Skip to main content
Top
Published in: Osteoporosis International 1/2016

01-01-2016 | Original Article

Abnormal subchondral bone microstructure following steroid administration is involved in the early pathogenesis of steroid-induced osteonecrosis

Authors: L. Wang, L. Zhang, H. Pan, S. Peng, X. Zhao, W. W. Lu

Published in: Osteoporosis International | Issue 1/2016

Login to get access

Abstract

Summary

Loss of bone microstructure integrity is thought to be related to osteonecrosis. But the relationship between the time when bone microstructure integrity loss appears and the onset of osteonecrosis has not yet been determined. Our study demonstrated abnormal changes of subchondral bone microstructure involved in the early pathogenesis of osteonecrosis.

Introduction

Using a rabbit model, we investigated the changes of subchondral bone microstructure following steroid administration to identify the onset of abnormal bone microstructure development in steroid-induced osteonecrosis.

Methods

Fifty-five adult female Japanese White rabbits (mean body weight 3.5 kg; mean age 24 months) were used and randomly divided among three time points (3, 7, and 14 days) consisting of 15 rabbits each, received a single intramuscular injection of methylprednisolone acetate (MP; Pfizer Manufacturing Belgium NV) at a dose of 4 mg/kg, and a control group consisting of 10 rabbits was fed and housed under identical conditions but were not given steroid injections. A micro-CT scanner was applied to detect changes in the trabecular region of subchondral bone of excised femoral head samples. Parameters including bone volume fraction (BV/TV), bone surface (BS), trabecular bone pattern factor (Tb.Pf), trabecular thickness/number/separation (Tb.Th, Tb.N, and Tb.Sp), and structure model index (SMI) were evaluated using the software CTAn (SkyScan). After micro-CT scans, bilateral femoral heads were cut in the coronal plane at a thickness of 4 μm. The sections were then stained with haematoxylin-eosin and used for the diagnosis of osteonecrosis and the rate of development of osteonecrosis.

Results

The BV/TV, BS, Tb.Th and Tb.N demonstrated a time-dependent decline from 3, 7, and 14 days compared with the control group, while the Tb.Pf, Tb.Sp and SMI demonstrated an increase at 3, 7, and 14 days compared with the control group. For the histopathology portion, osteonecrosis was not seen 3 days after steroid treatment, but was present 7 days after treatment and was obvious 14 days after treatment. Furthermore, the rate of osteonecrosis appearing between 7 and 14 days was not significantly different. In addition, the presence and variation of BV/TV, BS, Tb.Pf, Tb.Th, Tb.N, and SMI demonstrated significant changes at 7 days compared with the control group except Tb.Sp (at 14 days) and this is the time when osteonecrosis is thought to occur in this model.

Conclusion

This study demonstrated that osteonecrosis in rabbits is chronologically associated with changes in subchondral bone microstructure.
Literature
1.
go back to reference Lavernia CJ, Sierra RJ, Grieco FR (1999) Osteonecrosis of the femoral head. J Am Acad Orthop Surg 7:250–261PubMed Lavernia CJ, Sierra RJ, Grieco FR (1999) Osteonecrosis of the femoral head. J Am Acad Orthop Surg 7:250–261PubMed
2.
go back to reference Chang CC, Greenspan A, Gershwin ME (1993) Osteonecrosis: current perspectives on pathogenesis and treatment. Semin Arthritis Rheum 23:47–69PubMedCrossRef Chang CC, Greenspan A, Gershwin ME (1993) Osteonecrosis: current perspectives on pathogenesis and treatment. Semin Arthritis Rheum 23:47–69PubMedCrossRef
3.
4.
go back to reference Amanatullah DF, Strauss EJ, Di Cesare PE (2011) Current management options for osteonecrosis of the femoral head: part 1, diagnosis and nonoperative management. Am J Orthop (Belle Mead NJ) 40:E186–E192 Amanatullah DF, Strauss EJ, Di Cesare PE (2011) Current management options for osteonecrosis of the femoral head: part 1, diagnosis and nonoperative management. Am J Orthop (Belle Mead NJ) 40:E186–E192
5.
go back to reference Amanatullah DF, Strauss EJ, Di Cesare PE (2011) Current management options for osteonecrosis of the femoral head: part II, operative management. Am J Orthop (Belle Mead NJ) 40:E216–E225 Amanatullah DF, Strauss EJ, Di Cesare PE (2011) Current management options for osteonecrosis of the femoral head: part II, operative management. Am J Orthop (Belle Mead NJ) 40:E216–E225
6.
go back to reference Tan X, Cai D, Wu Y, Liu B, Rong L, Chen Z, Zhao Q (2006) Comparative analysis of serum proteomes: discovery of proteins associated with osteonecrosis of the femoral head. Transl Res 148:114–119PubMedCrossRef Tan X, Cai D, Wu Y, Liu B, Rong L, Chen Z, Zhao Q (2006) Comparative analysis of serum proteomes: discovery of proteins associated with osteonecrosis of the femoral head. Transl Res 148:114–119PubMedCrossRef
7.
go back to reference Wu X, Yang S, Wang H, Meng C, Xu W, Duan D, Liu X (2013) G-CSF/SCF exert beneficial effects via anti-apoptosis in rabbits with steroid-associated osteonecrosis. Exp Mol Pathol 94:247–254PubMedCrossRef Wu X, Yang S, Wang H, Meng C, Xu W, Duan D, Liu X (2013) G-CSF/SCF exert beneficial effects via anti-apoptosis in rabbits with steroid-associated osteonecrosis. Exp Mol Pathol 94:247–254PubMedCrossRef
8.
go back to reference Fisher DE, Bickel WH (1971) Corticosteroid-induced avascular necrosis. A clinical study of seventy-seven patients. J Bone Joint Surg Am 53:859–873PubMed Fisher DE, Bickel WH (1971) Corticosteroid-induced avascular necrosis. A clinical study of seventy-seven patients. J Bone Joint Surg Am 53:859–873PubMed
9.
go back to reference Mont MA, Hungerford DS (1995) Non-traumatic avascular necrosis of the femoral head. J Bone Joint Surg Am 77:459–474PubMed Mont MA, Hungerford DS (1995) Non-traumatic avascular necrosis of the femoral head. J Bone Joint Surg Am 77:459–474PubMed
10.
go back to reference Maillefert JF, Tavernier C, Toubeau M, Brunotte F (1996) Non-traumatic avascular necrosis of the femoral head. J Bone Joint Surg Am 78:473–474PubMed Maillefert JF, Tavernier C, Toubeau M, Brunotte F (1996) Non-traumatic avascular necrosis of the femoral head. J Bone Joint Surg Am 78:473–474PubMed
11.
go back to reference Aimaiti A, Wufuer M, Wang YH, Saiyiti M, Cui L, Yusufu A (2011) Can bisphenol A diglycidyl ether (BADGE) administration prevent steroid-induced femoral head osteonecrosis in the early stage? Med Hypotheses 77:282–285PubMedCrossRef Aimaiti A, Wufuer M, Wang YH, Saiyiti M, Cui L, Yusufu A (2011) Can bisphenol A diglycidyl ether (BADGE) administration prevent steroid-induced femoral head osteonecrosis in the early stage? Med Hypotheses 77:282–285PubMedCrossRef
12.
go back to reference Kerachian MA, Seguin C, Harvey EJ (2009) Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J Steroid Biochem Mol Biol 114:121–128PubMedCrossRef Kerachian MA, Seguin C, Harvey EJ (2009) Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J Steroid Biochem Mol Biol 114:121–128PubMedCrossRef
13.
go back to reference Liu Y, Porta A, Peng X, Gengaro K, Cunningham EB, Li H, Dominguez LA, Bellido T, Christakos S (2004) Prevention of glucocorticoid-induced apoptosis in osteocytes and osteoblasts by calbindin-D28k. J Bone Miner Res 19:479–490PubMedCrossRef Liu Y, Porta A, Peng X, Gengaro K, Cunningham EB, Li H, Dominguez LA, Bellido T, Christakos S (2004) Prevention of glucocorticoid-induced apoptosis in osteocytes and osteoblasts by calbindin-D28k. J Bone Miner Res 19:479–490PubMedCrossRef
14.
go back to reference Weinstein RS, Nicholas RW, Manolagas SC (2000) Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J Clin Endocrinol Metab 85:2907–2912PubMed Weinstein RS, Nicholas RW, Manolagas SC (2000) Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J Clin Endocrinol Metab 85:2907–2912PubMed
15.
go back to reference Lee SH, Rho J, Jeong D, Sul JY, Kim T, Kim N, Kang JS, Miyamoto T, Suda T, Lee SK, Pignolo RJ, Koczon-Jaremko B, Lorenzo J, Choi Y (2006) v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation. Nat Med 12:1403–1409PubMedCrossRef Lee SH, Rho J, Jeong D, Sul JY, Kim T, Kim N, Kang JS, Miyamoto T, Suda T, Lee SK, Pignolo RJ, Koczon-Jaremko B, Lorenzo J, Choi Y (2006) v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation. Nat Med 12:1403–1409PubMedCrossRef
16.
go back to reference Kubota K, Sakikawa C, Katsumata M, Nakamura T, Wakabayashi K (2002) Platelet-derived growth factor BB secreted from osteoclasts acts as an osteoblastogenesis inhibitory factor. J Bone Miner Res 17:257–265PubMedCrossRef Kubota K, Sakikawa C, Katsumata M, Nakamura T, Wakabayashi K (2002) Platelet-derived growth factor BB secreted from osteoclasts acts as an osteoblastogenesis inhibitory factor. J Bone Miner Res 17:257–265PubMedCrossRef
17.
go back to reference Wang L, Wang N, Li M, Wang K (2010) To investigate the role of the nervous system of bone in steroid-induced osteonecrosis in rabbits. Osteoporos Int 21:2057–2066PubMedCrossRef Wang L, Wang N, Li M, Wang K (2010) To investigate the role of the nervous system of bone in steroid-induced osteonecrosis in rabbits. Osteoporos Int 21:2057–2066PubMedCrossRef
18.
go back to reference Jiang Y, Zhang Y, Chen W, Liu C, Li X, Sun D, Liu Z, Xu Y, Mao X, Guo Q, Lin N (2014) Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling. J Transl Med 12:334PubMedPubMedCentralCrossRef Jiang Y, Zhang Y, Chen W, Liu C, Li X, Sun D, Liu Z, Xu Y, Mao X, Guo Q, Lin N (2014) Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling. J Transl Med 12:334PubMedPubMedCentralCrossRef
19.
go back to reference Mikami T, Ichiseki T, Kaneuji A, Ueda Y, Sugimori T, Fukui K, Matsumoto T (2010) Prevention of steroid-induced osteonecrosis by intravenous administration of vitamin E in a rabbit model. J Orthop Sci 15:674–677PubMedCrossRef Mikami T, Ichiseki T, Kaneuji A, Ueda Y, Sugimori T, Fukui K, Matsumoto T (2010) Prevention of steroid-induced osteonecrosis by intravenous administration of vitamin E in a rabbit model. J Orthop Sci 15:674–677PubMedCrossRef
20.
go back to reference Ichiseki T, Kaneuji A, Katsuda S, Ueda Y, Sugimori T, Matsumoto T (2005) DNA oxidation injury in bone early after steroid administration is involved in the pathogenesis of steroid-induced osteonecrosis. Rheumatology (Oxford) 44:456–460CrossRef Ichiseki T, Kaneuji A, Katsuda S, Ueda Y, Sugimori T, Matsumoto T (2005) DNA oxidation injury in bone early after steroid administration is involved in the pathogenesis of steroid-induced osteonecrosis. Rheumatology (Oxford) 44:456–460CrossRef
21.
go back to reference Kabata T, Kubo T, Matsumoto T, Hirata T, Fujioka M, Takahashi KA, Yagishita S, Kobayashi M, Tomita K (2005) Onset of steroid-induced osteonecrosis in rabbits and its relationship to hyperlipaemia and increased free fatty acids. Rheumatology (Oxford) 44:1233–1237CrossRef Kabata T, Kubo T, Matsumoto T, Hirata T, Fujioka M, Takahashi KA, Yagishita S, Kobayashi M, Tomita K (2005) Onset of steroid-induced osteonecrosis in rabbits and its relationship to hyperlipaemia and increased free fatty acids. Rheumatology (Oxford) 44:1233–1237CrossRef
22.
go back to reference Kabata T, Kubo T, Matsumoto T, Nishino M, Tomita K, Katsuda S, Horii T, Uto N, Kitajima I (2000) Apoptotic cell death in steroid induced osteonecrosis: an experimental study in rabbits. J Rheumatol 27:2166–2171PubMed Kabata T, Kubo T, Matsumoto T, Nishino M, Tomita K, Katsuda S, Horii T, Uto N, Kitajima I (2000) Apoptotic cell death in steroid induced osteonecrosis: an experimental study in rabbits. J Rheumatol 27:2166–2171PubMed
23.
go back to reference Ichiseki T, Matsumoto T, Nishino M, Kaneuji A, Katsuda S (2004) Oxidative stress and vascular permeability in steroid-induced osteonecrosis model. J Orthop Sci 9:509–515PubMedCrossRef Ichiseki T, Matsumoto T, Nishino M, Kaneuji A, Katsuda S (2004) Oxidative stress and vascular permeability in steroid-induced osteonecrosis model. J Orthop Sci 9:509–515PubMedCrossRef
24.
go back to reference Hildebrand T, Ruegsegger P (1997) Quantification of bone microarchitecture with the structure model index. Comput Methods Biomech Biomed Engin 1:15–23PubMedCrossRef Hildebrand T, Ruegsegger P (1997) Quantification of bone microarchitecture with the structure model index. Comput Methods Biomech Biomed Engin 1:15–23PubMedCrossRef
25.
26.
go back to reference Allen MJ (2003) Biochemical markers of bone metabolism in animals: uses and limitations. Vet Clin Pathol 32:101–113PubMedCrossRef Allen MJ (2003) Biochemical markers of bone metabolism in animals: uses and limitations. Vet Clin Pathol 32:101–113PubMedCrossRef
28.
go back to reference Grote HJ, Amling M, Vogel M, Hahn M, Posl M, Delling G (1995) Intervertebral variation in trabecular microarchitecture throughout the normal spine in relation to age. Bone 16:301–308PubMedCrossRef Grote HJ, Amling M, Vogel M, Hahn M, Posl M, Delling G (1995) Intervertebral variation in trabecular microarchitecture throughout the normal spine in relation to age. Bone 16:301–308PubMedCrossRef
29.
go back to reference Hahn M, Vogel M, Pompesius-Kempa M, Delling G (1992) Trabecular bone pattern factor--a new parameter for simple quantification of bone microarchitecture. Bone 13:327–330PubMedCrossRef Hahn M, Vogel M, Pompesius-Kempa M, Delling G (1992) Trabecular bone pattern factor--a new parameter for simple quantification of bone microarchitecture. Bone 13:327–330PubMedCrossRef
30.
go back to reference Field RE, Cronin MD, Singh PJ, Burtenshaw C, Rushton N (2006) Bone remodeling around the Cambridge cup: a DEXA study of 50 hips over 2 years. Acta Orthop 77:726–732PubMedCrossRef Field RE, Cronin MD, Singh PJ, Burtenshaw C, Rushton N (2006) Bone remodeling around the Cambridge cup: a DEXA study of 50 hips over 2 years. Acta Orthop 77:726–732PubMedCrossRef
Metadata
Title
Abnormal subchondral bone microstructure following steroid administration is involved in the early pathogenesis of steroid-induced osteonecrosis
Authors
L. Wang
L. Zhang
H. Pan
S. Peng
X. Zhao
W. W. Lu
Publication date
01-01-2016
Publisher
Springer London
Published in
Osteoporosis International / Issue 1/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3225-8

Other articles of this Issue 1/2016

Osteoporosis International 1/2016 Go to the issue