Diagnostik und Therapie der Osteoporose bei Diabetes mellitus

Zusammenfassung

Ein Diabetes mellitus beeinträchtigt das Skelettsystem und ist ein starker Risikofaktor für die Entwicklung einer Osteoporose mit Fragilitätsfrakturen. Die zugrundeliegenden Mechanismen für die erhöhte Fragilität des Knochens sind unzureichend bekannt, umfassen jedoch direkte und indirekte Effekte einer chronischen Hyperglykämie auf den Knochenstoffwechsel. Beim Typ-1-Diabetes mellitus (T1DM) ist das Skelett deutlich stärker betroffen als beim Typ-2-Diabetes mellitus (T2DM), insbesondere durch diabetische Komplikationen. Die Knochendichte kann bei Patienten mit T2DM sogar erhöht sein, schützt aber offenbar aufgrund einer eingeschränkten Qualität weniger gut gegen Frakturen. Orale Antidiabetika vom Typ der Glitazone fördern den Knochenverlust und sollten daher bei Osteoporose vermieden werden. Ein körperlich aktiver und gesunder Lebensstil, eine konsequente Prävention und Therapie diabetischer Komplikationen sind zusammen mit einer Basistherapie bestehend aus Kalzium und Vitamin D die Säulen der Behandlung der Osteoporose bei T1DM und T2DM. Die Messung der Knochendichte und die Bestimmung anderer Risikofaktoren dienen der Festlegung einer risikoadaptierten spezifischen Therapie. Auch wenn sie nicht spezifisch bei Diabetikern untersucht wurden, scheinen sämtliche etablierte Osteo porosetherapien bei Patienten mit Diabetes mellitus wirksam zu sein.

Summary

The diagnosis of diabetes mellitus impairs the skeleton and represents a risk factor for osteoporotic fractures. The underlying mechanisms are not fully understood, but may include direct and indirect effects of chronic hyperglycemia on the skeleton. In general, bone metabolism is more severely affected in type 1 diabetes mellitus (T1DM) as compared to type 2 diabetes mellitus (T2DM), especially in the presence of diabetic complications. Bone mass may even be high or normal in patients with T2DM, but this does not confer protection against fractures as a result of reduced bone quality. Glitazones used as oral antidiabetic drugs promote bone loss and should not be used in patients with osteoporosis. A physically active lifestyle with healthy nutrition, including adequate uptake of calcium and vitamin D, along with comprehensive prevention of diabetic complications, represent basic therapeutic measures. Identification of risk factors, assessment of bone mineral density, and laboratory tests help to develop an individualized specific treatment plan. In patients with diabetes mellitus, all established osteoporosis drugs seem to be effective.

Schlüsselwörter

Diabetes mellitus - Osteoporose - Fragilitätsfrakturen

Keywords

Diabetes mellitus - osteoporosis - osteoporotic fracture

• Literatur

• 1 Ahmed L A, Joakimsen RM, Berntsen GK. et al. Diabetes mellitus and the risk of non-vertebral fractures: the Tromso study. Osteoporos Int 2006; 17: 495-500.
• 2 Bao XH, Wong V, Wang Q, Low LC. Prevalence of peripheral neuropathy with insulin-dependent diabetes mellitus. Pediatr Neurol 1999; 20: 204-209.
• 3 Barrett-Connor E, Holbrook TL. Sex differences in osteoporosis in older adults with noninsulindependent diabetes mellitus. JAMA 1992; 268: 3333-3337.
• 4 Barrett-Connor E, Weiss TW, McHorney CA. et al. Predictors of falls among postmenopausal women: results from the National Osteoporosis Risk Assessment (NORA). Osteoporos Int 2009; 20: 715-722.
• 5 Bilik D. et al. Thiazolidinediones and fractures: evidence from translating research into action for diabetes. J Clin Endocrinol Metab 2010; 95: 4560-4565.
• 6 Bischoff HA. et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 2003; 18: 343-351.
• 7 Bolland MJ. et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 2008; 336: 262-266.
• 8 Bonds DE. et al. Risk of fracture in women with type 2 diabetes: the Women’s Health Initiative Observational Study. J Clin Endocrinol Metab 2006; 91: 3404-3410.
• 9 Bouxsein ML. Bone structure and fracture risk: Do they go arm in arm?. J Bone Miner Res 2011; 26: 1389-1391.
• 10 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: 455-459.
• 11 Chaudhary SB. et al. Complications of ankle fracture in patients with diabetes. J Am Acad Orthop Surg 2008; 16: 159-170.
• 12 Compston JE, Smith EM, Matthews C, Schofield P. Whole body composition and regional bone mass in women with insulin-dependent diabetes mellitus. Clin Endocrinol 1994; 41: 289-293.
• 13 de Liefde II. et al. Bone mineral density and fracture risk in type2 diabetes mellitus: the Rotterdam Study. Osteoporos Int 2005; 16: 1713-1720.
• 14 Dobnig H. et al. Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. J Clin Endocrinol Metab 2006; 91: 3355-3363.
• 15 Ebeling PR. Osteoporosis in men. N Engl J Med 2008; 358: 1474-1482.
• 16 Egger M, Davey GSmith, Stettler C, Diem P. Risk of adverse effects of intensified treatment in insulin-dependent diabetes mellitus: a meta-analysis. Diabet Med 1997; 14: 919-928.
• 17 Favus MJ. Bisphosphonates for osteoporosis. N Engl J Med 2010; 363: 2027-2035.
• 18 Forst T. et al. Peripheral osteopenia in adult patients with insulin-dependent diabetes mellitus. Diabet Med 1995; 12: 874-879.
• 19 Grey A. et al. The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 2007; 92: 1305-1310.
• 20 Habib ZA. et al. Thiazolidinedione use and the longitudinal risk of fractures in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2010; 95: 592-600.
• 21 Hamann C, Kirschner S, Günther KP, Hofbauer LC. Bone, sweet bone – osteoporotic fractures in diabetes mellitus. Nat Rev Endocrinol 2012; 08: 297-305.
• 22 Hein GE. Glycation endproducts in osteoporosis--is there a pathophysiologic importance?. Clin Chim Acta 2006; 371: 32-36.
• 23 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-281.
• 24 Hui SL, Epstein S, Johnston Jr CC. A prospective study of bone mass in patients with type I diabetes. J Clin Endocrinol Metab 1985; 60: 74-80.
• 25 The Diabetes Control and Complications Trial Research Group. Hypoglycemia in the Diabetes Control and Complications Trial. Diabetes 1997; 46: 271-286.
• 26 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.
• 27 Johal KS, Boulton C, Moran CG. Hip fractures after falls in hospital: a retrospective observational cohort study. Injury 2009; 40: 201-204.
• 28 Kannus P, Sievänen H, Palvanen M. et al. Prevention of falls and consequent injuries in elderly people. Lancet 2005; 366: 1885-1893.
• 29 Kayath MJ, Dib SA, Vieira JG. Prevalence and magnitude of osteopenia associated with insulindependent diabetes mellitus. J Diabetes Complications 1994; 08: 97-104.
• 30 Keegan TH, 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.
• 31 Mastrandrea LD. et al. Young women with type 1 diabetes have lower bone mineral density that persists over time. Diabetes Care 2008; 31: 1729-1735.
• 32 Meier C. et al. Use of thiazolidinediones and fracture risk. Arch Intern Med 2008; 168: 820-825.
• 33 Melton LJ. et al. A bone structural basis for fracture risk in diabetes. J Clin Endocrinol Metab 2008; 93: 4804-4809.
• 34 Melton 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: 1334-1342.
• 35 Merlotti D, Gennari L, Dotta F. et al. Mechanisms of impaired bone strength in type 1 and 2 diabetes. Nutr Metab Cardiovasc Dis 2010; 20: 683-690.
• 36 Nathan DM. et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353: 2643-2653.
• 37 Nicodemus KK, Folsom AR. Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care 2001; 24: 1192-1197.
• 38 Norris R, Parker M. Diabetes mellitus and hip fracture: A study of 5966 cases. Injury 2011; 42: 1313-1316.
• 39 Patsch JM, Burghardt AJ, Yap SP. et al. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res 2013; 28: 313-324.
• 40 Priemel M. et al. Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25- hydroxyvitamin D in 675 patients. J. Bone Miner Res 2010; 25: 305-312.
• 41 Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet 2011; 377: 1276-1287.
• 42 Raisz LG. Screening for osteoporosis. N Engl J Med 2005; 353: 164-171.
• 43 Retzepi M, Donos N. The effect of diabetes mellitus on osseous healing. Clin Oral Implants Res 2010; 21: 673-681.
• 44 Saito M, Fujii K, Mori Y, Marumo K. Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int 2006; 17: 1514-1523.
• 45 Schwartz AV, Sellmeyer DE. Women, type 2 diabetes, and fracture risk. Curr Diab Rep 2004; 04: 364-369.
• 46 Schwartz AV. et al. Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 2006; 91: 3349-3354.
• 47 Schwartz AV. et al. Pentosidine and increased fracture risk in older adults with type 2 diabetes. J Clin Endocrinol Metab 2009; 94: 2380-2386.
• 48 Schwartz AV. et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 2011; 305: 2184-2192.
• 49 Seeman E, Delmas PD. Bone quality – the material and structural basis of bone strength and fragility. N Engl J Med 2006; 354: 2250-2261.
• 50 Strotmeyer ES. et al. Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging and body composition study. Arch Intern Med 2005; 165: 1612-1617.
• 51 Strotmeyer ES, Cauley JA. Diabetes mellitus, bone mineral density, and fracture risk. Curr Opin Endocrinol Diabetes Obes 2007; 14: 429-435.
• 52 Strotmeyer ES. et al. Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: The Health, Aging, and Body Composition Study. J Bone Miner Res 2004; 19: 1084-1091.
• 53 Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc 2011; 86: 50-60.
• 54 Tinetti ME. Clinical Practice. Preventing falls in elderly persons. N Engl J Med 2003; 348: 42-49.
• 55 van Daele PL. et al. Bone density in noninsulindependent diabetes mellitus. The Rotterdam Study. Ann Intern Med 1995; 122: 409-414.
• 56 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.
• 57 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: 427-444.
• 58 Vestergaard P, Rejnmark L, Mosekilde L. Diabetes and its complications and their relationship with risk of fractures in type 1 and 2 diabetes. Calcif Tissue Int 2009; 84: 45-55.
• 59 Vestergaard P, Rejnmark L, Mosekilde L. Are antiresorptive drugs effective against fractures in patients with diabetes?. Calcif Tissue Int 2011; 88: 209-214.
• 60 Vischer UM. et al. A call to incorporate the prevention and treatment of geriatric disorders in the management of diabetes in the elderly. Diabetes Metab 2009; 35: 168-177.
• 61 Volpato S, Leville 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: 1539-1545.
• 62 Wallace C. et al. Incidence of falls, risk factors for falls, and fall-related fractures in individuals with diabetes and prior foot ulcer. Diabetes Care 2002; 25: 1983-1986.
• 63 Weber G. et al. Bone mass in young patients with type I diabetes. Bone Miner 1990; 08: 23-30.
• 64 Wukich DK, Kline AJ. The management of ankle fractures in patients with diabetes. J Bone Joint Surg Am 2008; 90: 1570-1578.
• 65 Yamamoto M, Yamaguchi T, Yamauchi M, Sugimoto T. Low serum level of the endogenous secretory receptor for advanced glycation end products (esRAGE) is a risk factor for prevalent vertebral fractures independent of bone mineral density in patients with type 2 diabetes. Diabetes Care 2009; 32: 2263-2268.
• 66 Yaturu S, Bryant B, Jain SK. Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men. Diabetes Care 2007; 30: 1574-1576.