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

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 (microCT) can directly quantify mouse trabecular and cortical bone structure with an isotropic resolution of 6 microm(3). MicroCT 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. MicroCT 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, microCT 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.

Food Restriction Causes Low Bone Strength and Microarchitectural Deterioration in Exercised Growing Male Rats

“…Mechanical loading-induced bone alteration is achieved by an increase of bone formation and a decrease of bone resorption (9). Moreover, trabecular bone thickness and trabecular bone number increase are induced by exercise (10,11).…”

Improvement of intertrochanteric bone quality in osteoporotic female rats after injection of polylactic acid-polyglycolic acid copolymer/collagen type I microspheres combined with bone mesenchymal stem cells

“…Thus, in the diagnosis and treatment of osteoporosis, bone structural change has great significance. Micro-CT is an accurate, 3D and non-invasive method of measuring bone microstructure, assessing bone quality and predicting bone strength [28,29]. The 3D measurement and 3D imaging method can be directly used for bone morphogenetic parameters.…”

In Vivo mouse imaging and spectroscopy in drug discovery

“…Micro-CT has proven to be a powerful technique for analyzing bone structure and density in mice (267)(268)(269)(270)(271). For instance, Barck et al (268) combined micro-CT with an automated image analysis algorithm to quantify cortical bone loss and periosteal new bone formation for therapeutic evaluation in a murine model of CIA (Fig.…”