Accession Number
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)

Denosumab is a novel, fully human IgG2 monoclonal antibody specific to receptor activator of nuclear factor kappa-B ligand (RANKL), suppresses bone resorption markers in patients with a variety of metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Chemically, it consists of 2 heavy and 2 light chains. Each light chain consists of 215 amino acids. Each heavy chain consists of 448 amino acids with 4 intramolecular disulfides. FDA approved on June 1, 2010.

Protein structure
Protein chemical formula
Protein average weight
144700.0 Da
> Denosumab αOPGL-1 heavy chain sequence
> Denosumab αOPGL-1 light chain sequence
Download FASTA Format
Not Available
External IDs
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ProliaSolution60 mgSubcutaneousAmgenNot applicableNot applicableCanada
ProliaSolution60 mgSubcutaneousAmgen2010-08-12Not applicableCanada
ProliaInjection60 mg/1mLSubcutaneousAMGEN INC2010-06-05Not applicableUs
XgevaInjection120 mg/1.7mLSubcutaneousAMGEN INC2010-11-18Not applicableUs
XgevaInjection, solution120 mgSubcutaneousAmgen Europe B.V.2011-07-13Not applicableEu
XgevaSolution120 mgSubcutaneousAmgen2011-06-06Not applicableCanada
XgevaInjection, solution120 mgSubcutaneousAmgen Europe B.V.2011-07-13Not applicableEu
XgevaInjection, solution120 mgSubcutaneousAmgen Europe B.V.2011-07-13Not applicableEu
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Ranmark (Daiichi Sankyo)
CAS number



Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Associated Conditions

In clinical studies, treatment with 60 mg of Prolia resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e. osteocalcin and procollagen type 1 N-terminal peptide [PlNP]) were observed starting 1 month after the first dose of Prolia.

Mechanism of action

Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. 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.

ATumor necrosis factor ligand superfamily member 11
Additional Data Available
Adverse Effects

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Blackbox Warnings

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When 60 mg of denosumab was subcutaneously administered to healthy subjects after fasting for 12 hours, the pharmacokinetic parameters are as follows: Cmax = 6.75 mcg/mL; Tmax= 10 days (range of 3 to 21 days); AUC (0-16 weeks) = 316 mcg•day/mL. Denosumab does not accumulate following multiple doses once every 6 months. The pharmacokinetics of denosumab were not affected by the formation of antibodies.

Volume of distribution
Not Available
Protein binding
Not Available
Not Available
Route of elimination
Not Available
Half life

25.4 days

Not Available

In patients with postmenopausal osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials. In male patients with osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. In patients experiencing bone loss due to hormone ablation for cancer, the most common adverse reactions (≥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials

Affected organisms
  • Humans and other mammals
Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Denosumab is combined with 2-Methoxyethanol.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Denosumab is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbataceptThe risk or severity of adverse effects can be increased when Denosumab is combined with Abatacept.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Denosumab.
AbetimusThe risk or severity of adverse effects can be increased when Denosumab is combined with Abetimus.
AbituzumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Abituzumab.
AbrilumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Abrilumab.
ActeosideThe risk or severity of adverse effects can be increased when Denosumab is combined with Acteoside.
AdalimumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Adalimumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Denosumab.
Additional Data Available
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    Extended Description

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  • Evidence Level
    Evidence Level

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  • Action

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Food Interactions
Not Available


General References
  1. Malan J, Ettinger K, Naumann E, Beirne OR: The relationship of denosumab pharmacology and osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Dec;114(6):671-6. doi: 10.1016/j.oooo.2012.08.439. [PubMed:23159111]
  2. Link [Link]
  3. Link [Link]
External Links
PubChem Substance
RxList Drug Page Drug Page
ATC Codes
M05BX04 — Denosumab
AHFS Codes
  • 92:24.00 — Bone Resorption Inhibitors
FDA label
Download (226 KB)
Download (97.5 KB)

Clinical Trials

Clinical Trials
0Active Not RecruitingTreatmentAnorexia Nervosa (AN) / Atypical Anorexia Nervosa / Bone Density / Bone Loss / Eating Disorder1
0CompletedBasic ScienceAging / Bone Loss1
0RecruitingPreventionOvarian Carcinoma1
0RecruitingTreatmentBreast Cancer1
0RecruitingTreatmentBreast Neoplasm Female / Early Breast Cancer / Hormone Receptor Negative Neoplasm / Hormone Receptor Positive Tumor / Stage II Breast Cancer1
1Active Not RecruitingTreatmentAdvanced Malignant Neoplasm / Metastatic Malignant Neoplasm / Recurrent Malignant Neoplasm / Refractory Malignant Neoplasm1
1Active Not RecruitingTreatmentPostmenopausal Osteoporosis (PMO)1
1CompletedNot AvailableHealthy Volunteers1
1CompletedBasic ScienceHealthy Volunteer, Female, Breast1
1CompletedBasic ScienceHypersensitivity, Delayed / Immune Tolerance/Drug Effects / Immunosuppression / Ultraviolet Rays1
1CompletedPreventionBreast Cancer Prevention / Mammographic Density1
1CompletedPreventionHealthy People1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
1CompletedTreatmentImpaired kidney function1
1Not Yet RecruitingTreatmentHealthy Adults1
1RecruitingPreventionArthroplasty, Replacement, Hip1
1RecruitingTreatmentHealthy People1
1TerminatedTreatmentOne to five years postmenopausal / Osteopenia / Osteoporosis / Rheumatoid Arthritis1
1WithdrawnPreventionDisorder Related to Bone Marrow Transplantation1
1, 2CompletedTreatmentBone Cyst Aneurysmal / Pathological Fractures / Recurrent Disease / Refractory Tumors1
1, 2CompletedTreatmentCrohn's Disease (CD)1
1, 2RecruitingTreatmentMelanoma / Melanoma Stage Iii / Melanoma Stage Iv1
1, 2WithdrawnTreatmentDermatomyositis / Glucocorticoid-induced Osteoporosis / Osteoporosis / Polyarthritis / Rheumatoid Arthritis, Juvenile / Systemic Lupus Erythematosus (SLE) / Vasculitis1
2Active Not RecruitingPreventionAdult Idiopathic Generalized Osteoporosis1
2Active Not RecruitingPreventionOsteolysis1
2Active Not RecruitingTreatmentBreast Cancer1
2Active Not RecruitingTreatmentChildhood Osteosarcoma / Metastatic Bone Sarcomas / Recurrent Osteosarcoma / Refractory Osteosarcoma / Stage IV Osteosarcoma AJCC v7 / Stage IVA Osteosarcoma AJCC v7 / Stage IVB Osteosarcoma AJCC v71
2Active Not RecruitingTreatmentHER2 Positive Breast Cancers / Inflammatory carcinoma of the breast / Invasive Ductal Breast Carcinoma / Malignant Neoplasm of Female Breast / Mucinous Breast Cancer Stage II / Tubular Breast Cancer Stage II / Tubular Breast Cancer Stage III1
2Active Not RecruitingTreatmentMen Infertility1
2Active Not RecruitingTreatmentNeoplasms, Breast1
2Active Not RecruitingTreatmentOsteoarthritis of the Hands1
2Active Not RecruitingTreatmentOsteoporosis1
2Active Not RecruitingTreatmentRevision Surgery of Total Hip Arthroplasty1
2Active Not RecruitingTreatmentRheumatoid Arthritis1
2CompletedPreventionAmbulation Difficulty / Osteoarthritis, Hip1
2CompletedSupportive CareBone Metastases in Subjects With Advanced Breast Cancer / Breast Cancer / Metastases1
2CompletedSupportive CareLow Bone Mass / Low Bone Mineral Density / Osteoporosis / Postmenopausal Osteoporosis (PMO)1
2CompletedTreatmentBenign GCT / Benign Giant Cell Tumors / GCT / Giant Cell Tumors / Giant Cell Tumors of Bone / Malignancies1
2CompletedTreatmentBreast Cancer / Endocrine Cancer / Head and Neck Carcinoma / Hypercalcemia of Malignancy / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers / Lymphoma, Hodgkins / Malignant Lymphomas / Malignant Neoplasm of Colon / Metastatic Cancers / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Parathyroid Neoplasms / Renal Cancers / Thyroid Cancers1
2CompletedTreatmentCalcific Aortic Stenosis1
2CompletedTreatmentGCT / Giant Cell Tumors of Bone1
2CompletedTreatmentInfertility / Sperm / Testis1
2CompletedTreatmentLow Bone Mineral Density1
2CompletedTreatmentLow Bone Mineral Density / Postmenopausal Osteoporosis (PMO)1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentOsteogenesis Imperfecta (OI)1
2CompletedTreatmentOsteoporosis / Thalassemia Major (TM)1
2CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
2CompletedTreatmentRelapsed or Plateau-Phase Multiple Myeloma1
2CompletedTreatmentRheumatoid Arthritis1
2Enrolling by InvitationTreatmentBone Diseases / Pain1
2Not Yet RecruitingPreventionOsteoporosis1
2Not Yet RecruitingPreventionSpinal Cord Injury (=3 Years) / Sublesional Bone Loss Secondary to SCI1
2Not Yet RecruitingTreatmentSmoldering Multiple Myeloma (SMM)1
2RecruitingPreventionDense Breasts1
2RecruitingPreventionMultiple Myeloma (MM)1
2RecruitingPreventionOsteoporosis / Type 2 Diabetes Mellitus1
2RecruitingSupportive CareAllogeneic Hematopoietic Stem Cell Transplantation Recipient / Osteopenia / Osteoporosis1
2RecruitingTreatmentAneurysmal Bone Cysts / Chondroblastoma / Chondromyxoid Fibroma / Giant Cell Granuloma / Osteoblastoma1
2RecruitingTreatmentBone Giant Cell Tumor1
2RecruitingTreatmentBone Metastases / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentBreast Cancer1
2RecruitingTreatmentCancer, Bladder / Renal Cancers / Transitional Cell Carcinoma / Ureteral Cancer1
2RecruitingTreatmentCutaneous Melanoma / Malignant Melanoma of Skin / Melanoma / Melanoma (Skin) / Melanoma Stage Iii / Melanoma Stage Iv1
2RecruitingTreatmentEBV Related Carcinoma / Nasopharyngeal Carcinoma1
2RecruitingTreatmentGouty Arthritis1
2RecruitingTreatmentKidney Transplant; Complications / Osteoporosis / Renal Osteodystrophy1
2RecruitingTreatmentLangerhans Cell Histiocytosis (LCH)1
2RecruitingTreatmentMetastatic Kidney Cancer / Renal Cell Carcinoma, Clear Cell1
2RecruitingTreatmentMultiple Myeloma (MM)1
2SuspendedTreatmentBone Metastases / Castration-Resistant Prostate Cancer (CRPC) / Metastatic Cancers1
2SuspendedTreatmentMetastatic Medullary Thyroid Cancer1
2TerminatedTreatmentBreast Cancer1
2TerminatedTreatmentBreast Carcinoma Metastatic in the Bone / Circulating Tumor Cell Count / Estrogen Receptor Positive / HER2/Neu Negative / Progesterone Receptor Positive / Stage IV Breast Cancer1
2TerminatedTreatmentEarly Breast Cancer1
2TerminatedTreatmentProstate Cancer1
2WithdrawnBasic ScienceNeoplasms, Breast1
2, 3RecruitingTreatmentOsteoporosis, Osteopenia / Renal Transplant Recipient Patients1
3Active Not RecruitingSupportive CareBreast Cancer1
3Active Not RecruitingSupportive CareMetastatic Renal Cell Carcinoma1
3Active Not RecruitingTreatmentNon-small Cell Lung Cancer (NSCLC), Stage IV1
3Active Not RecruitingTreatmentOsteogenesis Imperfecta (OI)1
3CompletedPreventionHormone Refractory Prostate Cancer / Hormone-Refractory Prostate Cancer1
3CompletedPreventionPostmenopausal Osteoporosis (PMO)1
3CompletedSupportive CareBone Metastases3
3CompletedSupportive CareBone Metastases in Men With Hormone-Refractory Prostate Cancer / Bone Metastases in Subjects With Advanced Breast Cancer / Bone Metastases in Subjects With Advanced Cancer or Multiple Myeloma1
3CompletedSupportive CareBone Metastases / Malignancies / Malignancies, Hematologic / Multiple Myeloma (MM) / Multiple Myeloma Bone Lesions / Oncology1
3CompletedSupportive CareCataracts / Low Bone Mineral Density / Malignancies / Osteopenia / Osteoporosis / Prostate Cancer1
3CompletedSupportive CareLow Bone Mass / Low Bone Mineral Density / Osteoporosis / Postmenopausal Osteoporosis (PMO)1
3CompletedTreatmentBone Metastases in Men With Hormone-Refractory Prostate Cancer / Bone Metastases in Subjects With Advanced Breast Cancer1
3CompletedTreatmentBreast Cancer / Low Bone Mineral Density / Osteopenia1
3CompletedTreatmentCarcinoma NOS / Castrate-resistant Prostate Cancer (CRPC) / Malignancies / Prostate Cancer / Tumors1
3CompletedTreatmentCastrate-resistant Prostate Cancer (CRPC)1
3CompletedTreatmentCharcot Joint of Foot1
3CompletedTreatmentChronic Kidney Disease (CKD) / Osteoporosis1
3CompletedTreatmentFractures, Bone1
3CompletedTreatmentGlucocorticoid-induced Ostepor / Steroid-induced Osteopor / Steroid-induced Osteopor, Glucocorticoid-induced Ostepor / Steroid-induced Osteopor., Glucocorticoid-induced Ostepor1
3CompletedTreatmentLow Bone Mass / Low Bone Mineral Density / Males With Osteoporosis / Osteopenia / Osteoporosis1
3CompletedTreatmentLow Bone Mineral Density1
3CompletedTreatmentLow Bone Mineral Density / Osteopenia / Osteoporosis1
3CompletedTreatmentOsteopenia / Osteoporosis2
3CompletedTreatmentParathyroid Adenomas / Parathyroid Hyperplasia / Primary Hyperparathyroidism1
3CompletedTreatmentPostmenopausal Osteoporosis (PMO)7
3CompletedTreatmentProstate Cancer1
3Not Yet RecruitingTreatmentIdiopathic Inflammatory Myopathies / Osteoporosis, Osteopenia1
3RecruitingPreventionBreast Cancer1
3RecruitingPreventionGiant Cell Tumors of Bone1
3RecruitingSupportive CareBone Metastases / Metastatic Breast Cancer / Metastatic Hormone Refractory Prostate Cancer1
3RecruitingTreatmentEvaluate the Safety and Efficacy of Denosumab in Pediatric Subjects With / Glucocorticoid-induced Osteoporosis1
3RecruitingTreatmentOsteogenesis Imperfecta (OI)1
3RecruitingTreatmentOsteoporosis / Systemic Mastocytosis1
3RecruitingTreatmentPostmenopausal Women With Osteoporosis1
3TerminatedTreatmentAnorexia Nervosa (AN)1
3TerminatedTreatmentBreast Cancer1
3TerminatedTreatmentOsteoporosis / Thalassemia Majors (Beta-Thalassemia Major)1
4Active Not RecruitingDiagnosticPostmenopausal Osteoporosis (PMO) / Type 2 Diabetes Mellitus1
4Active Not RecruitingSupportive CareGiant Cell Tumors of Bone1
4Active Not RecruitingTreatmentBreast Cancer / Metastasis / Prostate Cancer1
4Active Not RecruitingTreatmentOsteoporosis1
4Active Not RecruitingTreatmentPostmenopausal Osteoporosis (PMO)1
4CompletedPreventionBone Resorption1
4CompletedPreventionOsteoarthritis, Hip1
4CompletedTreatmentMetabolic Bone Disease1
4CompletedTreatmentPostmenopausal Osteoporosis (PMO)3
4CompletedTreatmentPrimary Hyperparathyroidism1
4CompletedTreatmentRheumatoid Arthritis1
4Enrolling by InvitationPreventionSpine Deformity1
4Not Yet RecruitingDiagnosticCystic Fibrosis (CF)1
4RecruitingPreventionArthralgia Generalized / Osteoporosis / Osteoporotic Fractures1
4RecruitingPreventionBariatric Surgery Candidate / Bone Loss1
4RecruitingTreatmentFemale With Osteoporosis and Chronic Kidney Disease1
4RecruitingTreatmentOsteoporosis / Postmenopausal Osteoporosis (PMO)1
4RecruitingTreatmentOsteoporosis / Primary Hyperparathyroidism1
4RecruitingTreatmentOsteoporosis / Spinal Cord Injuries (SCI)1
4RecruitingTreatmentPostmenopausal Osteoporosis (PMO)1
4RecruitingTreatmentSecondary Osteoporosis / Spinal Cord Injuries (SCI)1
4SuspendedTreatmentBone Marrow Oedema Syndrome / High Turnover Bone Disease / Quality of Life1
4SuspendedTreatmentOsteoporosis / Osteoporotic Fractures / Postmenopausal Osteoporosis (PMO)1
4WithdrawnNot AvailableMetastatic Bone Disease / Tumors, Solid1
Not AvailableActive Not RecruitingNot AvailableOsteoporosis / Post Menopausal Osteoperosis, Male Osteoperosis1
Not AvailableCompletedNot AvailableFractures, Bone / Osteoporosis1
Not AvailableCompletedNot AvailablePostmenopausal Osteoporosis (PMO)2
Not AvailableCompletedNot AvailableXGEVA Off-label Use1
Not AvailableCompletedTreatmentPostmenopausal Osteoporosis (PMO)1
Not AvailableCompletedTreatmentRheumatoid Arthritis1
Not AvailableNot Yet RecruitingNot AvailableGiant Cell Tumors of Bone1
Not AvailableRecruitingNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableRecruitingNot AvailableOsteoporosis2
Not AvailableRecruitingNot AvailablePostmenopausal Osteoporosis (PMO)1


Not Available
Not Available
Dosage forms
InjectionSubcutaneous60 mg/1mL
SolutionSubcutaneous60 mg
InjectionSubcutaneous120 mg/1.7mL
Injection, solutionSubcutaneous120 mg
SolutionSubcutaneous120 mg
Not Available
Patent NumberPediatric ExtensionApprovedExpires (estimated)
Additional Data Available
  • Filed On
    Filed On

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Experimental Properties
Not Available


Not Available
Organic Compounds
Super Class
Organic Acids
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Alternative Parents
Not Available
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available


Pharmacological action
General Function
Tumor necrosis factor receptor superfamily binding
Specific Function
Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be...
Gene Name
Uniprot ID
Uniprot Name
Tumor necrosis factor ligand superfamily member 11
Molecular Weight
35477.81 Da
  1. Lipton A, Jun S: RANKL inhibition in the treatment of bone metastases. Curr Opin Support Palliat Care. 2008 Sep;2(3):197-203. doi: 10.1097/SPC.0b013e32830baac2. [PubMed:18685421]
  2. Westenfeld R, Ketteler M, Brandenburg VM: Anti-RANKL therapy--implications for the bone-vascular-axis in CKD? Denosumab in post-menopausal women with low bone mineral density. Nephrol Dial Transplant. 2006 Aug;21(8):2075-7. Epub 2006 May 15. [PubMed:16702197]

Drug created on March 19, 2008 10:43 / Updated on May 30, 2020 00:22

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