodontitis, we demonstrated that strontium ranelate—a medication with both antiresorptive and osteoanabolic properties—was effective in reducing alveolar bone loss under both estrogen-sufficient and estrogen-deficient conditions, decreasing bone resorption markers such as RANKL, alongside increased expression of bone formation markers like osteocalcin and osteopontin. This evidence concerns the gene SPP1 and periodontitis.