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One Year of Transgenic Overexpression of Osteoprotegerin in Rats Suppressed Bone Resorption and Increased Vertebral Bone Volume, Density, and Strength1*

One Year of Transgenic Overexpression of Osteoprotegerin in Rats Suppressed Bone Resorption and... RANKL is an essential mediator of bone resorption, and its activity is inhibited by osteoprotegerin (OPG). Transgenic (Tg) rats were engineered to continuously overexpress OPG to study the effects of continuous long‐term RANKL inhibition on bone volume, density, and strength. Lumbar vertebrae, femurs, and blood were obtained from 1‐yr‐old female OPG‐Tg rats (n = 32) and from age‐matched wildtype (WT) controls (n = 23). OPG‐Tg rats had significantly greater serum OPG (up to 260‐fold) and significantly lower serum TRACP5b and osteocalcin compared with WT controls. Vertebral histomorphometry showed significant reductions in osteoclasts and bone turnover parameters in OPG‐Tg rats versus WT controls, and these reductions were associated with significantly greater peak load in vertebrae tested through compression. No apparent differences in bone material properties were observed in OPG‐Tg rat vertebrae, based on their unchanged intrinsic strength parameters and their normal linear relationship between vertebral bone mass and strength. Femurs from OPG‐Tg rats were of normal length but showed mild osteopetrotic changes, including reduced periosteal perimeter (−6%) and an associated reduction in bending strength. Serum OPG levels in WT rats showed no correlations with any measured parameter of bone turnover, mass, or strength, whereas the supraphysiological serum OPG levels in OPG‐Tg rats correlated negatively with bone turnover parameters and positively with vertebral bone mass and strength parameters. In summary, low bone turnover after 1 yr of OPG overexpression in rats was associated with increased vertebral bone mass and proportional increases in bone strength, with no evidence for deleterious effects on vertebral material properties. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Bone and Mineral Research Oxford University Press

One Year of Transgenic Overexpression of Osteoprotegerin in Rats Suppressed Bone Resorption and Increased Vertebral Bone Volume, Density, and Strength1*

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References (61)

Publisher
Oxford University Press
Copyright
Copyright © 2009 ASBMR
ISSN
0884-0431
eISSN
1523-4681
DOI
10.1359/jbmr.090215
Publisher site
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Abstract

RANKL is an essential mediator of bone resorption, and its activity is inhibited by osteoprotegerin (OPG). Transgenic (Tg) rats were engineered to continuously overexpress OPG to study the effects of continuous long‐term RANKL inhibition on bone volume, density, and strength. Lumbar vertebrae, femurs, and blood were obtained from 1‐yr‐old female OPG‐Tg rats (n = 32) and from age‐matched wildtype (WT) controls (n = 23). OPG‐Tg rats had significantly greater serum OPG (up to 260‐fold) and significantly lower serum TRACP5b and osteocalcin compared with WT controls. Vertebral histomorphometry showed significant reductions in osteoclasts and bone turnover parameters in OPG‐Tg rats versus WT controls, and these reductions were associated with significantly greater peak load in vertebrae tested through compression. No apparent differences in bone material properties were observed in OPG‐Tg rat vertebrae, based on their unchanged intrinsic strength parameters and their normal linear relationship between vertebral bone mass and strength. Femurs from OPG‐Tg rats were of normal length but showed mild osteopetrotic changes, including reduced periosteal perimeter (−6%) and an associated reduction in bending strength. Serum OPG levels in WT rats showed no correlations with any measured parameter of bone turnover, mass, or strength, whereas the supraphysiological serum OPG levels in OPG‐Tg rats correlated negatively with bone turnover parameters and positively with vertebral bone mass and strength parameters. In summary, low bone turnover after 1 yr of OPG overexpression in rats was associated with increased vertebral bone mass and proportional increases in bone strength, with no evidence for deleterious effects on vertebral material properties.

Journal

Journal of Bone and Mineral Research – Oxford University Press

Published: Dec 4, 2009

Keywords: RANKL; osteoprotegerin; bone quality; bone resorption; bone strength

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