How does denosumab (Prolia) affect calcium levels in patients with osteoporosis?

From the Guidelines

Denosumab (Prolia) can cause hypocalcemia (low blood calcium levels) in patients with osteoporosis, and it is recommended to include supplemental calcium and monitor serum calcium level when prescribing denosumab. This medication works by inhibiting RANK ligand, which reduces osteoclast activity and bone resorption 1. Since bone resorption is a major source of calcium release into the bloodstream, blocking this process can lead to decreased serum calcium levels.

Key Considerations

• Patients taking denosumab should be monitored for symptoms of hypocalcemia such as muscle cramps, numbness, or tingling sensations.
• To prevent this side effect, patients should take calcium and vitamin D supplements while on denosumab therapy.
• Typically, 1000-1200 mg of calcium and 800-1000 IU of vitamin D daily are recommended.
• Patients with severe kidney disease, vitamin D deficiency, or parathyroid disorders are at higher risk for developing hypocalcemia and may require more careful monitoring 1.

Monitoring and Supplementation

• Blood calcium levels should be checked before starting treatment, within two weeks after the initial dose, and periodically thereafter, especially in high-risk patients.
• Adequate calcium and vitamin D supplementation should begin at least two weeks before the first denosumab injection to minimize the risk of hypocalcemia 1.

From the FDA Drug Label

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. If you have advanced chronic kidney disease (may or may not be on kidney dialysis), Prolia may increase your risk for severe low calcium levels in your blood, which could result in hospitalization, life-threatening events and death A mineral and bone disorder associated with kidney disease called chronic kidney disease-mineral bone disorder (CKD-MBD) may increase your risk for severe low calcium levels in blood. Before you start Prolia and during treatment, your doctor may need to do certain blood tests to check for CKD-MBD. 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 numbness or tingling in your fingers, toes, or around your mouth

Denosumab (Prolia) can lower calcium levels in the blood, and patients with low blood calcium before starting treatment may experience worsening of this condition.

• Patients with advanced chronic kidney disease may be at increased risk for severe low calcium levels.
• Calcium and vitamin D supplements may be prescribed to help prevent low calcium levels.
• Patients should report symptoms of low blood calcium to their doctor immediately. 2

From the Research

Denosumab and Calcium Levels

• Denosumab (Prolia) is a medication used to treat osteoporosis, and it can affect calcium levels in patients 3, 4, 5.
• Studies have shown that denosumab can cause hypocalcemia (low calcium levels) in some patients, especially those with advanced chronic kidney disease (CKD) 3, 4.
• The risk of hypocalcemia is higher after the initial dose of denosumab, and the magnitude of serum calcium decrease is smaller after subsequent doses 3.

Predictors of Hypocalcemia

• Pretreatment serum calcium and creatinine levels are major predictors of hypocalcemia in patients treated with denosumab 4.
• Parathyroid hormone levels can also predict hypocalcemia in patients with normal renal function and vitamin D levels 5.
• Vitamin D and calcium supplementation can help prevent hypocalcemia in patients treated with denosumab 6, 7.

Importance of Vitamin D and Calcium Supplementation

• Vitamin D and calcium supplementation can stop the decrease in calcium caused by denosumab and inhibit bone metabolism to a greater extent 6.
• Continuous vitamin D and calcium supplementation can significantly improve lumbar bone mineral density (BMD) over a period of four years of denosumab therapy 7.
• Vitamin D and calcium supplementation is especially important for improving hip BMD at 12 months and lumbar BMD from 24 to 48 months 7.