Microstructural abnormalities are evident by histology but not HR-pQCT at the periosteal cortex of the human tibia under CVD and T2D conditions

Garita, Barbara; Maligro, Jenna; Sadoughi, Saghi; Wu, Po Hung; Liebenberg, Ellen; Horvai, Andrew E.; Link, Thomas M.; Kazakia, Galateia J.

doi:10.1016/j.medntd.2021.100062

Cited by 6 publications

(5 citation statements)

References 42 publications

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“…Although manually correcting for contours and computing cortical porosity using direct volumetric and morphometric approaches ensures better estimation of porosity, (24) it does underestimate porosity because of the elimination of smaller and/or incomplete pores or pores that are at the periosteal boundaries due to partial volume effects and low attenuation. (45) Notably, despite the increased cortical porosity, we found that overall stiffness and failure load increased, similar to studies in both humans (21,(32)(33)(34)(35) and animals. (46,47) This may be because the increase in cortical porosity is due to the development of small voids that represent only a small fraction of the cortical bone (48) and because absolute changes in cortical porosity are relatively small and thus do not have a substantial impact on whole bone FE-based strength parameters.…”

Section: Discussionsupporting

confidence: 88%

Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT

Agarwal

Shiau

Kamanda‐Kosseh

et al. 2020

Journal of Bone and Mineral Research

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Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in skeletal microstructure. We have reported that sequential treatment with teriparatide and denosumab improves central skeletal bone mineral density (BMD) by dual-energy Xray absorptiometry and central QCT in PreMenIOP. We conducted preplanned analyses of high-resolution peripheral quantitative computed tomography (HR-pQCT) scans from teriparatide and denosumab extension studies to measure effects on volumetric BMD (vBMD), microarchitecture, and estimated strength at the distal radius and tibia. Of 41 women enrolled in the parent teriparatide study (20 mcg daily), 34 enrolled in the HR-pQCT study. HR-pQCT participants initially received teriparatide (N = 24) or placebo (N = 10) for 6 months; all then received teriparatide for 24 months. After teriparatide, 26 enrolled in the phase 2B denosumab extension (60 mg q6M) for 24 months. Primary outcomes were percentage change in vBMD, microstructure, and stiffness after teriparatide and after denosumab. Changes after sequential teriparatide and denosumab were secondary outcomes. After teriparatide, significant improvements were seen in tibial trabecular number (3.3%, p = 0.01), cortical area and thickness (both 2.7%, p < 0.001), and radial trabecular microarchitecture (number: 6.8%, thickness: 2.2%, separation: À5.1%, all p < 0.02). Despite increases in cortical porosity and decreases in cortical density, whole-bone stiffness and failure load increased at both sites. After denosumab, increases in total (3.5%, p < 0.001 and 3.3%, p = 0.02) and cortical vBMD (1.7% and 3.2%; both p < 0.01), and failure load (1.1% and 3.6%; both p < 0.05) were seen at tibia and radius, respectively. Trabecular density (3.5%, p < 0.001) and number (2.4%, p = 0.03) increased at the tibia, while thickness (3.0%, p = 0.02) increased at the radius. After 48 months of sequential treatment, significant increases in total vBMD (tibia: p < 0.001; radius: p = 0.01), trabecular microstructure (p < 0.05), cortical thickness (tibia: p < 0.001; radius: p = 0.02), and whole bone strength (p < 0.02) were seen at both sites. Significant increases in total vBMD and bone strength parameters after sequential treatment with teriparatide followed by denosumab support the use of this regimen in PreMenIOP.

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Section: Discussionsupporting

confidence: 88%

Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT

Agarwal

Shiau

Kamanda‐Kosseh

et al. 2020

Journal of Bone and Mineral Research

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“…DCE-MRI uses contrast enhancement characteristics to identify and assess intracortical vessels. The distinction between cortical pore metrics and intracortical vessel metrics is important because cortical porosity, even in the mid-cortical and periosteal regions of the cortex, can contain adiposity rather than – or in addition to – vasculature ( Garita et al, 2021 ; Wu et al, 2019 ; Goldenstein et al, 2010 ). We found higher average vessel volume and diameter in T2D.…”

Section: Discussionmentioning

confidence: 99%

“…Previous imaging studies have advanced the knowledge, but – so far – no study has been able to elucidate the biological mechanisms driving Ct.Po. The vascular system, as one of the primary contents of pore space ( Garita et al, 2021 ), could be involved in a pathological process that leads to pore expansion. This process would require resorption of cortical bone for vascular canals.…”

Section: Introductionmentioning

confidence: 99%

Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics

Löffler,

Wu,

Pirmoazen

et al. 2024

Bone Reports

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“…In a different approach, an inversion recovery UTE (IR-UTE) sequence that suppresses the signal from pore water is combined with a UTE sequence to calculate a suppression index, an inverse indicator of cortical porosity [30]. A caveat of these approaches is that a significant portion of intracortical porosity can contain fat rather than vasculature (as detailed in the introduction [7,8]) and therefore these metrics of pore water cannot fully represent intracortical porosity.…”

Section: Ultrashort Echo-time Magnetic Resonance Imagingmentioning

confidence: 99%

“…The historical understanding of cortical pore content was focused on vessels within osteonal pore space and marrow adipocytes within transition zone 'trabecularized' endocortical spaces. However, our recent histological and imaging studies [7,8] have documented that vessels and adipocytes have a more diverse distribution throughout the intracortical pore space than previously appreciated. In histological samples from cadaver specimens (including donors with cardiovascular disease and type 2 diabetes), we found evidence of large, sub-periosteal pores containing primarily adipocytes, with sparse evidence of capillaries and connective fibrous tissue (Fig.…”

Section: Introductionmentioning

confidence: 97%

MR-based techniques for intracortical vessel visualization and characterization: understanding the impact of microvascular disease on skeletal health

Löffler

Kazakia

2023

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of reviewThe relationships between bone vasculature and bone microstructure and strength remain incompletely understood. Addressing this gap will require in vivo imaging capabilities. We describe the relevant vascular anatomy of compact bone, review current magnetic resonance imaging (MRI)-based techniques that allow in vivo assessment of intracortical vasculature, and finally present preliminary studies that apply these techniques to investigate changes in intracortical vessels in aging and disease.Recent findingsUltra-short echo time MRI (UTE MRI), dynamic contrast-enhanced MRI (DCE-MRI), and susceptibility-weighted MRI techniques are able to probe intracortical vasculature. Applied to patients with type 2 diabetes, DCE-MRI was able to find significantly larger intracortical vessels compared to nondiabetic controls. Using the same technique, a significantly larger number of smaller vessels was observed in patients with microvascular disease compared to those without. Preliminary data on perfusion MRI showed decreased cortical perfusion with age.SummaryDevelopment of in vivo techniques for intracortical vessel visualization and characterization will enable the exploration of interactions between the vascular and skeletal systems, and further our understanding of drivers of cortical pore expansion. As we investigate potential pathways of cortical pore expansion, appropriate treatment and prevention strategies will be clarified.

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Microstructural abnormalities are evident by histology but not HR-pQCT at the periosteal cortex of the human tibia under CVD and T2D conditions

Cited by 6 publications

References 42 publications

Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT

Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT

Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics

MR-based techniques for intracortical vessel visualization and characterization: understanding the impact of microvascular disease on skeletal health

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