Abstract
Background
High-dose administration of a steroid hormone has been associated with a major risk of osteonecrosis. In this study we investigated the effects of a steroid hormone on the incidence of osteonecrosis of the femoral head in stroke-prone spontaneously hypertensive rats/Nagasaki (SHRSP/Ngsks).
Methods
A total of 71 SHRSP/Ngsks were divided into two groups: a control group (C group, n = 40) and a steroid hormone group (S group, n = 31) given 5 mg (about 20 mg/kg) of methylprednisolone acetate during the 17th week of age. We compared the groups' laboratory data, histological appearance, incidence of osteonecrosis, and expression of oxidative stress on immunohistochemical analysis using the monoclonal antibodies anti-4HNE and anti-8OHdG.
Results
The S group showed an increase in total cholesterol, with the amounts of high-density lipoprotein, low-density lipoprotein, and triglycerides all significantly higher than in the C group. Histological examination showed that the frequency of necrosis of the femoral head was significantly higher in the S group (95.2%) than in the C group (51.2%). Most of the histological features of the osteonecrosis demonstrated typical features of a similar sort in the two groups. However, the S group showed bone marrow spaces in the femoral head that were occupied by an increased number of adipocytes and that were swollen, partially degenerative, and necrotic. On immunohistochemical analysis, the stains of anti-4HNE and anti-8OHdG antibody were stronger in the S group than in the C group.
Conclusions
This study confirmed, to a remarkable degree, the suspicion that the administration of steroid hormone increases the number of adipocytes in marrow. Fat degeneration and necrosis, considered early signs of osteonecrosis, were also observed. It has been hypothesized that osteonecrosis is produced by the ischemic change accompanying compartment pressure load in marrow, where fat degeneration, necrosis, and endothelial cell injury might occur together with oxidative stress.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
MA Mont LC Jones DS Hungerford (2006) ArticleTitleCurrent concepts review: nontraumatic osteonecrosis of the femoral head: ten years later J Bone Joint Surg Am 88 1117–32 10.2106/JBJS.E.01041 Occurrence Handle10.2106/JBJS.E.01041 Occurrence Handle16651589
PA Cheras (1997) Role of hyperlipidemia, hypercoagulability, and hypofibrinolysis in osteonecrosis and osteoarthritis JR Urbaniak JP Jones SuffixJr (Eds) Osteonecrosis: etiology, diagnosis, and treatment American Academy of Orthopedic Surgeons Rosemont, IL 97–104
CJ Glueck RA Freiberg RN Fontaine T Tracy P Wang (2001) ArticleTitleHypofibrinolysis, thrombophilia, osteonecrosis Clin Orthop 386 19–33 10.1097/00003086-200105000-00004 Occurrence Handle10.1097/00003086-200105000-00004 Occurrence Handle11347834
M Matui S Saito K Ohzono N Sugano M Saito K Takaoka et al. (1992) ArticleTitleExperimental steroid-induced osteonecrosis in adult rabbits with hypersensitivity vasculitis Clin Orthop 277 61–72
S Saito A Inoue K Ono (1987) ArticleTitleIntramedullary haemorrhage as a possible cause of avascular necrosis of the femoral head: the histology of 16 femoral heads at the silent stage J Bone Joint Surg Br 69 346–51 Occurrence Handle1:STN:280:DyaL2s3it1Cksg%3D%3D Occurrence Handle3584182
EW Gold OD Fox S Weissfeld PH Curtiss (1978) ArticleTitleCorticosteroid-induced avascular necrosis: an experimental study in rabbits Clin Orthop 135 272–80 Occurrence Handle1:CAS:528:DyaE1MXktVGh Occurrence Handle709939
K Kawai A Tamaki K Hirohata (1985) ArticleTitleSteroid-induced accumulation of lipid in the osteocytes of the rabbit femoral head J Bone Joint Surg Am 67 755–62 Occurrence Handle1:STN:280:DyaL2M3gslyksQ%3D%3D Occurrence Handle3997928
H Maruno T Shimizu K Kawai K Hirohata (1991) ArticleTitleThe response of osteocytes to a lipid clearing agent in steroid-treated rabbits J Bone Joint Surg Br 73 911–5 Occurrence Handle1:STN:280:DyaK38%2FmsVKisw%3D%3D Occurrence Handle1955435
GJ Wang DE Sweet SI Reger RC Thompson (1977) ArticleTitleFat-cell changes as a mechanism of avascular necrosis of the femoral head in cortisone-treated rabbits J Bone Joint Surg Am 59 729–35 Occurrence Handle1:STN:280:DyaE1c%2FgsFGmtQ%3D%3D Occurrence Handle908695
GJ Wang Q Cui (1997) The pathogenesis of steroid-induced osteonecrosis and the effect of lipid-clearing agents on this mechanism JR Urbaniak JP Jones SuffixJr (Eds) Osteonecrosis: etiology, diagnosis, and treatment American Academy of Orthopedic Surgeons Rosemont, IL 159–65
S Inoue M Horii T Asano M Fujioka T Ogura M Shibatani et al. (2003) ArticleTitleRisk factors for nontraumatic osteonecrosis of the femoral head after renal transplantation J Orthop Sci 8 751–6 10.1007/s00776-003-0716-9 Occurrence Handle10.1007/s00776-003-0716-9 Occurrence Handle14648260
JDF Calder L Buttery PA Revell M Pearse JM Polak (2004) ArticleTitleApoptosis: a significant cause of bone cell death in osteonecrosis of the femoral head J Bone Joint Surg Br 86 1209–13 10.1302/0301-620X.86B8.14834 Occurrence Handle10.1302/0301-620X.86B8.14834 Occurrence Handle1:STN:280:DC%2BD2crpsFWqsQ%3D%3D Occurrence Handle15568539
T Kabata T Kubo T Matsumoto M Nishino K Tomita S Katsuda et al. (2000) ArticleTitleApoptosis cell death in steroid induced osteonecrosis: an experimental study in rabbits J Rheumatol 27 2166–71 Occurrence Handle1:STN:280:DC%2BD3cvkt1akug%3D%3D Occurrence Handle10990229
T Ichiseki T Matsumoto M Nishino A Kaneuji S Katsuda (2004) ArticleTitleOxidative stress and vascular permeability in steroid-induced osteonecrosis model J Orthop Sci 9 509–15 10.1007/s00776-004-0816-1 Occurrence Handle10.1007/s00776-004-0816-1 Occurrence Handle1:CAS:528:DC%2BD2cXnvVektbg%3D Occurrence Handle15449127
K Iwasaki T Hirano K Sagara Y Nishimura (1992) ArticleTitleIdiopathic necrosis of the femoral epiphyseal nucleus in rats Clin Orthop 277 31–40 Occurrence Handle1555355
T Yamamoto K Sueishi Y Sugioka (1997) The pathogenesis of osteonecrosis based on animal models JR Urbaniak JP Jones SuffixJr (Eds) Osteonecrosis: etiology, diagnosis, and treatment American Academy of Orthopedic Surgeons Rosemont, IL 167–73
J Arlet (1993) A traumatic necrosis of the femoral head: general report A Schoutens J Arlet JWM Gardeniers SPF Hughes (Eds) Bone circulation and vascularization in normal and pathological conditions Plenum New York 235–40
RP Ficat (1985) ArticleTitleIdiopathic bone necrosis of the femoral head: early diagnosis and treatment J Bone Joint Surg Br 67 3–9 Occurrence Handle1:STN:280:DyaL2M7gsFWmuw%3D%3D Occurrence Handle3155745
JPH Hauzeur JL Pasteels (1993) Bone biopsy as diagnostic criteria for aseptic necrosis of the femoral head A Schoutens J Arlet JWM Gardeniers SPF Hughes (Eds) Bone circulation and vascularization in normal and pathological conditions Plenum New York 277–81
JP Jones SuffixJr (1993) Pathophysiology of osteonecrosis A Schoutens J Arlet JWM Gardeniers SPF Hughes (Eds) Bone circulation and vascularization in normal and pathological conditions Plenum New York 249–61
TW Bauer BN Stulberg (1993) The histology of osteonecrosis and its distinction from histologic artifacts A Schoutens J Arlet JWM Gardeniers SPF Hughes (Eds) Bone circulation and vascularization in normal and pathological conditions Plenum New York 283–92
W Drescher T Schneider C Becker J Hobolth W Ruther ES Hansen et al. (2001) ArticleTitleSelective reduction of bone blood flow by short-term treatment with high-dose methylprednisolone: an experimental study in pigs J Bone Joint Surg Br 83 274–7 10.1302/0301-620X.83B2.10323 Occurrence Handle10.1302/0301-620X.83B2.10323 Occurrence Handle1:STN:280:DC%2BD3M3hslGgtw%3D%3D Occurrence Handle11284580
K Miyanishi T Yamamoto T Irisa A Yamashita S Jingushi Y Noguti et al. (2002) ArticleTitleBone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis Bone 30 185–90 10.1016/S8756-3282(01)00663-9 Occurrence Handle10.1016/S8756-3282(01)00663-9 Occurrence Handle1:STN:280:DC%2BD38%2FpvVCjtg%3D%3D Occurrence Handle11792583
G Motomura T Yamamoto K Miyanishi S Jingushi Y Iwamoto (2004) ArticleTitleCombined effects of an anticoagulant and a lipid-lowering agent on the prevention of steroid-induced osteonecrosis in rabbits Arthritis Rheum 50 3387–91 10.1002/art.20517 Occurrence Handle10.1002/art.20517 Occurrence Handle1:CAS:528:DC%2BD2cXpvFait78%3D Occurrence Handle15476219
RS Weinstein RL Jilka AM Parfitt SC Manolagas (1998) ArticleTitleInhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids: potential mechanisms of their deleterious effects on bone J Clin Invest 102 274–82 10.1172/JCI2799 Occurrence Handle10.1172/JCI2799 Occurrence Handle1:CAS:528:DyaK1cXkslOktrc%3D Occurrence Handle9664068
Author information
Authors and Affiliations
About this article
Cite this article
Murata, M., Kumagai, K., Miyata, N. et al. Osteonecrosis in stroke-prone spontaneously hypertensive rats: effect of glucocorticoid. J Orthop Sci 12, 289–295 (2007). https://doi.org/10.1007/s00776-007-1129-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00776-007-1129-y