title: The use of micro-CT to evaluate cortical bone geometry and strength in nude rats: correlation with mechanical testing, pQCT and DXA.
abstract: In both clinical and experimental settings, access to quantitative methods enabling the objective evaluation of cortical bone mass, structure, geometry and strength are essential for the assessment of efficacy and safety of different treatments aimed to improve bone strength. The ability of non-invasive methodologies (DXA, pQCT and micro-CT) to assess and quantify cortical bone mass and geometry was tested in a nude rat model in which bone loss was induced by surgical castration. Treatment with a bone antiresorptive (alendronate) or a bone forming (PTH) drug was used to: (A) validate the nude rat model in terms of bone metabolism, (B) test the ability of each technology to detect change in cortical bone geometry and (C) correlate cortical bone geometry with bone strength data obtained by 3-point bending method. Our observations regarding effect of castration and treatment with PTH and alendronate on cortical bone parameters in nude rats is in general agreement with previously published data obtained in immunocompetent male rats under similar experimental conditions. Data presented here support the hypothesis that nude rats have similar bone physiology and response to known bone therapies to that observed in normal rats and therefore could be effectively used to predict skeletal response in humans. All three technologies deployed in this study (DXA, pQCT and micro-CT) proved useful in describing cancellous and/or cortical bone parameters and positive correlations were demonstrated between data obtained by different methods. The cross-sectional area of a bone structure is crucial for resisting loads in bending or torsion and is described as "areal moment of inertia" for bending, and as "polar moment of inertia" in torsion. Novel, three-dimensional micro-CT methodology used in this study to assess geometry of cortical bone provides data that accurately describes cortical bone geometry and parallels cortical bone strength results obtained by the 3-point bending method. Our micro-CT data meet the criteria of providing quick, reproducible and accurate answers regarding cortical bone geometry as a predictor of cortical bone strength.
authors.affiliation: Comparative Physiology and Medicine, Safety Sciences, Pfizer Inc, Eastern Point Road 8274-1312, Groton, CT 06340, USA. cedo.bagi@pfizer.com
authors.forename: Cedo M
authors.initials: CM
authors.lastname: Bagi
authors.forename: Nels
authors.initials: N
authors.lastname: Hanson
authors.forename: Catharine
authors.initials: C
authors.lastname: Andresen
authors.forename: Richard
authors.initials: R
authors.lastname: Pero
authors.forename: Roland
authors.initials: R
authors.lastname: Lariviere
authors.forename: Charles H
authors.initials: CH
authors.lastname: Turner
authors.forename: Andres
authors.initials: A
authors.lastname: Laib
mesh_terms: D015502:Absorptiometry, Photon; D019386:Alendronate / Q000627:therapeutic use; D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D005269:Femur / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009919:Orchiectomy; D010024:Osteoporosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000031:analogs & derivatives / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011897:Random Allocation; D051381:Rats; D011923:Rats, Nude; D013314:Stress, Mechanical; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography
chemical_list: D050071:Bone Density Conservation Agents; C470125:PTH protein, human; D010281:Parathyroid Hormone; D019386:Alendronate