Help relieve bone pain and prevent broken bones in some types of cancer that arise from or spread to the bones. Denosumab prevents rankl from binding to rank, which inhibits osteoclast formation, function and survival, leading to decreased bone loss and destruction. Based on clinical trials using a lower dose of denosumab, patients with a. The discoverx pathhunter bioassay for denosumab uses a u2 os cell line expressing rank and an i.
Bisphosphonates or denosumab are given in addition to other cancer treatment medications. A new therapy for osteoporosis cleveland clinic cme. Denosumab is a human monoclonal antibody igg2 that targets and binds with high affinity and specificity to rankl, preventing activation of its receptor, rank, on. Characterised by reduced bone mineral density bmd and weakened bone structure 2,3,68, osteoporosis decreases bone. Brown4 osteoporosis is a systemic skeletal disease that increases with age and is common among postmeno. Be used to remove excess calcium in the blood that is a problem with some types of cancer, if other treatments have not worked.
These may be given along with chemotherapy, endocrine therapy, or radiotherapy. Denosumab binds with high specificity and affinity to the cytokine rankl, inhibiting its action. The most common side effects are joint and muscle pain in the arms or legs denosumab is a rankl inhibitor, which works by preventing the. Denosumab is a rankl inhibitor, which works by preventing the development of osteoclasts, which are cells that break down bone bone resorption. Based on animal findings and mechanism of action, denosumab may cause fetal harm if administered to pregnant women. Denosumab trade names prolia and xgeva is a human monoclonal antibody for the treatment of osteoporosis, treatmentinduced bone loss, metastases to bone, and giant cell tumor of bone.
Increased bone turnover after aromatase inhibition was shown to mobilise. Adjuvant denosumab in postmenopausal patients with hormone. Debu tripathy, md, coleader, womens cancer program, norris. Denosumab is a fully human immunoglobulin g2 monoclonal antibody with high affinity and specificity for human rankl. Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappab ligand rankl, an osteoclast differentiating factor. Confirm pregnancy status prior to initiation of therapy in women with reproductive potential. This leads to a different onset and offset of action compared. Denosumab circulates in blood and extracellular fluid.
Based on findings in animals and its mechanism of action, denosumab can cause fetal harm when administered to a pregnant woman. In conclusion, these data demonstrate that in postmenopausal women with low bmd, the effects of 60 mg denosumab every 6 months for 24 months on bmd and btm are reversible upon treatment discontinuation for 24 months, reflecting the biological mechanism of action of denosumab. As an essential mediator of osteoclast activity, increased rank ligand may lead to increased bone loss 1,8. The mechanism of action of denosumab in the management of these tumors and the associated side effects are discussed in detail. As with all therapeutic proteins, there is potential for immunogenicity.
Page 2 full prescribing information 1 indications and usage. Second, unlike bisphosphonates, denosumab is not incorporated into the sites of bone remodeling, which explains its reversible mechanism of action. Denosumab, a fully human monoclonal igg 2 antibody, is a bone resorption inhibitor. Denosumab for osteoporosis outline mechanism of action effect on fracture risk effect on bone turnover and density longterm effect on bone density safety the characteristics of denosumab and its mechanism of action. A new therapy for osteoporosis by candice gehret, pharm. This mechanism of action decreases bone resorption which leads to improved bone density denosumab is administered once every 6 months as a 60. During treatment, calcium and vitamin d supplementation is important. Clinical trial agreements a guide to key words and phrases pdf. Thus, continued therapy is required to maintain treatment effects. Potential placental transfer of human igg is dependent upon the igg subclass and gestational age, generally increasing as pregnancy progresses. Prolia denosumab is a human igg2 monoclonal antibody with affinity and specificity for human rankl receptor activator of nuclear factor kappab ligand. Osteoporosis is defined s th eru cl di o nf b due to an imbalance in bone removal resorption and replacement.
Briefly, denosumab is a fully human monoclonal antibody that inhibits rankl and helps regulate turnover in. Denosumab acts by a novel mechanism and is administered twice yearly by subcutaneous injection. Prolia binds to rankl, a transmembrane or soluble protein essential for the formation, function, and survival of. Abstractdenosumab is a novel antiresorptive drug that has been approved for use as a firstline drug for primary and secondary prevention of osteoporotic fractures. To describe the mechanisms of action of denosumab, a novel antiresorptive. Denosumab improves bone mass, microstructure and strength in animal models and humans, thus reducing fractures. Reflecting a fundamentally different mechanism of action 26, denosumab has a stronger influence on cortical bone remodeling than alendronate 27,28. Denosumab is the newest antiresorptive agent, with a novel mechanism of action. In headtohead studies, denosumab and improved bmd more. Aug 31, 2012 denosumab prolia is a human recombinant monoclonal antibody that is approved for the treatment of postmenopausal osteoporosis in women at high or increased risk of fracture in the us, the eu and several other countries. Research highlights denosumab is the first rank ligand inhibitor to target osteoclasts. Details of the compositeendpoint analysis showed that nonhistologically verified distant metastases and new primary cancers were reduced in the denosumab group, and there was no difference between the intervention and placebo groups. Second, the exact mechanism of action of adjuvant denosumab on diseasefree survival remains to be understood.
Denosumab trade names prolia and xgeva is a human monoclonal antibody for the treatment of osteoporosis, treatmentinduced bone loss, metastases to bone, and giant cell tumor of bone denosumab is contraindicated in people with low blood calcium levels. B reporter protein that is tagged with one fragment of a. Denosumab prolia and xgeva medical clinical policy. The mechanism of action of denosumab in bone is displayed in figure 1. Bisphosphonates and denosumab for breast cancer cochrane. Effects of denosumab treatment and discontinuation on bone. Prolia denosumab is a fully human monoclonal antibody that specifically binds to and inhibits the receptor activator of nfkappab.
The goal of bisphosphonates and denosumab differs based on the womens breast cancer status. Identified by osteoporosis canada clinical practice guidelines as a firstline agent for treatment of. Prolia binds to rankl, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Brown4 osteoporosis is a systemic skeletal disease that increases with age and is common among postmenopausal women 15. Xgeva mechanism of action xgeva denosumab for hcps. Denosumab delayed the time to a first sre by 16 % median of 20. Denosumab is a human igg2 monoclonal antibody that inhibits binding of the receptor activator of nuclear factor kappab ligand rankl, part of the tumor necrosis factor family to rank.
Current use in the treatment of primary bone tumors. It inhibits osteoclast formation, decreases bone resorption, increases bone mineral density bmd, and reduces the risk of fracture. Prolia is an antiresorptive rank ligand inhibitor, and its mechanism of action makes it different than a bisphosphonate. Companies developing a biosimilar are required to demonstrate that the proposed biosimilar is highly similar to the innovator material, using a mechanismofaction moabased assay.
Denosumab is a fully human monoclonal antibody that targets the receptor activator of nf. Please see prolia full prescribing information, including medication guide. Denosumab vs zoledronic acid for bonetargeted therapy in. By binding to rankl, denosumab inhibits rankl from activating its only receptor rank on the surface of osteoclasts and their precursors. Of note, after up to 3 years of treatment, no patients developed denosumabneutralizing antibodies. Denosumab is a human monoclonal antibody that binds to the human rank ligand rankl on the surface of osteoclasts and their precursors. Learn about the mechanism of action of prolia denosumab when used to treat women with postmenopausal osteoporosis at high risk for fracture. Denosumab is a fully human monoclonal igg2 antibody against rankl, a key mediator of osteoclast formation, function and survival. Several hypotheses about the mechanism of action by which denosumab reduces disease recurrence have been proposed. Xgeva label pdf prolia label pdf 8 use in specific populations.
Jan 26, 2020 based on the mechanism of action and data from animal reproduction studies, in utero exposure to denosumab may cause fetal harm. Mechanism of action differences are not meant to imply clinical efficacy. Osteoporosis is defined s th eru cl di o nf b due to an. Denosumab is a humanized monoclonal antibody igg 2. Sep 12, 2012 denosumab is the newest antiresorptive agent, with a novel mechanism of action. Prolia binds to rankl, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone. Denosumab is a human monoclonal antibody igg2 that targets and binds with high affinity and specificity to rankl, preventing activation of its receptor, rank, on the surface of osteoclast precursors and osteoclasts. Superiority of denosumab to zoledronic acid for prevention of skeletalrelated events.
Mechanism of action and pharmacokinetics indications and status adverse effects dosing administration guidelines special precautions interactions recommended clinical monitoring supplementary public funding references disclaimer. Aug 01, 2011 denosumab is a human immunoglobulin g2 monoclonal antibody with affinity and specificity for human rankl. Perform an oral examination and appropriate preventive dentistry prior to the initiation of xgeva and periodically during xgeva therapy. The effect of a single dose of osteoprotegerin in postmenopausal women. Be used to treat giant cell tumour of bone in some patients. Denosumab is a human immunoglobulin g2 monoclonal antibody with affinity and specificity for human rankl.
A phase iii trial compared denosumab to zoledronic acid in patients with at least 1 osteolytic lesion. Prolia denosumab injection, for subcutaneous use initial u. Denosumab is a novel, fully human igg2 monoclonal antibody specific to receptor activator of nuclear factor kappab. B ligand and inhibits bone resorption by inhibiting osteoclast formation. These may be given along with chemotherapy, endocrine. In utero exposure in cynomolgus monkeys dosed monthly with.
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