Abstract
Advanced imaging techniques, which are noninvasive and nondestructive, can provide structural information about bone beyond simple bone densitometry. As the mechanical competence of trabecular bone is a function of its apparent density and 3D distribution, assessment of 3D trabecular structural characteristics may improve our ability to understand the pathophysiology of osteoporosis, to test the efficacy of pharmaceutical intervention, and to estimate bone biomechanical properties. We studied ovariectomy-induced osteopenia in rats with various treatments. Micro-CT is also useful for studying osteoporosis in mice and phenotypes of mice with gene manipulation. Micro-CT can quantify osteogenesis in mouse Ilizarov leg-lengthening procedures, osteoconduction in rat cranial defect models, and structural changes in arthritic rabbits, rats, and mice. Micro-CT can reproducibly quantify 3D microarchitecture of new bone formation inside the pores of titanium prosthesis implants is rabbits. In clinical studies, we evaluated longitudinal changes in iliac crests in premenopausal and postmenopausal women. Paired bone biopsies from post-menopausal women with osteoporotic fracture shows that 3D trabecular microstructure deteriorates in the iliac crest of postmenopausal osteoporotic women without active treatment. Three-dimensional microstructural parameters can predict fracture. Treatment of PTH in postmenopausal women with osteoporosis significantly improved trabecular morphology with a shift toward a more plate-like structure, increased trabecular connectivity, and increased cortical thickness. Paired bone biopsy specimens from the iliac crest in postmenopausal women with osteoporosis before and after beginning estrogen replacement therapy demonstrated in post-treatment biopsies a significant change in the ratio of plates to rods. High-resolution MR and µMR have received considerable attention both as research tools and potential clinical tools for assessment of osteoporosis. It has been used in studying human specimens or animal models of osteoporosis with various treatment strategies.
MR microscopy has been shown to capable of differentiating trabecular structure in the distal radius and the calcaneus in postmenopausal women with or without osteoporotic fracture. It has been used in studying human specimens or animals models of osteoporosis with various treatment strategies. A high field MR study show that ovariectomy in ewes induces deterioration of trabecular microstructure and biomechanical property of the femoral neck. These changes are prevented by calcitonin in a dose-dependent manner. Univariate analysis and multivariate stepwise regression analysis indicate that microarchitecture of trabecular bone contributes significantly to its biomechanical characteristics, independent of BMD measured in the femoral neck. Combination of trabecular microstructure with BMD improves prediction of bone quality.
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References
Anumula SS, Magland J, Zhang H, Ong H, Wehrli SW, Wehrli FW (2005) Multimodality study of the compositional and mechanical implications of hypomineralization in a rabbit model of osteomalacia. J Bone Miner Res 20(Suppl 1):S332
Bergo MO, Gavino B, Ross J, Schmidt WK, Hong C, Kendall LV, Mohr A, Meta M, Genant H, Jiang Y, Wisner ER, Van Bruggen N, Carano RA, Michaelis S, Griffey SM, Young SG (2002) Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect. Proc Natl Acad Sci USA 99:13049–13054
Bonse U, Busch F, Gunnewig O, Beckmann F, Pahl R, Delling G, Hahn M, Graeff W (1994) 3D computed X-ray tomography of human cancellous bone at 8 µ m spatial and 10−4 energy resolution. Bone Miner 25:25–38
Borah B, Dufresne T (2003) 3D micro CT applications in osteoporosis: a clinical perspective. Abstract Book of the First µCT User Workshop, Philadelphia
Chen D, Qiao M, Story B, Zhao M, Jiang Y, Zhao J, Feng J, Xie Y, Huang S, Roberts A, Karsenty G, Mundy G (2003) BMP signaling through the Smad1 pathway is required for normal postnatal bone formation. J Bone Miner Res 18:S6
Dempster DW, Cosman F, Kurland E, Muller R, Nieves J, Woelfert L, Shane E, Plavetic K, Bilezikian J, Lindsay R (2000) Two-and three-dimensional structural analysis of paired biopsies from osteoporotic patients before and after treatment with parathyroid hormone. J Bone Miner Res 15:S194
Feldkamp LA, Goldstein SA, Parfift AM, Jesioil G, Kleerekoper M (1989) The direct examination of three-dimensional bone architecture in vitro by computed tomography. J Bone Miner Res 4:3–11
Flynn M J, Seifert HA, Irving TC, Lai B (2001) Measurement of bone mineralization in whole trabeculae using 3D X-ray microtomography. Proc Int Symp on Bone Biotechnology and Histotechnology, Phoenix, Arizona, p 28
Gabet Y, Kohavi D, Levy J, DiMarchi R, Chorev M, Müller R, Bab I (2005) Parathyroid hormone 1–34 enhances titanium implant osseointegration and peri-implant bone parameters in rat tibial model of low density trabecular bone: a micro CT analysis. J Bone Miner Res 20(Suppl 1):S430
Grodzins L (1983) Optimum energy for X-ray transmission tomography of small samples. Nucl Instrum Methods 206:541–543
Guilak F (1994) Volume and surface area of viable chondrocytes in situ using geometric modeling of sense confocal sections. J Microsc 173:245–256
Han B, Brodie T, Shen Y, Triantafillou J, Scates P, Willams J (2001) Subchondral bone changes in an ACLT model of osteoarthritis in the dog. Proc Int Symp on Bone Biotechnology and Histotechnology, Phoenix, Arizona, p 31
He B, Jiang Y, Zhao J, Genant HK, Goltzman D, Karaplis AC (2000) Quantitative assessment of three-dimensional trabecular bone microstructure in PTHrP wild type and heterozygousnull mice using micro-computed tomography. J Bone Miner Res 15:S186
Hildebrand T, Rüegsegger P (1997a) Quantification of bone microarchitecture with the structure model index. Comp Meth Biomech Biomed Eng 1:15–23
Hildebrand T, Rüegsegger P (1997b) A new method for the model independent assessment of thickness in three-dimensional images. J Microsc 185:67–75
Holdsworth DW, Robarts JP, Thornton MM (2001) Validation of cone-beam reconstruction for bone micro-CT. Proc Int Symp on Bone Biotechnology and Histotechnology, Phoenix, Arizona, p 33
Hwang SN, Wehrli FW, Williams JL (1997) Probability-based structural parameters from three-dimensional nuclear magnetic resonance images as predictors of trabecular bone strength. Med Phys 24:1255–1261
Jara H, Wehrli FW, Chung H, Ford JC (1993) High-resolution variable flip angle 3D MR imaging of trabecular microstructure in vivo. Magn Reson Med 29:528–539
Jiang Y, Zhao J, Genant HK, Dequeker J, Geusens P (1997) Long-term changes in bone mineral and biomechanical properties of vertebrae and femur in aging, dietary calcium restricted and/or estrogen-deprived/-replaced rats. J Bone Miner Res 19:820–831
Jiang Y, Zhao J, Augat P, Ouyang X, Lu Y, Majumdar S, Genant HK (1998) Trabecular bone mineral and calculated structure of human bone specimens scanned by peripheral quantitative computed tomography: relation to biomechanical properties. J Bone Miner Res 13:1783–1790
Jiang Y, Zhao J, Prevrhal S, Genant HK (1999b) Three-dimensional trabecular microstructure, bone mineral density, and biomechanical properties of the vertebral body of ovariectomized rats with estrogen replacement therapy. J Bone Miner Res 14(S1):S534
Jiang Y, Zhao J, Recker RR, Draper MW, Genant HK (2000) Longitudinal changes between premenopausal and postmenopausal in three-dimensional trabecular microstructural characteristics of human iliac crest bone biopsies. J Bone Miner Res 15:S184
Jiang Y, Zhao J, Mitlak BH, Wang O, Genant HK, Eriksen EF (2003a) Recombinant human parathyroid hormone (1–34) (teriparatide) improves both cortical and cancellous bone structure. J Bone Miner Res 18:1932–1941
Jiang Y, Zhao J, Eriksen EF, Genant HK (2003b) Reproducibility of micro CT quantification of 3D microarchitecture of the trabecular and cortical bone in the iliac crest of post-menopausal osteoporotic women and their treatment with teriparatide [rhPTH(1–34)]. RSNA’03:571
Jiang Y, Zhao J, An YH (2005a) Three-dimensional microarchitecture of the new bone formation on the prosthetic implant: reproducibility of micro CT assessment. J Bone Miner Res 20(Suppl 1):S335
Jiang Y, Zhao J, Geusens P, Liao EY, Adriaensens P, Gelan J, Azria M, Boonen S, Caulin F, Lynch JA, Ouyang X, Genant HK (2005b) Femoral neck trabecular microstructure in ovariectomized ewes treated with calcitonin: MRI microscopic evaluation. J Bone Miner Res 20:125–130
Kapadia RD, High W, Bertolini D, Sarkar SK (1993) MR microscopy: a novel diagnostic tool in osteoporosis research. In: Christiansen C (ed) Fourth Int Symp on Osteoprosis and Consensus Development Conference, Hong Kong, 28 pp
Kinney JH, Lane NE, Haupt DL (1995) In vivo, three-dimensional microscopy of trabecular bone. J Bone Miner Res 10:264–270
Kinney JH, Haupt DL, Balooch M, Ladd AJ, Ryaby JT, Lane NE (2000) Three-dimensional morphometry of the L6 vertebra in the ovariectomized rat model of osteoporosis: biomechanical implications. J Bone Miner Res 15:1981–1991
Kuhn JL, Goldstein SA, Feldkamp LA, Jesion G (1990) Evaluation of a microcomputed tomography system to study trabecular bone structure. J Orthop Res 8:833–842
Lane NE, Thompson JM, Strewler GJ, Kinney JH (1995) Intermittent treatment with human parathyroid hormone (hPTH[1–34]) increased trabecular bone volume but not connectivity in osteopenic rats. J Bone Miner Res 10:1470–1477
Lane NE, Haupt D, Kimmel DB, Modin G, Kinney JH (1999) Early estrogen replacement therapy reverses the rapid loss of trabecular bone volume and prevents further deterioration of connectivity in the rat. J Bone Miner Res 14:206–214
Link T, Majumdar S, Augat P, Lin J, Newitt D, Lang T, Lu Y, Lane N, Genant HK (1998) In vivo high resolution MRI of the calcaneus: differences in trabecular structure in osteoporotic patients. J Bone Miner Res 13:1175–1182
Majumdar S, Kothari M, Augat P, Newitt DC, Lin JC, Lang T, Lu Y, Genant HK (1998) High-resolution magnetic resonance imaging: three-dimensional bone architecture and biome-chanical properties. Bone 22:445–454
Moreau IA, Smith SY, Guldberg RE, Turner CH, Newman MK, Fox J (2005) Treatment of osteopenic rhesus monkeys with parathyroid hormone 1–84 for 16 months improves vertebral trabecular bone quantity and quality. J Bone Miner Res 20(Suppl 1):S412
Mosekilde L (1993) Vertebral structure and strength in vivo and in vitro. Calcif Tissue Int 53:S121–S125
Odgaard A, Gundersen HJG (1993) Quantification of connectivity in cancellous bone, with special emphasis on 3D reconstruction. Bone 14:173–182
Peyrin F, Salome M, Cloetens P, Ludwig W, Ritman, Ruegsegger P, Laval-Jeantet AM, Baruchel J (1998) What do micro-CT examinations reveal at various resolutions: a study of the same trabecular bone samples at the 14, 7, and 2 micron level. Presented, Symposium on Bone Architecture and the Competence of Bone, Ittingen, Switzerland pp 3–5
Rüegsegger P, Koller B, Muller R (1996) A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int 58:24–29
Smith CB, Silver MD (1994) Comparison between single slice CT and volume CT. In: Czichos HCH, Schnitger D (eds) Int Symp on Computerized Tomography for Industrial Applications, Bundesministerium des Innern, Bundesanstalt fur Materialforschung und-prufung, Berlin, Germany
Stampa B, Kühn B, Heller M and C-C Glüer (1998) Rods or plates: a new algorithm to characterize bone structure using 3D magnetic resonance imaging. Presented at the 13th International Bone Densitometry Workshop, 4–8 October 1998, Wisconsin
Takeshita S, Namba N, Zhao J, Jiang Y, Genant HK, Silva MJ, Brodt MD, Helgason CD, Kalesnikoff J, Rauh MJ, Humphries RK, Krystal G, Teitelbaum SL, Ross FP (2002) SHIP-deficient mice are severely osteoporotic due to increased numbers of hyper-resorptive osteoclasts. Nature Med 8:943–949
Turner CH, Hsieh YF, Muller R, Bouxsein ML, Rosen CJ, McCrann ME, Donahue LR, Beamer WG (2001) Variation in bone biomechanical properties, microstructure, and density in BXH recombinant inbred mice. J Bone Miner Res 16:206–213
Van Rietbergen B (2003) Finite element modeling. Abstract Book of the First µCT User Workshop, Philadelphia
Wehrli FW, Hwang SN, Ma J, Song HK, Ford JC, Haddad JG (1998) Cancellous bone volume and structure in the forearm: noninvasive assessment with MR microimaging and image processing. Radiology 206:347–357
Wu Y, Ackerman JL, Dai G, Chelsler DA, Hrovat M, Snyder BD, Nazarian A, Glimcher MJ (2005) Solid bone matrix of rat femur imaged by water and fat suppressed proton magnetic resonance imaging. J Bone Miner Res 20(Suppl 1):S223
Yang D, Bouxsein M, Chiusaroli R, Schipani E, Pajevic P, Guo J, Singh R, Bringhurst FR (2005) Signaling selective PTH (1–34) analogs accelerate bone formation. J Bone Miner Res 20(Suppl 1):S102
Yao W, Balooch G, Nalla R, Zhou J, Jiang Y, Wronski T, Lane N (2005) Restoration of cancellous bone connectivity and strength in ovariectomized mice treated with basic fibroblast growth factor and followed by an anti-resorptive agent. J Bone Miner Res 20(Suppl 1):S345
Zhao J, Jiang Y, Genant HK (2000a) Three-dimensional trabecular microstructure and biomechanical properties and their relationship in different bone quality models. Radiology 217(P): 411
Zhao J, Jiang Y, Prevrhal S, Genant HK (2000b) Effects of low dose long-term sodium fluoride on three-dimensional trabecular microstructure, bone mineral, and biomechanical properties of rat vertebral body. J Bone Miner Res 15:816
Zhao J, Jiang Y, Shen V, Bain S, Genant HK (2000c) µCT and pQCT assessments of a murine model of postmenopausal osteoporosis and estrogen therapy. Osteoporosis Int 11(S3):S11
Zhao J, Jiang Y, Vedi S, Compston JE, Genant HK (2002) Longitudinal changes in three-dimensional trabecular microarchitecture of paired iliac crest bone biopsies before and after estrogen replacement therapy in postmenopausal women. J Bone Miner Res 17:S208
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Jiang, YB., Jacobson, J., Genant, H.K., Zhao, J. (2007). Application of Micro-CT and MRI in Clinical and Preclinical Studies of Osteoporosis and Related Disorders. In: Qin, L., Genant, H.K., Griffith, J.F., Leung, K.S. (eds) Advanced Bioimaging Technologies in Assessment of the Quality of Bone and Scaffold Materials. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-45456-4_24
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DOI: https://doi.org/10.1007/978-3-540-45456-4_24
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