%0 Journal Article
%T Role of sclerostin deletion in bisphosphonate-induced osteonecrosis of the jaw.
%A Nakashima F
%A Matsuda S
%A Ninomiya Y
%A Ueda T
%A Yasuda K
%A Hatano S
%A Shimada S
%A Furutama D
%A Memida T
%A Kajiya M
%A Shukunami C
%A Ouhara K
%A Mizuno N
%J Bone
%V 187
%N 0
%D 2024 Oct 15
%M 39019131
%F 4.626
%R 10.1016/j.bone.2024.117200
%X <B>OBJECTIVE: </B>Bone resorption inhibitors, such as bisphosphonates (BP) and denosumab, are frequently used for the management of osteoporosis. Although both drugs reduce the risk of osteoporotic fractures, they are associated with a serious side effect known as medication-related osteonecrosis of the jaw (MRONJ). Sclerostin antibodies (romosozumab) increase bone formation and decrease the risk of osteoporotic fractures: however, their anti-resorptive effect increases ONJ. Thus, this study aimed to elucidate the role of sclerostin deletion in the development of MRONJ.<BR><B>METHODS: </B>Sclerostin knockout (SostΔ26/Δ26) mice were used to confirm the development of ONJ by performing tooth extractions. To confirm the role of sclerostin deficiency in a more ONJ-prone situation, we used the BP-induced ONJ model in combination with severe periodontitis to evaluate the development of ONJ and bone formation in wild-type (WT) and SostΔ26/Δ26 mice. Wound healing assay using gingival fibroblasts with or without sclerostin stimulation and tooth extraction socket healing were evaluated in the WT and SostΔ26/Δ26 mice.<BR><B>RESULTS: </B>ONJ was not detected in the extraction socket of SostΔ26/Δ26 mice. Moreover, the incidence of ONJ was significantly lower in the SostΔ26/Δ26 mice treated with BP compared to that of the WT mice. Osteogenic proteins, osteocalcin, and runt-related transcription factor 2, were expressed in the bone surface in SostΔ26/Δ26 mice. Recombinant sclerostin inhibited gingival fibroblast migration. The wound healing rate of the extraction socket was faster in SostΔ26/Δ26 mice than in WT mice.<BR><B>CONCLUSIONS: </B>Sclerostin deficiency did not cause ONJ and reduced the risk of developing BP-induced ONJ. Enhanced bone formation and wound healing were observed in the tooth extraction socket. The use of romosozumab (anti-sclerostin antibody) has proven to be safe for surgical procedures of the jaw.