Submitted on January 21, 2003
Accepted on April 4, 2003
Receptor Activator of NF-
B Ligand Arrests Bone Growth and Promotes Cortical Bone Resorption in Growing Rats
Nansie A McHugh1*, Haydee M Vercesi1, Robert W Egan1, and John A Hey1
1 Department of Allergy, Schering-Plough Research Institute, Kenilworth, NJ, USA
* To whom correspondence should be addressed. E-mail: nansie.mchugh{at}spcorp.com.
Receptor activator of NF-
B ligand (RANKL), produced by osteoblastic lineage cells and activated T cells, is an essential factor for osteoclast differentiation, activation and survival. Therefore, RANKL is a focal point of therapies targeting bone diseases where there is an imbalance of bone metabolism in favor of bone resorption. The current study assesses the effects of exogenous RANKL on growing bone. RANKL (100µg/kg/day for 7 days) administered to Sprague-Dawley weanling rats caused major deficits in growth, appearance and bone mineral densities (BMD). Urinary deoxypyridinoline crosslinks, a measure of bone turnover, were higher in the RANKL-treated rats (p=0.031) and the bone mineral content was lower (p<0.001). The final BMD of the RANKL-treated rats was lower (p=0.039) than the control rats (19 ± 7mg/cm3 vs. 38 ± 5mg/cm3). Moreover, calculated cortical bone density in each bone slice (total BMD - trabecular BMD), indicated there was only 5% cortical bone remaining in RANKL-treated rats. We conclude that therapies targeting RANKL are likely to have effects on cortical as well as trabecular bone density.
