Signs of irreversible architectural changes occur early in the development of experimental osteoporosis as assessed by in vivo micro-CT.
Using in vivo micro-computed tomography, we assessed bone loss in the rat during the first twelve weeks after ovariectomy when structural changes were most rapid. Significant changes to the trabecular architecture were observed, including irreversible changes reflected by reduction in connectivity after only two weeks. This highlights that topological changes to the structure occur early in this experimental model of osteoporosis.


BACKGROUND
The purpose of this study was to establish a longitudinal time course of bone loss in the ovariectomized (OVX) rat model during the initial twelve-week period where structural changes are most rapid, and to identify when irreversible changes occur using in vivo micro-computed tomography (micro-CT).


METHODS
The proximal tibiae of OVX (N = 10) and sham (N = 10) operated mature female Wistar rats were micro-CT scanned every two weeks from week 0 to week 12, excluding week 10. Changes in architecture were quantified using direct three-dimensional techniques and serum osteocalcin and CTX-I was measured at weeks 0, 6 and 12. Biomechanical properties were determined from femoral three-point bending and L-4 vertebral compression at the end of the protocol. ANOVA and paired t-tests were used to analyze the longitudinal and endpoint data, respectively.


RESULTS
All of the measured architectural parameters changed significantly over the study in the OVX group, including irreversible changes reflected by connectivity density after two weeks. Osteocalcin concentration was elevated in the OVX group. Moderate changes in the mechanical properties of the femora midshaft and vertebrae were observed.


CONCLUSIONS
Changes to the bone architecture and mechanics within twelve weeks after OVX highlight the importance of early diagnosis and treatment of osteoporosis.
Campbell
G M
GM
Department of Mechanical and Manufacturing Engineering, University of Calgary, 2500 University Drive, N.W., Calgary, Alberta, T2N 1N4, Canada.
Buie
H R
HR
Boyd
S K
SK
D015502:Absorptiometry, Photon; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density; D016723:Bone Remodeling; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005269:Femur / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000503:physiopathology; D015675:Osteocalcin / Q000378:metabolism; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D010052:Ovariectomy; D010455:Peptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013977:Tibia / Q000000981:diagnostic imaging; D055114:X-Ray Microtomography / Q000379:methods*
D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin