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Peptide

Denosumab (Prolia/Xgeva)

Denosumab is a fully human monoclonal antibody that inhibits RANKL (receptor activator of nuclear factor-κB ligand), the key mediator of osteoclast formation and activity. FDA-approved in 2010 for osteoporosis (Prolia, 60mg every 6 months) and bone metastases (Xgeva, 120mg monthly). The landmark FREEDOM trial demonstrated significant reductions in vertebral, hip, and nonvertebral fractures, with benefits sustained up to 10 years in extension studies.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade A
Conditions studied
3
Outcomes
14
Graded outcomes
8312

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

3 conditions, plus general outcomes

Bone Health

Bone Health: outcomes studied for Denosumab (Prolia/Xgeva)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Bone Turnover Markers

Rapid and sustained reduction in bone resorption markers (CTX) within days of administration.

Improves (the measure goes down)Large effect34 studies

Studies that measured bone turnover markers

and 24 more in the citations list

Osteoporosis

Osteoporosis: outcomes studied for Denosumab (Prolia/Xgeva)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Vertebral Fracture Risk

FREEDOM trial showed 68% reduction in new vertebral fractures (2.3% vs 7.2% placebo, P<0.001) over 3 years in postmenopausal women.

Improves (the measure goes down)Large effect32 studies

Studies that measured vertebral fracture risk

and 22 more in the citations list

Hip Fracture Risk

FREEDOM trial showed 40% reduction in hip fractures (0.7% vs 1.2% placebo, HR 0.60, P=0.04) over 3 years.

Improves (the measure goes down)Moderate effect32 studies

Studies that measured hip fracture risk

and 22 more in the citations list

Nonvertebral Fracture Risk

FREEDOM trial showed 20% reduction in nonvertebral fractures (6.5% vs 8.0% placebo, HR 0.80, P=0.01) over 3 years.

Improves (the measure goes down)Moderate effect32 studies

Studies that measured nonvertebral fracture risk

and 22 more in the citations list

Lumbar Spine BMD

10-year extension showed 21.7% increase in lumbar spine BMD from baseline, with continued gains without plateau.

Improves (the measure goes up)Large effect27 studies

Studies that measured lumbar spine bmd

and 17 more in the citations list

Total Hip BMD

10-year extension showed 9.2% increase in total hip BMD from baseline with sustained improvement.

Improves (the measure goes up)Large effect27 studies

Studies that measured total hip bmd

and 17 more in the citations list

Femoral Neck BMD

10-year extension showed 9.0% increase in femoral neck BMD from baseline.

Improves (the measure goes up)Large effect27 studies

Bone Cancer

  • Skeletal-Related Events (Cancer): improves
Bone Cancer: outcomes studied for Denosumab (Prolia/Xgeva)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Skeletal-Related Events (Cancer)

Xgeva (120mg monthly) reduces skeletal-related events in patients with bone metastases from solid tumors.

Improves (the measure goes down)Moderate effect22 studies

Studies that measured skeletal-related events (cancer)

and 12 more in the citations list

General

  • Bone Mineral Density: improves
  • Anti-Cancer Activity: improves
  • Safety/Tolerability: improves
General: outcomes studied for Denosumab (Prolia/Xgeva)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Bone Mineral Density

29 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Moderate effect28 studies

Studies that measured bone mineral density

and 18 more in the citations list

Anti-Cancer Activity

19 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Moderate effect24 studies

Studies that measured anti-cancer activity

and 14 more in the citations list

Safety/Tolerability

6 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Small effect18 studies

Studies that measured safety/tolerability

and 8 more in the citations list

Immune Function

3 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Small effect15 studies

Studies that measured immune function

and 5 more in the citations list

Kidney Function

2 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Small effect14 studies

Studies that measured kidney function

and 4 more in the citations list

Muscle Mass/Function

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect14 studies

Key findings

  • Bone Turnover MarkersBone HealthImproves (the measure goes down)
  • Vertebral Fracture RiskOsteoporosisImproves (the measure goes down)
  • Hip Fracture RiskOsteoporosisImproves (the measure goes down)

Studies cited

64 studies from PubMed

  1. Denosumab-bbdz: A Review of the Interchangeable Biosimilar for the Treatment of Osteoporosis.The Annals of pharmacotherapy, 2026 · PMID 40509651
  2. Long-Term Efficacy and Safety of Denosumab: Insights beyond 10 Years of UseEndocr Pract, 2025 · PMID 39801038
  3. Target tolerance improvement of the immunogenicity assay developed for analysing samples from clinical trials of RGB-14, a proposed biosimilar to Prolia/Xgeva.Journal of immunological methods, 2025 · PMID 40368321
  4. Impact of denosumab on muscle health in older adults in long-term care.Bone, 2025 · PMID 40460961
  5. Safety and Efficacy of Denosumab in Children With Osteogenesis Imperfecta-the First Prospective Comparative Study.The Journal of clinical endocrinology and metabolism, 2024 · PMID 38198649
  6. Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, active-controlled, Phase 3 trial in postmenopausal women with osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2024 · PMID 39042292
  7. Efficacy and safety of denosumab and teriparatide versus oral bisphosphonates to treat postmenopausal osteoporosis: a systematic review and meta-analysis.Frontiers in endocrinology, 2024 · PMID 39286276
  8. Denosumab as treatment of central giant cell granuloma of the jaws. a scoping review.Oral and maxillofacial surgery, 2024 · PMID 38539018
  9. Effect of denosumab, an anti-osteoporosis drug, on vascular calcification: A meta-analysis.Medicine, 2024 · PMID 39287246
  10. Exploring Denosumab's potential in aneurysmal bone cyst treatment: A scoping review.Journal of orthopaedic surgery (Hong Kong), 2024 · PMID 39445490
  11. Superiority of denosumab over bisphosphonates in preventing and treating glucocorticoid-induced osteoporosis: a systematic review and meta-analysis with GRADE quality assessment.Frontiers in endocrinology, 2024 · PMID 39744180
  12. Denosumab and muscle performance.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2023 · PMID 36378303
  13. The clinical effectiveness of denosumab (Prolia®) in patients with hormone-sensitive cancer receiving endocrine therapy, compared to bisphosphonates, selective estrogen receptor modulators (SERM), and placebo: a systematic review and network meta-analysis.Archives of osteoporosis, 2023 · PMID 36624318
  14. Association between preoperative denosumab and the risk of local recurrence in patients with giant cell tumor of bone: A meta-analysis and systematic review.Journal of cancer research and therapeutics, 2023 · PMID 37006039
  15. The Clinical Effectiveness of Denosumab (Prolia®) for the Treatment of Osteoporosis in Postmenopausal Women, Compared to Bisphosphonates, Selective Estrogen Receptor Modulators (SERM), and Placebo: A Systematic Review and Network Meta-Analysis.Calcified tissue international, 2023 · PMID 37016189
  16. Histopathological response to denosumab in giant cell tumours of bone - A review of 11 cases.Journal of cancer research and therapeutics, 2023 · PMID 37470608
  17. Denosumab in elderly osteoporotic patients. A narrative review.La Clinica terapeutica, 2023 · PMID 38048119
  18. Denosumab in the Treatment of Osteoporosis: 10 Years Later: A Narrative ReviewAdv Ther, 2022 · PMID 34762286
  19. Safety of denosumab versus zoledronic acid in the older adults with osteoporosis: a meta-analysis of cohort studies.Archives of osteoporosis, 2022 · PMID 35715524
  20. Cost-effectiveness analyses of denosumab for osteoporosis: a systematic review.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2022 · PMID 35059777
  21. Discontinuing Denosumab: Can It Be Done Safely? A Review of the Literature.Endocrinology and metabolism (Seoul, Korea), 2022 · PMID 35417954
  22. Denosumab Use in Adults With Fibrous Dysplasia: Case Reports and Review of the Literature.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2022 · PMID 35952985
  23. The role of neoadjuvant denosumab in the treatment of aneurysmal bone cysts: a case series and review of the literature.Journal of neurosurgery. Pediatrics, 2022 · PMID 36282899
  24. Denosumab in chronic kidney disease: a narrative review of treatment efficacy and safety.Archives of osteoporosis, 2021 · PMID 34319515
  25. The safety profile of denosumab in oncology beyond the safety of denosumab as an anti-osteoporotic agent: still more to learn.Expert opinion on drug safety, 2021 · PMID 33287586
  26. Is denosumab associated with an increased risk for infection in patients with low bone mineral density? A systematic review and meta-analysis of randomized controlled trials.International journal of rheumatic diseases, 2021 · PMID 33793076
  27. Denosumab biosimilar in postmenopausal osteoporotic women: A randomized, assessor-blind, active-controlled clinical trial.Indian journal of pharmacology, 2021 · PMID 33975993
  28. Denosumab in the treatment of giant cell tumor of the spine. Preliminary report, review of the literature and protocol proposal.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2020 · PMID 31098716
  29. Is Treatment with Denosumab Associated with Local Recurrence in Patients with Giant Cell Tumor of Bone Treated with Curettage? A Systematic Review.Clinical orthopaedics and related research, 2020 · PMID 31794487
  30. Hypocalcaemia following denosumab in prostate cancer: A clinical review.Clinical endocrinology, 2020 · PMID 32017154
  31. Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis.BMC musculoskeletal disorders, 2020 · PMID 32312263
  32. Hypercalcemia upon denosumab withdrawal in primary hyperparathyroidism: a case report and literature review.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2020 · PMID 33057735
  33. A Review on the Role of Denosumab in Fracture Prevention.Drug design, development and therapy, 2020 · PMID 33061307
  34. Relationship Between Bone Mineral Density T-Score and Nonvertebral Fracture Risk Over 10 Years of Denosumab TreatmentJ Bone Miner Res, 2019 · PMID 31566908
  35. Denosumab versus bisphosphonates for the treatment of bone metastases from solid tumors: a systematic review.The European journal of health economics : HEPAC : health economics in prevention and care, 2019 · PMID 30382484
  36. Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature.Archives of orthopaedic and trauma surgery, 2019 · PMID 30877429
  37. One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2019 · PMID 30508316
  38. Effects of denosumab on bone metabolism and bone mineral density in kidney transplant patients: a systematic review and meta-analysis.Archives of osteoporosis, 2019 · PMID 30852679
  39. Denosumab for Reducing Risk of Fractures in Postmenopausal Women.American family physician, 2019 · PMID 31038897
  40. Denosumab-related osteonecrosis of the jaw: a report of 2 cases and review of the literature.General dentistry, 2019 · PMID 30644830
  41. Denosumab in the treatment of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis.Drug design, development and therapy, 2019 · PMID 31616133
  42. Denosumab: A Review in Postmenopausal OsteoporosisDrugs Aging, 2018 · PMID 29435849
  43. Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its ExtensionJ Bone Miner Res, 2018 · PMID 29105841
  44. Denosumab for the treatment of bone disease in solid tumors and multiple myeloma.Future oncology (London, England), 2018 · PMID 29052442
  45. Denosumab: A Unique Perspective on Adherence and Cost-effectiveness Compared With Oral Bisphosphonates in Osteoporosis Patients.The Annals of pharmacotherapy, 2018 · PMID 29616561
  46. Denosumab in the treatment of glucocorticoid-induced osteoporosis.Rheumatology international, 2018 · PMID 30019224
  47. Denosumab compared to bisphosphonates to treat postmenopausal osteoporosis: a meta-analysis.Journal of orthopaedic surgery and research, 2018 · PMID 30071889
  48. Immunoallergic interstitial nephritis secondary to denosumab.Joint bone spine, 2018 · PMID 28115267
  49. Effects of Denosumab After Treatment Discontinuation : A Review of the Literature.The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists, 2018 · PMID 29720299
  50. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extensionLancet Diabetes Endocrinol, 2017 · PMID 28546097
  51. Denosumab: Prevention and management of hypocalcemia, osteonecrosis of the jaw and atypical fractures.Asia-Pacific journal of clinical oncology, 2017 · PMID 27862983
  52. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS.Bone, 2017 · PMID 28789921
  53. A comprehensive review of denosumab for bone metastasis in patients with solid tumors.Current medical research and opinion, 2016 · PMID 26451465
  54. Palliative Oncology: Denosumab.The American journal of hospice & palliative care, 2015 · PMID 24928835
  55. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial.Lancet (London, England), 2015 · PMID 26144908
  56. Denosumab in osteoporosis.Expert opinion on drug safety, 2014 · PMID 24289327
  57. Denosumab in breast cancer treatment.European journal of pharmacology, 2013 · PMID 23545361
  58. Denosumab: mechanism of action and clinical outcomesInt J Clin Pract, 2012 · PMID 22967310
  59. Randomized comparison of denosumab and zoledronic acid to prevent skeletal-related events in patients with bone metastases from prostate cancerLancet, 2011 · PMID 21353746
  60. Anti-cancer actions of denosumab.Current osteoporosis reports, 2011 · PMID 21874289
  61. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapyJ Bone Miner Res, 2010 · PMID 21248681
  62. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind studyJ Clin Oncol, 2010 · PMID 22419768
  63. Denosumab for the treatment of osteoporosisOsteoporos Int, 2010 · PMID 20124268
  64. Denosumab for prevention of fractures in postmenopausal women with osteoporosisN Engl J Med, 2009 · PMID 19671655