Update Ätiologie/Risikofaktoren bei Osteonekrosen und Osteonekrose bei Kortikoidtherapie

Zusammenfassung

Schon seit Beginn der 1980iger-Jahre wird eine multifaktorielle Genese der Osteonekrose postuliert. Neueste Untersuchungen fokussieren auf die Endstreckengefäße. Die Summe der Risikofaktoren führt durch erkrankte Endothelien zum Verschluss der Endgefäße mit der Folge der umschriebenen Nekrose eines typischen Knochenbezirks. Diese Theorie der endothelialen Dysfunktion wird durch molekularmedizinische Verfahren unterstützt. Besonders das VEGF (vascular endothelial growth factor) der Knochenmarkszellen steht im Mittelpunkt des Interesses, da dieser Wachstumfaktor die Angiogenese und damit die Regenerationsfähigkeit des Knochens anzeigt. Bei Osteonekrose wird er vermindert und/oder in abnormer Variante exprimiert. Für die kortisoninduzierte Osteonekrose, deren Verständnis durch zahlreiche Tiermodelluntersuchungen deutlich verbessert wurde, gilt, dass sie durch kumulative Gabe oder durch sehr hohe Einzeldosen ausgelöst wird. Die Regenerationsfähigkeit ist beim Risikofaktor Kortison deutlich niedriger als bei anderen Risikofaktoren wie Alkohol.

Summary

The multifactorial concept of osteonecrosis is postulated since the 1980s. New studies focused on function of the terminal vessels. Accumulated risk factors lead to clotted vessels by endothelial disease. The consequences are located necrosis of typical bone areas. This concept of endothelial dysfunction is supported by molecular technique. Especially VEGF (vascular endothelial growth factor) stands in the centre of attention, because the growth factor mediated angiogenesis and bone regeneration. VEGF is down regulated in osteonecrosis and/or expressed in an abnormal variant. A lot of studies with animals were done in the field of steroidinduced osteonecrosis. Accumulated dosages and peak doses of steroids provoke osteonecrosis. The regeneration ability is still inferior in steroid-induced osteonecrosis in comparison to other risk factors like alcohol.

Schlüsselwörter

Nicht traumatische Osteonekrose - Osteonekrose bei Kortikoidtherapie - VEGF

Keywords

Non-traumatic osteonecrosis - osteonecrosis and steroids - vascular endothelial growth factor

• Literatur

• 1 Chang C. et al. Osteonecrosis. In: Firestein GS, Budd RC, Harris ED. et al. Textbook of Rheumatology. Philadelphia: Sanders; 2009: 1611-1628.
• 2 Chen WM. et al. Autosomal dominant avascular necrosis of femoral head in two Taiwanese pedigrees and linkage to chromosome 12q13. Am J Hum Gen 2004; 75: 310.
• 3 Gangji V, Hanzeno JP. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. J Bone Joint Surg Am 2005; 87: 106-112.
• 4 Glassman SD. et al. The effect of cigarette smoking and smoking cessation on spinal fusion. Spine 2000; 25: 2608-2615.
• 5 Glueck CJ. et al. The plasminogen activator inhibitor-1 gene, hyperfibrinolysis and osteonocrosis. Clin Orthop Relat Res 1999; 366: 133-146.
• 6 Griffith JF. et al. Osteonecrosis of hip an knee in patients with severe acute respiratory syndrome treated with steroids. Radiology 2005; 235: 168-175.
• 7 Fischer T, Wildt L. Glucocorticoids and HELLPSyndrom. Gynäkologe 1999; 32: 783-790.
• 8 Hirota Y. et al. Association of alcohol intake, cigarette smoking an occupational status with the risk of idiopathic steonecrosis of the femoral head. Am J Epidemiol 1993; 137: 530-538.
• 9 Hofmann S. et al. Die Osteonekrose im Erwachsenenalter. In: Wirth CJ, Zichner L. Orthopädie und Orthopädische Chirurgie—Becken, Hüfte. Stuttgart, New York: Thieme; 2002: 289-306.
• 10 Hong N, Du XK. Avascular necrosis of bone in severe acute respiratory syndrome. Clin Radiolog 2004; 59: 602-608.
• 11 Jäger M, Krauspe R. Osteonekrose: Pathogenese—Diagnostik—Therapie—Verlauf. Auflage. Bremen: UNI-MED; 2007
• 12 Jones JP. Epidemiologische Risikofaktoren für die nichttraumatische Osteonekrose. Orthopäde 2000; 29: 370-379.
• 13 Jones LC, Hungerford DS. Osteonecrosis: etiology, diagnosis and treatment. Current Opin Rheumatology 2004; 16: 443-449.
• 14 Kabata T. et al. Onset of steroid-induced osteonecrosis in rabbits and its relationship to hyperlipidaemia and increased free fatty acids. Rheumatology 2005; 44: 1233-1237.
• 15 Kang P. et al. Effects of an anticoagulant and a lipid-lowering agent on the prevention of steroidinduced osteonecrosis in rabbits. Int J Exp Pathology 2010; 91: 235-243.
• 16 Katz K. et al. The pattern of bone disease in transfusion-dependent thalassemia major patients. Isr J Med Sci 1994; 30: 577-580.
• 17 Kenzora JE. Ischemic necrosis of femoral head, Part I. Accumulative cell stress: a hypothesis for the etiology of idiopathic osteonecrosis. Instr Course Lect 1983; 36: 633-636.
• 18 Kerachian MA. et al. New insights into the pathogenesis of glucocorticoid-induced avascular necrosis. Arthritis Research& Therapy 2010; 12: R124.
• 19 Lieberman JR. et al. Osteonecrosis of the hip: Management in the twenty-first century. J Bone Joint Surg Am 2002; 94: 833-853.
• 20 Liu YF. et al. Type II collagen gene variants and inherited osteonecrosis of the femoral head. N Engl J Med 2005; 352 (22) 2294-2301.
• 21 Matsuo K. et al. Influence of alcohol intake, cigarette smoking and accupational status on idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res 1988; 234: 115-123.
• 22 McColl MD. et al. Risk factors for pregnancy associated venous thromboembolism. Thromb Haemost 1997; 78: 1183-1188.
• 23 Mont MA, Hungerford DS. Current concepts Review: Non traumatic avascular necrosis of the femoral head. J Bone Joint Surg 1995; 77: 459-474.
• 24 Mont MA, Jones LC, Hungerford DS. Current concepts Review: Non traumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg 2006; 88: 1117-1132.
• 25 Mwale D. et al. Abnormal vascular endothelial growth factor expression in mesenchymal stem cells from both osteonecrotic and osteoarthritic hips. Bull NYU Hospital Joint Disea 2011; 69 (Suppl. 01) 56-61.
• 26 Nobillot R. et al. Idiopathic osteonecrosis of the hip in twins. Ann Rheum Disease 1994; 53: 702.
• 27 Orlic D. et al. Frequency of idiopathic aseptic necrosis in medically treated alcoholics. Int Orthop 1990; 14: 383-386.
• 28 Powell C. et al. Steroid induced osteonecrosis: An analysis of steroid dosing risk. Autoimmunity Reviews 2010; 9: 721-743.
• 29 Rader CP. et al. Ergebnisse der Hüftkopfanbohrung bei der Hüftkopfnekrose des Erwachsenen—4 bis 18 Jahre Verlaufskontrolle. Z Orthop 1997; 135: 494-498.
• 30 Seguin C. et al. Non-traumatic necrosis of bone (osteonecrosis) is associated with enfothelial cell activation but not thrombophilia. Rheumatology 2008; 47: 1151-1155.
• 31 Tong P. et al. Gene expression profile of steroid-induced necrosis of femoral head of rats. Calcif Tissue Int 2011; 89 (04) 271-284.
• 32 Wang G. et al. Changes in femoral head blood supply and vascular endothelial growth factors. J Int Med Res 2010; 38: 1060-1069.
• 33 Wang GJ. et al. The pathogenesis and prevention of steroid induced osteonecrosis. Clin Orthop 2000; 370: 295-310.
• 34 Wang Y. et al. Alcohol-induced adipogenesis in bone and marrow: a possible mechanism for osteonecrosis. Clin Orthop 2003; 410: 213-224.