Therapeutic ultrasound prevents delayed healing of socket, possibly BRONJ, humorally

Objectives: Our earlier studies suggested that jaw-bone osteoblasts are distinct from calvarial and long bone cells in that function and survival depend on mechanical stimulation. In mandibular cells, RANKL and BCl-2 were nearly undetectable unless exposing them to low-intensity pulsed ultrasound (LIPUS), which is widely accepted as fracture treatment. We hypothesized that the loss of occlusal force by tooth extraction may increase the risk of delayed healing. Together with other risk factors, it may also play a role in initiating bisphosphonate-related osteonecrosis of the jaw (BRONJ). In our BRONJ model, rats mimic postmenopausal osteoporosis patients receiving alendronate (ALN) also affected with periodontitis. The aim of this study is to characterize the effect of LIPUS on healing of the tooth socket, potentially as a therapeutic tool for BRONJ.
Methods: Initially, maxillary first molars (M1) were removed from aged female Wistar rats and exposed to daily LIPUS for 2 weeks. In another experiment, ovariectomized aged rats pretreated with subcutaneous alendronate injections were further topically administered cultures of Porphyromonas gingivalis (Pg) to the M1. After removing M1, LIPUS was applied daily in one experimental group extrabuccally to the socket for 4 weeks.
Results: In the initial experiment, immuno-staining increased in the socket alveolar bone for VEGF/CD34. LIPUS-treated rats’ tibia bone marrow cells showed increased staining for CXCR4. In the experiment with ALN, ALN+Pg group showed 1) socket epithelia did not heal, 2) the periosteal reaction (new bone formation) occurred in the alveolar bone ridge, and 3) BMD was lower in the alveolus, all of which were prevented by the daily LIPUS. Furthermore, significantly lowered mRNA levels of VEGF/CD31, Bcl-2, RANKL, and CD68 in the tibia bone marrow were also restored by LIPUS.
Conclusions: LIPUS exerted humoral effects and prevented BRONJ-like pathophysiology induced by tooth removal by inhibiting inflammation and normalizing the socket healing processes.