Denosumab

Denosumab products bind to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Denosumab products prevent RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors.

• Conexxence is a RANK ligand (RANKL) inhibitor indicated for treatment: of postmenopausal women with osteoporosis at high risk for fracture ( 1.1 ) to increase bone mass in men with osteoporosis at high risk for fracture ( 1.2 ) of glucocorticoid-induced osteoporosis in men and women at high risk for fracture ( 1.3 ) to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer ( 1.4 ) to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer ( 1.5 ) 1.1 Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture Conexxence is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, denosumab reduces the incidence of vertebral, nonvertebral, and hip fractures [see Clinical Studies ( 14.1 )].ICD-10: C50.919, C61, M81.0

• Conexxence is contraindicated in: Patients with hypocalcemia: Pre-existing hypocalcemia must be corrected prior to initiating therapy with Conexxence [see Warnings and Precautions ( 5.1 )] . Pregnant women: Denosumab products may cause fetal harm when administered to a pregnant woman.contraindicated

Pregnancy must be ruled out prior to administration of Conexxence. ( 2.1 ) Before initiating Conexxence in patients with advanced chronic kidney disease, including dialysis patients, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone, serum calcium, 25(OH) vitamin D, and 1,25(OH)2 vitamin D. ( 2.2 , 5.1 , 8.6 ) Conexxence should be administered by a healthcare provider. ( 2.3 ) Administer 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. ( 2.3 ) Instruct patients to take calcium 1000 mg daily and at least 400 IU vitamin D daily. ( 2.3 ) 2.1 Pregnancy Testing Prior to Initiation of Conexxence Pregnancy must be ruled out prior to administration of Conexxence. Perform pregnancy testing in all females of reproductive potential prior to administration of Conexxence. Based on findings in animals, denosumab products can cause fetal harm when administered to pregnant women [see Use in Specific Populations ( 8.1 , 8.3 )] . 2.2 Laboratory Testing in Patients with Advanced Chronic Kidney Disease Prior to Initiation of Conexxence In patients with advanced chronic kidney disease [i.e., estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m 2 ], including dialysis-dependent patients, evaluate for the presence of chronic kidney disease mineral and bone disorder (CKD-MBD) with intact parathyroid hormone (iPTH), serum calcium, 25(OH) vitamin D, and 1,25 (OH)2 vitamin D prior to decisions regarding Conexxence treatment.

Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating Conexxence. May worsen, especially in patients with renal impairment. Adequately supplement all patients with calcium and vitamin D. Concomitant use of calcimimetic drugs may also worsen hypocalcemia risk. Evaluate for presence of chronic kidney disease mineral-bone disorder. Monitor serum calcium. ( 5.1 ) Same Active Ingredient: Patients receiving Conexxence should not receive other denosumab products concomitantly ( 5.2 ) Hypersensitivity including anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs. ( 5.3 ) Osteonecrosis of the jaw: Has been reported with denosumab products. Monitor for symptoms. ( 5.4 ) Atypical femoral fractures: Have been reported. Evaluate patients with thigh or groin pain to rule out a femoral fracture. ( 5.5 ) Multiple vertebral fractures have been reported following treatment discontinuation. Patients should be transitioned to another antiresorptive agent if Conexxence is discontinued. ( 5.6 ) Serious infections including skin infections: May occur, including those leading to hospitalization. Advise patients to seek prompt medical attention if they develop signs or symptoms of infection, including cellulitis. ( 5.7 ) Dermatologic reactions: Dermatitis, rashes, and eczema have been reported. Consider discontinuing Conexxence if severe symptoms develop. ( 5.8 ) Severe bone, joint, muscle pain may occur. Discontinue use if severe symptoms develop.

The following serious adverse reactions are discussed below and also elsewhere in the labeling: Severe Hypocalcemia and Mineral Metabolism Changes [see Warnings and Precautions ( 5.1 )] Hypersensitivity [see Warnings and Precautions ( 5.3 )] Osteonecrosis of the Jaw [see Warnings and Precautions ( 5.4 )] Atypical Subtrochanteric and Diaphyseal Femoral Fractures [see Warnings and Precautions ( 5.5 )] Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation of Treatment [see Warnings and Precautions ( 5.6 )] Serious Infections [see Warnings and Precautions ( 5.7 )] Dermatologic Adverse Reactions [see Warnings and Precautions ( 5.8 )] The most common adverse reactions reported with denosumab products in patients with postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. The most common adverse reactions reported with denosumab products in men with osteoporosis are back pain, arthralgia, and nasopharyngitis. The most common adverse reactions reported with denosumab products in patients with glucocorticoid-induced osteoporosis are back pain, hypertension, bronchitis, and headache. The most common (per patient incidence ≥ 10%) adverse reactions reported with denosumab products in patients with bone loss receiving androgen deprivation therapy for prostate cancer or adjuvant aromatase inhibitor therapy for breast cancer are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials.

Pregnant women and females of reproductive potential: Denosumab products may cause fetal harm when administered to pregnant women. Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of Conexxence. ( 8.1 , 8.3 ) Pediatric patients: Conexxence is not approved for use in pediatric patients. ( 8.4 ) Renal impairment: No dose adjustment is necessary in patients with renal impairment. Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m 2 ), including dialysis-dependent patients, are at greater risk of severe hypocalcemia. The presence of underlying chronic kidney disease-mineral bone disorder markedly increases the risk of hypocalcemia. ( 5.1 , 8.6 ) 8.1 Pregnancy Risk Summary Conexxence is contraindicated for use in pregnant women because it may cause harm to a fetus. There are insufficient data with denosumab products use in pregnant women to inform any drug-associated risks for adverse developmental outcomes. In utero denosumab exposure from cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes, abnormal bone growth, and decreased neonatal growth [see Data ] .

Metabolism

In a study conducted in healthy male and female volunteers (n = 73, age range: 18 to 64 years) following a single subcutaneously administered denosumab dose of 60 mg, the mean area-under-the-concentration-time curve up to 16 weeks (AUC 0-16 weeks ) of denosumab was 316 mcg⋅day/mL (standard deviation [SD] = 101 mcg⋅day/mL). The mean maximum denosumab concentration (C max ) was 6.75 mcg/mL (SD = 1.89 mcg/mL).

• Jun 1, 2010BLABLA125320Amgen
• Mar 5, 2024BLABLA761362Sandoz Inc
• Feb 13, 2025BLABLA761392Samsung Bioepis Co Ltd
• Feb 28, 2025BLABLA761404Celltrion Inc
• Mar 25, 2025BLABLA761398Fresenius Kabi Usa Llc
• Aug 29, 2025BLABLA761444Shanghai Henlius Biotech
• Sep 16, 2025BLABLA761436Biocon Biologics Inc
• Sep 26, 2025BLABLA761439Hikma Pharmaceuticals Usa Inc

1. 1Off Label Use36,58518%
2. 2Death20,08710%
3. 3Arthralgia8,7634.4%
4. 4Osteonecrosis Of Jaw8,5214.3%
5. 5Fatigue7,5913.8%
6. 6Pain In Extremity6,9503.5%
7. 7Pain6,8383.5%
8. 8Back Pain6,8223.4%
9. 9Nausea5,3742.7%
10. 10Diarrhoea5,2172.6%
11. 11Fall5,0372.5%
12. 12Rash4,2682.2%
13. 13Myalgia4,2022.1%
14. 14Asthenia4,0092.0%
15. 15Bone Pain4,0092.0%

Recent PubMed references pinned to Denosumab as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• RANKL Inhibition and the Risk of Ocular Hypertension and Primary Open-Angle Glaucoma.
  Investigative ophthalmology & visual science · 2026 · Tsai CY, Weng CH, Sheen YJ, et al.
  PMID 42240269DOI 10.1167/iovs.67.6.8
• Comparative efficacy and safety of odanacatib, abaloparatide, denosumab, teriparatide, and bisphosphonates for male osteoporosis: a systematic review and network meta-analysis.
  Frontiers in endocrinology · 2026 · Lu C, Zhang L, Xue C, et al.
  PMID 42181204DOI 10.3389/fendo.2026.1836818
• Targeting RANKL-independent osteoclastogenesis overcomes denosumab resistance in models of ER+ breast cancer bone metastasis.
  The Journal of clinical investigation · 2026 · Lin Q, Luo J, Duan Z, et al.
  PMID 42138086DOI 10.1172/JCI199285
• The impact of denosumab and calcitriol on asthma risk and lung function: a drug target mendelian randomization study.
  European journal of clinical pharmacology · 2026 · Jiang Z, Zhang M, Wu M, et al.
  PMID 42104117DOI 10.1007/s00228-026-04051-5
• Efficacy and safety of denosumab, zoledronic acid and alendronate on bone mineral density and trabecular bone score in men with osteoporosis.
  Age and ageing · 2026 · Zhou B, Zhang Y, Yu W, et al.
  PMID 42096654DOI 10.1093/ageing/afag121
• Denosumab as Second-Line Treatment in Patients With Metastatic Breast Cancer: A Retrospective Descriptive Pilot Study From a Single Institution.
  Cancer control : journal of the Moffitt Cancer Center · 2026 · To B, Wright LE, Doto D, et al.
  PMID 42076835DOI 10.1177/10732748261427825
• Deciphering transcriptome alterations in bone marrow immune cells at single-cell resolution under denosumab treatment.
  International immunopharmacology · 2026 · Lin X, Yang H, Liang D, et al.
  PMID 41997054DOI 10.1016/j.intimp.2026.116663
• A clinical study on the effects of teriparatide and denosumab on bone metabolism and gut microbiota in osteoporotic fracture patients.
  Archives of osteoporosis · 2026 · Deng J, Su S, Tian L, et al.
  PMID 41949681DOI 10.1007/s11657-026-01697-7

The 10 most recently updated of 330 ClinicalTrials.gov registrations naming Denosumab as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Abaloparatide Added to Ongoing Denosumab vs Continued Denosumab Alone
  Active not recruiting · Phase 4 · Interventional · 70 enrolled · Hospital for Special Surgery, New York
  NCT04467983updated 2026-06-08
• Contribution of Bone to Urine Citrate
  Enrolling by invitation · Observational · 25 enrolled · University of Texas Southwestern Medical Center
  NCT06811363updated 2026-06-03
• Response of Bony Metastasis to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers With Actionable Driver Mutations.
  Recruiting · Observational · 100 enrolled · University of Colorado, Denver
  NCT03958565updated 2026-06-03
• A Study for the Evaluation of Efficacy and Safety of Prolia® in Participants With Glucocorticoid-induced Osteoporosis in Mainland China
  Active not recruiting · Phase 4 · Interventional · 102 enrolled · Amgen
  NCT06588153updated 2026-05-27
• Romosozumab Versus Denosumab in Glucocorticoid-induced Osteoporosis: an Extended Observation of a Randomized Controlled Trial at 48 Months
  Completed · Phase 4 · Interventional · 54 enrolled · Tuen Mun Hospital
  NCT06472050updated 2026-05-05
• Markers of Osteoporosis in Cystic Fibrosis
  Recruiting · Phase 4 · Interventional · 100 enrolled · University of Texas Southwestern Medical Center
  NCT03921060updated 2026-05-05
• Zanzalintinib for Metastatic Clear Cell Renal Cell Carcinoma With Bone Metastases
  Not yet recruiting · Phase 2 · Interventional · 20 enrolled · Kelly Fitzgerald, MD
  NCT07043608updated 2026-05-01
• Denosumab (DMAB) Discontinuation And Switching In Glucocorticoid-Induced Osteoporosis (GIOP): A Pilot Study
  Completed · Phase 4 · Interventional · 45 enrolled · University of Alabama at Birmingham
  NCT04177940updated 2026-04-23
• Clinical Relevance of Modifying RANKL Signaling During Folliculogenesis
  Recruiting · Interventional · 100 enrolled · Peter Humaidan
  NCT07546552updated 2026-04-22
• Zunsemetinib in Combination With Capecitabine in Patients With Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer With Bone Metastasis
  Recruiting · Phase 1 · Phase 2 · Interventional · 152 enrolled · Washington University School of Medicine
  NCT06374459updated 2026-04-20

Frequently asked questions

How does Denosumab work?

Denosumab products bind to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Denosumab products prevent RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors.

What is Denosumab used for?

According to FDA labeling, Denosumab carries indications including: Conexxence is a RANK ligand (RANKL) inhibitor indicated for treatment: of postmenopausal women with osteoporosis at high risk for fracture ( 1.1 ) to increase bone mass in men with osteoporosis at high risk for fracture ( 1.2 ) of glucocorticoid-induced osteoporosis in men and women at high risk for fracture ( 1.3 ) to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer ( 1.4 ) to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer ( 1.5 ) 1.1 Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture Conexxence is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, denosumab reduces the incidence of vertebral, nonvertebral, and hip fractures [see Clinical Studies ( 14.1 )].. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Denosumab?

Denosumab is classified as Other drugs affecting bone structure and mineralization, RANK Ligand Inhibitor, RANK Ligand Blocking Activity, Bone Resorption Inhibition.

What are the brand names for Denosumab?

Denosumab is marketed under brand names including Aukelso, Bildyos, Bilprevda, Bomyntra, Boncresa, Bosaya, Conexxence, Enoby.

What are the contraindications for Denosumab?

Denosumab labeling lists contraindications including: Conexxence is contraindicated in: Patients with hypocalcemia: Pre-existing hypocalcemia must be corrected prior to initiating therapy with Conexxence [see Warnings and Precautions ( 5.1 )] . Pregnant women: Denosumab products may cause fetal harm when administered to a pregnant woman.. Always consult the full prescribing information and a clinician.