From the Guidelines
The main mechanism behind hypercalcemia in multiple myeloma is excess bone resorption from myeloma bone disease, leading to the excessive release of calcium into the blood. This is due to the imbalance between bone resorption and formation, as myeloma cells produce proteins that inhibit osteoblast activity, preventing new bone formation, while stimulating osteoclasts to break down bone at an accelerated rate 1. The symptoms of hypercalcemia include polyuria and gastrointestinal disturbances, with progressive dehydration and decreases in glomerular filtration rate, which can be treated with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin 1. Some key points to consider in the treatment of hypercalcemia in multiple myeloma include:
- The use of bisphosphonates, such as zoledronic acid, pamidronate, and ibandronate, to inhibit osteoclast activity 1
- The importance of addressing the underlying myeloma with appropriate chemotherapy regimens
- The need to prevent infections, such as pneumocystis jiroveci pneumonia, herpes zoster, and antifungal prophylaxis, especially in patients receiving high-dose dexamethasone or PI-based and antibody-based therapies 1. Overall, the treatment of hypercalcemia in multiple myeloma requires a comprehensive approach that addresses the underlying disease, as well as the symptoms and complications associated with hypercalcemia.
From the Research
Mechanism of Hypercalcemia in Multiple Myeloma
The main mechanism behind hypercalcemia in multiple myeloma involves:
- Local osteolytic hypercalcemia: caused by increased osteoclastic bone resorption due to local factors in the bone marrow, such as cytokines (e.g., IL-1, IL-6, TNF-beta) and growth factors (e.g., RANKL) derived from myeloma cells 2, 3
- Humoral hypercalcemia of malignancy: caused by systemic factors, such as parathyroid hormone-related protein (PTHrP), which can act on bone and kidney to increase calcium levels 2, 4
Key Mediators of Osteoclastic Bone Resorption
Key mediators of osteoclastic bone resorption in multiple myeloma include:
- Receptor activator of nuclear factor-kappaB ligand (RANKL) 3
- Macrophage inflammatory protein-1alpha 3
- Dickkopf 1, which can stimulate osteoclast formation and activity 3
Clinical Implications
Hypercalcemia in multiple myeloma is associated with poor outcomes, including inferior survival 4. Early detection and treatment of hypercalcemia are important to prevent serious complications, such as acute renal failure and coma 5. Bisphosphonates are recommended as an effective therapy for hypercalcemia in myeloma 5.