A 54 y/o woman comes to the physician because of a 5-day history of severe mid-back pain Physical examination shows point tenderness over the T6 vertebra. Serum studies show acalcium concentration of 13.4 mg/dl; urinalysis shows Bence Jones proteins. Which of the following is the most likely cause of this patient’s hyper-calcemia?

Local interleukin-1 (IL-1) and tumor necrosis factor effect

The underlying disease is Multiple Myloma: Hypercalcemia in multiple myeloma, where there is bone marrow infiltration by tumor has been ascribed to the release of osteoclast activating factors by the tumor cells. Osteoclast-induced bone resorption may occur in discrete focal areas (lytic lesions) or throughout the skeleton. The high rate of bone resorption is associated with an absence of osteoblast-mediated bone formation, resulting in diffuse bone loss. The uncoupling of bone resorption and formation results from paracrine factors, which enhance osteoclast formation and activity and inhibit the capacity for marrow stromal cells to differentiate into osteoblasts. In multiple myeloma, various studies have implicated interleukin (IL)-6, RANKL (from TNF family), macrophage inflammatory protein 1a, osteoclast activating factor [aka IL-1], osteoprotegerin, and IL-3 as factors contributing to the development of lytic bone disease and hypercalcemia.