Review Investigates Hypophosphatemia in Multiple Myeloma

A new literature review assessed the causes and consequences of hypophosphatemia in patients with multiple myeloma. The condition is an electrolyte abnormality commonly found in patients with underlying malignancies and is linked with adverse prognoses. It is generally defined as serum phosphate levels below 2.5 mg/dL, and can result from cancer’s effects on the kidneys or bones. It may also be an adverse effect of treatment.

“Phosphorus levels are regulated through a number of mechanisms, including parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), vitamin D, and other electrolyte levels themselves,” researchers explained in Cureus.

Because of this, any disease process that affects these regulatory hormones or molecules could lead to phosphorus disorders that are difficult to control. In addition, any factor that leads to increased losses could result in phosphorus depletion.

However, when it comes to hypophosphatemia, “Clinically, the findings are nonspecific, and the diagnosis is frequently delayed,” the authors said.

Symptoms can include weakness in minor cases and encephalopathy and impaired cardiac function in more severe cases.

Multiple myeloma can affect phosphorus levels through a variety of pathways. Therefore, gaining a deeper understanding of the mechanics that lead to hypophosphatemia in these patients could help providers identify at-risk individuals who may benefit from routine phosphate monitoring, the authors wrote.

They searched PubMed for published literature on the association between multiple myeloma and hypophosphatemia. Among their principal findings were that tumor-induced osteopenia (TIO) can occur with multiple myeloma; that bisphosphonates can cause calcium levels to drop, which stimulates PTH release, predisposing patients to significant hypophosphatemia; and that many modern medications used to manage multiple myeloma have been associated with hypophosphatemia.

Fanconi syndrome is another potential complication, with research showing it can be triggered by medications like antibiotics and chemotherapy, and primary conditions like hematologic malignancies, the investigators said. Some small studies have indicated hypophosphatemia brought on by Fanconi syndrome can even lead to osteomalacia.

Although there is insufficient evidence to prove chemotherapy is effective at treating the syndrome in patients with multiple myeloma, one study found bortezomib may be effective.

Bisphosphonates have several indications in multiple myeloma but can lead to severe hypophosphatemia. In addition, monoclonal antibodies have been used to treat multiple myeloma—although patients taking these treatments can develop some degree of hypophosphatemia. Proteasome inhibitors are also associated with the condition.

The study authors note of the cases included in the review, “The proteasome inhibitors and monoclonal antibodies were combined with other treatments, including immunomodulators and corticosteroids, raising the possibility of confounding effects or synergy.”

For those with spurious hypophosphatemia due to paraprotein interference with laboratory assays, this condition should be treated as a differential diagnosis, the researchers added. This is especially true in patients with asymptomatic severe hypophosphatemia, persistent hypophosphatemia despite repeated repletion, or impaired glomerular filtration rate with hypophosphatemia.

Overall, “multiple myeloma, through various effects on bone, predisposes patients to significant phosphate derangements, including hypophosphatemia, predisposing patients to significant cardiac and neurological morbidity,” authors concluded. “Currently, there is a lot of evidence that hypophosphatemia worsens clinical outcomes.”

Reference

Cancarevic I, Ilyas U, Nassar M. Hypophosphatemia in patients with multiple myeloma. Cureus. Published online June 15, 2023. doi:10.7759/cureus.40487