Products
Denosumab is commercially available as a solution for injection in a prefilled syringe (Prolia). The antibody was approved in many countries, in the United States, and in the EU in 2010. Denosumab is also used in tumor therapy (Xgeva). This article relates to osteoporosis treatment.
Structure and properties
Denosumab is a human IgG2 monoclonal antibody with a molecular mass of 147 kDa. The drug is produced by biotechnological methods.
Effects
Denosumab (ATC M05BX04) has antiresorptive properties. The antibody decreases bone resorption, thereby increasing bone mass and strength. Thus, it reduces the risk of fracture during therapy. The effects are based on binding to RANK ligand (RANKL). RANKL stands for . It is a soluble and transmembrane protein necessary for osteoclast formation, function and survival. Denosumab prevents RANKL from activating its receptor RANK, which is localized on the surface of osteoclasts and their precursors. The half-life is in the range of 26 days. Unlike bisphosphonates, denosumab is not incorporated into bone.
Indications
- For the treatment of osteoporosis in postmenopausal women to prevent vertebral and nonvertebral fractures.
- Treatment to increase bone mineral density in men with osteoporosis and increased risk of fracture.
- Adjunctive treatment in women with breast cancer under adjuvant treatment with aromatase inhibitors and in men with prostate cancer under hormone ablation therapy when there is an increased risk of fracture.
Dosage
According to the professional information. The solution for injection is administered as a subcutaneous injection once every 6 months. Administration is possible on the thigh, abdomen, or upper arm. Patients must receive adequate calcium and vitamin D supplementation. The semiannual injection provides an advantage for treatment adherence.
Contraindications
- Hypersensitivity
- Hypocalcemia
- Pregnancy
Full precautions can be found in the drug label.
Adverse effects
The most common possible adverse effects include limb pain and musculoskeletal pain. After stopping the drug, bone mineral density returns to pretreatment baseline levels or even lower within several months. This causes the risk of fracture to increase again. Multiple fractures of the spine have been reported (Lamy et al., 2017). Bone density loss can be prevented in some patients by administration of a bisphosphonate or other antiresorptive agents. Incidentally, no rebound is observed after completion of bisphosphonate therapy. Other serious and rare side effects include osteonecrosis of the jaw, atypical femoral fractures, and hypocalcemia.
