Biologic – RANKL inhibitor
ATC code: M05BX04 (Denosumab)
Brand names
Prolia, Xgeva, Acvybra, Bildyos, Bilprevda
A fully human IgG2 monoclonal antibody binding RANKL (receptor activator of NF-κB ligand). Blocks RANKL interaction with RANK on osteoclasts and precursors – suppresses osteoclast formation, activation, and survival. More pronounced bone resorption reduction than bisphosphonates. Unlike bisphosphonates, no bone accumulation – effect fully reverses within 6 months of discontinuation, leading to rebound (rapid resumption of bone resorption and risk of multiple vertebral fractures).
Second line
Second-line for postmenopausal osteoporosis with high fracture risk after bisphosphonate failure or intolerance per AACE/ACE 2020 and SEIOMM 2024. Dose 60 mg subcutaneously every 6 months. FREEDOM showed 68% reduction in vertebral fracture risk and 40% in hip fracture. After discontinuation, switch to a bisphosphonate to prevent rebound (multiple vertebral fracture risk within 6–18 months of stopping).
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Denosumab is a monoclonal antibody against RANKL. It is prescribed for osteoporosis with high fracture risk (especially in postmenopausal women and men with prostate cancer on androgen deprivation therapy) and for prevention of skeletal events in bone metastases (NOGG 2021, AACE 2020). In anti-aging circles, denosumab is promoted as a biological for anti-aging of bones in healthy postmenopausal women without confirmed osteoporosis. In people without confirmed osteoporosis, no clinical studies of prophylactic use exist. The drug has serious risks: osteonecrosis of the jaw (especially after dental procedures), atypical femoral fractures, hypocalcemia, severe infections, and on discontinuation a risk of multiple vertebral fractures (requires immediate transition to a bisphosphonate). If denosumab was prescribed without confirmed osteoporosis, consider seeking a second opinion.
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Animal studies show embryo-fetal defects. Not used during planned pregnancy or in pregnancy.
No data. Not used during lactation.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Denosumab is evaluated for the following indications with varying evidence strength: Postmenopausal osteoporosis (evidence tier A), Anti-aging and longevity (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Denosumab (≥ 1 in 100): Musculoskeletal pain, Hypercholesterolemia, Urinary tract infections, Back pain, Injection site reactions. See the Safety section for uncommon and serious reactions.
FDA category D. Animal studies show embryo-fetal defects. Not used during planned pregnancy or in pregnancy.
No data. Not used during lactation.
Denosumab is contraindicated in: Denosumab hypersensitivity; Hypocalcemia; Pregnancy – with caution; Lactation; Age under 18. Full list in the Safety section.