Clin Orthop Surg.  2010 Dec;2(4):250-255. 10.4055/cios.2010.2.4.250.

Apoptosis in the Osteonecrosis of the Femoral Head

Affiliations
  • 1Department of Orthopedic Surgery, Ulsan University Hospital, Ulsan, Korea.
  • 2University of Notre Dame College of Science, Notre Dame, IN, USA.
  • 3Department of Orthopedic Surgery, Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea. shlee2@amc.seoul.kr

Abstract

BACKGROUND
Osteonecrosis of the femoral head is classified into idiopathic and secondary forms. A number of etiological factors in the development of osteonecrosis have been suggested but the biological mechanisms are still unclear. Recently, some reports suggested that the apoptosis is closely related to osteonecrosis of the femoral head. Therefore, this study examined the expression of apoptosis in osteonecrosis of the femoral head.
METHODS
Of the patients diagnosed preoperatively with osteonecrosis and underwent total hip replacement arthroplasty between August 2004 and July 2005, 58 patients (58 hips) were available for this study. Their diagnoses were confirmed by the postoperative pathology findings. Tissue samples of the femoral head sections were terminal deoxynucleotydyl transferase mediated dUTP nick-end labeling (TUNEL) stained using an in situ cell death detection POD kit. The number of total and TUNEL-positive osteocytes, and the average ratio of TUNEL-positive cells were calculated and analyzed according to the cause.
RESULTS
Osteonecrosis was steroid-induced in 8 cases (13.8%), alcohol-induced in 29 cases (50%), post-traumatic in 6 cases (10.3%) and idiopathic in 15 cases (25.9%). The percentage of TUNEL-positive osteocytes was high in patients with steroid- and alcohol-induced osteonecrosis of the femoral head but low in patients with post-traumatic and idiopathic osteonecrosis. The difference in the percentage of TUNEL-positive osteocytes between these groups was significant (p < 0.05).
CONCLUSIONS
Apoptosis might play an important role in the pathogenesis of osteonecrosis of the femoral head induced by steroid and alcohol. These findings highlight a need for further research into the role of apoptosis in the development of osteonecrosis of the femoral head.

Keyword

Osteonecrosis of the femoral head; Apoptosis

MeSH Terms

Adult
Aged
Aged, 80 and over
*Apoptosis
Female
Femur Head/*pathology
Femur Head Necrosis/etiology/*pathology/surgery
Humans
In Situ Nick-End Labeling
Male
Middle Aged

Figure

  • Fig. 1 After the terminal deoxynucleotydyl transferase mediated dUTP nick-end labeling (TUNEL) reaction, (A) condensed apoptotic osteocytes in cancellous bone from a femoral head removed from a patient with steroid-induced osteonecrosis show intense green fluorescence (× 400). (B) In a patient with alcohol-induced osteonecrosis, intermediate fluorescence is shown (× 100). Non-apoptotic cells are not visible using immunofluorescence microscopy. (C) In a patient with idiopathic osteonecrosis, no fluorescence is shown (× 100).

  • Fig. 2 Optical microscopy shows (A) extensive apoptosis in femoral head osteocytes from a patient with steroid-induced osteonecrosis, (B) absence of apoptotic osteocytes in a patient with idiopathic osteonecrosis and (C) moderate apoptotic osteocytes in a patient with alcohol-induced osteonecrosis. The apoptotic osteocytes were stained brown with diaminobenzidine substrates, whereas non-apoptotic osteocytes are stained blue with hematoxylin (× 400).


Reference

1. Burke TJ, Schrier RW. Schrier RW, Gottschalk CW, editors. Pathophysiology of cell ischemia. Diseases of the kidney. 1993. 5th ed. Boston: Little Brown Company;1257–1286.
2. Calder JD, Buttery L, Revell PA, Pearse M, Polak JM. Apoptosis: a significant cause of bone cell death in osteonecrosis of the femoral head. J Bone Joint Surg Br. 2004. 86(8):1209–1213.
3. Weinstein RS, Nicholas RW, Manolagas SC. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J Clin Endocrinol Metab. 2000. 85(8):2907–2912.
Article
4. Rudin CM, Thompson CB. Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu Rev Med. 1997. 48:267–281.
Article
5. Beeri R, Symon Z, Brezis M, et al. Rapid DNA fragmentation from hypoxia along the thick ascending limb of rat kidneys. Kidney Int. 1995. 47(6):1806–1810.
Article
6. Hagar H, Ueda N, Shah SV. Endonuclease induced DNA damage and cell death in chemical hypoxic injury to LLC-PK1 cells. Kidney Int. 1996. 49(2):355–361.
Article
7. Hagar H, Ueda N, Shah SV. Role of reactive oxygen metabolites in DNA damage and cell death in chemical hypoxic injury to LLC-PK1 cells. Am J Physiol. 1996. 271(1 Pt 2):F209–F215.
Article
8. Weinberg JM. The cell biology of ischemic renal injury. Kidney Int. 1991. 39(3):476–500.
Article
9. Buckwalter JA, Einhorn TA, Simon SR. Orthopaedic basic science. 2000. 2nd ed. Iowa: American Academy of Orthopaedic Surgeons;516–522.
10. Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992. 119(3):493–501.
Article
11. Cohen GM, Sun XM, Snowden RT, Dinsdale D, Skilleter DN. Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J. 1992. 286(Pt 2):331–334.
Article
12. Collins RJ, Harmon BV, Gobe GC, Kerr JF. Internucleosomal DNA cleavage should not be the sole criterion for identifying apoptosis. Int J Radiat Biol. 1992. 61(4):451–453.
Article
13. Vis AN, Kranse R, Nigg AL, van der Kwast TH. Quantitative analysis of the decay of immunoreactivity in stored prostate needle biopsy sections. Am J Clin Pathol. 2000. 113(3):369–373.
Article
14. Manne U, Myers RB, Srivastava S, Grizzle WE. Re: loss of tumor marker-immunostaining intensity on stored paraffin slides of breast cancer. J Natl Cancer Inst. 1997. 89(8):585–586.
Article
15. Harrington KD, Murray WR, Kountz SL, Belzer FO. Avascular necrosis of bone after renal transplantation. J Bone Joint Surg Am. 1971. 53(2):203–215.
Article
16. Abeles M, Urman JD, Rothfield NF. Aseptic necrosis of bone in systemic lupus erythematosus: relationship to corticosteroid therapy. Arch Intern Med. 1978. 138(5):750–754.
Article
17. Zizic TM, Marcoux C, Hungerford DS, Dansereau JV, Stevens MB. Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosus. Am J Med. 1985. 79(5):596–604.
Article
18. Bergstein JM, Wiens C, Fish AJ, Vernier RL, Michael A. Avascular necrosis of bone in systemic lupus erythematosus. J Pediatr. 1974. 85(1):31–35.
Article
19. Hurley RM, Steinberg RH, Patriquin H, Drummond KN. A vascular necrosis of the femoral head in childhood systemic lupus erythematosus. Can Med Assoc J. 1974. 111(8):781–784.
20. Nishiyama K, Okinaga A. Osteonecrosis after renal transplantation in children. Clin Orthop Relat Res. 1993. (295):168–171.
Article
21. Wang Y, Li Y, Mao K, Li J, Cui Q, Wang GJ. Alcohol-induced adipogenesis in bone and marrow: a possible mechanism for osteonecrosis. Clin Orthop Relat Res. 2003. (410):213–224.
Article
22. Fisher DE, Bickel WH, Holley KE, Ellefson RD. Corticosteroid-induced aseptic necrosis: II. Experimental study. Clin Orthop Relat Res. 1972. (84):200–206.
23. Glimcher MJ, Kenzora JE. The biology of osteonecrosis of the human femoral head and its clinical implications. III. Discussion of the etiology and genesis of the pathological sequelae: commments on treatment. Clin Orthop Relat Res. 1979. (140):273–312.
24. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids: potential mechanisms of their deleterious effects on bone. J Clin Invest. 1998. 102(2):274–282.
Article
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