Knochenstoffwechsel, Umbaumarker und Diabetes

 

 Buy Article Permissions and Reprints

Zusammenfassung

Patienten mit Diabetes mellitus Typ 1 (T1DM) und Typ 2 (T2DM) haben ein erhöhtes Frakturrisiko. Während die Knochendichte beim T1DM vermindert ist, haben Patienten mit T2DM eine höhere Knochendichte. Als Marker der Knochenformation ist Osteocalcin niedriger als bei Gesunden, während der Resorptionsmarker C-terminales Kollagen Typ 1-Telopeptid (CTX) nicht oder nur sehr gering vermindert ist. Das Frakturrisiko wird durch spezifische Veränderungen im Knochenstoffwechsel beeinflusst. Dazu zählen die anabole Funktion des Insulins auf die Knochenformation, Veränderungen der Leptin/Adiponectin-Achse und direkte Effekte der Hyperglykämie auf die Knochenzellen. Die Festigkeit des Knochens wird durch eine vermehrt ablaufende Bildung von advancend glycation endproducts (AGEs) beeinträchtigt. Das Risiko zu stürzen ist ein weiterer wesentlicher Faktor, der in direktem Zusammenhang mit bereits vorhandenen diabetischen Folgeerkrankungen wie Neuropathie oder Retinopathie steht. Orale Diabetesmedikamente wie die Glitazone können zu einem erhöhten Frakturrisiko beitragen. Die Risikobewertung für die Bruchfestigkeit des Knochens erfolgt nach den üblichen Gesichtspunkten unter Einbeziehung der Knochendichte, muss allerdings eine differenzierte Betrachtung individueller weiterer, von der Knochendichte unabhängiger Faktoren einschließen. Eine optimale Einstellung des Glukosestoffwechsels ist auch hinsichtlich möglicher Veränderungen im Knochenstoffwechsel von Bedeutung.

Summary

Diabetes mellitus negatively affects the skeleton and increases the fracture risk in both, type 1 (T1DM) and type 2 (T2DM) diabetes. Bone mineral density is decreased in T1DM and increased in T2DM. Bone formation marker osteocalcin is reduced while bone resorption marker C-terminal cross-linked telopeptide (CTX) is normal or only slightly reduced. The increased fracture risk is attributed to specific changes in bone metabolism. Among them are the anabolic function of insulin on bone formation, disturbances of the leptin/adiponectin axis and impairments of bone cell function by hyperglycemia. Bone structure and bone strength is impaired by increased formation of advanced glycation endproducts (AGEs). Risk of falls contributes to the occurrence of fractures and is increased by the presence of diabetic retinopathy and neuropathy. The class of oral antidiabetic drugs known as glitazones can promote bone loss and osteoporotic fractures. The risk assessment for osteoporotic fractures is performed on the basis of bone mineral density measurements but must individually include other independent risk factors. T1DM and therapy of T2DM with glitazones are considered as independent risk factors for fractures and request action of careful individual investigation of the patients overall risk. The quality of glycemic control is critical for most of diabetes related disturbances of bone integrity.

• Literatur

• 1 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 (05) 495-505.
  CrossrefPubMedGoogle Scholar
• 2 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 (07) 1292-1299.
  CrossrefPubMedGoogle Scholar
• 3 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. 2013 Oct 23.
  PubMedGoogle Scholar
• 4 Schwartz AV, Vittinghoff E, Sellmeyer DE. et al. Diabetes-related complications, glycemic control, and falls in older adults. Diabetes Care 2008; 31 (03) 391-396.
  CrossrefPubMedGoogle Scholar
• 5 Volpato S, Leveille SG, Blaum C. et al. Risk factors for falls in older disabled women with diabetes: the women’s health and aging study. J Gerontol A Biol Sci Med Sci 2005; 60 (12) 1539-1545.
  CrossrefPubMedGoogle Scholar
• 6 Hofbauer LC, Brueck CC, Singh SK, Dobnig H. Osteoporosis in patients with diabetes mellitus. J Bone Miner Res 2007; 22 (09) 1317-1328.
  CrossrefPubMedGoogle Scholar
• 7 Pan H, Wu N, Yang T, He W. Association between bone mineral density and type 1 diabetes mellitus: a meta-analysis of cross-sectional studies. Diabetes Metab Res Rev. 2013 Dec 16.
  PubMedGoogle Scholar
• 8 Neumann T, Samann A, Lodes S. et al. Glycaemic control is positively associated with prevalent fractures but not with bone mineral density in patients with Type 1 diabetes. Diabet Med 2011; 28 (07) 872-875.
  CrossrefPubMedGoogle Scholar
• 9 Schwartz AV, Ewing SK, Porzig AM. et al. Diabetes and change in bone mineral density at the hip, calcaneus, spine, and radius in older women. Front Endocrinol (Lausanne) 2013; 04: 62.
  Google Scholar
• 10 Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes - a meta-analysis. Osteoporos Int 2007; 18 (04) 427-444.
  CrossrefPubMedGoogle Scholar
• 11 Starup-Linde J. Diabetes, biochemical markers of bone turnover, diabetes control, and bone. Front Endocrinol (Lausanne) 2013; 04: 21.
  Google Scholar
• 12 Delmas PD. What do we know about biochemical bone markers?. Baillieres Clin Obstet Gynaecol 1991; 05 (04) 817-830.
  CrossrefPubMedGoogle Scholar
• 13 Abd SMEl Dayem, El-Shehaby AM, Abd AEl Gafar. et al. Bone density, body composition, and markers of bone remodeling in type 1 diabetic patients. Scand J Clin Lab Invest 2011; 71 (05) 387-393.
  CrossrefPubMedGoogle Scholar
• 14 Motyl KJ, McCabe LR, Schwartz AV. Bone and glucose metabolism: a two-way street. Arch Biochem Biophys 2010; 503 (01) 2-10.
  CrossrefPubMedGoogle Scholar
• 15 Clowes JA, Allen HC, Prentis DM. et al. Octreotide abolishes the acute decrease in bone turnover in response to oral glucose. J Clin Endocrinol Metab 2003; 88 (10) 4867-4873.
  CrossrefPubMedGoogle Scholar
• 16 Khalil N, Sutton-Tyrrell K, Strotmeyer ES. et al. Menopausal bone changes and incident fractures in diabetic women: a cohort study. Osteoporos Int 2011; 22 (05) 1367-1376.
  CrossrefPubMedGoogle Scholar
• 17 McCabe LR. Understanding the pathology and mechanisms of type I diabetic bone loss. J Cell Biochem 2007; 102 (06) 1343-1357.
  CrossrefPubMedGoogle Scholar
• 18 Goh SY, Cooper ME. Clinical review: The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 2008; 93 (04) 1143-1152.
  CrossrefPubMedGoogle Scholar
• 19 Busch M, Franke S, Ruster C, Wolf G. Advanced glycation end-products and the kidney. Eur J Clin Invest 2010; 40 (08) 742-755.
  CrossrefPubMedGoogle Scholar
• 20 Roy B. Biomolecular basis of the role of diabetes mellitus in osteoporosis and bone fractures. World J Diabetes 2013; 04 (04) 101-113.
  CrossrefPubMedGoogle Scholar
• 21 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 (02) 195-214.
  CrossrefPubMedGoogle Scholar
• 22 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. J Clin Endocrinol Metab 2008; 93 (03) 1013-1019.
  CrossrefPubMedGoogle Scholar
• 23 Neumann T, Lodes S, Kastner B. et al. High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control. Osteoporos Int 2014; 25 (05) 1527-1533.
  CrossrefPubMedGoogle Scholar
• 24 Thrailkill KM, Lumpkin Jr 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 (05) E735-E745.
  CrossrefPubMedGoogle Scholar
• 25 Campos MMPastor, Lopez-Ibarra PJ, Escobar-Jimenez F. et al. Intensive insulin therapy and bone mineral density in type 1 diabetes mellitus: a prospective study. Osteoporos Int 2000; 11 (05) 455-459.
  CrossrefPubMedGoogle Scholar
• 26 Giustina A, Mazziotti G, Canalis E. Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 2008; Aug; 29 (05) a535-559.
  Google Scholar
• 27 Rosen CJ. Clinical practice. Vitamin D insufficiency. N Engl J Med 2011; 364 (03) 248-254.
  PubMedGoogle Scholar
• 28 Mathieu C, Gysemans C, Giulietti A, Bouillon R. Vitamin D and diabetes. Diabetologia 2005; 48 (07) 1247-1257.
  CrossrefPubMedGoogle Scholar
• 29 Atkins GJ, Rowe PS, Lim HP. et al. Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism. J Bone Miner Res 2011; 26 (07) 1425-1436.
  CrossrefPubMedGoogle Scholar
• 30 Neumann T, Hofbauer LC, Rauner M. et al. Clinical and endocrine correlates of circulating sclerostin levels in patients with type 1 diabetes mellitus. Clin Endocrinol (Oxf). 2013 Nov 15.
  PubMedGoogle Scholar
• 31 Garcia-Martin A, Rozas-Moreno P, Reyes-Garcia R. et al. Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2012; 97 (01) 234-241.
  CrossrefPubMedGoogle Scholar
• 32 Yamamoto M, Yamauchi M, Sugimoto T. Elevated sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2013; 98 (10) 4030-4037.
  CrossrefPubMedGoogle Scholar
• 33 Glauber HS, Vollmer WM, Nevitt MC. et al. Body weight versus body fat distribution, adiposity, and frame size as predictors of bone density. J Clin Endocrinol Metab 1995; 80 (04) 1118-1123.
  PubMedGoogle Scholar
• 34 Ducy P, Amling M, Takeda S. et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000; 100 (02) 197-207.
  CrossrefPubMedGoogle Scholar
• 35 Ng KW. Regulation of glucose metabolism and the skeleton. Clin Endocrinol (Oxf) 2011; 75 (02) 147-155.
  CrossrefPubMedGoogle Scholar
• 36 Fazeli PK, Horowitz MC, MacDougald OA. et al. Marrow fat and bone - new perspectives. J Clin Endocrinol Metab 2013; 98 (03) 935-945.
  CrossrefPubMedGoogle Scholar
• 37 Wehrli FW, Hopkins JA, Hwang SN. et al. Crosssectional study of osteopenia with quantitative MR imaging and bone densitometry. Radiology 2000; 217 (02) 527-538.
  CrossrefPubMedGoogle Scholar
• 38 Lee NK, Sowa H, Hinoi E. et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130 (03) 456-469.
  CrossrefPubMedGoogle Scholar
• 39 Gravenstein KS, Napora JK, Short RG. et al. Crosssectional evidence of a signaling pathway from bone homeostasis to glucose metabolism. J Clin Endocrinol Metab 2011; 96 (06) E884-E890.
  CrossrefPubMedGoogle Scholar
• 40 Kindblom JM, Ohlsson C, Ljunggren O. et al. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 2009; 24 (05) 785-791.
  CrossrefPubMedGoogle Scholar
• 41 Kiechl S, Wittmann J, Giaccari A. et al. Blockade of receptor activator of nuclear factor-kappaB (RANKL) signaling improves hepatic insulin resistance and prevents development of diabetes mellitus. Nat Med 2013; 19 (03) 358-363.
  CrossrefPubMedGoogle Scholar
• 42 Schwartz AV, Schafer AL, Grey A. et al. Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials. J Bone Miner Res 2013; 28 (06) 1348-1354.
  CrossrefPubMedGoogle Scholar
• 43 Schwartz AV, Margolis KL, Sellmeyer DE. et al. Intensive glycemic control is not associated with fractures or falls in the ACCORD randomized trial. Diabetes Care 2012; 35 (07) 1525-1531.
  CrossrefPubMedGoogle Scholar
• 44 Rzonca SO, Suva LJ, Gaddy D. et al. Bone is a target for the antidiabetic compound rosiglitazone. Endocrinology 2004; 145 (01) 401-406.
  CrossrefPubMedGoogle Scholar
• 45 Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. Cmaj 2009; 180 (01) 32-39.
  CrossrefPubMedGoogle Scholar
• 46 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 (02) 199-203.
  CrossrefPubMedGoogle Scholar
• 47 McIntosh CH, Widenmaier S, Kim SJ. Pleiotropic actions of the incretin hormones. Vitam Horm 2010; 84: 21-79.
  PubMedGoogle Scholar
• 48 DVO e. V. DVO-Leitlinie 2009 zur Prophylaxe, Diagnostik und Therapie der Osteoporose bei Erwachsenen. Osteologie 2009; 18: 304-328.
  Google Scholar
• 49 Schwartz AV, Vittinghoff E, Bauer DC. et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 2011; 305 (21) 2184-2192.
  CrossrefPubMedGoogle Scholar
• 50 Vestergaard P, Rejnmark L, Mosekilde L. Are antiresorptive drugs effective against fractures in patients with diabetes?. Calcif Tissue Int 2011; 88 (03) 209-214.
  CrossrefPubMedGoogle Scholar
• 51 Iwamoto J, Sato Y, Uzawa M. et al. Three-year experience with alendronate treatment in postmenopausal osteoporotic Japanese women with or without type 2 diabetes. Diabetes Res Clin Pract 2011; 93 (02) 166-173.
  CrossrefPubMedGoogle Scholar
• 52 Holick MF, Binkley NC, Bischoff-Ferrari HA. et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96 (07) 1911-1930.
  CrossrefPubMedGoogle Scholar
• 53 Liu CJ, Latham NK. Progressive resistance strength training for improving physical function in older adults. Cochrane Database Syst Rev 2009; 03: CD002759.
  Google Scholar