Skip to main content
SpringerLink
Log in

Pronounced risk of nontraumatic osteonecrosis of the femoral head among cigarette smokers who have never used oral corticosteroids: a multicenter case–control study in Japan

  • Original Article
  • Published:
Journal of Orthopaedic Science

Abstract

Background

Cigarette smoking has been linked to an increased risk of nontraumatic osteonecrosis of the femoral head (ONFH) in previous studies. However, the effect of smoking amount, duration and cessation, and interaction with corticosteroids remains unclear. The purpose of this study was to precisely evaluate the effects of smoking and the interaction with corticosteroid use.

Methods

This was a multicenter, matched case–control study in Japan. Cases were defined as patients who were newly diagnosed with ONFH at an initial visit or during the previous year if they were referred patients. For each case, matched controls were selected from patients without ONFH. The matching conditions were sex, age, and ethnicity. A logistic regression model was used to compute odds ratios (OR) and 95 % confidence intervals (95 % CI).

Results

We compared 72 cases with 244 matched controls. ORs were 3.89 (95 % CI 1.46–10.4) for current smokers, 3.89 (1.22–12.4) for smokers consuming more than 20 cigarettes per day, 4.26 (1.32–13.7) for smokers with 26 pack–years or more, and 3.11 (0.92–11.5) for smokers with a history of 29 years or more, with significant or marginally significant dose–response relationships. OR for current smokers was 10.3 among those who had never used corticosteroids and 1.56 among past or current corticosteroid users (P for interaction 0.010).

Conclusions

Our results revealed that heavier cigarette smoking was associated with a higher risk of ONFH. The elevated risk from cigarette smoking was markedly pronounced among those who had never used oral corticosteroids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mont MA, Zywiel MG, Marker DR, McGrath MS, Delanois RE. The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review. J Bone Joint Surg Am. 2010;92:2165–70.

    Article  PubMed  Google Scholar 

  2. Fukushima W, Fujioka M, Kubo T, Tamakoshi A, Nagai M, Hirota Y. Nationwide epidemiologic survey of idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res. 2010;468:2715–24.

    Article  PubMed  Google Scholar 

  3. Mont MA, Jones LC, Hungerford DS. Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am. 2006;88:1117–32.

    Article  PubMed  Google Scholar 

  4. Hirota Y, Hirohata T, Fukuda K, Mori M, Yanagawa H, Ohno Y, Sugioka Y. Association of alcohol intake, cigarette smoking, and occupational status with the risk of idiopathic osteonecrosis of the femoral head. Am J Epidemiol. 1993;137:530–8.

    CAS  PubMed  Google Scholar 

  5. Matsuo K, Hirohata T, Sugioka Y, Ikeda M, Fukuda A. Influence of alcohol intake, cigarette smoking, and occupational status on idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res. 1988;234:115–23.

    PubMed  Google Scholar 

  6. Aldridge JM 3rd, Urbaniak JR. Avascular necrosis of the femoral head: etiology, pathophysiology, classification, and current treatment guidelines. Am J Orthop. 2004;33:327–32.

    Article  PubMed  Google Scholar 

  7. Mont MA, Glueck CJ, Pacheco IH, Wang P, Hungerford DS, Petri M. Risk factors for osteonecrosis in systemic lupus erythematosus. J Rheumatol. 1997;24:654–62.

    CAS  PubMed  Google Scholar 

  8. Inoue S, Horii M, Asano T, Fujioka M, Ogura T, Shibatani M, Kim WC, Nakagawa M, Tanaka T, Hirota Y, Kubo T. Risk factors for nontraumatic osteonecrosis of the femoral head after renal transplantation. J Orthop Sci. 2003;8:751–6.

    Article  PubMed  Google Scholar 

  9. LaPorte DM, Mont MA, Mohan V, Jones LC, Hungerford DS. Multifocal osteonecrosis. J Rheumatol. 1998;25:1968–74.

    CAS  PubMed  Google Scholar 

  10. Shibata A, Fukuda K, Inoue A, Higuchi F, Miyake H, Nishi M, Mori M, Ishii S, Nagao M, Yanagawa H. Flushing pattern and idiopathic avascular necrosis of the femoral head. J Epidemiol. 1996;6:37–43.

    Article  CAS  PubMed  Google Scholar 

  11. Sakata R. A case–control study of association between life-style, alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 genotype and idiopathic osteonecrosis of the femoral head. Kurume Med J. 2003;50:121–30.

    Article  PubMed  Google Scholar 

  12. Glueck CJ, Freiberg RA, Oghene J, Fontaine RN, Wang P. Association between the T-786C eNOS polymorphism and idiopathic osteonecrosis of the head of the femur. J Bone Joint Surg Am. 2007;89:2460–8.

    Article  PubMed  Google Scholar 

  13. Koo KH, Lee JS, Lee YJ, Kim KJ, Yoo JJ, Kim HJ. Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis. J Orthop Res. 2006;24:1722–8.

    Article  CAS  PubMed  Google Scholar 

  14. Sakaguchi M, Tanaka T, Fukushima W, Kubo T. Multicenter Case–Control Study Group. Impact of oral corticosteroid use for idiopathic osteonecrosis of the femoral head: a nationwide multicenter case-control study in Japan. J Orthop Sci. 2010;15:185–91.

    Article  CAS  PubMed  Google Scholar 

  15. Sugano N, Kubo T, Takaoka K, Ohzono K, Hotokebuchi T, Matsumoto T, Igarashi H, Ninomiya S. Diagnostic criteria for non-traumatic osteonecrosis of the femoral head: a multicentre study. J Bone Joint Surg Br. 1999;81-B:590–5.

    Article  Google Scholar 

  16. Japan Health Promotion & Fitness Foundation (2012). Health-net: tobacco or health. (http://www.health-net.or.jp/tobacco/front.html).

  17. Fox SW, Chow JWM. Nitric oxide synthase in bone cells. Bone. 1998;23:1–6.

    Article  CAS  PubMed  Google Scholar 

  18. Ichiseki T, Kaneuji A, Ueda Y, Nakagawa S, Mikami T, Fukui K, Matsumoto T. Osteonecrosis development in a novel rat model characterized by a single application of oxidative stress. Arthr Rheum. 2011;63:2138–41.

    Article  CAS  Google Scholar 

  19. Ichiseki T, Kaneuji A, Katsuda S, Ueda Y, Sugimori T, Matsumoto T. DNA oxidation injury in bone early after steroid administration is involved in the pathogenesis of steroid-induced osteonecrosis. Rheumatology (Oxford). 2005;44:456–60.

    Article  CAS  Google Scholar 

  20. Murata M, Kumagai K, Miyata N, Osaki M, Shindo H. Osteonecrosis in stroke-prone spontaneously hypertensive rats: effect of glucocorticoid. J Orthop Sci. 2007;12:289–95.

    Article  CAS  PubMed  Google Scholar 

  21. Kerachian MA, Séguin C, Harvey EJ. Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J Steroid Biochem Mol Biol. 2009;114:121–8.

    Article  CAS  PubMed  Google Scholar 

  22. Yamamoto T, Irisa T, Sugioka Y, Sueishi K. Effects of pulse methylprednisolone on bone and marrow tissues: corticosteroid-induced osteonecrosis in rabbits. Arthr Rheum. 1997;40:2055–64.

    Article  CAS  Google Scholar 

  23. Miyanishi K, Yamamoto T, Irisa T, Yamashita A, Jingushi S, Noguchi Y, Iwamoto Y. Bone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis. Bone. 2002;30:185–90.

    Article  CAS  PubMed  Google Scholar 

  24. Gál K, Cseh A, Szalay B, Rusai K, Vannay A, Lukácsovits J, Heemann U, Szabó AJ, Losonczy G, Tamási L, Müller V. Effect of cigarette smoke and dexamethasone on Hsp72 system of alveolar epithelial cells. Cell Stress Chaperones. 2011;16:369–78.

    Article  PubMed  Google Scholar 

  25. Bose M, Whittal RM, Gairola CG, Bose HS. Molecular mechanism of reduction in pregnenolone synthesis by cigarette smoke. Toxicol Appl Pharmacol. 2008;229:56–64.

    Article  CAS  PubMed  Google Scholar 

  26. Wagenknecht LE, Burke GL, Perkins LL, Haley NJ, Friedman GD. Misclassification of smoking status in the CARDIA study: a comparison of self-report with serum cotinine levels. Am J Public Health. 1992;82:33–6.

    Article  CAS  PubMed  Google Scholar 

  27. Lewis SJ, Cherry NM, McL Niven R, Barber PV, Wilde K, Povey AC. Cotinine levels and self-reported smoking status in patients attending a bronchoscopy clinic. Biomarkers. 2003;8:218–28.

    Article  CAS  PubMed  Google Scholar 

  28. Martínez ME, Reid M, Jiang R, Einspahr J, Alberts DS. Accuracy of self-reported smoking status among participants in a chemoprevention trial. Prev Med. 2004;38:492–7.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Research Committee on the Idiopathic Osteonecrosis of the Femoral Head of the Ministry of Health, Labor, and Welfare of Japan. The authors are grateful to the following members of the Idiopathic ONF Multicenter Case–Control Study Group: Drs S. Jingushi and T. Yamamoto, Kyushu University; Drs T. Nishii and N. Sugano, Osaka University; Drs K. Sakai and K. Ohzono, Osaka Medical Center; Drs A. Kaneuji and T. Matsumoto, Kanazawa Medical University; Drs H. Horiuchi and S. Kobayashi, Shinshu University; Drs M. Kawasaki and Y. Hasegawa, Nagoya University; Drs T. Teranishi and T. Matsuno, Asahikawa Medical College; K. Takaoka, Osaka City University; and M. Fujioka, Kyoto Prefectural University of Medicine.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Public Health, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    Shinji Takahashi, Wakaba Fukushima & Yoshio Hirota

  2. Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Toshikazu Kubo

  3. Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Yukihide Iwamoto

  4. Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    Shinji Takahashi & Hiroaki Nakamura

Authors
  1. Shinji Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wakaba Fukushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshikazu Kubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yukihide Iwamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshio Hirota
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroaki Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shinji Takahashi.

About this article

Cite this article

Takahashi, S., Fukushima, W., Kubo, T. et al. Pronounced risk of nontraumatic osteonecrosis of the femoral head among cigarette smokers who have never used oral corticosteroids: a multicenter case–control study in Japan. J Orthop Sci 17, 730–736 (2012). https://doi.org/10.1007/s00776-012-0293-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00776-012-0293-x

Keywords

Search

Navigation