Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials

Abstract

Denosumab, a fully humanized monoclonal neutralizing antibody, inhibits activation of the RANK/RANKL/OPG signaling pathway through competitive binding with RANKL, thereby inhibiting osteoclast-mediated bone resorption. Denosumab inhibits bone loss; therefore, it is used to treat metabolic bone diseases (including postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis), in clinical practice. Since then, multiple effects of denosumab have been discovered. A growing body of evidence suggests that denosumab has a variety of pharmacological activities and broad potential in clinical diseases such as osteoarthritis, bone tumors, and other autoimmune diseases. Currently, Denosumab is emerging as a treatment for patients with malignancy bone metastases, and it also shows direct or indirect anti-tumor effects in preclinical models and clinical applications. However, as an innovative drug, its clinical use for bone metastasis of malignant tumors is still insufficient, and its mechanism of action needs to be further investigated. This review systematically summarizes the pharmacological mechanism of action of denosumab and the current understanding and clinical practice of the use of denosumab for bone metastasis of malignant tumors to help clinicians and researchers deepen their understanding of denosumab.

Unraveling the Relationship Between Osteoporosis, Treatment Modalities, and Oral Health: A Comprehensive Review

“…While denosumab has shown efficacy in reducing fracture risk, its effects on oral health are less extensively studied than bisphosphonates. Dental practitioners should be aware of potential impacts on bone healing and collaborate closely with physicians to manage patients receiving denosumab, particularly in dental surgeries or extractions [ 28 ].…”

The RANK–RANKL–OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer

“…Denosumab exhibits primate-specific activity, while OPG-Fc is utilized in murine models due to their highly similar mechanisms of action. Denosumab effectively inhibits bone resorption and cancer-induced bone destruction by competitively binding RANKL and blocking the differentiation, activation, and survival of osteoclasts [115]. Therefore, denosumab is indicated and FDA-approved for the following: postmenopausal and glucocorticoid-induced osteoporosis, androgen deprivation-induced and aromatase inhibitor-induced bone loss, prevention of SRE secondary to multiple myeloma or bone metastasis, giant cell tumors, and hypercalcemia of malignancy [15,116].…”

Prosztatarákos betegek csontegészségének megőrzése az onkológiai kezelés során

“…A progenitor osteoclast sejteken lévő RANK receptorhoz kapcsolódva az osteoclastok differenciálódását és a csontreszorpciót serkentik. A prosztatadaganatos sejtek specifikus fehérje kibocsájtásával serkentik a RANKL expresszióját az osteoblastokon, ezáltal a csont felszívódását okozzák, amely következtében több terük lesz a növekedéshez a csontvelőn belül (9). A fenti mechanizmusok alaposabb megértése a prosztatadaganatok gyógyszeres kezelésének új támadáspontjait jelenthetik.…”