Bone regeneration is inherently patient-specific, shaped by individual differences in skeletal metabolism, cellular responsiveness, inflammatory signaling, and local remodeling dynamics. Despite major advances in orthopedic and regenerative medicine, current clinical strategies still largely apply uniform solutions to biologically heterogeneous conditions, often resulting in suboptimal healing, particularly in rare skeletal disorders and complex clinical scenarios such as spinal fusion. The emerging concept of personalized skeletal medicine emphasizes the need to modulate the balance between bone formation and bone resorption in a targeted manner, taking into account the dynamic interplay between osteoinduction and remodeling that ultimately determines the quality and persistence of newly formed bone.

Osteogrow-C is an innovative autologous bone graft substitute composed of recombinant human Bone Morphogenetic Protein 6 (rhBMP6) delivered within an autologous blood coagulum, combined with synthetic calcium phosphate ceramics that enhance implant biomechanical properties. To further address the diversity of bone remodeling dynamics across challenging biological environments, zoledronate (ZOL), a potent antiresorptive agent, was incorporated into the ceramic phase, resulting in an advanced formulation termed Osteogrow-D. This approach was designed to modulate local bone remodeling by preserving newly formed bone while maintaining robust osteoinduction. Such control of remodeling dynamics is particularly relevant in conditions characterized by dysregulated bone remodeling and increased osteoclastic activity, including rare diseases such as congenital pseudoarthrosis and demanding clinical settings such as spinal fusion.

The efficacy of Osteogrow-D was evaluated in two complementary preclinical models reflecting diverse regenerative environments: a rat ectopic bone formation model and a rabbit posterolateral spinal fusion (PLF) model. In both models, zoledronate was bound to synthetic calcium phosphate ceramics and combined with autologous blood containing rhBMP6. Following coagulation, implants were placed subcutaneously in rats or between adjacent transverse processes in rabbits. Bone formation, mineralized tissue volume, structural integrity, and persistence were assessed over 14–15 weeks using micro-computed tomography, histomorphometry, and detailed histological analyses. Early bone induction was comparable between Osteogrow-C and Osteogrow-D, demonstrating that local zoledronate incorporation did not impair rhBMP6-mediated osteogenesis. However, at later time points, Osteogrow-D exhibited significantly greater bone volume and improved preservation of mineralized tissue, indicating effective modulation of bone resorption. In the rabbit PLF model, Osteogrow-D further resulted in increased bone volume and tissue density, supporting its translational relevance for complex spinal reconstruction.

Overall, this work highlights how targeted regulation of bone remodeling can enhance regeneration across diverse biological and clinical contexts. By integrating osteoinductive signaling with controlled regulation of bone remodeling, Osteogrow-D represents a platform for personalized bone regeneration. These findings support the concept that tailoring regenerative strategies to specific remodeling environments may improve skeletal repair and provide a framework for future patient-centered approaches in regenerative medicine.