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The FASEB Journal Express Article doi:10.1096/fj.01-0913fje
Published online June 21, 2002

Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton

Stefan Judex, Leah-Rae Donahue, and Clinton Rubin

E-mail contact: stefan.judex{at}sunysb.edu

The structure of the adult skeleton is determined, in large part, by its genome. Whether genetic variations may influence the effectiveness of interventions to combat skeletal diseases remains unknown. The differential response of trabecular bone to an anabolic (low-level mechanical vibration) and a catabolic (disuse) mechanical stimulus were evaluated in three strains of adult mice. In low bone-mineral-density C57BL/6J mice, the low-level mechanical signal caused significantly larger bone formation rates (BFR) in the proximal tibia, but the removal of functional weight bearing did not significantly alter BFR. In mid-density BALB/cByJ mice, mechanical stimulation also increased BFR, whereas disuse significantly decreased BFR. In contrast, neither anabolic nor catabolic mechanical signals influenced any index of bone formation in high-density C3H/HeJ mice. Together, data from this study indicate that the sensitivity of trabecular tissue to both anabolic and catabolic stimuli is influenced by the genome. Extrapolated to humans, these results may explain in part why prophylaxes for low bone mass are not universally effective, yet also indicate that there may be a genotypic indication of people who are at reduced risk of suffering from bone loss.

Key words: trabecular bone · mechanical intervention · high-frequency mechanical stimuli · genetic variation · bone formation · osteoporosis




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