EFFECT OF TRANSFORMING GROWTH-FACTOR-ALPHA, PARATHYROID HORMONE-RELATED PROTEIN, OR THEIR COMBINATION ON BONE HISTOMORPHOMETRY

Transforming growth factor alpha (TGF alpha) has been implicated in the pathogenesis of inhibited bone formation in hypercalcemia of malignancy. We evaluted the effects of infusions of vehicle or TGF alpha (0.25 mu/h), or parathyroid hormone-related protein (1-34) (PTHrP) (0.025 mu g/h) alone, or a combination of TGF alpha and PTHrP on bone histomorphometry in mice. The peptides were infused for 6 days via Alzet osmotic minipumps. TGF alpha alone, PTHrP alone, or a combination of the two resulted in an increase in bone resorption as well as bone formation parameters. The increase in bone formation with the combination of TGF alpha and PTHrP was significantly greater than that seen with either peptide alone. Therefore, it is unlikely that TGF alpha is the factor responsible for inhibited bone formation in hypercalcemia of malignancy.