Subscribe to RSS
DOI: 10.1055/s-2000-10130
Georg Thieme Verlag Stuttgart · New York
Eine antiosteolytische Therapie bewahrt die Trabekelstruktur und die mechanischen Eigenschaften des Knochens in Tumorosteolysen
Anti-Osteolytic Therapy Preserves Trabecular Architecture and Mechanical Properties of Bone in Tumor Osteolysis.Publication History
Publication Date:
31 December 2000 (online)
Zusammenfassung.
Fragestellung: Da über den Effekt von tumorinduzierten Osteolysen auf die Mikroarchitektur des Knochens und die Knochenmasse wenig bekannt ist, haben wir die Technologie der Mikro-Computer-Tomographie (μCT) in einem etablierten Tiermodel zur Bestimmung der Knochenqualität in Tumorosteolysen angewandt. Das Ziel der vorliegenden Untersuchung war die Analyse der Veränderungen der Mikrostruktur des Knochens durch den Tumor und der Einfluss einer interventionellen antiosteolytischen Therapie mit einem Bisphosphonat. Methode: Zur Bestimmung der Knochenmasse und der Mikrostrukturparameter in Tumorosteolysen wurden 60 Rattenfemora, nach der Implantation von Walker-256-Tumorzellen und einer interventionellen Therapie mit einem Bisphosphonat, in einem μCT mit 200 Schnitten mit einem Schnittabstand von 30 μm gemessen. Zur Beurteilung der biomechanischen Eigenschaften der Knochen wurden alle Femora einem Torsionstest unterzogen und die maximale Torsionskraft und die Steifigkeit berechnet. Ergebnisse: Es zeigte sich klar, dass die Osteoklasten vermittelte Resorption des Knochens zu einer signifikanten Abnahme der Knochenmasse, der Knochenstabilität und der Mikrostrukturparameter führte. Eine Abnahme der Anzahl der Trabekel um 32 %, der Dicke der Trabekel um 11 %, des Knochenvolumens um 43 % und eine Zunahme des Abstandes der Trabekel von 83 % in den Osteolysen zeigen klar die Zerstörung des trabekularen Knochens durch den Tumor. Eine interventionelle Behandlung der Tiere mit einem Bisphosphonat resultierte in einer Zunahme des Knochenmineralgehaltes um 56 % und der maximale Torsionskraft um 72 % gegenüber den unbehandelten Kontrollknochen. Das Knochenvolumen nahm unter einer interventionellen Behandlung um 106 % zu, der Abstand der Trabekel nahm um 73 % ab und die Trabekeldicke nahm um 95 % zu. Schlussfolgerung: Diese Ergebnisse lassen den Schluss zu, dass eine Therapie mit dem Bisphosphonat Ibandronat von großem Vorteil in Bezug auf die Knochenqualität in Tumorosteolysen ist.
Purpose of the study: Little is known about the effect of a tumor on the trabecular architecture, therefore we employed an animal model for the assessment of bone quality in tumor osteolysis to determine the alterations of the trabecular architecture in tumor osteolysis and after an interventional treatment with a bisphosphonate. Methods: To assess the bone mass and the micro-architecture of the trabecular bone in tumor osteolysis we employed a micro-computed tomography system. For the assessment of the mechanical properties of the treated and non-treated tumor-bearing bones we used a torsion test. Results: The presence of a tumor in bone resulted in a reduction of bone mass, stability and architectural parameters. An interventional treatment of the animals with a bisphosphonate increased the bone mineral content, mechanical and architectural parameters compared to the non-treated, tumor-bearing animals. Conclusions: These results clearly show a beneficial effect of an antiosteolytic treatment with a bisphosphonate in regard of bone quality in tumor-induced osteolysis.
Schlüsselwörter:
Tumorosteolysen - Trabekelstruktur - Knochenqualität - Bisphosphonattherapie
Key words:
Bone quality - tumor osteolysis - trabecular architecture - bisphosphonate treatment
Literatur
- 01 Amling M, Delling G. Osteoklastenbiologie. Orthopäde. 1998;; 27 214-223
- 02 Bauss F. Ibandronate in malignant bone diseases and osteoporosis-preclinical results. Onkologie. 1997;; 20 204-208
- 03 Body J J. Metastatic bone disease: clinical and therapeutic aspects. Bone 13. 1992;; 1 57-62
- 04 Boissier S, Magnetto S, Frappart L, Cuzin B, Ebetino F H, Delmas P D, Clezardin P. Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res. 1997;; 57 3890-3894
- 05 Coleman R E. Skeletal complications of malignancy. Cancer. 1997;; 80 1588-1594
- 06 Crone-Mänzenbrock W, Carl U M. Dual-energy Ct-scan quantification of recalcification in osteolyses of the vertebral body due to mammary carcinoma in the course of antineoplastic treatment. Clin Expl Metastasis. 1990;; 8 173-179
- 07 Diel I J, Solomayer E F, Costa S D, Gollan C, Goemer R, Wallwiener D, Kaufmann M, Bastert G. Reduction in new metastases in breast cancer with adjuvant clodronate treatment. Engl J Med. 1998;; 6 357-363
- 08 Felsenberg D, Gowin W. Knochendichtemessung mit Zwei-Spektren-Methoden. Radiologe. 1999;; 39 186-193
- 09 Ferretti J L, Mondelo N, Capozza R F, Cointiy G R, Zanchetta J R, Montouri E. Effect of large dosis of olpadronate (dimethyl-pamidronate) on mineral density, cross-secional architecture, and mechanical properties of rat femurs. Bone. 1995;; 6 285-293
- 10 Fleisch H. The bisphosphonate ibandronate, given daily as well as discontinuously, decreases bone resorption and increases calcium retention as assessed by 45Ca kinetics in the intact rat. Osteoporos Int. 1996;; 6 166-170
- 11 Galasko C BS. The role of the orthopaedic surgeon in the treatment of bone pain. Cancer Surv. 1988;; 7 103-125
- 12 Genant H K, Lang T F, Engelke K, Glüer C C, Majumdar S, Jergas M. Advances in the noninvasive assessment of bone density, quality, and structure. Calcif Tissue lnt. 1996;; 59 10-15
- 13 Guaitani A, Polentarutti N, Filippeschi S, Marmonti L, Corti F, Italia C, Coccioli G, Donelli M G, Mantovani A, Garattini S. Effects of disodium etidronate in murine tumor models. Eur J Cancer Clin Oncol. 1984;; 20 685-693
- 14 Guy J A, Shea M, Morrissey R, Hayes W C. Continuous alendronate treatment throughout growth, maturation, and aging in the rat results in increases bone mass and mechanical properties. Calcif Tissue Int. 1993;; 53 283-288
- 15 Hipp J A, Springfield D, Hayes W C. Predicting pathologie fracture risk in the management of metastatic bone defects. Clin Orthop Rel Res. 1995;; 312 120-135
- 16 Hortobagyi G N, Theriault R L, Porter L, Blayney D, Lipton A, Sinoff C, Wheeler H, Simeone J F, Seaman J, Knight R D. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group. N Engl J Med. 1996;; 335 1785-1791
- 17 Jung A, Bornard J, Mermillod B, Edouard C, Meunier P J. Inhibition by diphosphonates of bone resorption induced by the Walker tumor of the rat. Cancer Res. 1984;; 44 3007-3011
- 18 Kanis J A, Powels T, Paterson A H, McCloskey E, Ashley S. Clodronate decreases the frequency of skeletal metastases in women with breast cancer. Bone. 1996;; 19 663-667
- 19 Kinney J H, Ryaby J T, Haupt D L, Lane N E. Three-dimensional in vivo morphometry of trabecular bone in the OVX rat model of osteoporosis. Technol Health Care. 1998;; 6 339-350
- 20 Krempien B, Bu P. Experimental studies on the influence of the bisphosphonate CL2MBP on bone conditioned media and their effect on tumor cell growth in vitro. J Bone Mineral Res. 1994;; 9 424
- 21 Kurth A A, Kim S-Z, Bauss F, Sedelmeyer I, Shea M. Preventative treatment with ibandronate improves bone quality in rat femora with tumor-induced osteolytic defects. Proceedings Orthopaedic Research Society 1998;: 566
- 22 Kurth A A, Kim S-Z, Sedelmeyer I, Hovy L, Bauss F. Treatment with Ibandronate preserves bone in experimental tumor-induced bone loss. J Bone Joint Surg [Br]. 2000;; 82-B 126-130
- 23 Kurth A A, Wang C, Shea M, Hayes W C. An animal model for the evaluation of biomechanical and densitometric properties of tumor induced bone loss. European Orthopaedic Research Society Annual Meeting 1997;: 17
- 24 Lane N E, Haupt D, Kimmel D B, Modin G, Kinney J H. Early estrogen replacement therapy reverses the rapid loss of trabecular bone volume and prevents further deterioration of connectivity in the rat. J Bone Miner Res. 1999;; 14 206-214
- 25 Mattila P, Knuuttila M, Kovanen V, Svanberg M. Improved Bone Biomechanical Properties in Rats after Oral Xylitol Administration. Calcif Tissue Int. 1999;; 64 340-344
- 26 Merz W A, Schenk R K. Quantitative structural analysis of human cancellous bone. Acta Anat. 1970;; 75 54-66
- 27 Müller R, Gerber S C, Hayes W C. Micro-compression: a novel technique for the nondestructive assessment of local bone failure. Technol Health Care. 1998;; 6 433-444
- 28 Müller R, Van Campenhout H, Van Damme B, Van Der Perre G, Dequeker J, Hildebrand T, Rüegsegger P. Morphometrie analysis of human bone biopsies: a quantitative structural comparison of histological sections and micro-computed tomography. Bone. 1998;; 23 59-66
- 29 Nemoto R, Sato S, Nishijima Y, Miakawa I, Koiso K, Harada M. Effects of a new bisphosphonate (AHBuBP) on osteolysis induced by human prostate cancer cells in nude mice. J Urol. 1990;; 144 770-774
- 30 Odgaard A. Three-dimensional methods for quantification of cancellous bone architecture. Bone. 1997;; 20 315-328
- 31 Orr F W, Sanchez-Sweatman O H, Kostenuik P, Singh G. Tumor-bone interactions in skeletal metastasis. Clin Orthop. 1995;; 312 19-33
- 32 Parfitt A M, Drezner M K, Glorieux F H et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res. 1987;; 2 595-610
- 33 Ravn P, Clemmesen B, Riis B J, Christiansen C. The effect on bone mass and bone markers of different doses of ibandronate: a new bisphosphonate for prevention and treatment of postmenopausal osteoporosis: a 1-year, randomized, double-blind, placebo-controlled dose-finding study. Bone. 1996;; 19 527-533
- 34 Reinbold W D, Wannemacher M, Hodapp N, Adler C P. Osteodensitometry of vertebral metastases after radiotherapy using quantitative computed tomography. Skeletal Radiology. 1989;; 18 517-521
- 35 Rizzoli R, Forni M, Schaad M A, Slosman D O, Sappino A P, Garcia J, Bonjour J P. Effects of oral clodronate on bone mineral density in patients with relapsing breast cancer. Bone. 1996;; 18 531-537
- 36 Rubens R D. Metastatic breast cancer. Curr Opin Oncol. 1993;; 5 991-995
- 37 Rüegsegger P, Koller B, Müller R. A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int. 1996;; 58 24-29
- 38 Sasaki A, Boyce B F, Story B, Wright K R, Chapman M, Boyce R, Mundy G R, Yoneda T. Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice. Cancer Res. 1995;; 55 3551-3557
-
39 Statistisches Bundesamt (Hrsg.).
Statistisches Jahrbuch der Bundesrepublik Deutschland 1995 (Gesundheitswesen). Metzler und Poeschel Stuttgart; 1995: - 40 Toolan B C, Shea M, Myers E R, Borchers R E, Seedor J G, Quartuccio H, Rodan G, Hayes W C. Effects of 4-amino-1-hydroxybutilidene bisphosphonate on bone biomechanics in rats. J Bone Miner Res. 1992;; 7 1399-1406
- 41 Wingen F, Schmahl D. Distribution of 3-amino-1-hydroxypropane-1,1-diphosphonicacid in rats and effects on rat osteosarcoma. Arzneimittelforschung. 1985;; 35 1565-1571
- 42 Xiao J, Müller R, Stevens M, Golden J, Seeherman H, Bouxsein M L. Evaluation of trabecular bone morphometry: Comparison of micro-computed tomography and histomorphometry in the rat proximal tibia. Bone. 1998;; 23 635
- 43 Yoneda T, Sasaki A, Dunstan C, Williams P J, Bauss F, De Clerck Y A. Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2. J Clin Invest. 1997;; 99 2509-2517
Dr. med. Andreas A. Kurth
Orthopädische Universitätsklinik Stiftung Friedrichsheim
Marienburgstr. 2
60528 Frankfurt/Main
Phone: Tel. 4 96 96 70 50
Fax: Fax 4 96 96 70 53 75
Email: E-mail: A.Kurth@em.uni-frankfurt.de