Skip to main content
Log in

The temporal characterization of marrow lipids and adipocytes in a rabbit model of glucocorticoid-induced osteoporosis

Skeletal Radiology Aims and scope Submit manuscript

Abstract

Objective

To characterize the temporal changes in marrow lipids content and adipocytes in the development of glucocorticoid-induced osteoporosis (GIOP) in rabbits using MR spectroscopy.

Subjects and methods

Twenty 20-week-old female rabbits were randomized to a control group and a GIOP group equally. Marrow lipids fraction and bone mineral density at the left proximal femur and L3–L4 vertebrae were measured by MR spectroscopy and dual-energy X-ray absorptiometry at week 0, 4, 8, and 12. Marrow adipocytes were quantitatively evaluated by histopathology.

Results

Marrow adiposity in the GIOP group showed a significant increase over time, with a variation of marrow lipids fraction (+35.9 %) at week 4 from baseline and it was maintained until week 12 (+75.2 %, p < 0.001 for all). The GIOP group demonstrated continuous deterioration of bone with significant difference between the two groups at week 8, followed by increased marrow fat with significant difference at week 4 (p < 0.05 for all). In comparison with the controls, marrow adipocyte density in the GIOP group increased by 57.1 % at week 8 and 35.4 % at week 12, respectively. A reduction (–13.3 %) in adipocyte mean diameter at week 8 (but an increase (+22.7 %) at week 12) were observed in the GIOP group compared with the control group (p < 0.05 for all). There was significant difference between two periods (p = 0.023) in adipocyte mean diameter in the GIOP group. The percentage area of marrow adipocytes in the GIOP group was 62.8 ± 8.7 % at week 8 and 79.2 ± 7.7 % at week 12, both of which were significantly higher than those of the controls (p < 0.05 for all).

Conclusions

Marrow adipogenesis is synchronized with bone loss in the development of GIOP, which was characterized by a significant increase in the number of small-sized marrow adipocytes in the relatively early stage and concomitant volume increase later on. MR spectroscopy appears to be the most powerful tool for detecting the sequential changes in marrow lipid content.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Majumdar SR, Lix LM, Yogendran M, Morin SN, Metge CJ, Leslie WD. Population-based trends in osteoporosis management after new initiations of long-term systemic glucocorticoids (1998–2008). J Clin Endocrinol Metab. 2012;97:1236–42.

    Article  PubMed  CAS  Google Scholar 

  2. Bultink IE, Baden M, Lems WF. Glucocorticoid-induced osteoporosis: an update on current pharmacotherapy and future directions. Expert Opin Pharmacother. 2013;14:185–97.

    Article  PubMed  CAS  Google Scholar 

  3. Li GW, Tang GY, Liu Y, Tang RB, Peng YF, Li W. MR spectroscopy and micro-CT in evaluation of osteoporosis model in rabbits: comparison with histopathology. Eur Radiol. 2012;22:923–9.

    Article  PubMed  Google Scholar 

  4. Li GW, Chang SX, Xu Z, Chen Y, Bao H, Shi X. Prediction of hip osteoporotic fractures from composite indices of femoral neck strength. Skeletal Radiol. 2013;42:195–201.

    Article  PubMed  Google Scholar 

  5. Van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum. 2003;48:3224–9.

    Article  PubMed  Google Scholar 

  6. Kalpakcioglu BB, Engelke K, Genant HK. Advanced imaging assessment of bone fragility in glucocorticoid-induced osteoporosis. Bone. 2011;48:1221–31.

    Article  PubMed  Google Scholar 

  7. Link TM. Osteoporosis imaging: state of the art and advanced imaging. Radiology. 2012;263:3–17.

    Article  PubMed  Google Scholar 

  8. Shen W, Chen J, Gantz M, et al. MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older adults. Eur J Clin Nutr. 2012;66:983–8.

    Article  PubMed  CAS  Google Scholar 

  9. Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology. 2001;2:165–71.

    Article  PubMed  CAS  Google Scholar 

  10. Li X, Kuo D, Schafer AL, et al. Quantification of vertebral bone marrow fat content using 3 Tesla MR spectroscopy: reproducibility, vertebral variation, and applications in osteoporosis. J Magn Reson Imaging. 2011;33:974–9.

    Article  PubMed  Google Scholar 

  11. Baum T, Yap SP, Karampinos DC, et al. Does vertebral bone marrow fat content correlate with abdominal adipose tissue, lumbar spine bonemineral density, and blood biomarkers in women with type 2 diabetes mellitus? J Magn Reson Imaging. 2012;35:117–24.

    Article  PubMed  Google Scholar 

  12. Castañeda S, Calvo E, Largo R, et al. Characterization of a new experimental model of osteoporosis in rabbits. J Bone Miner Metab. 2008;26:53–9.

    Article  PubMed  Google Scholar 

  13. Luppen CA, Blake CA, Ammirati KM, et al. Recombinant human bone morphogenetic protein-2 enhances osteotomy healing in glucocorticoid-treated rabbits. J Bone Miner Res. 2002;17:301–10.

    Article  PubMed  CAS  Google Scholar 

  14. Ebling WF, Szefler SJ, Jusko WJ. Methylprednisolone disposition in rabbits. Analysis, prodrug conversion, reversible metabolism, and comparison with man. Drug Metab Dispos. 1985;13:296–304.

    PubMed  CAS  Google Scholar 

  15. Carvas JS, Pereira RM, Caparbo VF, et al. A single dose of zoledronic acid reverses the deleterious effects of glucocorticoids on titanium implant osseointegration. Osteoporos Int. 2010;21:1723–9.

    Article  PubMed  CAS  Google Scholar 

  16. Castañeda S, Largo R, Calvo E, et al. Bone mineral measurements of subchondral and trabecular bone in healthy and osteoporotic rabbits. Skeletal Radiol. 2006;35:34–41.

    Article  PubMed  Google Scholar 

  17. Cohen A, Dempster DW, Stein EM, et al. Increased marrow adiposity in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab. 2012;97:2782–91.

    Article  PubMed  CAS  Google Scholar 

  18. Teitelbaum SL. Stem cells and osteoporosis therapy. Cell Stem Cell. 2010;7:553–4.

    Article  PubMed  CAS  Google Scholar 

  19. Kim KN, Kim BT, Kim KM, et al. The influence of exogenous fat and water on lumbar spine bone mineral density in healthy volunteers. Yonsei Med J. 2012;53:289–93.

    Article  PubMed  CAS  Google Scholar 

  20. Blake GM, Griffith JF, Yeung DK, et al. Effect of increasing vertebral marrow fat content on BMD measurement, T-Score status and fracture risk prediction by dual-energy X-ray absorptiometry. Bone. 2009;44:495–501.

    Article  PubMed  CAS  Google Scholar 

  21. Yeung DK, Griffith JF, Antonio GE, Lee FK, Woo J, Leung PC. Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study. J Magn Reson Imaging. 2005;22:279–85.

    Article  PubMed  Google Scholar 

  22. Fazeli PK, Bredella MA, Freedman L, et al. Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa. J Bone Miner Res. 2012;27:1864–71.

    Article  PubMed  CAS  Google Scholar 

  23. Lin L, Dai SD, Fan GY. Glucocorticoid-induced differentiation of primary cultured bone marrow mesenchymal cells into adipocytes is antagonized by exogenous Runx2. APMIS. 2010;118:595–605.

    PubMed  CAS  Google Scholar 

  24. Rosen CJ, Ackert-Bicknell C, Rodriguez JP, Pino AM. Marrow fat and the bone microenvironment: developmental, functional, and pathological implications. Crit Rev Eukaryot Gene Expr. 2009;19:109–24.

    Article  PubMed  CAS  Google Scholar 

  25. Naveiras O, Nardi V, Wenzel PL, et al. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. 2009;460:259–63.

    Article  PubMed  CAS  Google Scholar 

  26. Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol. 2006;2:35–43.

    Article  PubMed  CAS  Google Scholar 

  27. Wehrli FW, Hopkins JA, Hwang SN, Song HK, Snyder PJ, Haddad JG. Cross-sectional study of osteopenia with quantitative MR imaging and bone densitometry. Radiology. 2000;2172:527–38.

    Google Scholar 

  28. Veilleux A, Laberge PY, Morency J, Noël S, Luu-The V, Tchernof A. Expression of genes related to glucocorticoid action in human subcutaneous and omental adipose tissue. J Steroid Biochem Mol Biol. 2010;122:28–34.

    Article  PubMed  CAS  Google Scholar 

  29. Veilleux A, Rhéaume C, Daris M, Luu-The V, Tchernof A. Omental adipose tissue type 1 11 beta-hydroxysteroid dehydrogenase oxoreductase activity, body fat distribution, and metabolic alterations in women. J Clin Endocrinol Metab. 2009;94:3550–7.

    Article  PubMed  CAS  Google Scholar 

  30. Weinstein RS. Glucocorticoid-induced osteonecrosis. Endocrine. 2012;41:183–90.

    Article  PubMed  CAS  Google Scholar 

  31. Sheng HH, Zhang GG, Cheung WH, et al. Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development. J Orthop Surg Res. 2007;2:15.

    Article  PubMed  Google Scholar 

  32. Motomura G, Yamamoto T, Irisa T, Miyanishi K, Nishida K, Iwamoto Y. Dose effects of corticosteroids on the development of osteonecrosis in rabbits. J Rheumatol. 2008;35:2395–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the National Science Foundation for Young Scientists of China (No: 81202809). The authors would like to express their great appreciation to Yong-Ming Dai, Wei Fang, and Qin-Jiao Zhang for technical support. We wish to thank the editor and anonymous reviewers for comments that help us to improve the quality of our paper.

Conflict of interests

The authors have no conflicts of interest to declare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shi-Xin Chang.

Additional information

Guan-Wu Li and Zheng Xu contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, GW., Xu, Z., Chen, QW. et al. The temporal characterization of marrow lipids and adipocytes in a rabbit model of glucocorticoid-induced osteoporosis. Skeletal Radiol 42, 1235–1244 (2013). https://doi.org/10.1007/s00256-013-1659-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00256-013-1659-7

Keywords

Navigation