Glucocorticoid-Induced Changes in the Geometry of Osteoclast Resorption Cavities Affect Trabecular Bone Stiffness
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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.
KeywordsBiomechanics 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.
- 7.Helfrich MH, Ralston SH (eds) (2003) Bone research protocols. Humana Press, TotowaGoogle Scholar
- 18.Vanderoost J (2012) Relating bone structure to competence: role of local trabecular properties. PhD diss., Katholieke Universiteit LeuvenGoogle Scholar
- 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
- 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
- 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.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