From the Guidelines
Multiple myeloma itself does not directly increase parathyroid hormone (PTH) production. However, multiple myeloma can cause hypercalcemia through other mechanisms, primarily through the release of osteoclast-activating factors and cytokines by malignant plasma cells, as noted in the context of treating hypercalcemia with hydration, furosemide, bisphosphonates, steroids, and/or calcitonin 1. These factors stimulate bone resorption and calcium release into the bloodstream. In response to the resulting hypercalcemia, the body typically suppresses PTH production through negative feedback mechanisms. Some key points to consider include:
- The use of bisphosphonates, such as zoledronic acid, pamidronate, and ibandronate, to treat hypercalcemia 1
- The potential for kidney failure as a complication of multiple myeloma, which can lead to decreased vitamin D activation and calcium absorption, triggering increased PTH secretion
- The possibility of coincidental primary hyperparathyroidism in some myeloma patients, which is not caused by the myeloma itself
- Laboratory evaluation typically shows suppressed PTH levels when hypercalcemia is present, helping to distinguish myeloma-related hypercalcemia from primary hyperparathyroidism. Overall, the relationship between multiple myeloma and PTH production is indirect, with hypercalcemia being a key factor in the suppression of PTH production, as supported by the treatment approaches outlined 1.
From the Research
Multiple Myeloma and PTH Production
- Multiple myeloma is a disease characterized by the neoplastic proliferation of a clone of plasma cells that can lead to bone destruction 2.
- Hypercalcemia is a significant feature of patients with active multiple myeloma (MM) with extensive bone disease, and primary hyperparathyroidism (PHPT) is one of the most common causes of non-neoplastic hypercalcemia 3.
- Some preclinical data indicate that high secretion of parathyroid hormone (PTH) may have a negative impact on bone disease and MM progression 3.
- However, the relationship between multiple myeloma and PTH production is complex, and the evidence suggests that PTH may not be directly produced by myeloma cells 4.
- In fact, one study found that CD138+ cells from MM patients lack PTH receptor 1 and PTH-related peptide expressions, indicating that PTH could have a paracrine rather than a direct pro-tumoral effect 3.
Effects of PTH on Myeloma Growth and Bone Disease
- Daily administered PTH has been shown to increase bone mineral density of myelomatous bones and reduce tumor burden 4.
- PTH treatment also increased bone mineral density of uninvolved murine bones in myelomatous hosts and bone mineral density of implanted human bones in nonmyelomatous hosts 4.
- In myelomatous bone, PTH markedly increased the number of osteoblasts and bone-formation parameters, and the number of osteoclasts was unaffected or moderately reduced 4.
- Pretreatment with PTH before injecting myeloma cells increased bone mineral density of the implanted bone and delayed tumor progression 4.
Clinical Implications
- The concomitant diagnosis of MM and PHPT may not be so rare and should be considered for the clinical management of MM patients with hypercalcemia 3.
- Bisphosphonates, which are specific inhibitors of osteoclastic activity, are commonly used in the treatment of patients with multiple myeloma 2, 5.
- However, the role of bisphosphonates in improving overall survival (OS) remains unclear, and the evidence suggests that they may reduce pathological vertebral fractures and pain, but not mortality 2, 5.