Resorptive hypercalcemia in post-essential thrombocythemia myelofibrosis: treatment with denosumab.
BACKGROUND
Hypercalcemia associated with myelofibrosis is rare, and its pathogenesis and treatment are not known.


OBJECTIVE
We report a unique case of hypercalcemia associated with post-essential thrombocythemia myelofibrosis and review the clinical and laboratory features, pathogenesis, and responsiveness to treatment with the bone antiresorptive agent, denosumab.


RESULTS
A 62-yr-old woman with essential thrombocythemia presented with progression to myelofibrosis with lytic skull lesions and symptomatic hypercalcemia. Other causes of hypercalcemia were excluded. Her disturbance in calcium homeostasis was not PTH- or vitamin D-mediated, although this has been postulated in cases of hypercalcemia with the related entity of primary myelofibrosis. Her hypercalcemia was refractory to aggressive iv saline administration, furosemide, calcitonin, and pamidronate, but promptly improved after one 120-mg sc dose of the anti-receptor activator of nuclear factor κB (RANK) ligand monoclonal antibody, denosumab, with sustained normocalcemia for approximately 2 months. She died 6 months later from complications due to the leukemic transformation of her hematological disease.


CONCLUSIONS
The pathogenesis of myelofibrosis-related hypercalcemia could be due to multiple factors, particularly changes in the RANK ligand-RANK-osteoprotegerin system that lead to increased osteoclast activity. Although we did not measure these factors, denosumab holds promise in the treatment of malignancy-associated hypercalcemia and specifically that related to myelofibrosis. Hypercalcemia associated with myelofibrosis is rare, and its pathogenesis and treatment are not known.
Department of Endocrinology and Diabetes, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.
Nadia
N
Khoury
Julietta
J
Chang
Alejandro A
AA
Gru
Michael P
MP
Whyte
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001344:Autopsy; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D002118:Calcium / Q000097:blood; D000069448:Denosumab; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007938:Leukemia / Q000209:etiology; D008875:Middle Aged; D053244:Osteoprotegerin / Q000502:physiology; D055728:Primary Myelofibrosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D053245:RANK Ligand / Q000502:physiology; D013922:Thrombocytosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D061067:Antibodies, Monoclonal, Humanized; D053244:Osteoprotegerin; D053245:RANK Ligand; D000069448:Denosumab; D002118:Calcium