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J Appl Physiol 95: 672-676, 2003. First published April 11, 2003; doi:10.1152/japplphysiol.00056.2003
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Receptor activator of NF-{kappa}B ligand arrests bone growth and promotes cortical bone resorption in growing rats

Nansie A. McHugh, Haydee M. Vercesi, Robert W. Egan, and John A. Hey

Allergy Department, Schering-Plough Research Institute, Kenilworth, New Jersey 07033

Submitted 21 January 2003 ; accepted in final form 4 April 2003

Receptor activator of NF-{kappa}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 present study assesses the effects of exogenous RANKL on growing bone. RANKL (100 µg·kg-1·day-1 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 in the RANKL-treated rats was lower (P = 0.039) than in the control rats (19 ± 7 vs. 38 ± 5 mg/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.

receptor activator of nuclear factor-{kappa}B ligand; computed tomography; in vivo; osteopenia; juvenile


Address for reprint requests and other correspondence: N. A. McHugh, Schering-Plough Research Institute, Allergy Dept., 2015 Galloping Hill Rd., K15-1-1600, Kenilworth, NJ 07033 (E-mail: nansie.mchugh{at}spcorp.com).






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