Osteonecrosis of the jaw in a patient treated with alendronate and then denosumab: A case of dramatic amelioration by minocycline and then etidronate

Nitrogen-containing bisphosphonates (NBPs) and denosumab are widely-used anti-bone-resorptive agents. However, osteonecrosis of the jaw (ONJ) is a known side effect with each of them (called BRONJ or DRONJ, respectively). BRONJ and DRONJ are intractable, and no sound/solid treatments have been established. Some reports note that denosumab carries a greater risk of ONJ than NBPs, and that they mutually augment the risk. Our previous animal and in vitro studies led us to suppose that etidronate (a bisphosphonate not containing nitrogen) may be effective against BRONJ, and we reported that etidronate ameliorated BRONJ in all 13 of the patients we tested. Here, we add a case in which etidronate healed stage 3 ONJ caused by alendronate (an NBP) followed by denosumab. We first treated her with minocycline (a bacteriostatic antibiotic) and then etidronate. Pain and drainage disappeared with minocycline. Within 3 weeks after the start of etidronate, bone exposure was markedly reduced and it had disappeared within 6 months, being followed by osteogenesis in the injured area and fracture-line disappearance. These results suggest that (i) in the present patient, the major cause of ONJ might have been alendronate, with denosumab possibly promoting its progress, (ii) etidronate is effective against BRONJ caused not only by NBPs, but also by NBPs + denosumab, and (iii) minocycline is suitable as a combination drug with etidronate, because in addition to its bacteriostatic effect, minocycline has various effects helping to ameliorate ONJ, including analgesic, anti-inflammatory, and bone-forming effects together with its high affinity for bone.