Calcified Tissue International

, Volume 92, Issue 3, pp 240–250 | Cite as

Glucocorticoid-Induced Changes in the Geometry of Osteoclast Resorption Cavities Affect Trabecular Bone Stiffness

  • Jef Vanderoost
  • Kent Søe
  • Ditte Marie Horslev Merrild
  • Jean-Marie Delaissé
  • G. Harry van LentheEmail author
Original Research


Bone fracture risk can increase through bone microstructural changes observed in bone pathologies, such as glucocorticoid-induced osteoporosis. Resorption cavities present one of these microstructural aspects. We recently found that glucocorticoids (GCs) affect the shape of the resorption cavities. Specifically, we found that in the presence of GC osteoclasts (OCs) cultured on bone slices make more trenchlike cavities, compared to rather round cavities in the absence of GCs, while the total eroded surface remained constant. For this study, we hypothesized that trenchlike cavities affect bone strength differently compared to round cavities. To test this hypothesis, we cultured OCs on bone slices in the presence and absence of GC and quantified their dimensions. These data were used to model the effects of OC resorption cavities on bone mechanical properties using a validated beam-shell finite element model of trabecular bone. We demonstrated that a change in the geometry of resorption cavities is sufficient to affect bone competence. After correcting for the increased EV/BV with GCs, the difference to the control condition was no longer significant, indicating that the GC-induced increase in EV/BV, which is closely related to the shape of the cavities, highly determines the stiffness effect. The lumbar spine was the anatomic site most affected by the GC-induced changes on the shape of the cavities. These findings might explain the clinical observation that the prevalence of vertebral fractures during GC treatment increases more than hip, forearm and other nonvertebral fractures.


Biomechanics Bone architecture/structure Osteoclasts Osteoporosis: secondary/drug induced Steroid hormones: glucocorticoids 



We thank Vibeke Nielsen for technical assistance and Professor Flemming B. Sørensen (Department of Pathology, Vejle Hospital, Denmark) for granting us access to his equipment, enabling us to measure the dimensions of resorption cavitations. Supported in part by a grant from the Research Fund of the Region of Southern Denmark (08/8932), by Vejle Hospital/Lillebaelt Hospital, Denmark, and by grant STRT1/08/027 from the KU Leuven Research Fund.


  1. 1.
    Chavassieux P, Seeman E, Delmas PD (2007) Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease. Endocr Rev 28:151–164PubMedCrossRefGoogle Scholar
  2. 2.
    Canalis E, Mazziotti G, Giustina A, Bilezikian JP (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 18:1319–1328PubMedCrossRefGoogle Scholar
  3. 3.
    van Brussel MS, Bultink IE, Lems WF (2009) Prevention of glucocorticoid-induced osteoporosis. Expert Opin Pharmacother 10:997–1005PubMedCrossRefGoogle Scholar
  4. 4.
    Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610PubMedCrossRefGoogle Scholar
  5. 5.
    Garnero P (2009) Bone markers in osteoporosis. Curr Osteoporos Rep 7:84–90PubMedCrossRefGoogle Scholar
  6. 6.
    Lewiecki EM (2010) Bone densitometry and vertebral fracture assessment. Curr Osteoporos Rep 8:123–130PubMedCrossRefGoogle Scholar
  7. 7.
    Helfrich MH, Ralston SH (eds) (2003) Bone research protocols. Humana Press, TotowaGoogle Scholar
  8. 8.
    van Lenthe GH, Mueller TL, Wirth AJ, Muller R (2008) Quantification of bone structural parameters and mechanical competence at the distal radius. J Orthop Trauma 22:S66–S72PubMedCrossRefGoogle Scholar
  9. 9.
    Mueller TL, van Lenthe GH, Stauber M, Gratzke C, Eckstein F, Muller R (2009) Regional, age and gender differences in architectural measures of bone quality and their correlation to bone mechanical competence in the human radius of an elderly population. Bone 45:882–891PubMedCrossRefGoogle Scholar
  10. 10.
    Yeni YN, Fyhrie DP (2001) Finite element calculated uniaxial apparent stiffness is a consistent predictor of uniaxial apparent strength in human vertebral cancellous bone tested with different boundary conditions. J Biomech 34:1649–1654PubMedCrossRefGoogle Scholar
  11. 11.
    van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C (2003) Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 48:3224–3229PubMedCrossRefGoogle Scholar
  12. 12.
    van Staa TP (2006) The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. Calcif Tissue Int 79:129–137PubMedCrossRefGoogle Scholar
  13. 13.
    Alesci S, De Martino MU, Ilias I, Gold PW, Chrousos GP (2005) Glucocorticoid-induced osteoporosis: from basic mechanisms to clinical aspects. NeuroImmunoModulation 12:1–19PubMedCrossRefGoogle Scholar
  14. 14.
    Aaron JE, Francis RM, Peacock M, Makins NB (1989) Contrasting microanatomy of idiopathic and corticosteroid-induced osteoporosis. Clin Orthop Relat Res 243:294–305PubMedGoogle Scholar
  15. 15.
    Parikka V, Lehenkari P, Sassi ML, Halleen J, Risteli J, Harkonen P, Vaananen HK (2001) Estrogen reduces the depth of resorption pits by disturbing the organic bone matrix degradation activity of mature osteoclasts. Endocrinology 142:5371–5378PubMedCrossRefGoogle Scholar
  16. 16.
    Soe K, Delaisse JM (2010) Glucocorticoids maintain human osteoclasts in the active mode of their resorption cycle. J Bone Miner Res 25:2184–2192PubMedCrossRefGoogle Scholar
  17. 17.
    Vanderoost J, Jaecques SV, Van der PG, Boonen S, D’hooge J, Lauriks W, van Lenthe GH (2011) Fast and accurate specimen-specific simulation of trabecular bone elastic modulus using novel beam-shell finite element models. J Biomech 44:1566–1572PubMedCrossRefGoogle Scholar
  18. 18.
    Vanderoost J (2012) Relating bone structure to competence: role of local trabecular properties. PhD diss., Katholieke Universiteit LeuvenGoogle Scholar
  19. 19.
    Boissy P, Andersen TL, Abdallah BM, Kassem M, Plesner T, Delaisse JM (2005) Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoclast differentiation. Cancer Res 65:9943–9952PubMedCrossRefGoogle Scholar
  20. 20.
    Cooper MS, Rabbitt EH, Goddard PE, Bartlett WA, Hewison M, Stewart PM (2002) Osteoblastic 11 beta-hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid exposure. J Bone Miner Res 17:979–986PubMedCrossRefGoogle Scholar
  21. 21.
    Dequeker J (1994) Assessment of quality of bone in osteoporosis–BIOMED I: fundamental study of relevant bone. Clin Rheumatol 13(suppl 1):7–12PubMedGoogle Scholar
  22. 22.
    Hildebrand T, Laib A, Muller R, Dequeker J, Ruegsegger P (1999) Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res 14:1167–1174PubMedCrossRefGoogle Scholar
  23. 23.
    Aerssens J, Boonen S, Joly J, Dequeker J (1997) Variations in trabecular bone composition with anatomical site and age: potential implications for bone quality assessment. J Endocrinol 155:411–421PubMedCrossRefGoogle Scholar
  24. 24.
    Vedi S, Compston JE, Webb A, Tighe JR (1982) Histomorphometric analysis of bone biopsies from the iliac crest of normal British subjects. Metab Bone Dis Relat Res 4:231–236PubMedCrossRefGoogle Scholar
  25. 25.
    Croucher PI, Garrahan NJ, Mellish RW, Compston JE (1991) Age-related changes in resorption cavity characteristics in human trabecular bone. Osteoporos Int 1:257–261PubMedCrossRefGoogle Scholar
  26. 26.
    Croucher PI, Garrahan NJ, Compston JE (1993) Assessment of resorption cavity characteristics in trabecular bone: changes in primary and secondary osteoporosis. Bone 14:449–454PubMedCrossRefGoogle Scholar
  27. 27.
    Chavassieux PM, Arlot ME, Roux JP, Portero N, Daifotis A, Yates AJ, Hamdy NA, Malice MP, Freedholm D, Meunier PJ (2000) Effects of alendronate on bone quality and remodeling in glucocorticoid-induced osteoporosis: a histomorphometric analysis of transiliac biopsies. J Bone Miner Res 15:754–762PubMedCrossRefGoogle Scholar
  28. 28.
    Muller R, van Lenthe GH (2006) Trabecular bone failure at the microstructural level. Curr Osteoporos Rep 4:80–86PubMedCrossRefGoogle Scholar
  29. 29.
    Gentzsch C, Junge M, Pueschel K, Delling G, Kaiser E (2005) A scanning electron microscopy-based approach to quantify resorption lacunae applied to the trabecular bone of the femoral head. J Bone Miner Metab 23:205–211PubMedCrossRefGoogle Scholar
  30. 30.
    Gentzsch C, Delling G, Kaiser E (2003) Microstructural classification of resorption lacunae and perforations in human proximal femora. Calcif Tissue Int 72:698–709PubMedCrossRefGoogle Scholar
  31. 31.
    Jones SJ, Boyde A (1994) Questions of quality and quantity—a morphological view of bone biology. Acta Anatomica Nipponica 69:229–243PubMedGoogle Scholar
  32. 32.
    Boyde A, Maconnachie E, Reid SA, Delling G, Mundy GR (1986) Scanning electron-microscopy in bone pathology—review of methods, potential and applications. Scanning Electron Microsc 1986:1537–1554Google Scholar
  33. 33.
    Compston JE, Croucher PI (1991) Histomorphometric assessment of trabecular bone remodelling in osteoporosis. Bone Miner 14:91–102PubMedCrossRefGoogle Scholar
  34. 34.
    Seeman E, Delmas PD (2006) Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261PubMedCrossRefGoogle Scholar
  35. 35.
    Heaney RP (2003) Is the paradigm shifting? Bone 33:457–465PubMedCrossRefGoogle Scholar
  36. 36.
    Hernandez CJ, Gupta A, Keaveny TM (2006) A biomechanical analysis of the effects of resorption cavities on cancellous bone strength. J Bone Miner Res 21:1248–1255PubMedCrossRefGoogle Scholar
  37. 37.
    Eriksen EF, Mosekilde L, Melsen F (1985) Trabecular bone resorption depth decreases with age: differences between normal males and females. Bone 6:141–146PubMedCrossRefGoogle Scholar
  38. 38.
    Dalle CL, Bertoldo F, Valenti MT, Zenari S, Zanatta M, Sella S, Giannini S, Cascio VL (2005) Histomorphometric analysis of glucocorticoid-induced osteoporosis. Micron 36:645–652CrossRefGoogle Scholar
  39. 39.
    Seeman E, Delmas PD (2006) Bone quality–the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261PubMedCrossRefGoogle Scholar
  40. 40.
    van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000PubMedCrossRefGoogle Scholar
  41. 41.
    Dovio A, Perazzolo L, Saba L, Termine A, Capobianco M, Bertolotto A, Angeli A (2006) High-dose glucocorticoids increase serum levels of soluble IL-6 receptor alpha and its ratio to soluble gp130: an additional mechanism for early increased bone resorption. Eur J Endocrinol 154:745–751PubMedCrossRefGoogle Scholar
  42. 42.
    Dovio A, Perazzolo L, Osella G, Ventura M, Termine A, Milano E, Bertolotto A, Angeli A (2004) Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis. J Clin Endocrinol Metab 89:4923–4928PubMedCrossRefGoogle Scholar
  43. 43.
    De Vries F, Bracke M, Leufkens HG, Lammers JW, Cooper C, van Staa TP (2007) Fracture risk with intermittent high-dose oral glucocorticoid therapy. Arthritis Rheum 56:208–214PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Jef Vanderoost
    • 1
  • Kent Søe
    • 2
  • Ditte Marie Horslev Merrild
    • 2
  • Jean-Marie Delaissé
    • 2
  • G. Harry van Lenthe
    • 1
    Email author
  1. 1.Biomechanics Section, Department of Mechanical EngineeringKU LeuvenLeuvenBelgium
  2. 2.Department of Clinical Cell Biology, Vejle Hospital/Lillebaelt HospitalInstitute of Regional Health Services Research, University of Southern DenmarkVejleDenmark

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