The aminobisphosphonate risedronate preserves localized mineral and material properties of bone in the presence of glucocorticoids.
OBJECTIVE
Glucocorticoids (GCs) alter bone strength such that patients receiving these medications have a high rate of fragility-related fractures. The purpose of this study was to assess whether concurrent treatment with GCs (prednisolone) and risedronate (an aminobisphosphonate) would prevent the reduction in bone strength induced by GCs, in a mouse model of GC-induced bone loss and in patients enrolled in a clinical study.


METHODS
We evaluated mice treated with prednisolone pellets alone, GCs plus risedronate, or placebo alone and iliac crest biopsy specimens obtained from patients who were treated with GCs plus placebo or GCs plus risedronate for 1 year. We measured the mass, architecture, and physical and material properties of bone (subject to therapeutic treatments) at nanoscale to macroscopic dimensions, using synchrotron x-ray tomography, elastic modulus mapping, transmission electron microscopy, and small-angle x-ray scattering techniques.


RESULTS
GC treatment reduced trabecular bone mass, microarchitecture, and the degree of bone mineralization and elastic modulus within the trabeculae. Concurrent treatment with GCs and risedronate prevented the deterioration of trabecular bone architecture, reduced the degree of mineralization, and preserved elastic modulus within the trabeculae, in both mouse and human bone. In addition, treatment with risedronate plus GCs in mice appeared to preserve bone crystal orientation, compared with treatment with GCs alone.


CONCLUSIONS
Risedronate prevented the localized changes in mineral and material properties of bone induced by GCs, which may ultimately improve bone strength.
Balooch
Guive
G
Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Yao
Wei
W
Ager
Joel W
JW
Balooch
Mehdi
M
Nalla
Ravi K
RK
Porter
Alexandra E
AE
Ritchie
Robert O
RO
Lane
Nancy E
NE
D000818:Animals; D001696:Biomechanical Phenomena; D001706:Biopsy; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects*; D004347:Drug Interactions; D004548:Elasticity; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007085:Ilium / Q000000981:diagnostic imaging / Q000187:drug effects; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D011239:Prednisolone / Q000494:pharmacology*; D000068296:Risedronic Acid; D014056:Tomography, X-Ray
D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; D011239:Prednisolone; D000068296:Risedronic Acid; D012968:Etidronic Acid