Diabetes mellitus und Osteoporose

Zusammenfassung

Zahlreiche Studien belegen eine Assoziation der beiden großen Volkskrankheiten Diabetes mellitus und Osteoporose. Während bei Patienten mit Typ-1-Diabetes meist eine verminderte Knochendichte nachweisbar ist, weisen Typ-2-Diabetiker oft eine normale oder erhöhte Knochendichte auf. Bei beiden Formen des Diabetes mellitus scheint die Knochenbrüchigkeit der jeweils vorhandenen Knochenmasse jedoch erhöht. Eine gesteigerte Frakturgefährdung sowohl für Typ 1 als auch Typ 2 ist in Metaanalysen gut dokumentiert. Normale bis erhöhte Knochendichtewerte bei Typ-2-Diabetikern verzerren jedoch das Frakturrisikoprofil bei alleiniger Betrachtung der DXA-Messung, so dass ein vermehrtes Bewusstsein für Frakturen als Manifestation einer gestörten Knochenqualität notwendig ist. Verantwortliche Faktoren für das erhöhte Frakturrisiko können u. a. das Fehlen osteoanaboler Effekte durch Mangel an Insulin und anderer osteoanaboler Substanzen (z. B. IGF-1, Amylin, etc.) sein, eine vermehrte Bildung von Advanced Glycation End Products (AGE) sowie mikrovaskuläre und neuro pathische Komplikationen. Das Frakturrisiko insbesondere älterer Diabetiker ist zudem durch die erhöhte Sturzneigung bei Vorliegen diabetischer Sekundärkomplikationen gesteigert.

Summary

Numerous studies show an association between diabetes mellitus and osteoporosis. While low bone mineral density (BMD) is consistently observed in type 1 diabetes, patients with type 2 diabetes often show normal or increased BMD. Yet, both type 1 and type 2 diabetes are associated with a higher risk of fractures. Normal or increased BMD in type 2 diabetes may by misleading when judging the risk of fracture merely by DXA-scan. Increased awareness of altered bone quality as an underlying cause of fractures is necessary. Lack of insulin and other osteoanabolic factors (e. g. IGF-1, amylin), increased concentrations of AGE as well as microangiopathy and neuropathy may contribute to the increased fracture risk. In older patients with diabetes mellitus, the elevated fracture risk is additionally attributable to the higher risk of falling especially when secondary diabetic complications are present.

Schlüsselwörter

Diabetes mellitus - Osteoporose - Frakturen

Keywords

Diabetes mellitus - osteoporosis - fractures

• Literatur

• 1 Albright F, Reifenstein EC. Bone development in diabetic children: a roentgen study. Am J Med Sci 1948; 174: 313-319.
• 2 Kemink SA, Hermus AR, Swinkels LM. et al. Osteopenia in insulin-depent diabetes mellitus; prevalence and aspects of pathophysiology. J Endocrinol Invest 2000; 23: 295-303.
• 3 Vestergaard P. Discrepancies in bone mineral density and fracture risk in type 1 and type 2 diabetes – a metaanalysis. Osteoporos Int 2007; 18: 427-444.
• 4 Räkel A, Sheehy O, Rahmne E, Lelorier J. Osteoporosis among patients with type 1 and type 2 diabetes. Diabetes Metabol 2008; 34: 193-205.
• 5 Gunczler P, Lanes R, Paoli M. et al. Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2001; 14: 525-528.
• 6 Valerio G, del Puente A, Esposito-del Puente A. et al. The lumbar bone mineral density is affected by long-term poor metabolic control in adolescents with type 1 diabetes mellitus. Horm Res 2002; 58: 266-272.
• 7 Hofbauer LC, Brueck CC, Singh SK, Dobnig H. Osteoporosis in patients with diabetes mellitus. J Bone Miner Res 2007; 22: 1317-2138.
• 8 Melton 3^rd LJ, Leibson CL, Achenbach SJ. et al. Fracture risk in type 2 diabetes: update of a population-based study. J Bone Miner Res 2008; 23 (08) 1334-1342.
• 9 Schwartz AV, Sellmeyer DE. Women, type 2 diabetes, and fracture risk. Curr Diab Rep 2004; 4: 364-369.
• 10 Nicodemus KK, Folsom AR. Iowa Women´s health study. Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care 2001; 24: 1192-1197.
• 11 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.
• 12 Ivers RQ, Cumming RG, Mitchell P, Peduto AJ. Blue Mountains Eye Study. Diabetes and risk of fracture: The Blue Mountains Eye Study. Diabetes Care 2001; 24: 1198-1203.
• 13 DVO-Leitlinie 2009 zur Prophylaxe, Diagnostik und Therapie der Osteoporose bei Erwachsenen. Osteologie 2009; 18: 304-328.
• 14 Hamilton EJ, Rakic V, Davis WA. et al. Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes. Diabet Med 2009; 26: 45-52.
• 15 Verhaeghe J, Suiker AM, Einhorn TA. et al. Brittle bones in spontaneously diabetic female rats cannot be predicted by bone mineral measurements: studies in diabetic and ovariectomized rats. J Bone Miner Res 1994; 9: 1657-1667.
• 16 Bronský J, Prùsa R, Nevoral J. The role of amylin and related peptides in osteoporosis. Clin Chim Acta 2006; 373: 9-16.
• 17 Horcajada-Molteni MN, Davicco MJ, Lebecque P. et al. Amylin inhibits ovariectomy-induced bone loss in rats. J Endocrinol 2000; 165: 663-668.
• 18 Saito M, Marumo K. Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 2010; 21: 195-214.
• 19 Yamagishi S. Role of advanced glycation end products (AGEs) in osteoporosis in diabetes. Curr Drug Targets 2011; 12: 2096-2102.
• 20 Méndez JD, Xie J, Aguilar-Hernández M, Méndez-Valenzuela V. Trends in advanced glycation end products research in diabetes mellitus and its complications. Mol Cell Biochem 2010; 341: 33-41.
• 21 Andersen H. Motor dysfunction in diabetes. Diabetes Metab Res Rev 2012; 28: 89-92.
• 22 Boucher BJ. Vitamin D insufficiency and diabetes risks. Curr Drug Targets 2011; 12: 61-87.
• 23 Grossmann M, Gianatti EJ, Zajac JD. Testosterone and type 2 diabetes. Curr Opin Endocrinol Diabetes Obes 2010; 17: 247-256.
• 24 Wongdee K, Charoenphandhu N. Osteoporosis in diabetes mellitus: possible cellular and molecular mechanisms. World J Diabetes 2011; 2: 41-48.
• 25 Schaaf L. Erhöhtes Frakturrisiko bei Diabetikern. MMW - Fortschr Med 2011; 4: 45-46.
• 26 Monami M, Cresci B, Colombini A. et al. Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case-control study. Diabetes Care 2008; 31: 199-203.
• 27 Vestergaard P, Rejnmark L, Mosekilde L. Osteoporosis and fractures associated with drugs. Ugeskr Laeger 2008; 170: 1550-1555.
• 28 Molinuevo MS, Schurman L, McCarthy AD. et al. Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies. J Bone Miner Res 2010; 25: 211-221.
• 29 Schwartz AV, Sellmeyer DE, Vittinghoff E. et al. Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 2006; 91: 3349-3354.
• 30 Meier C, Kraenzlin ME, Bodmer M. et al. Use of thiazolidinediones and fracture risk. Arch Intern Med 2008; 168: 820-825.
• 31 Dormandy J, Bhattacharya M, van Troostenburg de Bruyn AR. PROactive investigators. Safety and tolerability of pioglitazone in high-risk patients with type 2 diabetes: an overview of data from PROactive. Drug Saf 2009; 32: 187-202.
• 32 Home PD, Pocock SJ, Beck-Nielsen H. et al. RECORD Study Team. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multi-centre, randomised, open-label trial. Lancet 2009; 373: 2125-2135.
• 33 Kahn SE, Haffner SM, Heise MA. et al. ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427-2443.
• 34 Nuche-Berenguer B, Moreno P, Esbrit P. et al. Effect of GLP-1 treatment on bone turnover in normal, type 2 diabetic, and insulin-resistant states. Calcif Tissue Int 2009; 84: 453-461.