Prostaglandin E₂ (PGE₂) is known to cause bone formation with activation of the EP₄ receptor being primarily responsible for its anabolic actions. Current bone anabolic therapies are typically protein-based biological therapies that require special formulations, lack stability, and are costly. Here, we show that KMN-159, a small molecule EP₄ receptor agonist, stimulates osteogenesis in a novel in vitro 3D model of osseointegration. We found that KMN-159 increased the expression of osteoblastic differentiation factors and promoted osteoblast function and bone remodeling in this model. KMN-159 elevated the Opg:Rankl ratio, indicating a shift towards bone formation.