Quantification of mineralized bone response to prostate cancer by noninvasive in vivo microCT and non-destructive ex vivo microCT and DXA in a mouse model.
BACKGROUND
To compare nondestructive in vivo and ex vivo micro-computed tomography (muCT) and ex vivo dual-energy-X-ray-absorptiometry (DXA) in characterizing mineralized cortical and trabecular bone response to prostate cancer involving the skeleton in a mouse model.


RESULTS
In vivo microCT was performed before and 10 weeks after implantation of human prostate cancer cells (MDA-PCa-2b) or vehicle into SCID mouse femora. After resection, femora were imaged by nondestructive ex vivo specimen microCT at three voxel sizes (31 micro, 16 micro, 8 micro) and DXA, and then sectioned for histomorphometric analysis of mineralized bone. Bone mineral density (BMD), trabecular parameters (number, TbN; separation, TbSp; thickness, TbTh) and mineralized bone volume/total bone volume (BV/TV) were compared and correlated among imaging methods and histomorphometry. Statistical tests were considered significant if P<0.05. Ten weeks post inoculation, diaphyseal BMD increased in the femur with tumor compared to the opposite femur by all modalities (p<0.005, n = 11). Diaphyseal BMD by in vivo microCT correlated with ex vivo 31 and 16 microm microCT and histomorphometry BV/TV (r = 0.91-0.94, P<0.001, n = 11). DXA BMD correlated less with bone histomorphometry (r = 0.73, P<0.001, n = 11) and DXA did not distinguish trabeculae from cortex. By in vivo and ex vivo microCT, trabecular BMD decreased (P<0.05, n = 11) as opposed to the cortex. Unlike BMD, trabecular morphologic parameters were threshold-dependent and when using "fixed-optimal-thresholds," all except TbTh demonstrated trabecular loss with tumor and correlated with histomorphometry (r = 0.73-0.90, P<0.05, n = 11).


CONCLUSIONS
Prostate cancer involving the skeleton can elicit a host bone response that differentially affects the cortex compared to trabeculae and that can be quantified noninvasively in vivo and nondestructively ex vivo.
Ravoori
Murali
M
Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Czaplinska
Aneta J
AJ
Sikes
Charles
C
Han
Lin
L
Johnson
Evan M
EM
Qiao
Wei
W
Ng
Chaan
C
Cody
Dianna D
DD
Murphy
William A
WA
Do
Kim-Anh
KA
Navone
Nora M
NM
Kundra
Vikas
V
D015502:Absorptiometry, Photon / Q000379:methods*; D000818:Animals; D015519:Bone Density / Q000502:physiology; D001842:Bone and Bones / Q000473:pathology*; D002113:Calcification, Physiologic; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005269:Femur / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000473:pathology*; D055114:X-Ray Microtomography / Q000379:methods*