Titanium is widely recognized for its biocompatibility and utility in maxillofacial and orthopedic surgery
however, its influence on bone remodeling biomarkers remains underexplored. This study investigates the effects of uncoated titanium plates on both the growth factors and diacylglycerols (DAGs) in the periostea of the maxilla and mandible, as DAG signaling is an essential secondary messenger molecule involved in intracellular signaling connected to various growth factors. The study group comprised 20 patients undergoing bimaxillary osteotomies using miniplates and screws made of Ti6Al4V titanium, from whom bone fixations were removed, while the control group included 20 patients operated on for dentofacial deformities (before the insertion of titanium fixations). Diacylglycerol levels in the serum and periosteum were analyzed using tandem mass spectrometry coupled with ultra-high performance liquid chromatography. Growth factors in the periosteum were measured via ELISA with commercially available assay kits. Our findings demonstrate a significant reduction in growth factors, including IGF-1, PDGF, and FGF-23, alongside decreased total DAG levels, suggesting titanium plate stabilization may modulate bone remodeling dynamics. Notably, while overall DAG levels declined, specific DAG species such as C16:0/16:0 and C18:0/18:0 were elevated, whereas polyunsaturated DAGs showed reductions, indicating selective regulation of lipid signaling pathways. Correlation analyses highlighted complex interactions between growth factors and DAGs, with distinct regional differences observed in the mandibular and maxillary periostea. These alterations may result from chronic titanium exposure, potentially inducing a low-grade immune response or modifying the local biochemical environment. This study emphasizes the need for further research into the long-term effects of titanium implants, particularly their influence on lipid metabolism, growth factor dynamics, and bone healing.