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Application of micro-ct assessment of 3-d bone microstructure in preclinical and clinical studies

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Abstract

As the mechanical competence of trabecular bone is a function of its apparent density and 3-D distribution, assessment of 3-D 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 have studied ovariectomy-induced osteopenia in rats and its treatment with agents such as estrogen and sodium fluoride. We have demonstrated that 3-D micro-computed tomography (µCT) can directly quantify mouse trabecular and cortical bone structure with an isotropic resolution of 6 µm3. µCT is also useful for studying osteoporosis in mice and phenotypes of mice with gene manipulation, such as SHIP-knockout mice, which are severely osteoporotic due to increased numbers of hyperresorptive osteoclasts, PTHrP heterozygous-null mice, and mice with Zmpste24 deficiency. µCT can quantify osteogenesis in mouse Ilizarov leg-lengthening procedures, osteoconduction in a rat cranial defect model, and structural changes in arthritic rabbits, rats, and mice. In clinical studies, we evaluated longitudinal changes in the iliac crests. Paired bone biopsies from the same premenopausal and postmenopausal women showed the changes in 3-D trabecular structure, such as decreased trabecular thickness, shifting of trabecular model from platelike structure to rodlike structure, and decreased degree of anisotropy were remarkable. Treatment with PTH in postmenopausal women with osteoporosis significantly improved trabecular morphology with a shift toward a more platelike structure, increased trabecular connectivity density, and increased cortical thickness. Paired bone biopsy specimens from the iliac crest in postmenopausal women with osteoporosis before and an average of 2 years after beginning of estrogen replacement therapy demonstrated that posttreatment biopsies showed a significant change in the ratio of plates to rods and statistically insignificant changes in other 3-D trabecular parameters. Thus, µCT can characterize 3-D structure of various animal models, and the longitudinal changes in 3-D bone microarchitectural integrity that deteriorates in the transmenopausal period, is preserved with HRT, and is improved with PTH treatment in postmenopausal women.

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Authors and Affiliations

  1. Osteoporosis and Arthritis Research Group, Department of Radiology, University of California-San Francisco, 94143-0628, San Francisco, CA, USA

    Yebin Jiang, Jenny Zhao & Harry K. Genant

  2. Institute of Endocrinology & Metabolism, the Second Xiang-Ya Hospital of Central South University, Hunan, China

    Er-Yuan Liao, Ru-Chun Dai & Xian-Ping Wu

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  1. Yebin Jiang
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  2. Jenny Zhao
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Correspondence to Yebin Jiang.

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Jiang, Y., Zhao, J., Liao, EY. et al. Application of micro-ct assessment of 3-d bone microstructure in preclinical and clinical studies. J Bone Miner Metab 23 (Suppl 1), 122–131 (2005). https://doi.org/10.1007/BF03026336

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