Effect of bisphosphonates on healing of tooth extraction wounds in infectious osteomyelitis of the jaw

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) and infectious osteomyelitis of the jaw (OMJ) in antiresorptive-naïve patients are different disease entities. Although osteoclast inhibition is at the center of the pathogenesis of ARONJ, the role of osteoclast inhibition in infectious OMJ is unknown. The objective of this study was to determine the effect of bisphosphonate osteoclast inhibition in infectious OMJ. Osteomyelitis was induced in mice by S. aureus inoculation. The establishment of OMJ was verified by the culture of bone marrow samples obtained from the mandible. Infected animals received either zoledronic acid (ZA) or saline starting at week-2. Treated animals along with non-infected animals underwent tooth extractions at week-4 post-infection. Healing was assessed every week using in vivo micro-computed tomography and intraoral photos. Animals were euthanized at week-8 and cervical lymph nodes were assessed for lymphatic and blood vessels. Tooth extraction wounds did not heal in animals with OMJ. These wounds were characterized by incomplete soft tissue coverage, sporadic bone fill in the sockets, and inflammatory cell accumulation in the connective tissue at 4 weeks after tooth extractions. Conversely, the majority of tooth extraction wounds in the infected animals treated with ZA had improved healing with better bone fill than even non-infected control animals. Consistently, atrophic lymphatic vessels were noted in the draining lymph nodes in animals with OMJ. However, infected animals treated with ZA had lymphatic vessels that were unaltered and showed a similar appearance to those in non-infected control animals. ZA treatment promoted wound healing in the jaw with infectious osteomyelitis. Clearly, antiresorptive therapy is contraindicated in patients with ARONJ. However, our finding suggests that osteoclast inhibition is potentially an effectual remedy for infectious OMJ in antiresorptive-naïve patients.