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What's the difference between Prolia and Reclast?

Medically reviewed by Carmen Pope, BPharm. Last updated on April 5, 2024.

Official answer


Prolia (denosumab) and Reclast (zoledronic acid) are injections that can be used to treat or prevent osteoporosis. But they each work differently because Prolia is a monoclonal antibody (it may also be called a miscellaneous bone resorption agent) and Reclast is a bisphosphonate which means they have different side effects, other uses, tolerability, and effectiveness profiles. Both are prescription medicines.

What is the difference in how Prolia and Reclast work?

Prolia is a monoclonal antibody that works by binding to a protein called RANKL on osteoclasts (the cells that break down bone), inhibiting their formation, function, and survival. This decreases bone breakdown and increases bone density and strength both in the outer layer of bone and the inner spongy layer. Reclast is a bisphosphonate that works by inhibiting osteoclasts which are responsible for breaking down and reabsorbing bone (by a process known as bone resorption). It also inhibits increased osteoclastic activity and the release of calcium by the skeleton induced by tumors.

Do Prolia and Reclast have different uses?

In addition to treating osteoporosis in postmenopausal women, Prolia may also be used to increase bone density in men with osteoporosis at high risk for fracture, to increase bone mass in men who have undergone androgen deprivation therapy for prostate cancer and in women receiving aromatase inhibitor therapy for breast cancer, and to treat glucocorticoid-induced osteoporosis.

Reclast may be used to prevent AND treat osteoporosis in postmenopausal women, to increase bone density in men with osteoporosis, to treat and prevent glucocorticoid-induced osteoporosis, and to treat Paget's disease of the bone in men and women.

What are the differences in administration between Prolia and Reclast?

Prolia can be self-administered by injection under the skin (subcutaneously) of the upper thigh, abdomen, or upper arm, once every six months. Reclast is administered directly into a vein (intravenously) which must be done by a healthcare provider. Reclast only requires administration every year for the treatment of osteoporosis, and every two years for the prevention of osteoporosis.

Which is better for kidney disease: Prolia or Reclast?

People with chronic kidney disease (CKD) are at high risk of bone fractures and Prolia has traditionally been preferred for people with kidney disease because it has not been associated with kidney failure like Reclast rarely has. However, Prolia has been associated with severe, life-threatening, hypocalcemia (low calcium levels) in people with advanced kidney disease -- those with chronic kidney disease-mineral bone disorder (CKD-MBD) are at an even higher risk. Although the dosage of Prolia does not need to be reduced in people with kidney disease, healthcare providers should evaluate people for the presence of CKD-MBD before starting treatment. Reclast should not be used by people with a creatinine clearance of less than 35 mL/min and in those with evidence of acute renal impairment due to an increased risk of renal failure. People with CKD who are given Prolia should have their calcium and vitamin D levels monitored regularly. People undergoing Prolia therapy need to receive calcium 1000mg daily and at least 400 IU of vitamin D daily.

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What are the differences in side effects between Prolia and Reclast?

The most common side effects of Prolia are back pain, constipation, muscle pain, pain in the hands or feet, high cholesterol levels, nasal congestion, and bladder infections (in women). Prolia may exacerbate low calcium levels, especially in people with advanced kidney disease, and has been associated with low energy or low trauma fractures of the femoral shaft. The risk of serious infections may also be increased. Skin reactions occur frequently in people receiving Prolia, and there have been reports of severe incapacitating bone, joint, or muscle pain associated with Prolia use. Prolia may suppress bone remodeling. Prolia has also been associated with osteonecrosis of the jaw. The risk of osteonecrosis of the jaw is greater in those who have received chemotherapy, radiation, or steroids. A routine oral examination should be completed by a dentist before Prolia is started. Severe allergic reactions have been reported with Prolia and symptoms have included low blood pressure, shortness of breath, facial and throat tightness, and rash.

The most common side effects of Reclast are fever, nausea, constipation, anemia, and shortness of breath. Low blood pressure, abdominal pain, and vomiting may also occur. A lowering in the levels of certain electrolytes such as phosphate, potassium, and magnesium can also happen and some people report insomnia, anxiety or confusion, coughing, and skeletal pain with Reclast. Long-term use of bisphosphonates such as Reclast has been associated with atypical femur fractures, osteonecrosis of the jaw, and esophageal cancer. The risk of osteonecrosis of the jaw is greater in those who have received chemotherapy, radiation, or steroids.

Is Prolia or Reclast available as a generic?

Prolia is not available as a generic but there is an interchangeable biosimilar available called Jubbonti. An interchangeable biosimilar is a biological product that can be substituted in the pharmacy for the reference biologic because there are no clinically meaningful differences in terms of safety, purity, and potency.

Reclast is available as a low-cost generic under the name of zoledronic acid.

Do people rate Prolia or Reclast better?

People rate Reclast better than Prolia on review sites with an average rating of 5.3 out of 10 for Reclast compared with 2.7 out of 10 for Prolia. 38% of reviewers reported a positive effect for Reclast compared with only 14% reporting a positive effect for Prolia. 40% of Reclast reviewers reported a negative effect compared with 79% of Prolia reviewers.

  • Reclast (zoledronic acid) [Package Insert]. 07/2022. Novartis Pharmaceuticals Corporation.
  • Prolia (denosumab). Product Label. 03/2024. Amgen Inc

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