Effects of glucocorticoid treatment on bone strength.
Glucocorticoids (GCs) are prescribed for the treatment of several diseases, but their long-term use causes osteoporosis. Current research suggests that GCs suppress the canonical Wnt/beta pathway, resulting in decreased expression of critical bone proteins. This study examined how bone structure and strength of high bone mass (HBM) mice and low density lipoprotein receptor-related protein 5 (LRP5) knockout (KO+/-) mice are affected by GC treatment in comparison to wild-type (WT) mice, and if changes were specific to either trabecular or cortical bone. Mice were treated with either prednisone or placebo. The femurs and L4 vertebral bodies were analyzed by micro-CT for structure and mechanically tested to determine strength and apparent material strength properties. Differences in all measured variables corresponding to GC treatment and genotype were tested using two-way ANOVA. GC treatment caused decreased structural strength parameters, weakened apparent material strength properties, and disruption of bone structure in HBM, but not LRP5+/- or WT, mice. Despite treatment-related loss, trabecular bone structure and strength remained elevated as compared to LRP5+/- and WT mice. In HBM femurs, both cortical and trabecular structure, but not strength parameters, were negatively affected by treatment. In HBM vertebral bodies, both structural and strength parameters were negatively affected by treatment.
Manolides
Andrew S
AS
ORC, Creighton University, Suite 4820, 610N, 30th Street, Omaha, NE 68131, USA.
Cullen
Diane M
DM
Akhter
Mohammed P
MP
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011241:Prednisone / Q000494:pharmacology; D013314:Stress, Mechanical; D055114:X-Ray Microtomography
D005938:Glucocorticoids; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; D011241:Prednisone