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Exp Clin Endocrinol Diabetes 2017; 125(04): 213-217
DOI: 10.1055/s-0042-123036
Review
© Georg Thieme Verlag KG Stuttgart · New York

Diabetes Mellitus and Bone Metabolism

Christian Kasperk
1   Medizinische Universitätsklinik Heidelberg, Abteilung Innere Medizin I und Klinische Chemie, INF, Heidelberg
,
Carmen Georgescu
4   Department of Endocrinology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Rumänien
,
Peter Nawroth
1   Medizinische Universitätsklinik Heidelberg, Abteilung Innere Medizin I und Klinische Chemie, INF, Heidelberg
2   Helmholtz Zentrum München, German Research Center for Environmental Health, Institute for Diabetes and Cancer, Ingolstädter Landstraße, Neuherberg
3   Deutsches Diabetes Zentrum (DDZ), an der Heinrich Heine Universität Düsseldorf, Auf’m Hennekamp, Düseldorf
› Author Affiliations
Further Information

Publication History

received 19 July 2016
first decision 12 October 2016

accepted 02 December 2016

Publication Date:
10 January 2017 (online)

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Abstract

Diabetes mellitus and bone metabolism affect mesenchymal tissues and have numerous epidemiological and pathophysiological associations in common. Diabetes mellitus affects bone metabolism and increases fracture risk. The pathophysiological mechanims how type 1 and type 2 diabetes impair bone metabolism and bone strength may differ which is outlined in this review. Direct metabolic effects in additon to centrally controlled endocrine loops exert suppressive effects on bone formation and may also stimulate bone Resorption. Decreased bone formation in combination with increased bone resorption strongly increases fracture risk.

Key words

bone - fracture risk - energy metabolism - Diabetes<Autoimmunity - osteoporosis
 

  • References

  • 1 Yang W, Dall TM, Halder P et al. American diabetes association: economic costs of diabetes in the US in 2012. Diabetes Care 2013; 36: 1033-1046
    CrossrefPubMedGoogle Scholar
  • 2 von der Recke P, Hansen MA, Hassager C. The association between low bone mass at the menopause and cardiovascular mortality. Am J Med 1999; 106: 273-278
    CrossrefPubMedGoogle Scholar
  • 3 Center JR, Nguyen TV, Schneider D et al. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 1999; 353: 878-882
    CrossrefPubMedGoogle Scholar
  • 4 Naves M, Rodriquez-Garcia M, Diaz-Lopez JB et al. Progression of vascular calcification is associated with greater bone loss and increased bone fractures. Osteoporosis International 2008; 19: 1161-1166
    CrossrefPubMedGoogle Scholar
  • 5 Kuro-o M, Matsumura Y, Aizawa H et al. Nabeshima Yi Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997; 390: 45-51
    CrossrefPubMedGoogle Scholar
  • 6 Abrahamsen B, van Staa T, Ariely R et al. Excess mortality following hip fracture: a systematic epidemiological review. Osteoporosis International 2009; 20: 1633-1650
    CrossrefPubMedGoogle Scholar
  • 7 Li C, Liu C, Lin W et al. Glycated hemoglobin level and risk of hip fracture in older people with type 2 diabetes: a competing risk analysis of Taiwan diabetes cohort study. J Bone Min Res 2015; 30: 1338-1346
    CrossrefPubMedGoogle Scholar
  • 8 Melton LJ, Leibson CL, Achenbach SJ et al. Fracture risk in type 2 Diabetes: update of a population based study. JBMR 2008; 23: 1334-1342
    CrossrefPubMedGoogle Scholar
  • 9 Schneider ALC, Williams EK, Brancati FL et al. Diabetes and risk of fracture related hospitalization: t he atherosclerosis risk in communities study. Diabetes Care 2013; 36: 1153-1158
    CrossrefPubMedGoogle Scholar
  • 10 Joshi A, Varthakavi P, Chadha M et al. A study of bone mineral density and its determinants in type 1 diabetes mellitus. J Osteoporosis 2013 article ID 397814
    PubMed
  • 11 Wedrychowicz A, Stec M, Sztefko K et al. Associations between bone, fat tissie and metabolic control in children and adolescents with type 1 diabetes mellitus. Exp Clin Endocrinol Diabetes 2014; 122: 491-495
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Thrailkill KM, Lumpkin CK, Bunn RC et al. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab 2005; 289: E735-E745
    CrossrefPubMedGoogle Scholar
  • 13 Melton LJ, Riggs BL, Leibson CL et al. A bone structural basis for fracture risk in diabetes. JCEM 2008; 93: 4804-4809
    CrossrefPubMedGoogle Scholar
  • 14 Hadjidakis D, Androulakis I, Mylonakis AM et al. Diabetes in postmenopause: different influence on bone mass according to age and disease duration. Exp Clin Endocrinol Diabetes 2009; 117: 199-204
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Ma L, Oei L, Jiang L et al. Association between bone mineral density and type 2 diabetes mellitus: a meta analysis of observational studies. Eur J Epidemiol 2012; 27: 319-332
    CrossrefPubMedGoogle Scholar
  • 16 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 Endocrinology Metabolism 2006; 91: 3404-3410
    PubMedGoogle Scholar
  • 17 Janghorbani M, van Dam RM, Willett WC et al. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 2007; 166: 495-505
    CrossrefPubMedGoogle Scholar
  • 18 Dytfeld J, Michalak M. Type 2 diabetes and risk of low enrgy fractures in postmenopausal women: meta-analysis of observational studies. Aging Clin Exp Res 2016 online
    PubMed
  • 19 Schwartz A, Vittinghoff E, Bauer DC et al. Assiciation of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 2011; 305: 2184-2192
    CrossrefPubMedGoogle Scholar
  • 20 Oei L, Zillikens MC, Dehghan A et al. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control. Diabetes Care 2013; 36: 1619-1628
    CrossrefPubMedGoogle Scholar
  • 21 Burghardt AJ, Issever AS, Schwartz AV et al. High resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. JCEM 2010; 95: 5045-5055
    CrossrefPubMedGoogle Scholar
  • 22 Yeni YN, Brown CU, Wang Z et al. The influence of boen morphology on fracture toughness of the femur and tibia. Bone 1997; 21: 453-459
    CrossrefPubMedGoogle Scholar
  • 23 Barth RW, Williams JL, Kaplan FS. Osteon morphometry in females with femoral neck fractures. Clin Orthopaedics Rel Res 1992; 283: 178-186
    PubMedGoogle Scholar
  • 24 Roscher P, Rinnerthaler S, Yates J et al. Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 2001; 29: 185-191
    CrossrefPubMedGoogle Scholar
  • 25 Borah Dufresne T, Nurre J. et al. Risedronate reduces intracortical porosity in women with osteoporosis. JBMR 2010; 25: 41-47
    CrossrefPubMedGoogle Scholar
  • 26 Keegan THM, Schwartz AV, Bauer DC et al. Effect of alendronate on bone mineral density and biochemical markers of bone turnover in type 2 diabetic women: the fracture intervention trial. Diabetes Care 2004; 27: 1547-1553
    CrossrefPubMedGoogle Scholar
  • 27 Hernandez RK, Do TP, Critchlow CW et al. Patient related risk factors for fracture lealing complications in the United Kingdom General Practice Research Database. Acta Orthopaedica 2012; 83: 653-660
    CrossrefPubMedGoogle Scholar
  • 28 Farr JN, Drake MT, Amin S et al. In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. JBMR 2014; 29: 787-795
    CrossrefPubMedGoogle Scholar
  • 29 Tang SY, Allen MR, Philipps R et al. Changes in non-enzymatic glycation and its association with altered mechanical properties following 1 year treatment with risedronate or alendronate. Osteoporosis International 2009; 20: 887-894
    CrossrefPubMedGoogle Scholar
  • 30 Furst JR, Bandeira LC, Wen-Wei F et al. Advanced glycation endproducts and bone material strength in type 2 diabetes. JCEM 2016; 101: 2502-2510
    CrossrefPubMedGoogle Scholar
  • 31 Farlay D, Armas LA, Gineyts E et al. Nonenzymatic glycation and degree of mineralization are higher in bone from fractured patients with type 1 diabetes mellitus. J Bone Min Res 2016; 31: 190-196
    CrossrefPubMedGoogle Scholar
  • 32 Yamamoto M, Yamaguchi T, Yamauchi M et al. Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with Type 2 diabetes mellitus. J Clin Endocrinol Metab 2008; 93: 1013-1019
    CrossrefPubMedGoogle Scholar
  • 33 Schwartz AV, Garnero P, Hillier TA et al. Pentosidine and increased fracture risk in older adults with type 2 diabetes. JCEM 2009; 94: 2380-2386
    CrossrefPubMedGoogle Scholar
  • 34 Kume S, Kato S, Yamagishi S et al. Advanced glycation and products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage and bone. JBMR 2005; 20: 1647-1658
    CrossrefPubMedGoogle Scholar
  • 35 Avila C, Huang RJ, Stevens MV et al. Platelet mitochondrial dysfunction is evident in type 2 diabetes in association with modifications of mitochondrial anti-oxidant stress proteins. Exp Clin Endocrinol Diabetes 2012; 120: 248-251
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Schwartz AV, Sigurdsson S, Hue TF et al. Vertebral bone marrow fat associated with lower trabecular BMD and prevalent vertebral fracture in older adults. J Clin Endocrinol Metab 2013; 98: 2294-2300
    CrossrefPubMedGoogle Scholar
  • 37 Gennari L, Merlotti D, Valenti R et al. Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes. JCEM 2012; 97: 1737-1744
    CrossrefPubMedGoogle Scholar
  • 38 Dobnig H, Piswanger-Sölkner JC, Roth M et al. Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. JCEM 2006; 91: 3355-3363
    CrossrefPubMedGoogle Scholar
  • 39 Lee NK, Sowa H, Hinoi E et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456-469
    CrossrefPubMedGoogle Scholar
  • 40 Lee N, Karsenty G. Reciprocal regulation of bone and energy metabolism. Trends in Endocrinology and Metabolism 2008; 19: 161-166
    CrossrefPubMedGoogle Scholar
  • 41 Zhao L, Jiang H, Papasian CJ et al. Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. JBMR 2008; 23: 17-29
    PubMedGoogle Scholar
  • 42 Khan MP, Singh AK, Joharapurkar AA et al. Pathophysiological mechanism of bone loss in type 2 diabetes involves inverse regulation of osteoblast function by PGC-1alpha and skeletal muscle atrogens: AdipoR1 as potential target for reversing diabetes induced osteopenia. Diabetes 2015; 64: 2609-2623
    CrossrefPubMedGoogle Scholar
  • 43 Liang H, Ward WF. PBGC-1alpha: a key regulator of energy metabolism. Adv Physiol Educ 2006; 30: 145-151
    CrossrefPubMedGoogle Scholar
  • 44 Hara K, Hirowatari Y, Shimura Y et al. Sserotonin levels in platelet poor plasma and whole blood in people with type 2 diabetes with chronic kidney disease. Diabetes Res Clin Pract 2011; 94: 167-171
    CrossrefPubMedGoogle Scholar
  • 45 Rosen C. Serotonin rising – the bone, brain, bowel connection. NEJM 2009; 360: 957-959
    CrossrefPubMedGoogle Scholar
  • 46 Ducy P, Karsenty G. The two faces of serotonin in bone biology. J Cell Biol 2010; 191: 7-13
    CrossrefPubMedGoogle Scholar
  • 47 Karsenty G, Oury F. The central regulation of bone mass, the first link between bone remodeling and enrgy metabolism. JCEM 2010; 95: 4795-4801
    CrossrefPubMedGoogle Scholar
  • 48 Chen XX, Yang T. Roles of leptin in bone metabolism and bone diseases. J Bone Min Metab 2015; 33: 474-485
    CrossrefPubMedGoogle Scholar
  • 49 Moerman EJ, Teng K, Lipschitz DA et al. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-y2 transcription factor and TGFß/BMP signaling pathways. Agin Cell 2004; 3: 379-389
    PubMedGoogle Scholar
  • 50 Justesen J, Stenderup K, Ebbesen EN et al. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2001; 2: 165-171
    CrossrefPubMedGoogle Scholar