Effect of intravenous bisphosphonates on release of basic fibroblast growth factor in serum of patients with cancer-associated hypercalcemia

Basic fibroblast growth factor (bFGF) is a potent tumor angiogenesis factor and normal constituent of bone extracellular matrix which does not normally circulate in serum of nonpregnant adult humans. We examined the effects of acute administration of intravenous bisphosphonates on release of bFGF in human serum. Twenty seven men and women (mean age, 64 yr) with cancer-associated hypercalcemia, the majority of whom had osseous metastases, were treated once with an intravenous bisphosphonate. Nearly all twelve patients with elevated baseline serum bFGF ranging from 5-27 pg/mL showed significant decreases in serum bFGF (2-7 days) after iv bisphosphonate treatment. The mathematical product of the patients' initial serum bFGF and intial serum calcium concentration, the 'Ca x bFGF product', was significantly negatively (r = -0.91, P < 0.001) correlated with the acute change in serum bFGF level. No consistent relationship was observed between serum bFGF and serum parathyroid hormone related peptide (PTHrP) levels in the hypercalcemic cancer patients. In a subset of patients with non-hematological malignancies and low baseline serum bFGF, acute changes in serum bFGF were significantly negatively (r = -0.66, P < 0.01) correlated with acute change in serum calcium concentration. These results indicate that release of bFGF in serum of patients with cancer-associated hypercalcemia likely depends predominantly on increased bone resorption. Acute change in low serum levels of bFGF in patients with cancer-associated hypercalcemia treated with intravenous bisphosphonates may be physiologically inversely regulated by acute change in the serum calcium concentration.