Denosumab
Regulatory sources consulted
- openfda-label-a1cd4ff2-cdab-41fa-b8f5-e2bc0faea49f
- ema-epar-EMEA/H/C/006398
- aemps-cima-1251983001
- PubMed PMID:40587168 ↗
- PubMed PMID:36282253 ↗
- PubMed PMID:37130601 ↗
- PubMed PMID:36592455 ↗
- PubMed PMID:35279261 ↗
- OpenFDA · M05BX04
- RxNorm rxcui 993449 ↗
Approved indications
- 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.
- Treatment to increase bone mass in men with osteoporosis at high risk for fracture.
- Treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone.
- Prevention of skeletal related events (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in adults with advanced malignancies involving bone.
- Treatment of adults and skeletally mature adolescents with giant cell tumour of bone that is unresectable or where surgical resection is likely to result in severe morbidity.
Contraindications
Absolute
- Pre-existing hypocalcemia. Must be corrected prior to initiating therapy.
- Pregnancy. May cause fetal harm.
- Known hypersensitivity to denosumab or any of its components.
Clinical warnings
- Boxed warning · SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE: Patients with advanced CKD (eGFR < 30 mL/min), including dialysis patients, are at greater risk of severe hypocalcemia, with fatal cases reported. The presence of CKD-Mineral and Bone Disorder (CKD-MBD) markedly increases the risk. — FDA
- Major warning · Osteonecrosis of the Jaw (ONJ): ONJ has been reported. Perform a routine oral examination prior to starting treatment. — FDA
- Major warning · Atypical Femoral Fractures: Increased risk of atypical subtrochanteric and diaphyseal femoral fractures has been reported. — FDA
- Major warning · Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation: Following discontinuation, an increased risk of MVF, sometimes referred to as a 'rebound effect', has been observed. Consider transitioning to an alternative antiresorptive agent if denosumab is discontinued. — FDA
Adverse events
Common (≥1%)
back pain · pain in extremity · musculoskeletal pain · hypercholesterolemia · cystitis · arthralgia · nasopharyngitis
Rare but serious
osteonecrosis of the jaw · atypical femoral fractures · severe hypocalcemia · serious infections · multiple vertebral fractures following discontinuation · rebound hypercalcemia after discontinuation
Pregnancy and lactation
FDA category: X
Contraindicated in pregnancy. May cause fetal harm. Pregnancy testing should be performed prior to initiating treatment. Females of reproductive potential should use effective contraception during therapy and for at least 5 months after the last dose.
Recent literature (PubMed)
Revisión que posiciona a denosumab como un agente antiresortivo de primera línea para la osteoporosis, recomendado cuando los bisfosfonatos están contraindicados o no se toleran, para reducir fracturas vertebrales y de cadera.
Revisión sistemática y metaanálisis en red que confirma con evidencia de certeza moderada a alta que denosumab reduce las fracturas de cadera, vertebrales clínicas y radiográficas, y otras fracturas clínicas en mujeres posmenopáusicas con osteoporosis.
Revisión que destaca la potente inhibición de la resorción ósea por denosumab, su administración semestral y el crítico riesgo de fracturas vertebrales de rebote si el tratamiento se interrumpe, lo que requiere una transición a otro antiresortivo.
Metaanálisis en red que compara tratamientos para la osteoporosis. Muestra que denosumab es menos eficaz que los agonistas del receptor de PTH y romosozumab en la reducción de fracturas clínicas, pero es superior al placebo.
Revisión sobre hipercalcemia que señala la hipercalcemia por la interrupción de denosumab como una causa rara pero reconocida, destacando un aspecto importante de la seguridad del fármaco relacionado con su discontinuación.