Denosumab

What it is and how it works

Mechanism of Action 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. 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.

Mechanism class: RANK Ligand Blocking Activity

Indications

Conexxence is a RANK ligand (RANKL) inhibitor indicated for treatment: of postmenopausal women with osteoporosis at high risk for fracture to increase bone mass in men with osteoporosis at high risk for fracture of glucocorticoid-induced osteoporosis in men and women at high risk for fracture to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer 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 .

Dosage and administration (summary)

Pregnancy must be ruled out prior to administration of Conexxence. 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. Administer 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. Instruct patients to take calcium 1000 mg daily and at least 400 IU vitamin D daily.

Contraindications

Conexxence is contraindicated in: Patients with hypocalcemia: Pre-existing hypocalcemia must be corrected prior to initiating therapy with Conexxence . Pregnant women: Denosumab products may cause fetal harm when administered to a pregnant woman. In women of reproductive potential, pregnancy testing should be performed prior to initiating treatment with Conexxence .

Warnings and precautions

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. Same Active Ingredient: Patients receiving Conexxence should not receive other denosumab products concomitantly Hypersensitivity including anaphylactic reactions may occur.

Pregnancy

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.

Storage and supply

Storage and Handling Store Conexxence refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Prior to administration, Conexxence may be allowed to reach room temperature up to 25°C (77°F) in the original container.

Source: Denosumab (Conexxence) — US FDA prescribing information, 2025-12-15, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.