Periodontal regeneration remains challenging because conventional therapy does not predictably restore lost periodontal tissues. This study compared the periodontal remodeling responses associated with locally administered denosumab (DNS) and recombinant human growth hormone (rhGH) in experimental periodontitis.

Twenty-four male New Zealand rabbits were randomly assigned to four groups: control, periodontitis (PDitis), PDitis treated with DNS, and PDitis treated with rhGH. Experimental periodontitis was induced by ligature placement and repeated inoculation with Porphyromonas gingivalis . Following disease induction, locally delivered DNS (3 mg) or rhGH (4 IU) gels were administered twice weekly for four weeks. Periodontal remodeling was evaluated using cone-beam computed tomography (CBCT), histological and histomorphometric analyses, and quantitative real-time polymerase chain reaction (qRT-PCR) assessment of bone remodeling–related genes.

Both DNS and rhGH improved periodontal healing compared with untreated periodontitis. DNS demonstrated greater preservation of alveolar bone height (facial bone height: 11.97 ± 0.05 mm vs. 9.96 ± 0.06 mm for rhGH and 9.00 ± 0.17 mm for PDitis; P = 0.004) and higher facial bone density (898.47 ± 9.95 vs. 708.34 ± 9.83 and 728.90 ± 6.08, respectively; P = 0.004). Histomorphometric analysis showed the greatest new bone formation in the rhGH group, with facial and lingual new bone fractions of 74.44 ± 16.80 % and 64.78 ± 6.38 %, respectively (P = 0.005 and P < 0.001). Both therapies significantly downregulated osteoclastogenesis-related gene expression, with DNS producing greater suppression of RANKL, NFATc1, ACP-5, and Ctsk than rhGH.

Within the limitations of this experimental study, DNS and rhGH were associated with distinct periodontal remodeling phenotypes in experimental periodontitis. DNS predominantly demonstrated an anti-resorptive remodeling profile characterized by preservation of mineralized bone architecture, whereas rhGH promoted a more anabolic high-turnover remodeling response associated with active new bone formation. These findings support the translational potential of locally delivered biologically targeted therapies as adjunctive approaches for periodontal regeneration.