Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice.
This study compares changes in bone microstructure in 6-month-old male GC-treated and female ovariectomized mice to their respective controls. In addition to a reduction in trabecular bone volume, GC treatment reduced bone mineral and elastic modulus of bone adjacent to osteocytes that was not observed in control mice nor estrogen-deficient mice. These microstructural changes in combination with the macrostructural changes could amplify the bone fragility in this metabolic bone disease.


BACKGROUND
Patients with glucocorticoid (GC)-induced secondary osteoporosis tend to fracture at higher bone mineral densities than patients with postmenopausal osteoporosis. This suggests that GCs may alter bone material properties in addition to BMD and bone macrostructure.


METHODS
Changes in trabecular bone structure, elastic modulus, and mineral to matrix ratio of the fifth lumbar vertebrae was assessed in prednisolone-treated mice and placebo-treated controls for comparison with estrogen-deficient mice and sham-operated controls. Compression testing of the third lumbar vertebrae was performed to assess whole bone strength.


RESULTS
Significant reductions in trabecular bone volume and whole bone strength occurred in both prednisolone-treated and estrogen-deficient mice compared with controls after 21 days (p < 0.05). The average elastic modulus over the entire surface of each trabecula was similar in all the experimental groups. However, localized changes within the trabeculae in areas surrounding the osteocyte lacunae were observed only in the prednisolone-treated mice. The size of the osteocyte lacunae was increased, reduced elastic modulus around the lacunae was observed, and a "halo" of hypomineralized bone surrounding the lacunae was observed. This was associated with reduced (nearly 40%) mineral to matrix ratio determined by Raman microspectroscopy. These localized changes in elastic modulus and bone mineral to matrix ratio were not observed in the other three experimental groups.


CONCLUSIONS
Based on these results, it seems that GCs may have direct effects on osteocytes, resulting in a modification of their microenvironment. These changes, including an enlargement of their lacunar space and the generation of a surrounding sphere of hypomineralized bone, seem to produce highly localized changes in bone material properties that may influence fracture risk.
Department of Medicine, University of California at Davis, Sacramento, California 95817, USA. nancy.lane@ucdmc.ucdavis.edu
Nancy E
NE
Lane
Wei
W
Yao
Mehdi
M
Balooch
Ravi K
RK
Nalla
Guive
G
Balooch
Stefan
S
Habelitz
John H
JH
Kinney
Lynda F
LF
Bonewald
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism; D019245:Compressive Strength; D004548:Elasticity; D004967:Estrogens / Q000172:deficiency; D005938:Glucocorticoids / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010011:Osteocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010919:Placebos; D011239:Prednisolone / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed
D015415:Biomarkers; D004967:Estrogens; D005938:Glucocorticoids; D010919:Placebos; D011239:Prednisolone