From the Guidelines
Bone metastases typically cause hypercalcemia, not hypocalcemia, due to increased bone breakdown and release of calcium into the bloodstream. When cancer spreads to the bones, it usually stimulates osteoclast activity, leading to increased bone destruction and release of calcium into the bloodstream [ 1 ]. This process is often mediated by factors like parathyroid hormone-related protein (PTHrP), which is produced by many tumors. The excessive calcium release from bone destruction overwhelms the kidneys' ability to excrete calcium, resulting in elevated serum calcium levels. Hypercalcemia is particularly common in metastases from breast, lung, and multiple myeloma [ 1 ].
Some key points to consider:
- Bone metastases can lead to hypercalcemia due to increased bone resorption [ 1 ]
- Hypercalcemia is a common complication of bone metastases, particularly in breast, lung, and multiple myeloma [ 1 ]
- In rare cases, some bone metastases might cause hypocalcemia, particularly in prostate cancer with extensive osteoblastic (bone-forming) metastases that rapidly incorporate calcium into new bone formation [ 1 ]
- Treatment of hypercalcemia often requires hydration, bisphosphonates, denosumab, or calcitonin depending on severity [ 1 ]
It's essential to note that while bone metastases can cause hypercalcemia, hypocalcemia can occur in certain situations, such as in patients with renal failure who cannot activate vitamin D [ 1 ]. However, hypercalcemia remains the much more common metabolic complication of bone metastases. Supplemental calcium and vitamin D are recommended to prevent hypocalcemia in patients receiving either denosumab or zoledronic acid [ 1 ].
From the FDA Drug Label
Xgeva is a RANK ligand (RANKL) inhibitor indicated for: Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. Hypocalcemia: Xgeva can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Multiple Myeloma: Most common adverse reactions (≥ 10%) were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache.
The FDA drug label does not directly answer if bone metastasis causes hypocalcemia. It does mention that the drug can cause hypocalcemia and that it is used to prevent skeletal-related events in patients with bone metastases from solid tumors, but it does not establish a direct causal relationship between bone metastasis and hypocalcemia 2.
From the Research
Bone Metastasis and Hypocalcemia
- Bone metastasis (bone mets) can lead to an increased risk of hypocalcemia, particularly in patients with prostate cancer and osteoblastic bone metastases 3
- The use of inhibitors of bone resorption, such as bisphosphonates and denosumab, can increase the risk of hypocalcemia in patients with bone metastasis 4, 5, 3, 6
Risk Factors for Hypocalcemia
- Reduced creatinine clearance and higher baseline bone turnover markers are important risk factors for developing hypocalcemia in patients with bone metastasis 4
- Vitamin D deficiency can increase the risk of hypocalcemia in patients with bone metastasis, particularly in those receiving bisphosphonate therapy 5, 6, 7
- Patients with extensive bone metastasis, such as those with breast cancer, are at higher risk of developing symptomatic hypocalcemia after treatment with zoledronic acid 6
Prevention and Management of Hypocalcemia
- Adequate calcium and vitamin D intake can substantially reduce the risk of hypocalcemia in patients with bone metastasis 4, 3
- Patients at risk of hypocalcemia should be identified before starting treatment with inhibitors of bone resorption and closely monitored during treatment 3
- Vitamin D and calcium supplementation should be considered in patients with bone metastasis, unless hypercalcemia is present 3