Effects of hypercalcemia-producing tumor extract and parathyroid hormone on osteoclast ultrastructure

Hypercalcemia is a frequent complication of cancer. Recently, parathyroid hormone-related protein has been isolated from tumors associated with this syndrome. In the present study, the effects of tumor-derived hypercalcemic factor and bovine parathyroid hormone (PTH) on bone were compared in an organ culture system using calvarial bones from newborn mice. Mouse calvaria were incubated for 72 h with control medium or media containing 0.15 mg/m tumor extract (TE) or 2 x 10(-9) M PTH. Bone resorption, as assessed by the amount of calcium released into the medium and the number of osteoclasts counted on light microscopy, was increased by both PTH and TE. On electron microscopy, areas for cytoplasm, ruffled border and clear zone were statistically increased in PTH- and TE-treated calvaria as compared to control. These values were not significantly different between PTH- and TE-treated calvaria. The study therefore demonstrates that the ultrastructural changes in osteoclasts induced by the hypercalcemia-producing TE are similar to those induced by PTH.