Differential modulation of zoledronate and etidronate in osseous healing of an extracted socket and tibia defect

Osteonecrosis of the jaw has been increasing after dentoalveolar surgery in patients treated with an antiresorptive bisphosphonate (BP), especially strong zoledronate (ZA). The pathophysiology underlying why osteonecrosis occurs exclusively in the jaw bone remains unclear. This study investigated skeletal site-specific bone healing during the use of BPs to explore the preferential incidence of osteonecrosis of the jaw bone.

Extraction of mandibular molar and creation of a tibia defect were performed in rats 2 weeks after weekly intravenous injections with the potent ZA and the weaker BP etidronate. Bone healing was evaluated radiographically and histologically 1 and 4 weeks after defect creation.

Bone healing at the extracted socket showed that resorption precedes bone formation, while it was the opposite at the tibia defect. ZA use potentially suppressed bone remodeling, which led to impaired healing at the extracted socket but full regeneration of the tibia defect. However, etidronate showed less suppression of bone remodeling and resulted in increased bone formation at the extracted socket and full regeneration of the tibia defect.

These results suggest that skeletal site-dependent differences in the bone healing process underlie BP-related preferential occurrence of osteonecrosis of the jaw bone.