The advent of molecular targeted therapies offers the hope of therapeutic 
advance in the fight against cancer. However, this hope is tempered by recent 
findings that certain targeted therapies may have unique side effects. The 
Hedgehog (HH) pathway is a potential target for treatment of several cancers, 
including basal cell carcinoma and a subset of medulloblastoma. Recent clinical 
trials in adults have shown responses to HH pathway inhibition in both basal 
cell carcinoma and medulloblastoma. However, concerns have been raised about the 
use of HH pathway inhibitors in children because of the role the HH pathway 
plays in development. Indeed, young mice treated with the HH pathway inhibitor 
HhAntag developed severe bone defects, including premature differentiation of 
chondrocytes, thinning of cortical bone, and fusion of the growth plate. In an 
effort to lessen the severity of bone defects caused by HhAntag, we treated 
young mice simultaneously with HhAntag and parathyroid hormone-related protein 
(PTHrP), which functions downstream of Indian Hedgehog to maintain chondrocytes 
in a proliferative state. The results show that whereas treatment with PTHrP 
causes a significant increase in trabecular bone, it does not prevent fusion of 
the growth plate induced by HhAntag.