Zusammenfassung
Ziel der Studie war die histomorphometrische und biomechanische Abschätzung des Einflusses der diabetischen Stoffwechsellage auf die Knochendefektheilung in Abhängigkeit von der Defektgröße bei spontandiabetischen BB/OK-Ratten. Anhand der Blutglukosespiegel und des Insulinbedarfs postoperativ wurden 120 spontandiabetische BB/OK-Ratten mit guter und schlechter diabetischer Stoffwechselführung gruppiert. 60 LEW.1A-Ratten dienten als normoglykämische Kontrolltiere. Knochendefekte unterschiedlicher Größe im distalen Femur wurden nach 2, 4 und 6 Wochen Heilung untersucht. Ausschließlich bei den Ratten mit schlechter diabetischer Stoffwechsellage zeigte sich bei einer Defektgröße ab 0,8 mm eine signifikante Abnahme struktureller Kalkulationen und bei einer Defektgröße ab 1,2 mm signifikant verringerte fluorochromabhängige Parameter für die Mineralisation, sowie eine signifikante Abnahme der biomechanischen Eigenschaften im Vergleich zu den Ratten mit guter diabetischer Stoffwechselführung und den Kontrollratten. Die Knochendefektheilung kleiner Defekte ist unabhängig von der diabetischen Stoffwechsellage spontandiabetischer BB/OK-Ratten. Mit kontrollierter Insulintherapie und resultierender guter diabetischer Stoffwechsellage können die schweren histomorphometrischen und biomechanischen Störungen bei der Knochendefektheilung größerer Defekte mit schlechter diabetischer Stoffwechsellage verhindert werden.
Abstract
The objective of this study was to examine changes in the histomorphometric and mechanical evaluation of the influence of the diabetic metabolic state on defect healing depending on the defect size in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats. Based on blood glucose levels and postoperative insulin requirements, 120 spontaneously diabetic BB/OK rats were divided into groups with well-compensated or poorly compensated metabolic state. Sixty LEW.1A rats served as the normoglycemic controls. Bone defects of different sizes were created proximal to the knee joint space and then allowed to heal for 2, 4, and 6 weeks. Bone defect sizes ≥0.8 mm showed significant differences in the structural calculations and bone defect sizes ≥1.2 mm showed a significant decrease of all fluorochrome-based parameters of mineralization exclusively in the rats with poorly compensated diabetic metabolic state as well as significantly decreased values of biomechanical properties in comparison to the spontaneously diabetic rats with well-compensated metabolic states and to the control rats. Bone repair of minor bone defects is independent of the diabetic metabolic state in the spontaneously diabetic BB/OK rats. With controlled insulin therapy and resultant well-compensated diabetic metabolic state, severe mineralization and biomechanical disorders in healing of larger bone defects in the poorly compensated diabetic metabolic state of the experimental animal can be avoided.
Literatur
Aickin M, Gensler H (1996) Adjusted for multiple testing when reporting research results: the Bonferroni vs Holm methods. Am J Publ Health 86: 726–728
Beam HA, Parsons JR, Li SS (2002) The effects of blood glucose control upon fracture healing in the BB Wistar rat with diabetes mellitus. J Orthop Res 20: 1210–1216
Brandle M, Zhou H, Smith BR et al. (2003) The direct medical cost of type 2 diabetes. Diabetes Care 26: 2300–2304
Diwan AD, Wang MX, Jang D, Zhu W, Murrell GAC (2000) Nitric oxid modulates fracture healing. J Bone Miner Res 15: 342–351
Einhorn T, Boskey AL, Gundberg CM, Vigorita VJ, Devlin VJ, Beyer MM (1988) The mineral and mechanical properties of bone in chronic experimental diabetes. J Orthop Res 6: 317–323
Funk JR, Hale JE, Cairmines D, Gooch HL, Hurwitz SR (2000) Biomechanical evaluation of early fracture healing in normal and diabetic rats. J Orthop Res 18: 126–132
Gordois A, Scuffham P, Shearer A, Oglesby A (2003) The health care costs of peripheral neuropathy for people with diabetes in the U.S. Diabetes Care 26: 1790–1795
el-Hakim IE (1999) The effect of fibrin stabilizing factor (F. XIII) on healing of bone defects in normal and uncontrolled diabetic rats. Int J Oral Maxillofac Surg 28: 304–308
Hunger-Dathe W, Braun A, Muller UA, Schiel R, Femerling M, Risse A (2003) Insulin pump therapy in patients with Type 1 Diabetes mellitus: Results of the Nationwide Quality Circle in Germany (ASD) 1999–2000. Exp Clin Endocrinol Diabetes 111: 428–434
Klöting I (1987) Differences between LEW rats and their congenic LEW.1A and LEW.1 W strains in body weight gain, plasma glucose and some hematologic traits. Z Versuchstierkd 29: 75–78
Klöting I, Voigt L (1991) BB/O(ttawa)K(arlsburg) rats: Features of a subline of diabetes-prone BB rats. Diabetes Res 18: 79–87
Klöting I, van den Brandt J, Kuttler B (2001) Genes of SHR rats protect spontaneously diabetic BB/OK rats from diabetes: Lessons from congenic BB.SHR rat strains. Biochem Biophys Res Commun 283: 399–405
Liebl A, Spannheimer A, Reitberger U, Gortz A (2002) Costs of long-term complications in type 2 diabetes patients in Germany. Results of the CODE-2 Study. Med Klin (Munich) 15: 713–719
Macey LR, Kana SM, Jingushi S, Terek RM, Borretos J, Bolander ME (1989) Defects of early fracture-healing in experimental diabetes. J Bone Joint Surg Am 71: 722–733
Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Maluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardisation of nomenclatur, symbols, and units. J Bone Miner Res 2: 595–610
Reddy GK, Stehno-Bittel L, Hamade S, Enwemeka CK (2001) The biomechanical integrity of bone in experimental diabetes. Diabetes Res Clin Pract 54: 1–8
Schenk RK, Olah AJ, Herrmann W (1984) Preparation of calcified tissues for light microscopy. In: Dickson GR (Hrsg) Methods of calcified tissues preparation. Elsevier, Amsterdam New York Oxford, pp 1–56
Seino Y, Ishida H (1995) Diabetic osteopenia: pathophysiology and clinical aspects. Diabetes Metab Rev 11: 21–35
Shearer A, Scuffham P, Gordois A, Oglesby A (2003) Predicted costs and outcomes from reduced vibration detection in people with diabetes in the US. Diabetes Care 26: 2305–2310
Simske SJ, Bateman TA, Smith EE, Ferguson VL, Chapes SK (2002) Effects of major histocompatibility complex class II knockout on mouse bone mechanical properties during development. Biomed Sci Instrum 38: 47–52
Steel RGD, Torrie JH (1981) Principles and procedures of statistics. A biometrical approach. McGraw-Hill, Singapore
Topping RE, Bolander ME, Balian G (1995) Type X Collagen in fracture callus and the effects of experimental diabetes. Clin Orthop 308: 220–228
Turner CH, Burr DB (1993) Basic biomechanical measurements of bone: a tutorial. Bone 14: 595–608
Verhaeghe J, Suiker AMH, Visser WJ, van Herck E, van Bree R, Bouillon R (1992) The effects of systemic insulin, insulin-like growth factor-I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats. Endocrinology 134: 485–492
Verhaeghe J, Thomssen JS, van Bree R, van Herck E, Bouillon R, Mosekilde L (2000) Effects of exercise and disuse on bone remodelling, bone mass, and biomechanical competencs in spontaneously diabetic female rats. Bone 27: 249–256
Wagenpfeil S, Neiss A, Goertz A, Reitberger U, Stammer H, Spannheimer A, Liebl A (2002) Bootstrap confidence intervals for costs-of-illness of type 2 diabetes mellitus in Germany. Value Health 5: 397–403
Weiss RE, Reddi AH (1980) Influence of experimental diabetes and insulin on matrix-induced cartilage and bone differentiation. Am J Physiol (Endocrinol Metab) 238: 200–207
Wolf E, Röser K, Hahn M, Welkerling H, Delling G (1992) Enzyme and immunohistochemistry on undecalcified bone and bone marrow biopsies after embedding in plastic: a new embedding method for routine application. Virchows Arch Pathol Anat 420: 17–24
Interessenkonflikt:
Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Follak, N., Klöting, I. & Merk, H. Knochenheilung in Bohrlochdefekten spontandiabetischer BB/OK-Ratten. Unfallchirurg 107, 750–760 (2004). https://doi.org/10.1007/s00113-004-0803-1
Issue Date:
DOI: https://doi.org/10.1007/s00113-004-0803-1