Osteoporose bei Typ-1-und Typ-2-Diabetes mellitus

Zusammenfassung

Diabetes mellitus und Osteoporose sind häufige Erkrankungen. Deshalb gibt es viele Patienten, die an beiden Krankheiten gleichzeitg leiden. Darüber hinaus stellt jedoch sowohl der Typ-1-als auch der Typ-2-Diabetes mellitus jeweils eine prädisponierende Erkrankung dar, die das Risiko für Osteoporose und Frakturen erhöht. Dabei ist das Risiko bei Typ-1-Diabetes mellitus stärker ausgeprägt, während bei Diabetes mellitus Typ 2 vor allem Patienten mit längerer Krankheitsdauer, schlechter Stoffwechsellage, Insulinpflichtigkeit und vaskulären Folgeschäden frakturgefährdet sind. Die Knochendichte ist bei Typ-1-Diabetes mellitus erniedrigt, während insbesondere adipöse Typ-2-Diabetes-Patienten auch höhere Knochendichtewerte aufweisen können. Das Fraktur-risiko wird nicht nur durch Veränderungen der Knochendichte und der Knochenarchitektur erhöht, sondern auch durch veränderte Knochenmaterialeigenschaften (veränderte Kollagen-Quervernetzung). Pathogenetische Faktoren sind Hyperglykämie, hormonelle Veränderungen, und der Einfluss von oralen Antidiabetika. Während Inkretine und DPP-4-Hemmer das Frakturrisiko zu senken scheinen, sind Glitazone mit höherem Risiko assoziiert. Auch SGLT-2-Hemmer könnten bei eingeschränkter Nierenfunktion mit einem höheren Frakturrisiko behaftet sein. Die Therapie der Osteoporose bei Diabetes mellitus unterscheidet sich nicht vom Vorgehen bei primärer Osteoporose. Die Effizienz von antiresorptiven Medikamenten wird nicht durch Diabetes mellitus beeinflusst.

Summary

Diabetes mellitus and osteoporosis occur with high prevalence. Therefore, there are many patients suffering from both diseases. However, both diabetes mellitus type 1 and type 2 are predisposing risk factors leading to a disease-associated increase in osteo porosis and fractures. Diabetes mellitus type 1 causes a marked increase in fracture risk, whereas in Diabetes mellitus type 2 fracture risk is dependent on disease duration, bad metabolic state, insulin therapy and vascular complications. Bone mineral density is decreased in diabetes mellitus type 1, whereas an increased mineral density may be found in type 2, especially when obesity is present. Fracture risk is related to bone mineral density and bone architecture, but also influenced by bone material quality like altered collagen crosslinking. Pathogenic factors are hyperglycaemia, hormonal changes, and the influence of oral antidiabetic drugs. Incretins (glucagon-like-peptides) and DPP-4-inhibitors seem to decrease the fracture risk, whereas glitazones increase the fracture risk. SGLT-2-inhibitors could be associated with an increased fracture risk in patients with impaired renal function. The treatment of osteoporosis in patients with diabetes mellitus is not different from the management of idiopathic osteoporosis. The efficacy of anti-resorptive treatment is not diminished by diabetes mellitus.

Schlüsselwörter

Diabetes mellitus - sekundäre Osteoporose - Frakturrisiko

Keywords

Diabetes mellitus - secondary osteoporosis - fracture risk

• Literatur

• 1 Neumann T. Knochenstoffwechsel, Umbaumarker und Diabetes. Osteologie 2014; 23: 91-96.
• 2 Janghorbani M, Van Dam RM, Willet WC. et al. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 2007; 166: 495-505.
• 3 Vestergaard P, Rejnmark L, Mosekilde L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 2005; 48: 1292-1299.
• 4 Zhukouskaya VV, Eller-Vainicher C, Vadzianava VV. et al. Prevalence of morphometric vertebral fractures in patients with type 1 diabetes. Diabetes Care 2013; 36: 1635-1640.
• 5 Hothersall EJ, Livingstone SJ, Looker HC. et al. Contemporary Risk of Hip Fracture in Type 1 and Type 2 Diabetes: A National Registry Study from Scotland. J Bone Miner Res 2014; 29: 1054-1060.
• 6 Dachverband deutschsprachiger osteologischer Fachgesellschaften (DVO). S3-Leitlinie Osteoporose. www.dv-osteologie.org.
• 7 Wyers CE, Vranken L, van der Velde RY. et al. Cardiovascular Risk Factor Analysis in Patients with a Recent Clinical Fracture at the Fracture Liaison Service. BioMed Research International 2014; 2014: 710945 doi: 10.1155/2014/710945. Epub 2014 Aug 27.
• 8 Jung JK, Kim HJ, Lee HK. et al. Fracture Incidence and Risk of Osteoporosis in Female Type 2 Diabetic Patients in Korea. Diabetes Metab J 2012; 36: 144.
• 9 Forsen L, Meyer HE, Midthjell K, Edna TH. Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trondelag Health Survey. Diabetologia 1999; 42: 920.
• 10 Napoli N, Strotmeyer ES, Ensrud KE. et al. Fracture risk in diabetic elderly men: the MrOS study. Diabetologia 2014; 57: 2057-2065.
• 11 Wallander M, Axelsson KF, Nilsson AG. et al. Type 2 Diabetes and Risk of Hip Fractures and Non-Skeletal Fall Injuries in the Elderly: A Study From the Fractures and Fall Injuries in the Elderly Cohort (FRAILCO). J Bone Miner Res 2017; 32: 449-460.
• 12 Botolin S, McCabe LR. Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. Journal of Cellular Biochemistry 2006; 99: 411-424.
• 13 Hough FS, Pierroz DD, Cooper C, Ferrari SL. and the IOF CSA Bone and Diabetes Working Group. European Journal of Endocrinology. 2016; 174: R127-R138.
• 14 Vashishth D, Gibson GJ, Khoury JI. et al. Influence of Nonenzymatic Glycation on Biomechanical Properties of Cortical Bone. Bone 2001; 28: 195-201.
• 15 Schwartz A, Garnero P. Hi Pentosidine and increased fracture risk in older adults with type 2 diabetes. J Clin Endocrinol Metab 2009; 94: 2380-2386.
• 16 Li C-I, Liu C-S, Lin W-Y. 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 Miner Res 2015; 30: 1338-1346.
• 17 Lee NK, Sowa H, Hinoi E. et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456-469.
• 18 Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates b cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. PNAS 2008; 105: 5266-5270.
• 19 Pittas AG, Harris SS, Eliades M. et al. Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 2009; 94: 827-832.
• 20 Levinger I, Jerums G, Stepto NK. et al. The Effect of Acute Exercise on Undercarboxylated Osteocalcin and Insulin Sensitivity in Obese Men. J Bone Mineral Res 2014; 29: 2571-2576.
• 21 Ma H, Ma JX, Xue P. et al. Osteoblast proliferation is enhanced upon the insulin receptor substrate 1 overexpression via PI3K signaling leading to down-regulation of NFkB and BAX Pathway. Exp Clin Endocrinol Diabetes 2015; 123: 126-131.
• 22 Turner RT, Kalra SP, Wong CP. et al. Peripheral Leptin Regulates Bone Formation. Journal of Bone and Mineral Research 2013; 28: 22-34.
• 23 Srikanthan P, Crandall CJ, Miller-Martinez D. et al. Insulin Resistance and Bone Strength: Findings From the Study of Midlife in the United States. J Bone Miner Res 2014; 29: 796-803.
• 24 Goulding A, Taylor RW. Plasma leptin values in relation to bone mass and densitiy and to dynamic biochemical markers of bone resorption and formation in postmenopausal women. Calcif Tissue Int 1998; 63: 456-458.
• 25 Lacombe J, Cairns BJ, Green J. et al., for the Million Women Study collaborators. The effects of age, adiposity, and physical activity on the risk of seven site-specific fractures in postmenopausal women. J Bone Miner Res 2016; 31: 1559-1568.
• 26 Ishii S, Cauley JA, Greendale GA, Nielsen C. et al. Pleiotropic Effects of Obesity on Fracture Risk: The Study of Women´s Health Across the Nation. J Bone Miner Res 2014; 29: 2561-2570.
• 27 Johansson H, Kanis JA, Oden A. et al. A Meta-Analysis of the association of fracture risk and body mass index in women. J Bone Miner Res 2014; 29: 223-233.
• 28 Scharla SH, Lempert UG. 25-hydroxyvitamin D and Vitamin D-Binding Protein (DBP) in patients with obesity and diabetes mellitus type 2. DGE-Tagung. 2016 Poster, URN:urn.nbn:de:101:1-201604282025.
• 29 Kadowaki S, Norman AW. Dietary vitamin D is essential for normal insulin secretion from the perfused rat pancreas. J Clin Invest 1984; 73: 759-766.
• 30 Chiu KC, Chu A, Go VLW, Saad MF. Hypovitaminosis D is associated with insulin resistance and b cell dysfunction. Am J Clin Nutr 2004; 79: 820-825.
• 31 Pittas AG, Dawson-Hughes B, Sun Q. et al. Plasma 25-Hydroxyvitamin D Concentration and Risk of Incident Type 2 Diabetes in Women. Diabetes Care 2010; 33: 2021-2023.
• 32 Gagnon C, Daly RM, Carpentier A. et al. Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion, Insulin Sensitivity and b-Cell Function in multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized, Placebo-Controlled Trial. PLOS ONE 2014; 09: e109607.
• 33 Karamali M, Ashrafi M, Razavi M. et al. The Effects of Calcium, Vitamins D and K co-Supplementation on Markers of Insulin Metabolism and Lipid Profiles in Vitamin D-Deficient Women with Poycystic Ovary Syndrome. Exp Clin Endocrinol Diabetes 2017; 125: 316-321.
• 34 Jorde R, Sollid ST, Svartberg J. et al. Vitamin D 20 000 IU per week for five years does not prevent progression from prediabetes to diabetes. J Clin Endocrinol Metab 2016; 101: 1647-1655.
• 35 Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2014; 02: 76-89.
• 36 Chandran M. Diabetes Drug Effects on the Skeleton. Calcif Tissue Int 2017; 100: 133-149.
• 37 Henriksen DB, Alexandersen P, Hartmann B. et al. Bone. 2009; 45: 833-842.
• 38 Monami M, Antenore A, Dicembrini I. et al. Dipeptidyl Peptidase-4 Inhibitors and Bone Fractures. A meta-analysis of randomized clinical trials. Diab Care 2011; 34: 2474-2476.
• 39 Driessen JH, van Onzenoort HA, Henry RM. et al., Use of dipeptidyl peptidase-4 inhibitors for type 2 diabetes mellitus and risk of fracture. Bone. 2014; 68: 124-130.
• 40 Dombrowski S, Kostev K, Jacob L. Use of dipeptidyl peptidase-4 inhibitors and risk of bone fracture in patients with type 2 diabetes in Germany – A retrospective analysis of real-world data. Osteo-poros Int 2017; 28: 2421-2428.
• 41 Kohan DE, Fioretto P, Tang W, List JF. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney International 2014; 85: 962-971.
• 42 Wanner C, Toto R, Gerich J. No increase in Bone Fractures with Empagliflozin (EMPA) in a Pooled Analysis of More Than 11,000 Patients with Type 2 Diabetes (T2DM). Kidney Week. 2013 46^th Ann Mtg of the American Society of Nephrology, Atlanta, 5-10 Nov 2013 (Poster).
• 43 Hadjidakis DJ, Raptis AE, Sfakianakis M. et al. Bone mineral density of both genders in Type 1 diabetes according to bone composition. Journal of Diabetes and its complications 2006; 20: 302-307.
• 44 Hadjidakis D, Androulakis II, 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.
• 45 Farr JN, Drake MT, Amin S. et al. In Vivo Assessment of Bone Quality in Postmenopausal Women With Type 2 Diabetes. J Bone Miner Res 2014; 29: 787.
• 46 Jepsen KJ, Schlecht SH. Biomechanical Mechanisms: Resolving the Apparent Conundrum of Why Individuals Tith Type II Diabetes Show Increased Fracture Incidence Despite Having Normal BMD. J Bone Miner Res 2014; 29: 784-786.
• 47 Rozadilla A, Nolla JM, Montana E. et al. Bone mineral density in patients with type 1 diabetes mellitus. Joint Bone Spine 2000; 67: 215-218.
• 48 Vestergaard P, Rejnmark L, Mosekilde L. Are antiresorptive drugs effective against fractures in patients with diabetes?. Calcif Tissue Int 2011; 88: 209-214.