Mineral-targeted alkaline phosphatase improves bone graft-mediated alveolar bone defect healing in mice

Alveolar bone loss challenges tooth retention and implant placement. Freeze-dried bone allograft (FDBA) is widely used for alveolar ridge preservation but has limitations in resorption rate and healing time. In this proof-of-concept study, we tested whether pro-mineralization enzyme, tissue-nonspecific alkaline phosphatase (TNAP) enhances bone healing.

Seven-week-old mice (n = 4-6/group; equal numbers of males and females) underwent maxillary molar extraction and standardized alveolar defect creation. Mice were assigned to sham, FDBA with saline (BGS) or FDBA with mineral-targeted TNAP-Fc-D₁₀ (BGT). Healing was assessed using microcomputed tomography (micro-CT), serum alkaline phosphatase (ALP) levels, histology, and immunohistochemistry, between 14- and 60-days post-procedure (dpp). Intergroup comparisons were analyzed by one-way ANOVA and post-hoc Tukey test (α = 0.05) RESULTS: At 14 dpp, the BGT group demonstrated significantly greater bone volume fraction (BV/TV) and bone mineral density (BMD) compared with BGS (p < 0.01, p < 0.05) and sham groups (p < 0.001). Alveolar bone volume was greater than sham (p < 0.001). Alveolar bone dimension (height and width) was significantly more stable in the BGT group (p < 0.05). Although BV/TV at 60 dpp showed no significant differences, BGT maintained higher BMD and alveolar bone width stability (p < 0.01). Histological and immunohistochemical analyses revealed increased new bone formation and greater bone marker expression in the short-term BGT group (p < 0.05). No changes in serum ALP levels were detected.

TNAP-Fc-D₁₀ with FDBA significantly enhances early alveolar bone healing and dimensional stability. While long-term volumetric gains were not observed, sustained improvements in mineral density and ridge preservation support TNAP as a promising biologic for alveolar ridge preservation.

When people lose teeth, keeping enough bone in the jaw is critical for future treatments like dental implants. A common material used to rebuild bone is called freeze-dried bone allograft (FDBA), but it does not always heal quickly or completely. In this study, we tested whether adding a special enzyme called TNAP, which helps build bones naturally, could make FDBA work better. After extracting teeth and creating bone defects in mice, we compared healing between three groups: control (sham), FDBA + saline, and FDBA + engineered TNAP-Fc-D₁₀. After 2 weeks, the group that received FDBA+TNAP-Fc-D₁₀ showed more new bone formation and better preservation of the size of the jawbone. Even after 2 months, their bone remained denser and more stable compared with the other groups. Importantly, we found no signs of unwanted side effects in the blood. These results suggest that adding TNAP-Fc-D₁₀ could make bone grafts more effective early on, helping preserve jaw structure better over time. More research is needed to fine-tune the treatment and see how well it works in humans.