DOI QR코드

DOI QR Code

Body Weight and Bone Density Changes in Patients with Ankylosing Spondylitis Receiving Anti-Tumor Necrosis Factor-${\alpha}$ Treatment

Anti-TNF-${\alpha}$ 치료를 받은 강직성 척추염 환자들의 체중과 골밀도 변화

  • Lee, Jangwon (Department of Internal Medicine, Wallace Memorial Baptist Hospital) ;
  • Jung, Minsuk (Department of Internal Medicine, Wallace Memorial Baptist Hospital) ;
  • Kim, Donghyun (Department of Internal Medicine, Wallace Memorial Baptist Hospital) ;
  • Lee, Seunghyun (Department of Internal Medicine, Wallace Memorial Baptist Hospital) ;
  • Oh, Sook Kyung (Department of Internal Medicine, Wallace Memorial Baptist Hospital) ;
  • Jo, Youngsun (Department of Internal Medicine, Wallace Memorial Baptist Hospital) ;
  • Byun, Sanghwan (Department of Internal Medicine, Wallace Memorial Baptist Hospital) ;
  • Nam, Kyoungmin (Department of Internal Medicine, Wallace Memorial Baptist Hospital) ;
  • Lee, Choongwon (Department of Internal Medicine, Wallace Memorial Baptist Hospital)
  • 이장원 (왈레스기념 침례병원 내과) ;
  • 정민석 (왈레스기념 침례병원 내과) ;
  • 김동현 (왈레스기념 침례병원 내과) ;
  • 이승현 (왈레스기념 침례병원 내과) ;
  • 오숙경 (왈레스기념 침례병원 내과) ;
  • 조영선 (왈레스기념 침례병원 내과) ;
  • 변상환 (왈레스기념 침례병원 내과) ;
  • 남경민 (왈레스기념 침례병원 내과) ;
  • 이충원 (왈레스기념 침례병원 내과)
  • Received : 2012.12.24
  • Accepted : 2013.06.07
  • Published : 2013.11.01

Abstract

Background/Aims: To determine the changes in body weight and bone mineral density in patients with ankylosing spondylitis (AS) receiving anti-tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) treatment. Methods: Thirty-one patients with AS (25 males and 6 females) who fulfilled the Modified New York Criteria for AS were included in this retrospective study. All patients had active disease that eventually required anti-TNF-${\alpha}$ treatment. Each patient received anti-TNF-${\alpha}$ treatment (etanercept 25 mg twice weekly or adalimumab 40 mg twice monthly) for more than 2 years. Body weight, disease activity as Bath ankylosing spondylitis disease activity index (BASDAI), C-reactive protein, erythrocyte sedimentation rate (ESR), lumbar bone mineral density (LBMD), and femoral bone mineral density (FBMD) were measured at baseline and at 1 and 2 years after initiating anti-TNF-${\alpha}$ treatment. Results: There was a significant increase in mean body weight at 1 year ($1.1{\pm}3.8kg$) and at 2 years ($1.7{\pm}4.8kg$) compared with baseline. The gains in mean BMD of the lumbar spine were significant at 1 year ($0.4{\pm}0.4$) and 2 years ($0.5{\pm}0.7$) compared with baseline. Mean BMD of the femur was also increased at 1 year ($0.08{\pm}0.7$) and 2 years ($0.1{\pm}0.8$) compared with baseline, but these differences were not statistically significant. There were significant decreases in BASDAI at 1 year ($-3.3{\pm}2.8$) and at 2 years ($-3.6{\pm}2.8$) compared with baseline. Conclusions: This study showed significant increases in body weight, lumbar BMD, and BASDAI at 1 year and 2 years in patients with ankylosing spondylitis after receiving anti-TNF-${\alpha}$ treatment.

목적: 본 연구의 목적은 강직성 척추염 환자에서 anti-tumor necrosis factor-${\alpha}$ (anti-TNF-${\alpha}$) 치료 후의 체중과 골밀도의 변화를 알아보고자 연구를 하였다. 방법: Modified New York Criteria에 의해 진단된 총 31명의 (남성 25명, 여성 6명) 강직성 척추염 환자들을 대상으로 하였다. 모든 환자들은 비스테로이드성 소염진통제(NSAIDs), sulfasalazine, methotrexate에도 반응하지 않고 질병활성도가 높아 anti-TNF-${\alpha}$ 치료를 2년 이상 시행하였다. Anti-TNF-${\alpha}$의 용량은 etanercept 25 mg 주 2회였고 adalimumab 40 mg 월 2회로 하였다. 체중과 골밀도를(dual energy X-ray absorptiometry) 비롯하여 질병활성도의 지표로 Bath ankylosing spondylitis (BASDAI), C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR) 등을 측정하였다. 결과: TNF-${\alpha}$ 길항제 치료 전과 비교했을 때 치료 1년 후와 2년 후의 몸무게의 평균은 $68.6{\pm}13.2kg$, $69.2{\pm}15.2kg$로 p value가 0.02로 통계적으로 유의한 차이를 보였으며 시간이 갈수록 값이 증가함을 알 수 있다(Fig. 1). TNF-${\alpha}$ 길항제 치료 전 요추부(제1-제4요추) 평균 골밀도는 $-0.2{\pm}1.6$이었고 치료 1년 후와 2년 후의 요추부 평균 골밀도는(Z-score로 변환 시) 각각 $0.1{\pm}1.6$, $0.2{\pm}1.6$으로 p value가 0.001이하로 통계적으로 매우 유의한 차이를 보였으며 시간이 갈수록 값이 증가함을 알 수 있다(Fig. 1). TNF-${\alpha}$ 길항제 치료 전 BASDAI는 $5.6{\pm}2.8$점이었고 치료 1년 후와 2년 후는 각각 $2.3{\pm}1.9$점, $2.0{\pm}1.8$점으로 p value가 0.01 미만으로 통계적으로 매우 유의한 감소 양상을 보였다. CRP는 TNF-${\alpha}$ 길항제 치료 전 $1.4{\pm}2.0mg/dL$였고 치료 1년 후와 2년 후는 각각 $0.3{\pm}0.3mg/dL$, $0.5{\pm}1.0mg/dL$로 p value가 0.01 미만으로 통계적으로 유의한 차이를 보였다. 결론: 강직성 척추염 환자들을 대상으로 한 골밀도와 체중의 변화에 대한 국내 자료는 외국에 비해 미미한 실정이다. 본 연구에서는 31명의 강직성 척추염 환자들을 대상으로 TNF-${\alpha}$ 길항제 치료 후 체중과 요추부 골밀도가 통계적으로 유의하게 증가함과 동시에 질병활성도의 지표의 BASDAI가 통계적으로 유의하게 감소하는 것을 확인하였기에 보고하는 바이다.

Keywords

References

  1. Gran JT, Husby G. Epidemiology of ankylosing spondylitis. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Semin Arthritis Rheumatology 1993;22: 319-334. https://doi.org/10.1016/S0049-0172(05)80011-3
  2. Braun J, Bollow M, Remlinger G, et al. Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum 1998;41:58-67. https://doi.org/10.1002/1529-0131(199801)41:1<58::AID-ART8>3.0.CO;2-G
  3. Gratacos J, Collado A, Filella X, et al. Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol 1994;33:927-931. https://doi.org/10.1093/rheumatology/33.10.927
  4. Braun J, Bollow M, Neure L, et al. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 1995;38:499-505. https://doi.org/10.1002/art.1780380407
  5. Yumet G, Shumate ML, Bryant P, Lin CM, Lang CH, Cooney RN. Tumor necrosis factor mediates hepatic growth hormone resistance during sepsis. Am J Physiol Endocrinol Metab 2002;283:E472-481. https://doi.org/10.1152/ajpendo.00107.2002
  6. Maillefert JF, Aho LS, El Maghraoui A, Dougados M, Roux C. Changes in bone density in patients with ankylosing spondylitis: a two-year follow-up study. Osteoporos Int 2001;12:605-609. https://doi.org/10.1007/s001980170084
  7. Truyens C, Torrico F, Angelo-Barrios A, et al. The cachexia associated with Trypanosoma cruzi acute infection in mice is attenuated by anti-TNF-alpha, but not by anti-IL-6 or anti-IFN-gamma antibodies. Parasite Immunol 1995;17: 561-568. https://doi.org/10.1111/j.1365-3024.1995.tb00999.x
  8. Strassmann G, Kambayashi T. Inhibition of experimental cancer cachexia by anti-cytokine and anti-cytokine-receptor therapy. Cytokines Mol Ther 1995;1:107-113.
  9. Briot K, Gossec L, Kolta S, Dougados M, Roux C. Prospective assessment of body weight, body composition, and bone density changes in patients with spondyloarthropathy receiving anti-tumor necrosis factor-alpha treatment. J Rheumatol 2008;35:855-861.
  10. Park HJ, Kim SH, Lee JE, Jun JB, Bae SC. Korean translation and validation of Bath ankylosing spondylitis disease activity index (BASDAI): a pilot test. Value Health. 2008;11:99-104.
  11. Writing Group for the ISCD Position Development Conference. Diagnosis of osteoporosis in men, premenopausal women, and children. J Clin Densitom 2004;7:17-26. https://doi.org/10.1385/JCD:7:1:17
  12. Kirchgessner TG, Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J Clin Invest 1997;100:2777-2782. https://doi.org/10.1172/JCI119824
  13. Allali F, Breban M, Porcher R, Maillefert JF, Dougados M, Roux C. Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumour necrosis factor alpha. Ann Rheum Dis 2003;62:347-349. https://doi.org/10.1136/ard.62.4.347
  14. Demis E, Roux C, Breban M, Dougados M. Infliximab in spondylarthropathy: influence on bone density. Clin Exp Rheumatol 2002;20(6 Suppl 28):S185-186.
  15. Son JH, Cha SW. Anti-TNF-$\alpha$ therapy for ankylosing spondylitis. Clin Orthop Surg 2010;2:28-33. https://doi.org/10.4055/cios.2010.2.1.28
  16. Krieckaert CL, Nurmohamed MT, Wolbink G, Lems WF. Changes in bone mineral density during long-term treatment with adalimumab in patients with rheumatoid arthritis: a cohort study. Rheumatology (Oxford) 2013;52:547-553. https://doi.org/10.1093/rheumatology/kes320

Cited by

  1. Weight Gain and Improvement of Osteoporosis with Anti-TNF Therapy vol.85, pp.5, 2013, https://doi.org/10.3904/kjm.2013.85.5.485