The authors have no conflict of interest.
Genetically Linked Site-Specificity of Disuse Osteoporosis†
Article first published online: 5 JAN 2004
Copyright © 2004 ASBMR
Journal of Bone and Mineral Research
Volume 19, Issue 4, pages 607–613, April 2004
How to Cite
Judex, S., Garman, R., Squire, M., Busa, B., Donahue, L.-R. and Rubin, C. (2004), Genetically Linked Site-Specificity of Disuse Osteoporosis. J Bone Miner Res, 19: 607–613. doi: 10.1359/JBMR.040110
- Issue published online: 2 DEC 2009
- Article first published online: 5 JAN 2004
- Manuscript Accepted: 4 NOV 2003
- Manuscript Revised: 24 OCT 2003
- Manuscript Received: 11 MAY 2003
- cortical bone;
- trabecular bone;
- mechanical stimuli;
- weight bearing;
- bed rest;
- space flight;
- genetic variations;
The genetic influence on bone loss in response to mechanical unloading was investigated within diaphyseal and distal femoral regions in three genetically distinct strains of mice. One mouse strain failed to lose bone after removal of function, whereas osteopenia was evident in multiple regions of the remaining two strains but in different areas of the bone.
Introduction: It is well recognized that susceptibility to osteoporosis is, in large measure, determined by the genome, but whether this influence is systemic or site-specific is not yet known. Here, the extent to which genetic variations influence regional bone loss caused by disuse was studied in the femora of adult female mice from three inbred strains.
Materials and Methods: Adult C57BL/6J (B6), C3H/HeJ (C3H), and BALB/cByJ (BALB) mice were subjected to 15–21 days of disuse, achieved by hindlimb suspension, and six distinct anatomical regions of the femur were analyzed by high-resolution μCT.
Results and Conclusions: In B6 mice, the amount of disuse stimulated bone loss was relatively uniform across all regions, with 20% loss of trabecular bone and 10% loss of cortical bone. The degree of bone loss in BALB mice varied greatly, ranging from 59% in the metaphysis to 3% in the proximal diaphysis. In this strain, the nonuniformity of bone loss was directly related to the nonuniform distribution of baseline bone morphology (r2 = 0.94). In direct contrast with BALB and B6, disuse failed to produce significant losses of bone in any of the analyzed regions of the C3H mice. Instead, these animals displayed a unique compensatory mechanism to disuse, where the large loss of calcified tissue from the endocortical surface (−24%) was compensated for by an expansion of the periosteal envelope (10%). These data indicate a strong, yet complex, genetic dependence of the site-specific regulation of bone remodeling in response to a powerful catabolic signal. Consequently, the skeletal region of interest and the genetic make-up of the individual may have to be considered interdependently when considering the pathogenesis of osteoporosis or the efficacy of an intervention to prevent or recover bone loss.