Denosumab: A New Agent in the Management of Hypercalcemia of Malignancy

Abstract

Hypercalcemia of malignancy is an oncologic emergency due to tumoral factors that stimulate osteoclast-mediated bone resorption. It requires a combination of recommended treatments (i.e., hydration, bisphosphonate and calcitonin), which may be deleterious in patients with compromised cardiac or renal function or may not control serum calcium levels long term. Recurrent or refractory hypercalcemia may preclude the use of chemotherapeutic agents needed to effectively treat the underlying cancer, which is the cause of hypercalcemia. Denosumab, a fully human monoclonal antibody against RANKL, inhibits the maturation, function and survival of osteoclasts. An open-label, single-arm study of denosumab in patients with hypercalcemia of malignancy despite recent bisphosphonate treatment revealed positive results. Thus, the US FDA recently approved denosumab for the indication of hypercalcemia of malignancy, increasing the options available for patients with this debilitating and life-threatening condition.

Hypercalcemia and cancer: Differential diagnosis and treatment

“…Modern‐generation intravenous bisphosphonates include pamidronate (60‐90 mg intravenously over 2‐6 hours) and zoledronic acid (4 mg intravenously over 15‐30 minutes). They are the most studied and are considered the most effective agents for treatment of the HCM . They work by inhibiting the osteoclasts from degrading bone through several mechanisms.…”

The Use of Low-Calcium Hemodialysis in the Treatment of Hypercalcemic Crisis

“…Since 2012, there have been numerous case reports reporting the effectiveness of denosumab in patients with cancer-associated hypercalcemia in tumors including multiple myeloma, renal cell carcinoma, ovarian cancer, and parathyroid carcinoma. So based on these reports in 2014, denosumab was approved by the Food and Drug Administration for the treatment of hypercalcemia refractory to bisphosphonates therapy [44]. …”

Denosumab treatment in patients with different courses of osteoporosis

“…Известно, что наряду с эф-фективным лечением сенильного ОП у мужчин [11], ДМБ обладает гипокальциемическим эффектом [12], в литера-туре имеются единичные сообщения о лечении им гипер-кальциемии [13]. В результате лечения ДМБ и колекальци-феролом у нашего пациента удалось достичь повышения МПК до уровня остеопении в бедренной кости, существен-но повысить МПК в лучевой кости, удержать уровень каль-ция в пределах верхних границ референсного интервала и существенно снизить активность костной резорбции, что в совокупности способствует профилактике перело-мов у этого больного.…”