Leukemia inhibitory factor produces hypercalcemia in rats without altering bone histomorphometry of the tibia

Leukemia inhibitory factor (LIF) is a single-chain polypeptide that previously was shown in mice to produce hypercalcemia and influence skeletal growth and turnover. We performed dose-response studies to determine if LIF alters the serum calcium or histomorphometry of the tibia in growing male rats. Forty animals were divided into five groups of eight animals each. Recombinant human LIF, 0.01, 0.1, 1, or 10 microg/100 g body wt, or vehicle was administered daily S.C. for 3 weeks. Compared with controls it was found that LIF increased mean serum calcium at the two highest doses (11.4 +/- 0.1 versus 10. 8 +/- 0.1 mg/dl, P = 0.0005 by one-way analysis of variance (ANOVA) but did not alter static or dynamic measurements of histomorphometry or length of the tibia. We conclude that in growing rats, high systemic concentrations of LIF result in hypercalcemia with no changes in bone turnover.