Prolia

Prolia (denosumab) is an injection that is administered subcutaneously (under the skin) once every 6 months by a healthcare provider to:

• Treat osteoporosis in postmenopausal women at high risk for fracture
• Increase bone mass in men with osteoporosis at high risk for fracture
• Treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture
• Increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

Bone is always breaking down and reforming. Everyone has osteoclasts that dissolve old and damaged bone and osteoblasts that form new bone and add growth to existing bone tissue. Prolia works by stopping the formation of osteoclasts before they can reach and damage the bone. It binds to RANKL, which is a protein on the membrane of osteoclasts that is essential for their formation, function, and survival. This inhibits osteoclast formation, which decreases bone resorption and increases bone mass and strength in both cortical (hard bone) and trabecular (spongy bone) bone. Prolia is a monoclonal antibody that targets and inhibits RANK ligand (RANKL).

Prolia was FDA-approved on June 1, 2010. There are currently 9 biosimilars to Prolia:

• Jubbonti (denosumab-bbdz), manufactured by Sandoz Inc. (FDA approval March 5, 2024).
• Ospomyv (denosumab-dssb), manufactured by Samsung Bioepis (FDA approval February 16, 2025)
• Stoboclo (denosumab-bmwo), manufactured by Celltrion (FDA approval February 28, 2025)
• Conexxence (denosumab-bnht), manufactured by Fresenius Kabi (FDA approval March 25, 2025)
• Bildyos (denosumab-nxxp), manufactured by Shanghai Henlius Biotech, Inc., for Organon LLC (FDA approval August 29, 2025)
• Bosaya (denosumab-kyqq), manufactured by Biocon Biologics Ltd. (FDA approval September 16, 2025)
• Enoby (denosumab-qbde), manufactured by Hikma Pharmaceuticals USA Inc. (FDA approval September 26, 2025)
• Osvyrti (denosumab-desu), manufactured by Accord BioPharma (FDA approval November 20, 2025)
• Boncresa (denosumab-mobz), manufactured by Amneal Pharmaceuticals LLC (FDA approval December 19, 2025).

Xgeva is another brand of denosumab that is used to prevent bone fractures, other skeletal conditions, and high blood calcium levels in certain people with cancer.

• Xgeva and Prolia have different dosages and uses and are not interchangeable (see Xgeva vs Prolia: How do they compare? for more information).

Prolia carries a boxed warning for life-threatening severe hypocalcemia (very low calcium levels); the risk is higher in patients with advanced chronic kidney disease (CKD), particularly those on dialysis. The risk increases even more in those with CKD who also have a condition known as mineral and bone disorder (CKD-MBD). Your healthcare provider will evaluate you for hypocalcemia and CKD-MBD before starting treatment and monitor you throughout. Pre-existing low calcium levels should be corrected before starting treatment.

If you receive Prolia, you should not receive any biosimilars to Prolia or Xgeva. Prolia contains the same medicine (denosumab).

Serious and life-threatening hypersensitivity reactions have occurred with Prolia, including anaphylaxis. Seek emergency help or tell your doctor immediately if you experience shortness of breath, throat tightness, swelling of the airways and throat, itching, low blood pressure, or hives.

Osteonecrosis of the jaw has been reported with Prolia. A routine oral exam should be performed before Prolia treatment, and preventive dentistry undertaken if necessary, especially for those with risk factors such as prior tooth extraction, dental implants, oral surgery, cancer, or poor oral hygiene. Good oral hygiene practices should be maintained during treatment with Prolia.

Atypical low-energy or low-trauma femoral fractures have been reported with Prolia. Contact your doctor immediately if you develop thigh or groin pain. Multiple vertebral fractures have been reported following Prolia discontinuation. Your healthcare provider should consider transitioning you to another antiresorptive agent.

Serious infections, including skin infections, may occur, including those leading to hospitalization. Seek emergency help or tell your healthcare provider immediately if you develop any signs or symptoms of an infection, including cellulitis (symptoms include a red, swollen, and painful area of skin that is warm and tender to the touch. Some people may also develop fever and chills.

Other severe side effects include severe skin rashes and eczema, bone over-suppression, or severe bone, joint, or muscle pain may occur. Tell your healthcare provider immediately.

Do not take this medicine if you:

• have been told by your doctor that your blood calcium level is too low
• are pregnant or plan to become pregnant
• are allergic to denosumab or any of the ingredients in this medicine.

Tell your doctor about all of your medical conditions, including if you:

• are allergic to denosumab or latex
• are taking a medicine called Xgeva (denosumab). Xgeva contains the same medicine as Prolia
• have low blood calcium
• cannot take daily calcium and vitamin D
• had parathyroid or thyroid surgery (glands located in your neck) or intestinal surgery
• have been told you have trouble absorbing minerals in your stomach or intestines (malabsorption syndrome)
• have kidney problems or are on kidney dialysis
• have a weak immune system
• are taking medicine that can lower your blood calcium levels
• plan to have dental surgery or teeth removed
• are pregnant or plan to become pregnant. Prolia may harm your unborn baby
• are breastfeeding or plan to breastfeed.

Pregnancy

For females who can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with Prolia. You should use an effective method of birth control (contraception) during treatment with Prolia and for at least 5 months after your last dose. Tell your doctor right away if you inadvertently become pregnant.

Breastfeeding

It is not known if Prolia passes into your breast milk. You and your doctor should decide if you will take Prolia or breastfeed. You should not do both.

Serious allergic reactions have happened in people who take Prolia. Call your doctor or go to your nearest emergency room right away if you have any symptoms of a serious allergic reaction such as low blood pressure (hypotension), trouble breathing, throat tightness, swelling of your face, lips, or tongue, rash, itching, or hives.

Prolia can cause serious side effects, including:

• Increased risk of severe low calcium levels in your blood (hypocalcemia). Prolia may lower the calcium levels in your blood. If you have low blood calcium before you start receiving Prolia, it may get worse during treatment. Your low blood calcium must be treated before you receive Prolia. Talk to your doctor before starting Prolia. Your doctor may prescribe calcium and vitamin D to help prevent low calcium levels in your blood while you take Prolia. Take calcium and vitamin D as your doctor tells you to. Most people with low blood calcium levels do not have symptoms, but some people may have symptoms. Call your doctor right away if you have symptoms of low blood calcium, such as spasms, twitches, or cramps in your muscles, or numbness or tingling in your fingers, toes, or around your mouth
• Severe jawbone problems (osteonecrosis). Your doctor should examine your mouth before you start Prolia. Your doctor may tell you to see your dentist before you start Prolia. You need to practice good mouth care during treatment with Prolia.
• Unusual thigh bone fractures. Symptoms of a fracture include new or unusual pain in your hip, groin, or thigh
• Increased risk of broken bones, including broken bones in the spine, after stopping, skipping, or delaying Prolia
• Serious infections in your skin, lower stomach area (abdomen), bladder, ear, or heart. You may need to go to the hospital for treatment if you develop an infection. Call your doctor right away if you develop: fever or chills skin that looks red or swollen and is hot or tender to the touch shortness of breath, cough that will not go away severe abdominal pain frequent or urgent need to urinate or a burning feeling when you urinate
• Skin problems such as inflammation of your skin (dermatitis), rash, and eczema. Call your doctor if you have any of the following symptoms that do not go away or get worse: redness, itching, small bumps or patches (rash), your skin is dry or feels like leather, blisters that ooze or become crusty, skin peeling
• Bone, joint, or muscle pain.

Common Prolia side effects may include:

• bladder infection (painful or difficult urination)
• lung infection (cough, shortness of breath)
• headache
• back pain, muscle or joint pain
• increased blood pressure
• cold symptoms such as a stuffy nose, sneezing, and a sore throat
• high cholesterol or
• pain in your arms or legs.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Prolia is an injection that will be given to you by a healthcare professional. Prolia is injected under your skin (subcutaneously).

• You will receive Prolia 1 time every 6 months.
• You should take calcium and vitamin D as your doctor tells you to while you receive Prolia.
• Take good care of your teeth and gums while you receive Prolia. Brush and floss your teeth regularly. If you need to have any dental work (especially surgery), tell the dentist ahead of time that you are using Prolia. You may need to stop using the medicine for a short time.

Talk with your doctor before starting Prolia treatment. After your treatment with Prolia is stopped, or if you skip or delay taking a dose, your risk of breaking bones, including bones in your spine, is increased. Your risk of having more than 1 broken bone in your spine is increased if you have already had a broken bone in your spine. Do not stop, skip, or delay taking Prolia without first talking with your doctor. If your Prolia treatment is stopped, talk to your doctor about other medicines that you can take.

• Your risk of bone fractures can increase when you stop, skip, or delay using Prolia. Do not stop using this medicine without first talking to your doctor.

Call your doctor for instructions if you miss a dose or miss an appointment for your Prolia injection. You should receive your missed injection as soon as possible.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Other drugs may interact with denosumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medications you are taking.

• The use of calcimimetic drugs, such as cinacalcet, may worsen the risk of hypocalcemia.
• The use of other drugs associated with ONJ, such as bisphosphonates, may increase the risk of developing ONJ.

See the prescribing information for a full list of interactions.

Keep Prolia in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton. Do not freeze.

Prolia may be kept out of the refrigerator for up to 14 days at room temperature [up to 77°F (25°C)] in the original carton to protect from light. Do not keep Prolia at temperatures above 77°F (25°C). Warm temperatures will affect how Prolia works.

Do not shake.

Keep Prolia and all medicines out of the reach of children.

Active: denosumab

Inactive: sorbitol, acetate, polysorbate 20, Water for Injection (USP), and sodium hydroxide

Amgen.

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There are 2 for Prolia.

Prolia (denosumab) - Amgen Inc.

Xgeva (denosumab) - Amgen Inc.

View Xgeva information in detail.

Prolia, Xgeva interchangeable products

Interchangeable biosimilar products can be dispensed by a pharmacist without the intervention of the prescriber of the reference product.

Pharmacy laws for biosimilar prescribing may vary by state.

Aukelso (denosumab-kyqq) - Biocon Biologics Inc.

View Aukelso information in detail.

Bildyos (denosumab-nxxp) - Shanghai Henlius Biotech, Inc.

View Bildyos information in detail.

Bilprevda (denosumab-nxxp) - Shanghai Henlius Biotech, Inc.

View Bilprevda information in detail.

Bomyntra (denosumab-bnht) - Fresenius Kabi USA, LLC

View Bomyntra information in detail.

Boncresa (denosumab-mobz) - Amneal Pharmaceuticals LLC

View Boncresa information in detail.

Bosaya (denosumab-kyqq) - Biocon Biologics Inc.

View Bosaya information in detail.

Conexxence (denosumab-bnht) - Fresenius Kabi USA, LLC

View Conexxence information in detail.

Degevma (denosumab-adet) - Teva Pharmaceuticals, Inc.

Degevma

Enoby (denosumab-qbde) - Hikma Pharmaceuticals USA Inc.

View Enoby information in detail.

Jubbonti (denosumab-bbdz) - Sandoz Inc.

View Jubbonti information in detail.

Jubereq (denosumab-desu) - Accord BioPharma Inc.

View Jubereq information in detail.

Osenvelt (denosumab-bmwo) - CELLTRION, Inc.

View Osenvelt information in detail.

Ospomyv (denosumab-dssb) - Samsung Bioepis Co., Ltd.

View Ospomyv information in detail.

Osvyrti (denosumab-desu) - Accord BioPharma Inc.

View Osvyrti information in detail.

Oziltus (denosumab-mobz) - Amneal Pharmaceuticals LLC

View Oziltus information in detail.

Ponlimsi (denosumab-adet) - Teva Pharmaceuticals, Inc.

Ponlimsi

Stoboclo (denosumab-bmwo) - CELLTRION, Inc.

View Stoboclo information in detail.

Wyost (denosumab-bbdz) - Sandoz Inc.

View Wyost information in detail.

Xbryk (denosumab-dssb) - Samsung Bioepis Co., Ltd.

Xbryk

Xtrenbo (denosumab-qbde) - Hikma Pharmaceuticals USA Inc.

View Xtrenbo information in detail.