Skip to main content
Top
Published in: European Radiology Experimental 1/2019

Open Access 01-12-2019 | Original article

Microcomputed tomography of the femur of diabetic rats: alterations of trabecular and cortical bone microarchitecture and vasculature—a feasibility study

Authors: David Zeitoun, Guavri Caliaperoumal, Morad Bensidhoum, Jean Marc Constans, Fani Anagnostou, Valérie Bousson

Published in: European Radiology Experimental | Issue 1/2019

Login to get access

Abstract

Background

To better understand bone fragility in type 2 diabetes mellitus and define the contribution of microcomputed tomography (micro-CT) to the evaluation of bone microarchitecture and vascularisation, we conducted an in vitro preliminary study on the femur of Zucker diabetic fatty (ZDF) rats and Zucker lean (ZL) rats. We first analysed bone microarchitecture, then determined whether micro-CT allowed to explore bone vascularisation, and finally looked for a link between these parameters.

Methods

Eight ZDF and six ZL rats were examined for bone microarchitecture (group 1), and six ZDF and six ZL rats were studied for bone vascularisation after Microfil® perfusion which is a radiopaque casting agent (group 2). In group 1, we used micro-CT to examine the trabecular and cortical bone microarchitecture of the femoral head, neck, shaft, and distal metaphysis. In group 2, micro-CT was used to study the blood vessels in the head, neck, and distal metaphysis.

Results

Compared to ZL rats, the ZDF rats exhibited significantly lower trabecular bone volume and number and higher trabecular separation in the three locations (p = 0.02, p = 0.02, p = 0.003). Cortical porosity was significantly higher in the ZDF rats at the neck and shaft (p = 0.001 and p = 0.005). We observed a dramatically poorer bone vascularisation in the femur of ZDF rats, especially in distal metaphysis (p < 0.047).

Conclusions

Micro-CT demonstrated not only significant alterations in the bone microarchitecture of the femurs of ZDF rats, but also significant alterations in bone vascularisation. Further studies are required to demonstrate the causal link between poor vascularisation and impaired bone architecture.
Literature
1.
go back to reference Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes. Diabetes Care 27:1047–1053CrossRef Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes. Diabetes Care 27:1047–1053CrossRef
2.
go back to reference Schwartz AV (2016) Epidemiology of fractures in type 2 diabetes. Bone 82:2–801 /03/2019 21:40:00CrossRef Schwartz AV (2016) Epidemiology of fractures in type 2 diabetes. Bone 82:2–801 /03/2019 21:40:00CrossRef
3.
go back to reference Leslie WD, Rubin MR, Schwartz AV, Kanis JA (2012) Type 2 diabetes and bone. J Bone Miner Res 27:2231–2237CrossRef Leslie WD, Rubin MR, Schwartz AV, Kanis JA (2012) Type 2 diabetes and bone. J Bone Miner Res 27:2231–2237CrossRef
4.
go back to reference Bonds DE, Larson JC, Schwartz AV et al (2006) Risk of fracture in women with type 2 diabetes: the women’s health initiative observational study. J Clin Endocrinol Metab 91:3404–3410CrossRef Bonds DE, Larson JC, Schwartz AV et al (2006) Risk of fracture in women with type 2 diabetes: the women’s health initiative observational study. J Clin Endocrinol Metab 91:3404–3410CrossRef
5.
go back to reference Vestergaard P (2006) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 18:427–444CrossRef Vestergaard P (2006) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 18:427–444CrossRef
6.
go back to reference Melton LJ 3rd, Riggs BL, Leibson CL et al (2008) A bone structural basis for fracture risk in diabetes. J Clin Endocrinol Metab 93:4804–4809CrossRef Melton LJ 3rd, Riggs BL, Leibson CL et al (2008) A bone structural basis for fracture risk in diabetes. J Clin Endocrinol Metab 93:4804–4809CrossRef
7.
go back to reference Janghorbani M, Dam RMV, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166:495–505CrossRef Janghorbani M, Dam RMV, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166:495–505CrossRef
8.
go back to reference Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2009) Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res 24:702–709CrossRef Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2009) Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res 24:702–709CrossRef
9.
go back to reference Semel J, Gray JM, Ahn HJ, Nasr H, Chen JJ (2010) Predictors of outcome following hip fracture rehabilitation. PM R 2:799–805CrossRef Semel J, Gray JM, Ahn HJ, Nasr H, Chen JJ (2010) Predictors of outcome following hip fracture rehabilitation. PM R 2:799–805CrossRef
10.
go back to reference Reistetter TA, Graham JE, Deutsch A, Markello SJ, Granger CV, Ottenbacher KJ (2011) Diabetes comorbidity and age influence rehabilitation outcomes after hip fracture. Diabetes Care 34:1375–1377CrossRef Reistetter TA, Graham JE, Deutsch A, Markello SJ, Granger CV, Ottenbacher KJ (2011) Diabetes comorbidity and age influence rehabilitation outcomes after hip fracture. Diabetes Care 34:1375–1377CrossRef
11.
go back to reference Hernandez RK, Do TP, Critchlow CW, Dent RE, Jick SS (2012) Patient-related risk factors for fracture-healing complications in the United Kingdom General Practice Research Database. Acta Orthop 83:653–660CrossRef Hernandez RK, Do TP, Critchlow CW, Dent RE, Jick SS (2012) Patient-related risk factors for fracture-healing complications in the United Kingdom General Practice Research Database. Acta Orthop 83:653–660CrossRef
12.
go back to reference Ma L, Oei L, Jiang L et al (2012) Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol 27:319–332CrossRef Ma L, Oei L, Jiang L et al (2012) Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol 27:319–332CrossRef
13.
go back to reference Deandrea S, Lucenteforte E, Bravi F, Foschi R, La Vecchia C, Negri E (2010) Risk factors for falls in community-dwelling older people: a systematic review and meta-analysis. Epidemiology 21:658–668CrossRef Deandrea S, Lucenteforte E, Bravi F, Foschi R, La Vecchia C, Negri E (2010) Risk factors for falls in community-dwelling older people: a systematic review and meta-analysis. Epidemiology 21:658–668CrossRef
14.
go back to reference Burghardt AJ, Issever AS, Schwartz AV et al (2010) High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 95:5045–5055CrossRef Burghardt AJ, Issever AS, Schwartz AV et al (2010) High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 95:5045–5055CrossRef
15.
go back to reference Farr JN, Drake MT, Amin S, Melton LJ 3rd, McCready LK, Khosla S (2014) In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res 29:787–795CrossRef Farr JN, Drake MT, Amin S, Melton LJ 3rd, McCready LK, Khosla S (2014) In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res 29:787–795CrossRef
16.
go back to reference Patsch JM, Li X, Baum T et al (2013) Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res 28:1721–1728CrossRef Patsch JM, Li X, Baum T et al (2013) Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res 28:1721–1728CrossRef
17.
go back to reference Hamann C, Goettsch C, Mettelsiefen J et al (2011) Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function. Am J Physiol Endocrinol Metab 301:E1220–E1228CrossRef Hamann C, Goettsch C, Mettelsiefen J et al (2011) Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function. Am J Physiol Endocrinol Metab 301:E1220–E1228CrossRef
18.
go back to reference Hamann C, Rauner M, Höhna Y et al (2013) Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus. J Bone Miner Res 28:627–638CrossRef Hamann C, Rauner M, Höhna Y et al (2013) Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus. J Bone Miner Res 28:627–638CrossRef
19.
go back to reference Reinwald S, Peterson RG, Allen MR, Burr DB (2009) Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models. Am J Physiol Endocrinol Metab 296:E765–E774CrossRef Reinwald S, Peterson RG, Allen MR, Burr DB (2009) Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models. Am J Physiol Endocrinol Metab 296:E765–E774CrossRef
20.
go back to reference Mathey J, Horcajada-Molteni MN, Chanteranne B et al (2002) Bone mass in obese diabetic Zucker rats: influence of treadmill running. Calcif Tissue Int 70:305–311CrossRef Mathey J, Horcajada-Molteni MN, Chanteranne B et al (2002) Bone mass in obese diabetic Zucker rats: influence of treadmill running. Calcif Tissue Int 70:305–311CrossRef
21.
go back to reference Prisby RD, Swift JM, Bloomfield SA, Hogan HA, Delp MD (2008) Altered bone mass, geometry and mechanical properties during the development and progression of type 2 diabetes in the Zucker diabetic fatty rat. J Endocrinol 199:379–388CrossRef Prisby RD, Swift JM, Bloomfield SA, Hogan HA, Delp MD (2008) Altered bone mass, geometry and mechanical properties during the development and progression of type 2 diabetes in the Zucker diabetic fatty rat. J Endocrinol 199:379–388CrossRef
22.
go back to reference Karim L, Bouxsein ML (2016) Effect of type 2 diabetes-related non-enzymatic glycation on bone biomechanical properties. Bone 82:21–27CrossRef Karim L, Bouxsein ML (2016) Effect of type 2 diabetes-related non-enzymatic glycation on bone biomechanical properties. Bone 82:21–27CrossRef
23.
go back to reference Karim L, Tang SY, Sroga GE, Vashishth D (2013) Differences in non-enzymatic glycation and collagen cross-links between human cortical and cancellous bone. Osteoporos Int 24:2441–2447CrossRef Karim L, Tang SY, Sroga GE, Vashishth D (2013) Differences in non-enzymatic glycation and collagen cross-links between human cortical and cancellous bone. Osteoporos Int 24:2441–2447CrossRef
24.
go back to reference Karim L, Vashishth D (2012) Heterogeneous glycation of cancellous bone and its association with bone quality and fragility. PLoS One 7:e35047CrossRef Karim L, Vashishth D (2012) Heterogeneous glycation of cancellous bone and its association with bone quality and fragility. PLoS One 7:e35047CrossRef
25.
go back to reference Shu A, Yin MT, Stein E et al (2012) Bone structure and turnover in type 2 diabetes mellitus. Osteoporos Int 23:635–641CrossRef Shu A, Yin MT, Stein E et al (2012) Bone structure and turnover in type 2 diabetes mellitus. Osteoporos Int 23:635–641CrossRef
26.
go back to reference Starup-Linde J, Vestergaard P (2016) Biochemical bone turnover markers in diabetes mellitus: a systematic review. Bone 82:69–78CrossRef Starup-Linde J, Vestergaard P (2016) Biochemical bone turnover markers in diabetes mellitus: a systematic review. Bone 82:69–78CrossRef
27.
go back to reference García-Martín A, Rozas-Moreno P, Reyes-García R et al (2011) Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 97:234–241CrossRef García-Martín A, Rozas-Moreno P, Reyes-García R et al (2011) Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 97:234–241CrossRef
28.
go back to reference Duvall CL, Taylor WR, Weiss D, Gulberg RE (2004) Quantitative microcomputed tomography analysis of collateral vessel development after ischemic injury. Am J Physiol Heart Circ Physiol 287:H302–H310CrossRef Duvall CL, Taylor WR, Weiss D, Gulberg RE (2004) Quantitative microcomputed tomography analysis of collateral vessel development after ischemic injury. Am J Physiol Heart Circ Physiol 287:H302–H310CrossRef
29.
go back to reference Roche B, David V, Vanden-Bossche A et al (2012) Structure and quantification of microvascularisation within mouse long bones: what and how should we measure? Bone 50:390–399CrossRef Roche B, David V, Vanden-Bossche A et al (2012) Structure and quantification of microvascularisation within mouse long bones: what and how should we measure? Bone 50:390–399CrossRef
30.
go back to reference Lafage-Proust MH, Roche B, Langer M et al (2015) Assessment of bone vascularization and its role in bone remodeling. Bonekey Rep 4:662 Lafage-Proust MH, Roche B, Langer M et al (2015) Assessment of bone vascularization and its role in bone remodeling. Bonekey Rep 4:662
31.
go back to reference Fei J, Peyrin F, Malaval L, Vico L, Lafage-Proust MH (2010) Imaging and quantitative assessment of long bone vascularization in the adult rat using microcomputed tomography. Anat Rec (Hoboken) 293:215–224CrossRef Fei J, Peyrin F, Malaval L, Vico L, Lafage-Proust MH (2010) Imaging and quantitative assessment of long bone vascularization in the adult rat using microcomputed tomography. Anat Rec (Hoboken) 293:215–224CrossRef
32.
go back to reference Werner C, Iversen BF, Therkildsen MH et al (1988) Contribution of the trabecular component to mechanical strength and bone mineral content of the femoral neck. An experimental study on cadaver bones. Scand J Clin Lab Invest 48:457–460CrossRef Werner C, Iversen BF, Therkildsen MH et al (1988) Contribution of the trabecular component to mechanical strength and bone mineral content of the femoral neck. An experimental study on cadaver bones. Scand J Clin Lab Invest 48:457–460CrossRef
33.
go back to reference Lotz JC, Cheal EJ, Hayes WC et al (1995) Stress distributions within the proximal femur during gait and falls: implications for osteoporotic fractures. Osteoporos Int 5:252–261CrossRef Lotz JC, Cheal EJ, Hayes WC et al (1995) Stress distributions within the proximal femur during gait and falls: implications for osteoporotic fractures. Osteoporos Int 5:252–261CrossRef
34.
go back to reference Hyldstrup L, Conway GS, Racz K et al (2012) Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency. Osteoporosis Int 23:2219–2226CrossRef Hyldstrup L, Conway GS, Racz K et al (2012) Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency. Osteoporosis Int 23:2219–2226CrossRef
35.
go back to reference Nyangoga H, Mercier P, Libouban H, Baslé MF, Chappard D (2011) Three-dimensional characterization of the vascular bed in bone metastasis of the rat by microcomputed tomography (MicroCT). PLoS One 6:e17336CrossRef Nyangoga H, Mercier P, Libouban H, Baslé MF, Chappard D (2011) Three-dimensional characterization of the vascular bed in bone metastasis of the rat by microcomputed tomography (MicroCT). PLoS One 6:e17336CrossRef
36.
go back to reference Engelke K, Karolczak M, Lutz A, Seibert U, Schaller S, Kalender W (1999) Micro-CT technology and application for assessing bone structure Radiologe 39:203–212 Engelke K, Karolczak M, Lutz A, Seibert U, Schaller S, Kalender W (1999) Micro-CT technology and application for assessing bone structure Radiologe 39:203–212
37.
go back to reference Stabley JN, Prisby RD, Behnke BJ, Delp MD (2015) Type 2 diabetes alters bone and marrow blood flow and vascular control mechanisms in the ZDF rat. J Endocrinol 225:47–58CrossRef Stabley JN, Prisby RD, Behnke BJ, Delp MD (2015) Type 2 diabetes alters bone and marrow blood flow and vascular control mechanisms in the ZDF rat. J Endocrinol 225:47–58CrossRef
38.
go back to reference Farr JN, Khosla S (2016) Determinants of bone strength and quality in diabetes mellitus in humans. Bone 82:28–34CrossRef Farr JN, Khosla S (2016) Determinants of bone strength and quality in diabetes mellitus in humans. Bone 82:28–34CrossRef
Metadata
Title
Microcomputed tomography of the femur of diabetic rats: alterations of trabecular and cortical bone microarchitecture and vasculature—a feasibility study
Authors
David Zeitoun
Guavri Caliaperoumal
Morad Bensidhoum
Jean Marc Constans
Fani Anagnostou
Valérie Bousson
Publication date
01-12-2019
Publisher
Springer International Publishing
Published in
European Radiology Experimental / Issue 1/2019
Electronic ISSN: 2509-9280
DOI
https://doi.org/10.1186/s41747-019-0094-5

Other articles of this Issue 1/2019

European Radiology Experimental 1/2019 Go to the issue