Denosumab, sold under the brand name Prolia among others, is a human

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

used for the treatment of

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

, treatment-induced bone loss,

metastases Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

to bone, and giant cell tumor of bone. The most common side effects are

joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...

and

muscle pain Myalgia or muscle pain is a painful sensation evolving from muscle tissue. It is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likely cause is viral infection, espec ...

in the arms or legs. Denosumab is an inhibitor of RANKL (receptor activator of nuclear factor kappa-Β ligand), which works by decreasing the development of

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...

s, which are cells that break down bone. Denosumab is a human monoclonal IgG2 antibody that targets the protein RANKL, which is essential for the formation, function and survival of osteoclasts, the cell type responsible for bone resorption. Denosumab binds to RANKL with high affinity and specificity, preventing the interaction between RANKL and RANK. Increased osteoclast activity stimulated by RANKL is a key mediator of bone destruction in metastatic bone disease. This leads to a reduction in osteoclast numbers and function, and a decrease in bone resorption, cancer-induced bone destruction. It also leads to a decrease in bone resorption in cortical and trabecular bones. It was developed by the biotechnology company

Amgen Amgen Inc. (formerly Applied Molecular Genetics Inc.) is an American multinational biopharmaceutical Corporation, company headquartered in Thousand Oaks, California. As one of the world's largest independent biotechnology companies, Amgen has a ...

Medical uses

Denosumab is used for those with

at high risk for

fracture Fracture is the appearance of a crack or complete separation of an object or material into two or more pieces under the action of stress (mechanics), stress. The fracture of a solid usually occurs due to the development of certain displacemen ...

s, bone loss due to certain medications, and in those with bone metastases.

Cancer

A 2012 meta-analysis found that denosumab was better than placebo,

zoledronic acid Zoledronic acid, also known as zoledronate and sold under the brand name Zometa among others, by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bon ...

, and

pamidronate Pamidronic acid or pamidronate disodium or APD (marketed as Aredia among others), is a nitrogen-containing bisphosphonate used to prevent osteoporosis. It was patented in 1971 and approved for medical use in 1987. Medical uses It is used to pr ...

, in reducing the risk of fractures in those with cancer.

Osteoporosis

In those with postmenopausal osteoporosis denosumab decreases the risk of fractures but increases the risk of infection. A 2013 review concluded that it is a reasonable treatment for postmenopausal osteoporosis. A 2017 review did not find benefit in males.

Mechanism of action

Bone remodeling 300 px, Bone tissue is removed by osteoclasts, and then new bone tissue is formed by osteoblasts. Both processes utilize cytokine ( Insulin-like_growth_factor.html" ;"title="TGF-β, Insulin-like growth factor">IGF) signalling. In osteology, bone ...

is the process by which the body continuously removes old bone tissue and replaces it with new bone. It is driven by various types of cells, most notably

osteoblast Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts fu ...

s (which secrete new bone) and

s (which break down bone);

osteocyte An osteocyte, an oblate-shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide an ...

s are also present in bone. Precursors to osteoclasts, called pre-osteoclasts, express surface receptors called

RANK A rank is a position in a hierarchy. It can be formally recognized—for example, cardinal, chief executive officer, general, professor—or unofficial. People Formal ranks * Academic rank * Corporate title * Diplomatic rank * Hierarchy ...

(receptor activator of

nuclear factor-kappa B Nuclear may refer to: Physics Relating to the nucleus of the atom: * Nuclear engineering * Nuclear physics * Nuclear power *Nuclear reactor *Nuclear weapon * Nuclear medicine *Radiation therapy *Nuclear warfare Mathematics * Nuclear space * Nu ...

). RANK is a member of the tumor necrosis factor receptor (TNFR) superfamily. RANK is activated by RANKL (the RANK-Ligand), which exists as cell surface molecules on osteoblasts. Activation of RANK by RANKL promotes the maturation of pre-osteoclasts into osteoclasts. Denosumab inhibits this maturation of osteoclasts by binding to and inhibiting RANKL. Denosumab mimics the natural action of

osteoprotegerin Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF) or tumour necrosis factor receptor superfamily member 11B (TNFRSF11B), is a cytokine receptor of the tumour necrosis factor (TNF) receptor superfamily encoded by th ...

, an endogenous RANKL inhibitor, that presents with decreasing concentrations (and perhaps decreased

effectiveness Effectiveness or effectivity is the capability of producing a desired result or the ability to produce desired output. When something is deemed effective, it means it has an intended or expected outcome, or produces a deep, vivid impression. Et ...

) in people with osteoporosis. This protects bone from degradation, and helps to counter the progression of the disease.

Contraindications and interactions

It is contraindicated in people with

hypocalcemia Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), while levels less than 2.1 ...

; sufficient calcium and

vitamin D Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...

levels must be reached before starting on denosumab therapy. Data regarding interactions with other drugs are missing. It is unlikely that denosumab exhibits any clinically relevant interactions. Denosumab works by lowering the hormonal message that leads to excessive osteoclast-driven bone removal and is active in the body for only six months. Similarly to

bisphosphonate Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed to treat osteoporosis. Evidence shows that they reduce the risk of fracture in ...

s, denosumab appears to be implicated in increasing the risk of

osteonecrosis of the jaw Osteonecrosis of the jaw (ONJ) is a severe bone disease (osteonecrosis) that affects the jaws (the maxilla and the mandible). Various forms of ONJ have been described since 1861, and a number of causes have been suggested in the literature. Osteo ...

(ONJ) following extraction of teeth or oral surgical procedures but, unlike bisphosphonate, the risk declines to zero approximately 6 months after injection. Invasive dental procedures should be avoided during this time.

Adverse effects

The most common side effects are

and

in the arms or legs. There is an increased risk of

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

s such as

cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...

(low blood calcium), hypersensitivity allergy reactions,

, and atypical femur fractures. Another trial showed significantly increased rates of

eczema Dermatitis is a term used for different types of skin inflammation, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened ...

and hospitalization due to infections of the skin. It has been proposed that the increase in infections under denosumab treatment might be connected to the role of RANKL in the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

. RANKL is expressed by

T helper cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...

, and is thought to be involved in

dendritic cell A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...

maturation. Discontinuation of denosumab is associated with a rebound increase in bone turnover. In rare cases this has led to severe hypercalcemia, but is common in children. Vertebral compression fractures have also occurred in some people after discontinuing treatment.

Society and culture

Legal status

United States

In August 2009, a meeting was held between Amgen and the Advisory Committee for Reproductive Health Drugs (ACRHD) of the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) to review the potential uses of denosumab. In October 2009, the FDA delayed approval of denosumab, stating that it needed more information. In June 2010, denosumab was approved by the FDA for use in postmenopausal women with risk of osteoporosis under the brand name Prolia, and in November 2010, as Xgeva for the prevention of skeleton-related events in people with bone metastases from solid

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s. Denosumab is the first RANKL inhibitor to be approved by the FDA. In June 2013, the FDA approved denosumab for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where resection would result in significant morbidity. In January 2024, the FDA added a

black box warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears near the beginning of the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administratio ...

to Prolia because of the risk of severe hypocalcemia in those with advanced kidney disease. An FDA review found that Prolia had resulted in "hospitalization, life-threatening events, and death" in that population. In March 2024, the FDA approved applications from

Sandoz Sandoz Group AG is a Swiss company that focuses on generic pharmaceuticals and biosimilars. Prior to October 2023, it was part of a division of Novartis that was established in 2003, when Novartis united all of its generics businesses under the ...

for Jubbonti (denosumab-bbdz), a

biosimilar A biosimilar (also known as follow-on biologic or subsequent entry biologic) is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. Biosimilars are officially approved ...

to Prolia; and Wyost (denosumab-bbdz), a biosimilar to Xgeva. In February 2025, the FDA approved denosumab-dssb, sold under the brand name Ospomyv, as a biosimiar to Prolia; and also sold under the brand name Xbryk as a biosimilar to Xgeva.fda.gov
/ref> In February 2025, the FDA approved denosumab-bmwo, sold under the brand name Stoboclo, as a biosimiar to Prolia;fda.gov
/ref> and sold under the brand name Osenvelt as a biosimilar to Xgeva. In March 2025, the FDA approved denosumab-bnht, sold under the brand name Bomyntra, as a biosimiar to Prolia;fda.gov
/ref> and sold under the brand name Conexxence as a biosimilar to Xgeva.

European Union

In December 2009, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

issued a positive opinion for denosumab for the treatment of postmenopausal osteoporosis in women and for the treatment of bone loss in men with hormone ablation therapy for prostate cancer. Denosumab, as Prolia, was authorized for medical use in the European Union in May 2010, and as Xgeva in July 2011. In March 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Jubbonti, intended for the treatment of osteoporosis in women who have been through menopause and in men at increased risk of fractures whose bone loss is linked to hormone ablation or long-term treatment with systemic glucocorticoid. The applicant for this medicinal product is Sandoz GmbH. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In March 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Wyost, intended for the prevention of bone complications in adults with advanced cancer involving bone and for the treatment of adults and skeletally mature adolescents with giant cell tumour of bone. The applicant for this medicinal product is Sandoz GmbH. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Denosumab, as Wyost,a biosimilar, was authorized for medical use in the European Union in May 2024 for all indications of denosumab treated by Xgeva. Denosumab, as Jubbonti, a biosimilar, was authorized for medical use in the EU in May 2024 for all indications of denosumab treated by Prolia. In November 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Obodence, intended for the treatment of osteoporosis in women who have been through menopause, treatment of bone loss linked to hormone ablation in men at increased risk of fractures, or treatment of bone loss associated with long-term treatment with systemic glucocorticoid. The applicant for this medicinal product is Samsung Bioepis NL B.V. Obodence is a biosimilar medicinal product that is highly similar to the reference product Prolia (denosumab), which was authorized in the EU in May 2010. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Obodence was authorized for medical use in the EU in February 2025. In November 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Xbryk, intended for the prevention of bone complications in adults with advanced cancer involving bone and for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone. The applicant for this medicinal product is Samsung Bioepis NL B.V. Xbryk is a biosimilar medicinal product that is highly similar to the reference product Xgeva (denosumab), which was authorized in the EU in July 2011. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Xbryk was authorized for medical use in the EU in February 2025. In December 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Osenvelt, intended for the prevention of bone complications in adults with advanced cancer involving bone and for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone. The applicant for this medicinal product is Celltrion Healthcare Hungary Kft. Osenvelt is a biosimilar medicinal product that is highly similar to the reference product Xgeva which was authorized in the EU in July 2011. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Osenvelt was authorized for medical use in the EU in February 2025. In December 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Stoboclo, intended for the treatment of osteoporosis in women who have been through menopause, bone loss linked to hormone ablation in men at increased risk of fractures and bone loss associated with long-term treatment with systemic glucocorticoid. The applicant for this medicinal product is Celltrion Healthcare Hungary Kft. Stoboclo is a biosimilar medicinal product that is highly similar to the reference product Prolia, which was authorized in the EU in May 2010. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Stoboclo was authorized for medical use in the EU in February 2025. In March 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Jubereq, intended for the prevention of skeletal-related events in adults with advanced malignancies involving bone and the treatment of adults and skeletally mature adolescents with giant cell tumor of bone. The applicant for this medicinal product is Accord Healthcare S.L.U. Jubereq is a biosimilar medicinal product that is highly similar to the reference product Xgeva (denosumab), which was authorized in the EU in July 2011. Jubereq was authorized for medical use in the EU in May 2025. In March 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Osvyrti, intended for the treatment of osteoporosis in women who have been through menopause, in men with prostate cancer who are at increased risk of fractures and whose bone loss is linked to hormone ablation, and people whose bone loss is linked to long-term treatment with systemic glucocorticoid. The applicant for this medicinal product is Accord Healthcare S.L.U. Osvyrti is a biosimilar medicinal product that is highly similar to the reference product Prolia (denosumab), which was authorized in the EU in May 2010. Osvyrti was authorized for medical use in the EU in May 2025. In April 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Denosumab BBL, intended for the treatment of osteoporosis in women who have been through menopause, treatment of bone loss linked to hormone ablation in men at increased risk of fractures or treatment of bone loss associated with long-term treatment with systemic glucocorticoid. The applicant for this medicinal product is Biosimilar Collaborations Ireland Limited. Denosumab BBL is a biosimilar medicinal product that is highly similar to the reference product Prolia (denosumab), which was authorized in the EU in May 2010. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In April 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Vevzuo, intended for the prevention of bone complications in adults with advanced cancer involving bone and the treatment of adults and skeletally mature adolescents with giant cell tumor of bone. The applicant for this medicinal product is Biosimilar Collaborations Ireland Limited. Vevzuo is a biosimilar medicinal product that is highly similar to the reference product Xgeva (denosumab), which was authorized in the EU in July 2011. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In April 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Yaxwer, intended for the prevention of bone complications in adults with advanced cancer involving bone and the treatment of adults and skeletally mature adolescents with giant cell tumor of bone. The applicant for this medicinal product is Gedeon Richter Plc. Yaxwer is a biosimilar medicinal product that is highly similar to the reference product Xgeva (denosumab), which was authorized in the EU in July 2011. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In April 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Junod, intended for the treatment of osteoporosis in women who have been through menopause, treatment of bone loss linked to hormone ablation in men at increased risk of fractures or treatment of bone loss associated with long-term treatment with systemic glucocorticoid. The applicant for this medicinal product is Gedeon Richter Plc. Junod is a biosimilar medicinal product that is highly similar to the reference product Prolia (denosumab), which was authorized in the EU in May 2010. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In April 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Zadenvi, intended for the treatment of osteoporosis in women who have been through menopause, treatment of bone loss linked to hormone ablation in men at increased risk of fractures or treatment of bone loss associated with long-term treatment with systemic glucocorticoid. The applicant for this medicinal product is Zentiva k.s. Zadenvi is a biosimilar medicinal product that is highly similar to the reference product Prolia (denosumab), which was authorized in the EU in May 2010. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In April 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Enwylma, intended for the prevention of bone complications in adults with advanced cancer involving bone and the treatment of adults and skeletally mature adolescents with giant cell tumour of bone. The applicant for this medicinal product is Zentiva k.s. Enwylma is a biosimilar medicinal product that is highly similar to the reference product Xgeva (denosumab), which was authorized in the EU in July 2011. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In April 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Denbrayce, intended for the prevention of bone complications in adults with advanced cancer involving bone and the treatment of adults and skeletally mature adolescents with giant cell tumor of bone. The applicant for this medicinal product is Mabxience Research S.L. Denbrayce is a biosimilar medicinal product that is highly similar to the reference product Xgeva (denosumab), which was authorized in the EU in July 2011. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In April 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Izamby, intended for the treatment of osteoporosis in women who have been through menopause, treatment of bone loss linked to hormone ablation in men at increased risk of fractures or treatment of bone loss associated with long-term treatment with systemic glucocorticoid. The applicant for this medicinal product is Mabxience Research SL. Izamby is a biosimilar medicinal product that is highly similar to the reference product Prolia (denosumab), which was authorized in the EU in May 2010. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In May 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Bomyntra, intended for the prevention of skeletal-related events in adults with advanced malignancies involving bone and the treatment of adults and skeletally mature adolescents with giant cell tumor of bone. The applicant for this medicinal product is Fresenius Kabi Deutschland GmbH. Bomyntra is a biosimilar medicinal product that is highly similar to the reference product Xgeva (denosumab), which was authorized in the EU in July 2011. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In May 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Conexxence, intended for the treatment of osteoporosis in women who have been through menopause, bone loss linked to hormone ablation in men with prostate cancer who are at increased risk of fractures, and bone loss in adults linked to long-term treatment with systemic glucocorticoid. The applicant for this medicinal product is Fresenius Kabi Deutschland GmbH. Conexxence is a biosimilar medicinal product that is highly similar to the reference product Prolia (denosumab), which was authorized in the EU in May 2010. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In May 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Rolcya, intended for the treatment of osteoporosis in women who have been through menopause, bone loss linked to hormone ablation in men with prostate cancer who are at increased risk of fractures and bone loss in adults linked to long-term treatment with systemic glucocorticoid. The applicant for this medicinal product is Sandoz GmbH. Rolcya is a biosimilar medicinal product that is highly similar to the reference product Prolia (denosumab), which was authorized in the EU in May 2010. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

Canada

Health Canada Health Canada (HC; )Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary units, department of the Gove ...

approved Jubbonti, a biosimilar to Prolia, in February 2024; and approved Wyost, a biosimilar to Xgeva, in March 2024.