HYPERCALCEMIA IN ACUTE MYELOBLASTIC-LEUKEMIA IS CAUSED BY OSTEOCLAST ACTIVATION

Hypercalcemia in adult T-cell leukemia has been attributed to increase d levels of 1,25-dihydroxyvitamin D (1,25(OH)2D), whereas in other typ es of leukemia, hypercalcemia has been blamed on direct skeletal invas ion by malignant cells, ectopic parathyroid hormone (PTH) production o r bone-resorbing cytokines. A 51-year-old man was studied who presente d with back pain, circulating myeloblasts, and hypercalcemia. The bone marrow revealed acute myeloblastic leukemia. While the ionized calciu m concentration was 8.17 mg/dL (normal, 4.73 to 5.21 mg/dL), the level s of PTH, PTH-related peptide, vitamin D, and thyroxine were normal or subnormal. Bone histomorphometry showed a decreased cortical width wi th intracortical erosion cavities dissecting into the marrow space. In cancellous bone, the osteoid area, osteoblast perimeter, and tetracyc line fluorescence were sparse, whereas the osteoclast perimeter was in creased. Persistent marrow fat, the general absence of trabecular narr owing, and the prompt response to calcitonin suggest that the osteocla sts caused the hypercalcemia and lytic lesions, rather than pressure a trophy or osteolysis by leukemic infiltration. Osteoclast activation a nd subsequent hypercalcemia may have been due to a locally produced cy tokine, such as interleukin-1beta or tumor necrosis factor.