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Erschienen in: Journal of Bone and Mineral Metabolism 6/2010

01.11.2010 | Original Article

Treatment of experimental osteonecrosis of the hip in adult rabbits with a single local injection of recombinant human FGF-2 microspheres

verfasst von: Yutaka Kuroda, Haruhiko Akiyama, Keiichi Kawanabe, Yasuhiko Tabata, Takashi Nakamura

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 6/2010

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Abstract

Basic fibroblast growth factor (FGF-2) exerts anabolic actions on bone formation. Here we investigated the potential effects of recombinant human FGF-2 (rhFGF-2) on the repair process of osteonecrosis of the femoral head (ONFH) and the development of secondary osteoarthritis (OA) in adult rabbits. ONFH was induced by intramuscular injection with methylprednisolone, and vascular occlusion of the capital femoral epiphysis by electrocoagulation, in adult Japanese white rabbits. Animals were randomized into two groups: treatment and control. The treatment group was given a single local injection into the femoral head of 100 μg rhFGF-2 in 100 μl gelatin hydrogel microspheres 8 weeks after the ONFH procedure, and the control group was given phosphate-buffered saline in 100 μl gelatin hydrogel microspheres. Morphological, histopathological, and radiologic analyses, including micro-computed tomography scans and magnetic resonance imaging, showed collapse of the femoral head and progression of articular cartilage degeneration in the control group at 16 weeks after the single local injection of rhFGF-2. In contrast, rhFGF-2 treatment resulted in new bone formation in the femoral head and prevented the femoral head from collapsing. In addition, the changes in OA, assessed by the modified Mankin score, was significantly lower in the treatment group. Our results indicate that a single local injection of rhFGF-2 microspheres promoted the repair of the osteonecrotic femoral head and inhibited femoral head collapse and OA progression. rhFGF-2 may be a promising strategy for the treatment of ONFH.
Literatur
1.
Zurück zum Zitat Hernigou P, Ooignard A, Nogier A, Manicom O (2004) Fate of very small asymptomatic stage-I osteonecrotic lesions of the hip. J Bone Joint Surg Am 86:2589–2593PubMed Hernigou P, Ooignard A, Nogier A, Manicom O (2004) Fate of very small asymptomatic stage-I osteonecrotic lesions of the hip. J Bone Joint Surg Am 86:2589–2593PubMed
2.
Zurück zum Zitat Mont MA, Jones LC, Hngerford DS (2006) Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am 88:1117–1132CrossRefPubMed Mont MA, Jones LC, Hngerford DS (2006) Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am 88:1117–1132CrossRefPubMed
3.
Zurück zum Zitat Marker DR, Seylee TM, McGrath MS, Delanois RE, Ulrich SD, Mont MA (2008) Treatment of early stage osteonecrosis of the femoral head. J Bone Joint Surg Am 90:175–187CrossRefPubMed Marker DR, Seylee TM, McGrath MS, Delanois RE, Ulrich SD, Mont MA (2008) Treatment of early stage osteonecrosis of the femoral head. J Bone Joint Surg Am 90:175–187CrossRefPubMed
4.
Zurück zum Zitat Mont MA, Jones LC, Einhorn TA, Hungerford DS, Reddi AH (1998) Osteonecrosis of the femoral head: potential treatment with growth and differentiation factors. Clin Orthop Relat Res 355:314–335CrossRef Mont MA, Jones LC, Einhorn TA, Hungerford DS, Reddi AH (1998) Osteonecrosis of the femoral head: potential treatment with growth and differentiation factors. Clin Orthop Relat Res 355:314–335CrossRef
5.
Zurück zum Zitat Lieberman JR, Conduah A, Urist MR (2004) Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein. Clin Orthop Relat Res 429:139–145CrossRefPubMed Lieberman JR, Conduah A, Urist MR (2004) Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein. Clin Orthop Relat Res 429:139–145CrossRefPubMed
6.
Zurück zum Zitat Gangji V, Hauzeur JP, Matos C, De Maertelaer V, Toungouz M, Lambermont M (2004) Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells: a pilot study. J Bone Joint Surg Am 86:1153–1160PubMed Gangji V, Hauzeur JP, Matos C, De Maertelaer V, Toungouz M, Lambermont M (2004) Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells: a pilot study. J Bone Joint Surg Am 86:1153–1160PubMed
7.
Zurück zum Zitat Hernigou P, Beaujean F (2002) Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res 405:14–23CrossRefPubMed Hernigou P, Beaujean F (2002) Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res 405:14–23CrossRefPubMed
8.
Zurück zum Zitat Desai MM, Sonone S, Bhasme V (2005) Efficacy of alendronate in the treatment of avascular necrosis of the hip. Rheumatology 44:1331–1332CrossRefPubMed Desai MM, Sonone S, Bhasme V (2005) Efficacy of alendronate in the treatment of avascular necrosis of the hip. Rheumatology 44:1331–1332CrossRefPubMed
9.
Zurück zum Zitat Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT, Lin RM (2005) The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. J Bone Joint Surg Am 87:2155–2159CrossRefPubMed Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT, Lin RM (2005) The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. J Bone Joint Surg Am 87:2155–2159CrossRefPubMed
10.
Zurück zum Zitat Cui Q, Wang CJ, Su CC, Balian G (1997) Lovastatin prevents steroid induced adipogenesis and osteonecrosis. Clin Orthop Relat Res 344:8–19CrossRefPubMed Cui Q, Wang CJ, Su CC, Balian G (1997) Lovastatin prevents steroid induced adipogenesis and osteonecrosis. Clin Orthop Relat Res 344:8–19CrossRefPubMed
11.
Zurück zum Zitat Pritchett JW (2001) Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin Orthop Relat Res 386:173–178CrossRefPubMed Pritchett JW (2001) Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin Orthop Relat Res 386:173–178CrossRefPubMed
12.
Zurück zum Zitat Canalis E, Centrella M, McCarthy T (1988) Effects of basic fibroblast growth factor on bone formation in vitro. J Clin Invest 81:1572–1577CrossRefPubMed Canalis E, Centrella M, McCarthy T (1988) Effects of basic fibroblast growth factor on bone formation in vitro. J Clin Invest 81:1572–1577CrossRefPubMed
13.
Zurück zum Zitat Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone biology and clinical applications. J Bone Joint Surg Am 84:1032–1044PubMed Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone biology and clinical applications. J Bone Joint Surg Am 84:1032–1044PubMed
14.
Zurück zum Zitat Itoh N, Orniz DM (2004) Evolution of the Fgf and Fgfr gene families. Trends Genet 20:563–569CrossRefPubMed Itoh N, Orniz DM (2004) Evolution of the Fgf and Fgfr gene families. Trends Genet 20:563–569CrossRefPubMed
15.
Zurück zum Zitat Kato T, Kawaguchi H, Hanada K, Aoyama Y, Nakamura T, Kuzutani K, Tamura M, Kurokawa T, Nakamura K (1998) Single local injection of recombinant fibroblast growth factor-2 stimulates healing of segmental bone defects in rabbit. J Orthop Res 16:654–659CrossRefPubMed Kato T, Kawaguchi H, Hanada K, Aoyama Y, Nakamura T, Kuzutani K, Tamura M, Kurokawa T, Nakamura K (1998) Single local injection of recombinant fibroblast growth factor-2 stimulates healing of segmental bone defects in rabbit. J Orthop Res 16:654–659CrossRefPubMed
16.
Zurück zum Zitat Nakamura T, Hara Y, Tagawa M, Yuge T, Fukuda H, Nigi H (1998) Recombinant human basic fibroblast growth factor accelerates fracture healing by enhancing callus remodeling in experimental dog tibial fracture. J Bone Miner Res 13:942–949CrossRefPubMed Nakamura T, Hara Y, Tagawa M, Yuge T, Fukuda H, Nigi H (1998) Recombinant human basic fibroblast growth factor accelerates fracture healing by enhancing callus remodeling in experimental dog tibial fracture. J Bone Miner Res 13:942–949CrossRefPubMed
17.
Zurück zum Zitat Chen WJ, Jingushi W, Aoyama I, Anzai J, Hirata G, Tamura M, Iwamoto Y (2004) Effects of FGF-2 on metaphyseal fracture in rabbit tibiae. J Bone Miner Metab 22:303–309CrossRefPubMed Chen WJ, Jingushi W, Aoyama I, Anzai J, Hirata G, Tamura M, Iwamoto Y (2004) Effects of FGF-2 on metaphyseal fracture in rabbit tibiae. J Bone Miner Metab 22:303–309CrossRefPubMed
18.
Zurück zum Zitat Tabata Y, Nagano A, Ikada Y (1999) Biodegradation of hydrogel carrier incorporating fibroblast growth factor. Tissue Eng 5:127–147CrossRefPubMed Tabata Y, Nagano A, Ikada Y (1999) Biodegradation of hydrogel carrier incorporating fibroblast growth factor. Tissue Eng 5:127–147CrossRefPubMed
19.
Zurück zum Zitat Yamamoto M, Ikeda Y, Tabata Y (2001) Controlled release of growth factors based on biodegradation of gelatin hydrogel. J Biomater Sci Polym Ed 12:77–88CrossRefPubMed Yamamoto M, Ikeda Y, Tabata Y (2001) Controlled release of growth factors based on biodegradation of gelatin hydrogel. J Biomater Sci Polym Ed 12:77–88CrossRefPubMed
20.
Zurück zum Zitat Tabata Y (2003) Tissue regeneration based on growth factor release. Tissue Eng 9(suppl 1):S5–S15CrossRefPubMed Tabata Y (2003) Tissue regeneration based on growth factor release. Tissue Eng 9(suppl 1):S5–S15CrossRefPubMed
21.
Zurück zum Zitat Tabata Y, Yamada K, Miyamoto S, Nagata I, Kikuchi H, Aoyama I, Tamura M, Ikada Y (1998) Bone regeneration by basic fibroblast growth factor complexed with biodegradable hydrogel. Biomaterials 19:807–815CrossRefPubMed Tabata Y, Yamada K, Miyamoto S, Nagata I, Kikuchi H, Aoyama I, Tamura M, Ikada Y (1998) Bone regeneration by basic fibroblast growth factor complexed with biodegradable hydrogel. Biomaterials 19:807–815CrossRefPubMed
22.
Zurück zum Zitat Tabata Y, Hijikata S, Muniruzzaman M, Ikada Y (1999) Neovascularization through biodegradable gelatin microspheres incorporating basic fibroblast growth factor. J Biomater Sci Polym Ed 10:79CrossRefPubMed Tabata Y, Hijikata S, Muniruzzaman M, Ikada Y (1999) Neovascularization through biodegradable gelatin microspheres incorporating basic fibroblast growth factor. J Biomater Sci Polym Ed 10:79CrossRefPubMed
23.
Zurück zum Zitat Sakakibara Y, Nishimura K, Tambara K, Yamamoto M, Lu F, Tabata Y, Komeda M (2001) Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation. J Thorac Cardiovasc Surg 124:50CrossRef Sakakibara Y, Nishimura K, Tambara K, Yamamoto M, Lu F, Tabata Y, Komeda M (2001) Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation. J Thorac Cardiovasc Surg 124:50CrossRef
24.
Zurück zum Zitat Kawaguchi H, Jingushi S, Izumi M, Fukunaga M, Matsushita T, Nakamura T, Mizuno K, Nakamura T, Nakamura K (2007) Local application of recombinant human fibroblast growth factor-2 on bone repair: a dose-escalation prospective trial on patients with osteotomy. J Orthop Res 25:480–487CrossRefPubMed Kawaguchi H, Jingushi S, Izumi M, Fukunaga M, Matsushita T, Nakamura T, Mizuno K, Nakamura T, Nakamura K (2007) Local application of recombinant human fibroblast growth factor-2 on bone repair: a dose-escalation prospective trial on patients with osteotomy. J Orthop Res 25:480–487CrossRefPubMed
25.
Zurück zum Zitat Tabata Y, Yamada K, Hong L, Miyamoto S, Hashimoto N, Ikada Y (1999) Skull bone regeneration in primates in response to basic fibroblast growth factor. J Neurosurg 91:851CrossRefPubMed Tabata Y, Yamada K, Hong L, Miyamoto S, Hashimoto N, Ikada Y (1999) Skull bone regeneration in primates in response to basic fibroblast growth factor. J Neurosurg 91:851CrossRefPubMed
26.
Zurück zum Zitat Norman D, Reis D, Zinman G, Misselevich I, Boss JH (1998) Vascular deprivation-induced necrosis of the femoral head of the rat. An experimental model of avascular osteonecrosis in the skeletally immature individual or Legg–Perthes disease. Int J Exp Pathol 79:173–181CrossRefPubMed Norman D, Reis D, Zinman G, Misselevich I, Boss JH (1998) Vascular deprivation-induced necrosis of the femoral head of the rat. An experimental model of avascular osteonecrosis in the skeletally immature individual or Legg–Perthes disease. Int J Exp Pathol 79:173–181CrossRefPubMed
27.
Zurück zum Zitat Hofstaetter JG, Wang J, Yan J, Glimcher MJ (2009) The effects of allendronate in the treatment of experimental osteonecrosis of the hip on adult rabbits. Osteoarthritis Cartil 17:362–370CrossRef Hofstaetter JG, Wang J, Yan J, Glimcher MJ (2009) The effects of allendronate in the treatment of experimental osteonecrosis of the hip on adult rabbits. Osteoarthritis Cartil 17:362–370CrossRef
28.
Zurück zum Zitat Okano K, Enomoto H, Osaki M, Shindo H (2008) Rotational acetabular osteotomy for advanced osteoarthritis secondary to developmental dysplasia of the hip. J Bone Joint Surg Br 90:23–26PubMed Okano K, Enomoto H, Osaki M, Shindo H (2008) Rotational acetabular osteotomy for advanced osteoarthritis secondary to developmental dysplasia of the hip. J Bone Joint Surg Br 90:23–26PubMed
29.
Zurück zum Zitat Magnussen RA, Guilak F, Vail TP (2005) Articular cartilage degeneration in post-collapse osteonecrosis of the femoral head. Radiographic staging, macroscopic grading, and histologic changes. J Bone Joint Surg Am 87:1272–1277CrossRefPubMed Magnussen RA, Guilak F, Vail TP (2005) Articular cartilage degeneration in post-collapse osteonecrosis of the femoral head. Radiographic staging, macroscopic grading, and histologic changes. J Bone Joint Surg Am 87:1272–1277CrossRefPubMed
30.
Zurück zum Zitat Ficat RP, Arlet J (1980) Functional investigation of bone under normal conditions. In: Hungerford DS (ed) Ischemia and necrosis of bone. Williams & Wilkins, Baltimore, pp 29–52 Ficat RP, Arlet J (1980) Functional investigation of bone under normal conditions. In: Hungerford DS (ed) Ischemia and necrosis of bone. Williams & Wilkins, Baltimore, pp 29–52
31.
Zurück zum Zitat Otsu N (1979) A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern 9:62–66CrossRef Otsu N (1979) A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern 9:62–66CrossRef
32.
Zurück zum Zitat Mankin HJ, Dorfman H, Lippiello L, Zarins A (1971) Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 53:523–537PubMed Mankin HJ, Dorfman H, Lippiello L, Zarins A (1971) Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 53:523–537PubMed
33.
Zurück zum Zitat Shida JI, Jingushi S, Izumi T, Ikenoue T, Iwamoto Y (2001) Basic fibroblast growth factor regulates expression of growth factors in rat epiphyseal chondrocytes. J Orthop Res 19:259–264CrossRefPubMed Shida JI, Jingushi S, Izumi T, Ikenoue T, Iwamoto Y (2001) Basic fibroblast growth factor regulates expression of growth factors in rat epiphyseal chondrocytes. J Orthop Res 19:259–264CrossRefPubMed
34.
Zurück zum Zitat Kawaguchi H, Pilbeam CC, Gronowicz G, Abreu C, Fletcher BS, Herschman HR, Raisz LG, Hurley MM (1995) Transcriptional induction of prostaglandin G/H synthase-2 by basic fibroblast growth factor. J Clin Invest 96:923–930CrossRefPubMed Kawaguchi H, Pilbeam CC, Gronowicz G, Abreu C, Fletcher BS, Herschman HR, Raisz LG, Hurley MM (1995) Transcriptional induction of prostaglandin G/H synthase-2 by basic fibroblast growth factor. J Clin Invest 96:923–930CrossRefPubMed
35.
Zurück zum Zitat Collin-Osdoby P, Rothe L, Bekker S, Anderson F, Huang Y, Osdoby P (2002) Basic fibroblast growth factor stimulates osteoclast recruitment, development, and bone pit resorption in association with angiogenesis in vivo on the chick chorioallantoic membrane and activates isolated avian osteoclast resorption in vitro. J Bone Miner Res 17:1859–1871CrossRefPubMed Collin-Osdoby P, Rothe L, Bekker S, Anderson F, Huang Y, Osdoby P (2002) Basic fibroblast growth factor stimulates osteoclast recruitment, development, and bone pit resorption in association with angiogenesis in vivo on the chick chorioallantoic membrane and activates isolated avian osteoclast resorption in vitro. J Bone Miner Res 17:1859–1871CrossRefPubMed
36.
Zurück zum Zitat Chikazu D, Hakeda Y, Ogata N, Nemoto K, Itabashi A, Takato T, Kumegawa M, Nakamura K, Kawaguchi H (2000) Fibroblast growth factor (FGF)-2 directly stimulates mature osteoclast function through activation of FGF receptor 1 and p42/p44 MAP kinase. J Biol Chem 6:31444–31450CrossRef Chikazu D, Hakeda Y, Ogata N, Nemoto K, Itabashi A, Takato T, Kumegawa M, Nakamura K, Kawaguchi H (2000) Fibroblast growth factor (FGF)-2 directly stimulates mature osteoclast function through activation of FGF receptor 1 and p42/p44 MAP kinase. J Biol Chem 6:31444–31450CrossRef
37.
Zurück zum Zitat Komaki H, Tanaka T, Chazono M, Kikuchi T (2006) Repair of segmental defects in rabbit tibiae using a complex β-tricalcium phosphate, type I collagen, and fibroblast growth factor-2. Biomaterials 27:5118–5126CrossRefPubMed Komaki H, Tanaka T, Chazono M, Kikuchi T (2006) Repair of segmental defects in rabbit tibiae using a complex β-tricalcium phosphate, type I collagen, and fibroblast growth factor-2. Biomaterials 27:5118–5126CrossRefPubMed
38.
Zurück zum Zitat Tsurushima H, Marushima A, Suzuki K, Oyane A, Sogo Y, Nakamura K, Matsumura A, Ito A (2010) Enhanced bone formation using hydroxyapatite ceramic coated with fibroblast growth factor-2. Acta Biomater doi:10.1016/j.actbio.2009.12.045 Tsurushima H, Marushima A, Suzuki K, Oyane A, Sogo Y, Nakamura K, Matsumura A, Ito A (2010) Enhanced bone formation using hydroxyapatite ceramic coated with fibroblast growth factor-2. Acta Biomater doi:10.​1016/​j.​actbio.​2009.​12.​045
39.
Zurück zum Zitat Hungerford MW, Mont MA (2000) Potential uses of cytokines and growth factors in treatment of osteonecrosis. Orthopade 29:442–448CrossRefPubMed Hungerford MW, Mont MA (2000) Potential uses of cytokines and growth factors in treatment of osteonecrosis. Orthopade 29:442–448CrossRefPubMed
40.
Zurück zum Zitat D’Amore PA, Smith SR (1993) Growth factor effects on cells of the vascular wall: a survey. Growth Factors 8:61–75CrossRefPubMed D’Amore PA, Smith SR (1993) Growth factor effects on cells of the vascular wall: a survey. Growth Factors 8:61–75CrossRefPubMed
41.
Zurück zum Zitat Ferrara N, Henzel WJ (1989) Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161:851–858CrossRefPubMed Ferrara N, Henzel WJ (1989) Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161:851–858CrossRefPubMed
Metadaten
Titel
Treatment of experimental osteonecrosis of the hip in adult rabbits with a single local injection of recombinant human FGF-2 microspheres
verfasst von
Yutaka Kuroda
Haruhiko Akiyama
Keiichi Kawanabe
Yasuhiko Tabata
Takashi Nakamura
Publikationsdatum
01.11.2010
Verlag
Springer Japan
Erschienen in
Journal of Bone and Mineral Metabolism / Ausgabe 6/2010
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-010-0172-5

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