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Arthritis und Rheuma 2008; 28(04): 196-201
DOI: 10.1055/s-0037-1620115
Diabetes und Rheuma
Schattauer GmbH

Osteoporose und Frakturrisiko bei Diabetes mellitus

Osteoporosis and fracture risk in diabetes mellitus
T. Neumann
1   Friedrich-Schiller-Universität Jena, Klinik für Innere Medizin III (Direktor: Prof. Dr. Gunter Wolf), Rheumatologie/Osteologie (Leiter: Prof. Dr. Gert Hein)
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Publication History

Publication Date:
24 December 2017 (online)

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Zusammenfassung

Diabetes mellitus und Osteoporose sind Erkrankungen, die bei älteren Patienten gehäuft auftreten. Osteoporotische Frakturen sind mit einer erheblichen Morbidität und Mortalität assoziiert. Neuere Untersuchungen zeigen, dass Patienten mit Diabetes mellitus ein erhöhtes Risiko für Frakturen der Hüfte, des Humerus und des Fußskeletts aufweisen. Ursächlich für dieses gesteigerte Frakturrisiko ist eine verminderte Knochenqualität, wobei die genauen Pathomechanismen der Störung noch nicht abschließend geklärt sind. Für Patienten mit Typ-1-Diabetes wurde in einigen Studien eine verringerte Knochendichte beschrieben, während Patienten mit Typ-2-Diabetes in den meisten Untersuchungen erhöhte Knochendichtewerte aufweisen. Das Frakturrisiko bei älteren Patienten mit Typ-2-Diabetes ist teilweise durch eine höhere Sturzneigung zu erklären. Diabetes- assoziierte Komorbiditäten wie Polyneuropathie oder Retinopathie können das Sturzrisiko direkt beeinflussen. Eine optimale Stoffwechselkontrolle sowie die Integration strukturierter Trainingsprogramme zur Konditionierung der muskuloskelettalen Funktion sollten Bestandteil des Gesamtbehandlungskonzeptes dieser Patienten sein.

Summary

Diabetes mellitus and osteoporosis affect a large proportion of older adults. Osteoporotic fractures have a major impact on morbidity and mortality. Recent cohort studies indicate that diabetes itself is associated with increased risk of fractures of the hip, proximal humerus and foot. Impaired bone quality may contribute to the increased fracture risk in diabetic patients. However, the mechanism resulting in reduced bone strength remains unclear. Observational studies suggest lower bone mineral density in patients with type 1 diabetes, whereas patients with type 2 diabetes have higher bone mineral density. Fracture risk in older patients is enhanced by more frequent falls. Diabetic microvascular complications such as polyneuropathy and retinopathy have direct impact on risk of falls. Appropriate metabolic control in combination with muscle strength and balance training should be concidered in an integrate concept of treatment.

Schlüsselwörter

Diabetes mellitus - Osteoporose - Knochendichte - Fraktur - Osteoblast - Osteoklast

Keywords

Diabetes mellitus - osteoporosis - bone density - fracture - osteoblast - osteoclast
 

  • Literatur

  • 1 Akune T, Ogata N, Hoshi K. et al. Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts. J Cell Biol 2002; 159: 147-156.
    CrossrefGoogle Scholar
  • 2 Barrett-Connor E, Holbrook TL. Sex differences in osteoporosis in older adults with non-insulin-dependent diabetes mellitus. JAMA 1992; 268: 3333-3337.
    CrossrefGoogle Scholar
  • 3 Barry EL, Gesek FA, Kaplan MR. et al. Expression of the sodium-chloride cotransporter in osteo-blast-like cells: effect of thiazide diuretics. Am J Physiol 1997; 272: C109-C116.
    CrossrefGoogle Scholar
  • 4 Berg AH, Scherer PE. Adiposetissue, inflammation, and cardiovascular disease. Circulation research 2005; 96: 939-949.
    CrossrefGoogle Scholar
  • 5 Bonfanti R, Mora S, Prinster C. et al. Bone modeling indexes at onset and during the first year of follow-Up in insulin-dependent diabetic children. Calcif Tissue Int 1997; 60: 397-400.
    CrossrefGoogle Scholar
  • 6 Bouillon R, Bex M, Van Herck E. et al. Influence of age, sex, and insulin on osteoblast function: osteoblast dysfunction in diabetes mellitus. J Clin Endocrinol Metab 1995; 80: 1194-1202.
    Google Scholar
  • 7 Campos Pastor MM, López-Ibarra PJ, Escobar-Jiménez F. et al. Intensive insulin therapy and bone mineral density in type 1 diabetes mellitus: a prospective study. Osteoporos Int 2000; 11: 455-459.
    CrossrefGoogle Scholar
  • 8 Cherruau M, Facchinetti P, Baroukh B, Saffar JL. Chemical sympathectomy impairs bone resorption in rats: a role for the sympathetic system on bone metabolism. Bone 1999; 25: 545-551.
    CrossrefGoogle Scholar
  • 9 Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002; 359: 1761-1767.
    CrossrefGoogle Scholar
  • 10 Dubey A, Aharonoff GB, Zuckerman JD, Koval KJ. The effects of diabetes on outcome after hip fracture. Bull Hosp Jt Dis 2000; 59: 94-98.
    Google Scholar
  • 11 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: 197-207.
    CrossrefGoogle Scholar
  • 12 Ellison DH, Velázquez H, Wright FS. Thiazide-sensitive sodium chloride cotransport in early distal tubule. Am J Physiol 1987; 253: F546-554.
    Google Scholar
  • 13 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: 920-925.
    CrossrefGoogle Scholar
  • 14 Fu L, Patel MS, Bradley A. et al. The molecular clock mediates leptin-regulated bone formation. Cell 2005; 122: 803-815.
    CrossrefGoogle Scholar
  • 15 Gillespie LD, Gillespie WJ, Robertson MC. et al. Interventions for preventing falls in elderly people. Cochrane Database Syst Rev 2003 CD000340.
    Google Scholar
  • 16 Glaxo Smith Kline. Clinical trial observation of an in-creased incidence of fractures in female patients who received long-term treatment with Avandia (rosiglita-zone maleate) tabletsfor type 2 diabetes mellitus (Lettersto Health Care Providers), Februar 2007. Available from www.fda.gov/medwatch/safety/2007/avandia_GSK_Ltr.pdf Accessed 15 March 2007
    Google Scholar
  • 17 Heath 3rd H., Melton 3rd LJ., Chu CP. Diabetes mellitus and risk of skeletal fracture. N Engl J Med 1980; 303: 567-570.
    CrossrefGoogle Scholar
  • 18 Holloway WR, Collier FM, Aitken CJ. et al. Leptin inhibits osteoclast generation. J Bone Miner Res 2002; 17: 200-209.
    CrossrefGoogle Scholar
  • 19 Isaia GC, Ardissone P, Di Stefano M. et al. Bone metabolism in type 2 diabetes mellitus. Acta Diabetol 1999; 36: 35-38.
    CrossrefGoogle Scholar
  • 20 Ivers RQ, Cumming RG, Mitchell P, Peduto AJ. Diabetes and risk of fracture: The Blue Mountains Eye Study. Diabetes Care 2001; 24: 1198-1203.
    CrossrefGoogle Scholar
  • 21 Janghorbani M, Feskanich D, Willett WC, Hu F. Prospective study of diabetes and risk of hip fracture: the Nurses' Health Study. Diabetes Care 2006; 29: 1573-1578.
    CrossrefGoogle Scholar
  • 22 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.
    CrossrefGoogle Scholar
  • 23 Johnell O, Kanis JA, Odén A. et al. Mortality after osteoporotic fractures. Osteoporos Int 2004; 15: 38-42.
    CrossrefGoogle Scholar
  • 24 Kanis JA, Johnell O, De Laet C. et al. Ameta-analysis of previous fracture and subsequent fracture risk. Bone 2004; 35: 375-382.
    CrossrefGoogle Scholar
  • 25 Kannus P, Sievänen H, Palvanen M. et al. Prevention of falls and consequent injuries in elderly people. Lancet 2005; 366: 1885-1893.
    CrossrefGoogle Scholar
  • 26 Kelsey JL, Browner WS, Seeley DG. et al. Risk factors for fractures of the distal forearm and proximal humerus. The Study of Osteoporotic Fractures Research Group. Am J Epidemiol 1992; 135: 477-489.
    CrossrefGoogle Scholar
  • 27 Kemink SA, Hermus AR, Swinkels LM. et al. Osteopenia in insulin-dependent diabetes mellitus; prevalence and aspects of pathophysiology. J Endocrinol Invest 2000; 23: 295-303.
    CrossrefGoogle Scholar
  • 28 Kenny RA, Richardson DA, Steen N. et al. Carotid sinus syndrome: amodifiable risk factor for no-naccidental falls in older adults (SAFE PACE). J Am Coll Cardiol 2001; 38: 1491-1496.
    CrossrefGoogle Scholar
  • 29 Lecka-Czernik B, Gubrij I, Moerman EJ. et al. Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPA Rgamma 2. J Cell Biochem 1999; 74: 357-371.
    CrossrefGoogle Scholar
  • 30 Liu EY, Wactawski-Wende J, Donahue RP. et al. Does low bone mineral density startin post-teenage years in women with type 1 diabetes?. Diabetes Care 2003; 26: 2365-2369.
    CrossrefGoogle Scholar
  • 31 Loder RT. The influence of diabetes mellitus on the healing of closed fractures. Clin Orthop Relat Res 1988; 210: 216.
    Google Scholar
  • 32 Lunt H, Florkowski CM, Cundy T. et al. Apopulation-based study of bone mineral density in women with longstanding type 1 (insulin dependent) diabetes. Diabetes Res Clin Pract 1998; 40: 31-38.
    CrossrefGoogle Scholar
  • 33 Melchior TM, Sørensen H, Torp-Pedersen C. Hip and distal arm fracture rates in peri- and post-menopausal insulin-treated diabetic females. J Intern Med 1994; 236: 203-208.
    CrossrefGoogle Scholar
  • 34 Melton 3rd LJ., Achenbach SJ, O'Fallon WM, Khosla S. Secondary osteoporosis and the risk of distal forearm fractures in men and women. Bone 2002; 31: 119-125.
    CrossrefGoogle Scholar
  • 35 Meyer HE, Tverdal A, Falch JA. Risk factors for hip fracture in middle-aged Norwegian women and men. Am J Epidemiol 1993; 137: 1203-1211.
    CrossrefGoogle Scholar
  • 36 Miao J, Brismar K, Nyrén O. et al. Elevated hip fracture risk in type 1 diabetic patients: a population-based cohort study in Sweden. Diabetes Care 2005; 28: 2850-2855.
    CrossrefGoogle Scholar
  • 37 Munoz-Torres M, Jodar E, Escobar-Jimenez F. et al. Bone mineral density measured by dual X-ray absorptiometry in Spanish patients with insulin-dependent diabetes mellitus. Calcif Tissue Int 1996; 58: 316-319.
    CrossrefGoogle Scholar
  • 38 Nicodemus KK, Folsom AR. Type 1 and type 2 diabetes and incident hip fractures in post-menopausal women. Diabetes Care 2001; 24: 1192-1197.
    CrossrefGoogle Scholar
  • 39 Ogata N, Chikazu D, Kubota N. et al. Insulin receptor substrate-1 in osteoblast is indispensable for maintaining bone turnover. J Clin Invest 2000; 105: 935-943.
    CrossrefGoogle Scholar
  • 40 Okazaki R, Totsuka Y, Hamano K. et al. Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover. J Clin Endocrinol Metab 1997; 82: 2915-2920.
    Google Scholar
  • 41 Orwoll ES, Bauer DC, Vogt TM, Fox KM. Axial bone mass in older women. Study of Osteoporotic Fractures Research Group. Ann Intern Med 1996; 124: 187-196.
    CrossrefGoogle Scholar
  • 42 Ottenbacher KJ, Ostir GV, Peek MK. et al. Diabetes mellitus as a risk factor for hip fracture in mexican american older adults. J Gerontol A Biol Sci Med Sci 2002; 57: M648-M653.
    CrossrefGoogle Scholar
  • 43 Pascual J, Argente J, Lopez MB. et al. Bone mineral density in children and adolescents with diabetes mellitus type 1 ofrecent onset. Calcif Tissue Int 1998; 62: 31-35.
    CrossrefGoogle Scholar
  • 44 Perez-Castrillon JL, Silva J, Justo I. et al. Effect of quinapril, quinapril-hydrochlorothiazide, and enalapril on the bone mass of hypertensive subjects: relationship with angiotensin converting enzyme polymorphisms. Am J Hypertens 2003; 16: 453-459.
    CrossrefGoogle Scholar
  • 45 Rozadilla A, Nolla JM, Montaña E. et al. Bone mineral density in patients with type 1 diabetes mellitus. Joint Bone Spine 2000; 67: 215-218.
    Google Scholar
  • 46 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.
    CrossrefGoogle Scholar
  • 47 Schwartz AV, Hillier TA, Sellmeyer DE. et al. Older women with diabetes have a higher risk of falls: a prospective study. Diabetes Care 2002; 25: 1749-1754.
    CrossrefPubMedGoogle Scholar
  • 48 Schwartz AV, Sellmeyer DE, Ensrud KE. et al. Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 2001; 86: 32-38.
    CrossrefGoogle Scholar
  • 49 Scragg R, Holdaway I, Singh V. et al. Serum 25-hydroxyvitamin D3 levels decreased in impaired glucose tolerance and diabetes mellitus. Diabetes Res Clin Pract 1995; 27: 181-188.
    CrossrefGoogle Scholar
  • 50 Services Do Ha H. Bone health and osteoporosis: a report of the Surgeon-General. In Rockville US.. Department of Health and Human Services, Office of the Surgeon General 2004
    Google Scholar
  • 51 Shimizu H, Nakagami H, Osako MK. et al. Angiotensin II accelerates osteoporosis by activating osteoclasts. FASEB J 2008; 22: 1-11.
    CrossrefGoogle Scholar
  • 52 Siris ES, Miller PD, Barrett-Connor E. et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment. JAMA 2001; 286: 2815-2822.
    CrossrefGoogle Scholar
  • 53 Sottile V, Seuwen K, Kneissel M. Enhanced marrow adipogenesis and bone resorption in estrogen deprived rats treated with the PPAR gamma agonist BRL 49653 (rosiglitazone). Calcif Tissue Int 2004; 75: 329-337.
    CrossrefGoogle Scholar
  • 54 Strotmeyer ES, Cauley JA, Orchard TJ. et al. Middle-aged premenopausal women with type 1 diabetes have lower bone mineral density and calcaneal quantitative ultrasound than non diabetic women. Diabetes Care 2006; 29: 306-311.
    CrossrefGoogle Scholar
  • 55 Strotmeyer ES, Cauley JA, Schwartz AV. 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.
    CrossrefGoogle Scholar
  • 56 Takeda. Observation of an increased incidence of fractures in female patients who received long-term treatment with ACTOS (pioglitazone HCl) tablets for type 2 diabetes mellitus (Letter to Health Care Providers), March 2007. Availablefrom www.fda.gov/medwatch/safety/2007/Actosmar0807.pdf Accessed 19 March 2007
    Google Scholar
  • 57 Takeda S, Elefteriou F, Levasseur R. et al. Leptin regulates bone formation via the sympathetic nervous system. Cell 2002; 111: 305-317.
    CrossrefGoogle Scholar
  • 58 Thomas T, Gori F, Khosla S. et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 1999; 140: 1630-1638.
    CrossrefGoogle Scholar
  • 59 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: E735-E745.
    CrossrefGoogle Scholar
  • 60 Tinetti ME. Clinical practice. Preventing falls in elderly persons. N Engl J Med 2003; 348: 42-49.
    CrossrefPubMedGoogle Scholar
  • 61 Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988; 319: 1701-1707.
    CrossrefGoogle Scholar
  • 62 Togari A. Adrenergic regulation of bone metabolism: possible involvement of sympathetic in nervation of osteoblastic and osteoclastic cells. Microsc Res Tech 2002; 58: 77-84.
    CrossrefGoogle Scholar
  • 63 Tuominen JT, Impivaara O, Puukka P, Rönnemaa T. Bone mineral density in patients with type 1 and type 2 diabetes. Diabetes Care 1999; 22: 1196-1200.
    CrossrefGoogle Scholar
  • 64 van Daele PL, Stolk RP, Burger H. et al. Bone density in non-insulin-dependent diabetes mellitus. The Rotterdam Study. Ann Intern Med 1995; 122: 409-414.
    CrossrefGoogle Scholar
  • 65 Vashishth D, Gibson GJ, Khoury I J.. et al. Influence of nonenzymatic glycation on biomechanical properties of cortical bone. Bone 2001; 28: 195-201.
    CrossrefGoogle Scholar
  • 66 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.
    CrossrefGoogle Scholar
  • 67 Vogt MT, Cauley JA, Tomaino MM. et al. Distal radius fractures in older women: a10-year follow-up study of descriptive characteristics and risk factors. The study of osteoporotic fractures. J Am Geriatr Soc 2002; 50: 97-103.
    CrossrefGoogle Scholar
  • 68 Wiens M, Etminan M, Gill SS, Takkouche B. Effects of antihypertensive drug treatments on fracture outcomes: a meta analysis of observational studies. J Intern Med 2006; 260: 350-362.
    CrossrefGoogle Scholar
  • 69 Yaturu S, Bryant B, Jain SK. Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men. Diabetes Care 2007; 30: 1574-1576.
    CrossrefGoogle Scholar