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Published in: BMC Endocrine Disorders 1/2018

Open Access 01-12-2018 | Research article

Type 2 diabetes affects bone cells precursors and bone turnover

Authors: Francesca Sassi, Ilaria Buondonno, Chiara Luppi, Elena Spertino, Emanuela Stratta, Marco Di Stefano, Marco Ravazzoli, Gianluca Isaia, Marina Trento, Pietro Passera, Massimo Porta, Giovanni Carlo Isaia, Patrizia D’Amelio

Published in: BMC Endocrine Disorders | Issue 1/2018

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Abstract

Background

Here we study the effect of type 2 diabetes (T2DM) on bone cell precursors, turnover and cytokines involved in the control of bone cell formation and activity.

Methods

We enrolled in the study 21 T2DM women and 21 non diabetic controls matched for age and body mass index (BMI). In each subject we measured bone cell precursors, Receptor Activator of Nuclear Factor κB (RANKL), Osteoprotegerin (OPG), Sclerostin (SCL) and Dickoppf-1 (DKK-1) as cytokines involved in the control of osteoblast and osteoclast formation and activity, bone density (BMD) and quality trough trabecular bone score (TBS) and bone turnover. T2DM patients and controls were compared for the analyzed variables by one way ANOVA for Gaussian ones and by Mann-Whitney or Kruskal-Wallis test for non-Gaussian variables.

Results

RANKL was decreased and DKK-1 increased in T2DM. Accordingly, patients with T2DM have lower bone turnover compared to controls. BMD and TBS were not significantly different from healthy controls. Bone precursor cells were more immature in T2DM. However the number of osteoclast precursors was increased and that of osteoblasts decreased.

Conclusions

Patients with T2DM have more immature bone cells precursors, with increased number of osteoclasts and decreased osteoblasts, confirming low bone turnover and reduced cytokines such as RANKL and DKK-1. BMD and TBS are not significantly altered in T2DM although, in contrast with other studies, this may be due to the match of patients and controls for BMI rather than age.
Literature
1.
go back to reference Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007;166:495–505.CrossRefPubMed Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007;166:495–505.CrossRefPubMed
2.
go back to reference Bonds DE, Larson JC, Schwartz AV, et al. Risk of fracture in women with type 2 diabetes: the Women’s health initiative observational study. J Clin Endocrinol Metab. 2006;91:3404–41.CrossRefPubMed Bonds DE, Larson JC, Schwartz AV, et al. Risk of fracture in women with type 2 diabetes: the Women’s health initiative observational study. J Clin Endocrinol Metab. 2006;91:3404–41.CrossRefPubMed
3.
go back to reference Dhaliwal R, Cibula D, Ghosh C, Weinstock RS, Moses AM. Bone quality assessment in type 2 diabetes mellitus. Osteoporos Int. 2014;25:1969–73.CrossRefPubMed Dhaliwal R, Cibula D, Ghosh C, Weinstock RS, Moses AM. Bone quality assessment in type 2 diabetes mellitus. Osteoporos Int. 2014;25:1969–73.CrossRefPubMed
4.
go back to reference Starup-Linde J, Vestergaard P. Management of endocrine disease: diabetes and osteoporosis: cause for concern? Eur J Endocrinol. 2015;173:R93–9.CrossRefPubMed Starup-Linde J, Vestergaard P. Management of endocrine disease: diabetes and osteoporosis: cause for concern? Eur J Endocrinol. 2015;173:R93–9.CrossRefPubMed
5.
go back to reference Xu F, Dong Y, Huang X, et al. Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes. Mol Med Rep. 2014;10:1935–41.CrossRefPubMed Xu F, Dong Y, Huang X, et al. Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes. Mol Med Rep. 2014;10:1935–41.CrossRefPubMed
7.
go back to reference Bridges MJ, Moochhala SH, Barbour J, Kelly CA. Influence of diabetes on peripheral bone mineral density in men: a controlled study. Acta Diabetol. 2005;42:82–6.CrossRefPubMed Bridges MJ, Moochhala SH, Barbour J, Kelly CA. Influence of diabetes on peripheral bone mineral density in men: a controlled study. Acta Diabetol. 2005;42:82–6.CrossRefPubMed
8.
go back to reference Wakasugi M, Wakao R, TawataM,Gan N, Koizumi K,Onaya T Bone mineral density measured by dual energy x-ray absorptiometry in patients with non-insulin-dependent diabetes mellitus Bone1993;14:29–33. Wakasugi M, Wakao R, TawataM,Gan N, Koizumi K,Onaya T Bone mineral density measured by dual energy x-ray absorptiometry in patients with non-insulin-dependent diabetes mellitus Bone1993;14:29–33.
9.
go back to reference Perez-Castrillon JL, De Luis D, Martin-EscuderoJC,Asensio T, del Amo R, Izaola O. Non-insulin-dependent diabetes, bone mineral density, and cardiovascular risk factors. J Diabetes Complicat 2004;18:317–321. Perez-Castrillon JL, De Luis D, Martin-EscuderoJC,Asensio T, del Amo R, Izaola O. Non-insulin-dependent diabetes, bone mineral density, and cardiovascular risk factors. J Diabetes Complicat 2004;18:317–321.
10.
go back to reference Evans AL, Paggiosi MA, Eastell R, Walsh JS. Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood. J Bone Miner Res. 2015;30:920–8.CrossRefPubMed Evans AL, Paggiosi MA, Eastell R, Walsh JS. Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood. J Bone Miner Res. 2015;30:920–8.CrossRefPubMed
12.
go back to reference Rosen CJ, Chesnut CH, Mallinak NJ. The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement or calcium supplementation. J Clin Endocrinol Metab. 1997; https://doi.org/10.1210/jcem.82.6.4004. Rosen CJ, Chesnut CH, Mallinak NJ. The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement or calcium supplementation. J Clin Endocrinol Metab. 1997; https://​doi.​org/​10.​1210/​jcem.​82.​6.​4004.
14.
go back to reference Oz SG, Guven GS, Kilicarslan A, Calik N, Beyazit Y, Sozen T. Evaluation of bone metabolism and bone mass in patients with type-2 diabetes mellitus. J Natl Med Assoc. 2006;98:1598–604.PubMedPubMedCentral Oz SG, Guven GS, Kilicarslan A, Calik N, Beyazit Y, Sozen T. Evaluation of bone metabolism and bone mass in patients with type-2 diabetes mellitus. J Natl Med Assoc. 2006;98:1598–604.PubMedPubMedCentral
16.
go back to reference Wang Y, Li YP, Paulson C, et al. Wnt and the Wnt signaling pathway in bone development and disease. In: Landmark Ed.Front Biosci; 2014. p. 379-407 Wang Y, Li YP, Paulson C, et al. Wnt and the Wnt signaling pathway in bone development and disease. In: Landmark Ed.Front Biosci; 2014. p. 379-407
18.
go back to reference Hie M, Iitsuka N, Otsuka T, et al. Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation. Int J Mol Med. 2011;28:455–62.PubMed Hie M, Iitsuka N, Otsuka T, et al. Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation. Int J Mol Med. 2011;28:455–62.PubMed
19.
go back to reference Gaudio A, Privitera F, Battaglia K, et al. Sclerostin levels associated with inhibition of the Wnt/β-catenin signaling and reduced bone turnover in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012;97:3744–50.CrossRefPubMed Gaudio A, Privitera F, Battaglia K, et al. Sclerostin levels associated with inhibition of the Wnt/β-catenin signaling and reduced bone turnover in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012;97:3744–50.CrossRefPubMed
20.
go back to reference García-Martín A, Rozas-MorenoP, Reyes-García R, et al. Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012;97:234–41. García-Martín A, Rozas-MorenoP, Reyes-García R, et al. Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012;97:234–41.
21.
go back to reference Lin CL, Wang JY, Ko JY, Huang YT, Kuo YH, Wang FS. Dickkopf-1 promotes hyperglycemia-induced accumulation of mesangial matrix and renal dysfunction. J Am Soc Nephrol. 2010;21:124–35.CrossRefPubMedPubMedCentral Lin CL, Wang JY, Ko JY, Huang YT, Kuo YH, Wang FS. Dickkopf-1 promotes hyperglycemia-induced accumulation of mesangial matrix and renal dysfunction. J Am Soc Nephrol. 2010;21:124–35.CrossRefPubMedPubMedCentral
22.
go back to reference Garcia-Martín A, Reyes-Garcia R, García-Fontana B, et al. Relationship of Dickkopf1 (DKK1) with cardiovascular disease and bone metabolism in caucasian type 2 diabetes mellitus. PLoS One. 2014;9:e111703.CrossRefPubMedPubMedCentral Garcia-Martín A, Reyes-Garcia R, García-Fontana B, et al. Relationship of Dickkopf1 (DKK1) with cardiovascular disease and bone metabolism in caucasian type 2 diabetes mellitus. PLoS One. 2014;9:e111703.CrossRefPubMedPubMedCentral
23.
go back to reference Gaudio A, Privitera F, Pulvirenti I, Canzonieri E, Rapisarda R, Fiore CE. The relationship between inhibitors of the Wntsignalling pathway (sclerostin and Dickkopf-1) and carotid intima-media thickness in postmenopausal women with type 2 diabetes mellitus. DiabVasc Dis Res. 2014;11:48–52.CrossRef Gaudio A, Privitera F, Pulvirenti I, Canzonieri E, Rapisarda R, Fiore CE. The relationship between inhibitors of the Wntsignalling pathway (sclerostin and Dickkopf-1) and carotid intima-media thickness in postmenopausal women with type 2 diabetes mellitus. DiabVasc Dis Res. 2014;11:48–52.CrossRef
24.
go back to reference Ndip A, Williams A, Jude EB, et al. The RANKL/RANK/OPG signaling pathway mediates medial arterial calcification in diabetic Charcot neuroarthropathy. Diabetes. 2011;60:2187–96.CrossRefPubMedPubMedCentral Ndip A, Williams A, Jude EB, et al. The RANKL/RANK/OPG signaling pathway mediates medial arterial calcification in diabetic Charcot neuroarthropathy. Diabetes. 2011;60:2187–96.CrossRefPubMedPubMedCentral
26.
go back to reference Consensus statement: Report and recommendations of the San Antonio conference on diabetic neuropathy. American Diabetes Association American Academy of Neurology. Diabetes Care. 1988;11:592–7. Consensus statement: Report and recommendations of the San Antonio conference on diabetic neuropathy. American Diabetes Association American Academy of Neurology. Diabetes Care. 1988;11:592–7.
27.
go back to reference D'Amelio P, Spertino E, Martino F, Isaia GC. Prevalence of postmenopausal osteoporosis in Italy and validation of decision rules for referring women for bone densitometry. Calcif Tissue Int. 2013;92:437–43.CrossRefPubMed D'Amelio P, Spertino E, Martino F, Isaia GC. Prevalence of postmenopausal osteoporosis in Italy and validation of decision rules for referring women for bone densitometry. Calcif Tissue Int. 2013;92:437–43.CrossRefPubMed
28.
go back to reference Kerkeni S, Kolta S, Fechtenbaum J, Roux C. Spinal deformity index (SDI) is a good predictor of incident vertebral fractures. Osteoporos Int. 2009;20:1547–52.CrossRefPubMed Kerkeni S, Kolta S, Fechtenbaum J, Roux C. Spinal deformity index (SDI) is a good predictor of incident vertebral fractures. Osteoporos Int. 2009;20:1547–52.CrossRefPubMed
29.
go back to reference Silva BC, Leslie WD, Resch H, et al. Trabecular bone score: a noninvasive analytical method based upon the DXA image. Bone Miner Res. 2014;29:518–30.CrossRef Silva BC, Leslie WD, Resch H, et al. Trabecular bone score: a noninvasive analytical method based upon the DXA image. Bone Miner Res. 2014;29:518–30.CrossRef
30.
go back to reference D'Amelio P, Cristofaro MA, Grimaldi A, et al. The role of circulating bone cell precursors in fracture healing. Calcif Tissue Int. 2010;86:463–9.CrossRefPubMed D'Amelio P, Cristofaro MA, Grimaldi A, et al. The role of circulating bone cell precursors in fracture healing. Calcif Tissue Int. 2010;86:463–9.CrossRefPubMed
31.
go back to reference Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S. Circulating osteoblast-lineage cells in humans. N Engl J Med. 2005;352:1959–66.CrossRefPubMed Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S. Circulating osteoblast-lineage cells in humans. N Engl J Med. 2005;352:1959–66.CrossRefPubMed
32.
go back to reference D'Amelio P, Tamone C, Sassi F, et al. Teriparatide increases the maturation of circulating osteoblast precursors. Osteoporos Int. 2012;23:1245–53.CrossRefPubMed D'Amelio P, Tamone C, Sassi F, et al. Teriparatide increases the maturation of circulating osteoblast precursors. Osteoporos Int. 2012;23:1245–53.CrossRefPubMed
33.
go back to reference Jackson AS, Pollock ML, Ward A. Generalized equations for predicting body density of women. Med Sci Sports Exerc. 1980;12:175–81.PubMed Jackson AS, Pollock ML, Ward A. Generalized equations for predicting body density of women. Med Sci Sports Exerc. 1980;12:175–81.PubMed
34.
go back to reference Choi YJ, Ock SY, Chung YS. Trabecular bone score (TBS) and TBS-adjusted fracture risk assessment tool are potential supplementary tools for the discrimination of morphometric vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Densitom. 2016; https://doi.org/10.1016/j.jocd.2016.04.001. Choi YJ, Ock SY, Chung YS. Trabecular bone score (TBS) and TBS-adjusted fracture risk assessment tool are potential supplementary tools for the discrimination of morphometric vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Densitom. 2016; https://​doi.​org/​10.​1016/​j.​jocd.​2016.​04.​001.
35.
go back to reference Purnamasari D, Puspitasari MD, Setiyohadi B, Nugroho P, Isbagio H. Low bone turnover in premenopausal women with type 2 diabetes mellitus as an early process of diabetes-associated bone alterations: a cross-sectional study. BMC Endocr Disord. 2017; https://doi.org/10.1186/s12902-017-0224-0. Purnamasari D, Puspitasari MD, Setiyohadi B, Nugroho P, Isbagio H. Low bone turnover in premenopausal women with type 2 diabetes mellitus as an early process of diabetes-associated bone alterations: a cross-sectional study. BMC Endocr Disord. 2017; https://​doi.​org/​10.​1186/​s12902-017-0224-0.
36.
go back to reference Armstrong ME, Cairns BJ, Banks E, Green J, Reeves GK, Beral V. Different effects of age, adiposity and physical activity on the risk of ankle, wrist and hip fractures in postmenopausal women. Bone. 2012;50:1394–400.CrossRefPubMedPubMedCentral Armstrong ME, Cairns BJ, Banks E, Green J, Reeves GK, Beral V. Different effects of age, adiposity and physical activity on the risk of ankle, wrist and hip fractures in postmenopausal women. Bone. 2012;50:1394–400.CrossRefPubMedPubMedCentral
37.
go back to reference De Laet C, Kanis JA, Oden A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int. 2005;16:1330–8.CrossRefPubMed De Laet C, Kanis JA, Oden A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int. 2005;16:1330–8.CrossRefPubMed
38.
go back to reference Prieto-Alhambra D, Premaor MO, Fina Aviles F, et al. The association between fracture and obesity is site-dependent: a population-based study in postmenopausal women. J Bone Miner Res. 2012;27:294–300.CrossRefPubMed Prieto-Alhambra D, Premaor MO, Fina Aviles F, et al. The association between fracture and obesity is site-dependent: a population-based study in postmenopausal women. J Bone Miner Res. 2012;27:294–300.CrossRefPubMed
39.
go back to reference Colaianni G, Brunetti G, Faienza MF, Colucci S, Grano M. Osteoporosis and obesity: role of Wnt pathway in human and murine models. World J Orthop. 2014;5:242–6.CrossRefPubMedPubMedCentral Colaianni G, Brunetti G, Faienza MF, Colucci S, Grano M. Osteoporosis and obesity: role of Wnt pathway in human and murine models. World J Orthop. 2014;5:242–6.CrossRefPubMedPubMedCentral
40.
go back to reference Isaia GC, D'Amelio P, Di Bella S, Tamone C. Is leptin the link between fat and bone mass? J Endocrinol Invest. 2005;28Suppl 10:61–5. Isaia GC, D'Amelio P, Di Bella S, Tamone C. Is leptin the link between fat and bone mass? J Endocrinol Invest. 2005;28Suppl 10:61–5.
41.
go back to reference Kim JH, Choi HJ, Ku EJ, et al. Trabecular bone score as an indicator for skeletal deterioration in diabetes. J ClinEndocrinol Metab. 2015;100:475–82.CrossRef Kim JH, Choi HJ, Ku EJ, et al. Trabecular bone score as an indicator for skeletal deterioration in diabetes. J ClinEndocrinol Metab. 2015;100:475–82.CrossRef
42.
go back to reference Xu J, Yue F, Wang J, Chen L, Qi W. High glucose inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation via downregulation of v-ATPase V0 subunit d2 and dendritic cell-specific transmembrane protein. Mol Med Rep. 2015;11:865–70.CrossRefPubMed Xu J, Yue F, Wang J, Chen L, Qi W. High glucose inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation via downregulation of v-ATPase V0 subunit d2 and dendritic cell-specific transmembrane protein. Mol Med Rep. 2015;11:865–70.CrossRefPubMed
43.
go back to reference Christman MA, Goetz DJ, Dickerson E, et al. Wnt5a is expressed in murine and human atherosclerotic lesions. Am J Physiol Heart Circ Physiol. 2008;294:H2864–70.CrossRefPubMed Christman MA, Goetz DJ, Dickerson E, et al. Wnt5a is expressed in murine and human atherosclerotic lesions. Am J Physiol Heart Circ Physiol. 2008;294:H2864–70.CrossRefPubMed
47.
48.
go back to reference Kalem MN, Kalem Z, Akgun N, Bakırarar B. The relationship between postmenopausal women's sclerostin levels and their bone density, age, body mass index, hormonal status, and smoking and consumption of coffee and dairy products. Arch Gynecol Obstet. 2017; https://doi.org/10.1007/s00404-017-4288-x. Kalem MN, Kalem Z, Akgun N, Bakırarar B. The relationship between postmenopausal women's sclerostin levels and their bone density, age, body mass index, hormonal status, and smoking and consumption of coffee and dairy products. Arch Gynecol Obstet. 2017; https://​doi.​org/​10.​1007/​s00404-017-4288-x.
52.
go back to reference D'Amelio P, Grimaldi A, Di Bella S, et al. Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone. 2008;43:92–100.CrossRefPubMed D'Amelio P, Grimaldi A, Di Bella S, et al. Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone. 2008;43:92–100.CrossRefPubMed
Metadata
Title
Type 2 diabetes affects bone cells precursors and bone turnover
Authors
Francesca Sassi
Ilaria Buondonno
Chiara Luppi
Elena Spertino
Emanuela Stratta
Marco Di Stefano
Marco Ravazzoli
Gianluca Isaia
Marina Trento
Pietro Passera
Massimo Porta
Giovanni Carlo Isaia
Patrizia D’Amelio
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2018
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-018-0283-x

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