Is strict use of denosumab or zoledronate Beneficial to patients with bone metastatic Disease?

Background: Metastatic bone disease presents significant global challenges, necessitating effective strategy to prevent skeletal-related events (SREs) such as fractures and spinal cord compression. Denosumab and zoledronic acid have emerged as promising therapeutic options. However, the optimal dosing intervals remain to be defined. Methods: This retrospective study, utilizing the institutional integrative medical database from single medical center, involving 1,045 adults with metastatic bone disease who had underwent surgery or radiotherapy for SREs. The study aimed to investigate whether extended dosing intervals for denosumab or zoledronate are associated with increased need for subsequent local treatment for subsequent SREs and a decreased risk of osteonecrosis of the jaw (ONJ). Patients receiving less than two doses within the initial six months after local treatment for bone metastasis were defined as the rarely-used group. The patients having 2-4 doses were in the occasionally-used group and those with more doses were in the strictly-used group. Results: The subsequent SRE incidences were 27%, 16%, and 18% for the rarely-used, occasionally-used, and strictly-used groups, respectively. The occasionally-used group demonstrated comparable risks of SREs to the strictly-used group, while the rarely-used group showed increased risks. The ONJ incidence was significantly higher in the strictly-used patients (12%) versus the occasionally-used (3%). Conclusion: A less frequent dosing schedule (2-4 injections in the first six months) for denosumab or zoledronic acid was associated with a lower ONJ risk without a significant increase in subsequent SRE risk after local treatment for bone metastasis in our study. Strict monthly dosing was associated with a higher ONJ risk in our series. These outcomes should be interpreted cautiously due to the retrospective design and heterogeneity of the primary tumors.