Sequential use of Romosozumab–Zoledronate May Increase risk of MRONJ: Study
Researchers have found in a new study that sequential use of romosozumab followed by zoledronate may heighten the risk of medication-related osteonecrosis of the jaw (MRONJ), highlighting the need for cautious clinical use
Bisphosphonates are widely used bone resorption inhibitors that suppress osteoclast activity. They are commonly prescribed for the treatment and management of conditions such as osteoporosis, metastatic cancer, and metabolic bone diseases (Hampson and Fogelman 2012). Since the initial reports by Marx (2003) and Ruggiero et al.This study aimed to assess the occurrence of medication-related osteonecrosis of the jaw (MRONJ) in mice following the sequential administration of romosozumab and zoledronate and to confirm their inhibitory effects on osteoclast differentiation in vitro. Thirty-five female C57BL/6 mice were divided into three groups: romosozumab followed by zoledronate (ROM+ ZOL), saline followed by zoledronate (ZOL), and control (Con) group receiving saline. After drug administration, the maxillary first molars were extracted. Bone healing and necrosis were evaluated using micro-computed tomography, histomorphometry, and immunohistochemistry. To investigate the mechanism underlying the in vivo study results, the effects of romosozumab and zoledronate were evaluated by analysing tartrate-resistant acid phosphatase staining and actin ring formation after differentiation of RAW 264.7 cells.
The ROM+ZOL group exhibited more severe bone necrosis than the ZOL and Con groups. The ROM+ZOL group demonstrated a lower bone volume fraction and a reduction in the number of sclerostin-positive cells, suggesting enhanced osteonecrosis when romosozumab was administered before zoledronate. Moreover, both zoledronate and romosozumab effectively suppressed osteoclast differentiation and function in vitro.
Sequential administration of romosozumab followed by zoledronate may exacerbate the risk of MRONJ, underscoring the need for careful consideration in clinical applications.
Reference:
Park, H.-S., S.Kim, S.-Y.An, R. H.Kim, J.Choi, and M.-Y.Kim. 2026. “Combined Effects of Romosozumab and Zoledronate on the Development of Osteonecrosis of the Jaw.” Oral Diseases1–11. https://doi.org/10.1111/odi.70331.
Sequential use, Romosozumab–Zoledronate, May, Increase, risk, MRONJ, Study, Park, H.-S., S.Kim, S.-Y.An, R. H.Kim, J.Choi, and M.-Y.Kim.
