*2.3. Antiresorptive Therapies*

Bisphosphonate therapy is the current standard of care for preventing SREs in patients with BM [30,31]. Bisphosphonates inhibit osteoclast-mediated bone resorption and have antitumor effects by inhibiting tumor cell proliferation, adhesion, and invasion; by inhibiting angiogenesis; and by inducing apoptosis [31]. Recently, denosumab, a monoclonal antibody to the receptor activator of nuclear factor-kappa B ligand (RANKL) that inhibits osteoclast activity. It has been frequently used in cases of BM, and it has proven superior to bisphosphonate zoledronic acid in the prevention of SREs [32].

The number of studies that examine the effects of antiresorptive therapy in patients with DTC-BM is still limited. Recent studies have reported that in patients with multiple thyroid BMs, treatment with bisphosphonates can improve QOL and reduce SREs [33–35]. Despite the occurrence of BMs, OS in DTC is often significantly better than in other cancers. The potential benefit of antiresorptive therapy in reducing SRE should be weighed against the adverse events associated with its long-term use, such as osteonecrosis of the jaw (ONJ) and atypical femoral fractures. There are no differences between the incidence rates of these adverse events in patients using bisphosphonates and those using denosumab [36,37]. Because patients with malignancies treated with chemotherapy or head and neck EBRT have a higher risk of ONJ, these patients have to undergo a careful dental evaluation before the start of antiresorptive therapies [30]. The potential harm and benefits of combination therapy with antiresorptive drugs and KIs should be verified because anti-angiogenic KI therapies have also been associated with ONJ without antiresorptive therapy in a patient with DTC [38].
