From the Guidelines
Denosumab is a fully human monoclonal antibody to RANKL, used to treat giant cell tumor of bone (GCTB), osteoporosis, and prevent bone complications in certain cancers, by suppressing the formation and activity of osteoclasts. It is typically administered as a monthly subcutaneous injection after three loading doses at weekly intervals 1. The medication is particularly valuable for patients who cannot tolerate or haven't responded to other osteoporosis treatments, and is also used in patients with metastases or where surgery is not possible or unacceptably morbid.
Some key points to consider when using denosumab include:
- The importance of daily calcium and vitamin D supplements to prevent hypocalcemia 1
- The potential for significant side effects, including hypocalcemia, arthralgias, and osteonecrosis of the jaw 1
- The need for careful management when discontinuing denosumab, as it can lead to rapid bone loss and increased fracture risk 1
- The recommendation to start denosumab in all breast cancer patients with bone metastases, whether they are symptomatic or not, and in patients with castration-resistant prostate cancer (CRPC) and bone metastases 1
In terms of dosing, denosumab is typically given as 120 mg (Xgeva) every four weeks for cancer-related bone issues 1. However, the optimal duration of treatment and the best approach for managing potential side effects are still being studied. Overall, denosumab is a valuable treatment option for patients with GCTB, osteoporosis, and certain types of cancer, and can help to reduce the risk of skeletal-related events and improve quality of life.
From the FDA Drug Label
Denosumab is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL (receptor activator of nuclear factor kappa-B ligand). Denosumab has an approximate molecular weight of 147 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells. Denosumab is a monoclonal antibody that binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption.
- Main Mechanism: Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.
- Key Points:
- Molecular Weight: 147 kDa
- Production: Genetically engineered mammalian (Chinese hamster ovary) cells
- Binding Affinity: Human RANKL
- Class: Human IgG2 monoclonal antibody 2
From the Research
Definition and Mechanism of Denosumab
- Denosumab is a human monoclonal antibody that specifically inhibits tumor-associated bone lysis through the RANKL pathway 3.
- It is a potent inhibitor of osteoclast differentiation and activity, used to treat osteoporosis and other bone-related diseases 4.
- Denosumab works by binding to and inhibiting RANK ligand, thereby reducing osteolytic activity and slowing disease progression 5.
Clinical Uses of Denosumab
- Denosumab is used as neoadjuvant therapy for giant-cell tumor of bone (GCTB) in surgical and non-surgical cases 3.
- It is also used to treat postmenopausal osteoporosis, bone loss associated with hormone ablation therapy, and prevention of skeletal-related events in patients with bone metastases from solid tumors 6.
- Denosumab is used in the treatment of glucocorticoid-induced osteoporosis, as well as for the prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer 7.
Efficacy and Safety of Denosumab
- Denosumab has shown potent anti-resorptive properties and anti-fracture efficacy, with a continuous gain of bone mineral density during long-term treatment 4.
- The most common adverse events associated with denosumab are fatigue, muscular pain, and hypocalcemia 3, 5.
- Denosumab has a positive clinical response in terms of pain relief, with a decrease in the morbidity of surgical procedures 3.
- However, there are concerns about an increased risk of multiple vertebral fractures following discontinuation of denosumab, and further study is needed to address questions regarding treatment duration and discontinuation 7.