What is the most likely cause of hypercalcemia in a patient with multiple myeloma showing Bence Jones proteins?

• A. Excessive parathyroid hormone production
• B. Local interleukin-1 and tumor necrosis factor effects
• C. Increased fractional calcium gastrointestinal absorption
• D. Excessive parathyroid hormone-related protein production

Answer: (B)

In a patient with multiple myeloma, the presence of hypercalcemia is frequently due to factors related to the malignancy itself, particularly the effects of local cytokines such as interleukin-1 and tumor necrosis factor. These cytokines can stimulate osteoclastic activity, leading to bone resorption and the release of calcium into the bloodstream. This process is common in multiple myeloma, where malignant plasma cells disrupt normal bone homeostasis.

Additionally, multiple myeloma often leads to the formation of lytic bone lesions, which further contribute to elevated calcium levels as they cause local destruction of bone tissue. The inflammatory cytokines produced by the tumor cells can directly enhance this osteoclastic activity, thus promoting the release of calcium.

In contrast to this mechanism, excessive production of parathyroid hormone or parathyroid hormone-related peptide typically results in hypercalcemia through different pathways. While these avenues can also cause increased calcium levels, in the context of multiple myeloma, cytokine-mediated bone resorption is a more direct and common cause of the observed hypercalcemia.

Therefore, understanding that local cytokine effects are primarily responsible for elevated calcium levels in the setting of multiple myeloma provides clarity on why this is the most