Semin Musculoskelet Radiol 2011; 15(5): 554-560
DOI: 10.1055/s-0031-1293500
© Thieme Medical Publishers

Musculoskeletal Complications of Severe Acute Respiratory Syndrome

James F. Griffith1
  • 1Department of Imaging and Interventional Radiology, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
Further Information

Publication History

Publication Date:
11 November 2011 (online)


The severe acute respiratory syndrome (SARS) was a highly infectious pneumonia that emerged in southern China early in 2003. A large number of SARS patients experienced large joint arthralgia, although this was, for the most part, not associated with any abnormality on magnetic resonance imaging. The main musculoskeletal complications of SARS were osteonecrosis and reduced bone mass, and these arose not from the disease per se but as a sequel to treatment of SARS with high-dose steroids. SARS patients were almost universally steroid naive with no other known predisposition to osteonecrosis. Prevalence of osteonecrosis in SARS patients treated with steroids ranged from 5% to 58%. Osteonecrosis most commonly affected the proximal femur and femoral condyles and was most strongly related to cumulative steroid dose and duration of steroid therapy. Osteonecrosis risk was <1% in patients receiving <3 g and 13% in patients receiving >3 g cumulative prednisolone-equivalent dose. Most osteonecrotic lesions tended to improve with a reduction in lesion volume over a follow-up period of 5 years. The relative reduction in osteonecrotic lesion volume was greatest for smaller lesions.


  • 1 Peiris J S, Yuen K Y, Osterhaus A D, Stöhr K. The severe acute respiratory syndrome.  N Engl J Med. 2003;  349 (25) 2431-2441
  • 2 Fung W K, Yu P LH. SARS case-fatality rates.  CMAJ. 2003;  169 (4) 277-278
  • 3 Wing P C, Nance P, Connell D G, Gagnon F. Risk of avascular necrosis following short term megadose methylprednisolone treatment.  Spinal Cord. 1998;  36 (9) 633-636
  • 4 Cook A M, Dzik-Jurasz A S, Padhani A R, Norman A, Huddart R A. The prevalence of avascular necrosis in patients treated with chemotherapy for testicular tumours.  Br J Cancer. 2001;  85 (11) 1624-1626
  • 5 Zizic T M, Marcoux C, Hungerford D S, Dansereau J V, Stevens M B. Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosus.  Am J Med. 1985;  79 (5) 596-604
  • 6 Wang Y X, Griffith J F, Kwok A W et al.. Reduced bone perfusion in proximal femur of subjects with decreased bone mineral density preferentially affects the femoral neck.  Bone. 2009;  45 (4) 711-715
  • 7 Griffith J F, Yeung D K, Tsang P H et al.. Compromised bone marrow perfusion in osteoporosis.  J Bone Miner Res. 2008;  23 (7) 1068-1075
  • 8 Weinstein R S, Nicholas R W, Manolagas S C. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip.  J Clin Endocrinol Metab. 2000;  85 (8) 2907-2912
  • 9 Schellinger D, Lin C S, Lim J, Hatipoglu H G, Pezzullo J C, Singer A J. Bone marrow fat and bone mineral density on proton MR spectroscopy and dual-energy X-ray absorptiometry: their ratio as a new indicator of bone weakening.  AJR Am J Roentgenol. 2004;  183 (6) 1761-1765
  • 10 Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin M E. Pathogenesis and natural history of osteonecrosis.  Semin Arthritis Rheum. 2002;  32 (2) 94-124
  • 11 Sun W, Wang B L, Liu B L et al.. Osteonecrosis in patients after severe acute respiratory syndrome (SARS): possible role of anticardiolipin antibodies.  J Clin Rheumatol. 2010;  16 (2) 61-63
  • 12 Zhang G, Sheng H, He Y X et al.. Continuous occurrence of both insufficient neovascularization and elevated vascular permeability in rabbit proximal femur during inadequate repair of steroid-associated osteonecrotic lesions.  Arthritis Rheum. 2009;  60 (10) 2966-2977
  • 13 Castro Jr F P, Barrack R L. Core decompression and conservative treatment for avascular necrosis of the femoral head: a meta-analysis.  Am J Orthop. 2000;  29 (3) 187-194
  • 14 Yuen M K, Leong L, Wong Y et al.. Use of magnetic resonance imaging for screening for avascular necrosis post-SARS.  Hong Kong Med J. 2008;  14 S14-S16
  • 15 Li Z R, Sun W, Qu H et al.. Clinical research of correlation between osteonecrosis and steroid [in Chinese].  Zhonghua Wai Ke Za Zhi. 2005;  43 (16) 1048-1053
  • 16 Hong N, Du X K. Avascular necrosis of bone in severe acute respiratory syndrome.  Clin Radiol. 2004;  59 (7) 602-608
  • 17 Lv H, de Vlas S J, Liu W et al.. Avascular osteonecrosis after treatment of SARS: a 3-year longitudinal study.  Trop Med Int Health. 2009;  14 (Suppl 1) 79-84
  • 18 Li Y M, Wang S X, Gao H S et al.. Factors of avascular necrosis of femoral head and osteoporosis in SARS patients' convalescence [in Chinese].  Zhonghua Yi Xue Za Zhi. 2004;  84 (16) 1348-1353
  • 19 Shen J, Liang B L, Zeng Q S et al.. Report on the investigation of lower extremity osteonecrosis with magnetic resonance imaging in recovered severe acute respiratory syndrome in Guangzhou [in Chinese].  Zhonghua Yi Xue Za Zhi. 2004;  84 (21) 1814-1817
  • 20 Griffith J F, Antonio G E, Kumta S M et al.. Osteonecrosis of hip and knee in patients with severe acute respiratory syndrome treated with steroids.  Radiology. 2005;  235 (1) 168-175
  • 21 Chan C W, Chiu W K, Chan C C, Chow E Y, Cheung H M, Ip P L. Osteonecrosis in children with severe acute respiratory syndrome.  Pediatr Infect Dis J. 2004;  23 (9) 888-890
  • 22 Steinberg M E, Steinberg D R. Classification systems for osteonecrosis: an overview.  Orthop Clin North Am. 2004;  35 (3) 273-283 vii-viii
  • 23 Steinberg M E, Hayken G D, Steinberg D R. A quantitative system for staging avascular necrosis.  J Bone Joint Surg Br. 1995;  77 (1) 34-41
  • 24 Antonio G E, Chan J CK, Griffith J F, Hui D SC, Ip M. Use of magnetic resonance imaging for screening for avascular necrosis in atypical pneumonia.  Hong Kong Med J. 2008;  14 S21-S22
  • 25 Chan M H, Chan P K, Griffith J F et al.. Steroid-induced osteonecrosis in severe acute respiratory syndrome: a retrospective analysis of biochemical markers of bone metabolism and corticosteroid therapy.  Pathology. 2006;  38 (3) 229-235
  • 26 Zhang N F, Li Z R, Wei H Y, Liu Z H, Hernigou P. Steroid-induced osteonecrosis: the number of lesions is related to the dosage.  J Bone Joint Surg Br. 2008;  90 (9) 1239-1243
  • 27 Hong N, Du X, Nie Z, Li S. Diffusion-weighted MR study of femoral head avascular necrosis in severe acute respiratory syndrome patients.  J Magn Reson Imaging. 2005;  22 (5) 661-664
  • 28 Hui D SC, Wong K T, Antonio G E, Tong M, Chan D P, Sung J JY. Long term sequalae of SARS: physical, neuropsychiatric and quality-of-life assessment.  Hong Kong Med J. 2009;  15 (Suppl 8) S21-S23
  • 29 Yao W, Cheng Z, Busse C, Pham A, Nakamura M C, Lane N E. Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis: a longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice.  Arthritis Rheum. 2008;  58 (6) 1674-1686
  • 30 Canalis E, Bilezikian J P, Angeli A, Giustina A. Perspectives on glucocorticoid-induced osteoporosis.  Bone. 2004;  34 (4) 593-598
  • 31 Lau E M, Chan F W, Hui D S, Wu A K, Leung P C. Reduced bone mineral density in male severe acute respiratory syndrome (SARS) patients in Hong Kong.  Bone. 2005;  37 (3) 420-424
  • 32 Hong X, Currier G W, Zhao X, Jiang Y, Zhou W, Wei J. Posttraumatic stress disorder in convalescent severe acute respiratory syndrome patients: a 4-year follow-up study.  Gen Hosp Psychiatry. 2009;  31 (6) 546-554
  • 33 Law R K, Lee E W, Poon P Y, Lau T C, Kwok K M, Chan A C. The functional capacity of healthcare workers with history of severe acute respiratory distress syndrome (SARS) complicated with avascular necrosis—case report.  Work. 2008;  30 (1) 17-26
  • 34 Mont M A, Jones L C, Hungerford D S. Nontraumatic osteonecrosis of the femoral head: ten years later.  J Bone Joint Surg Am. 2006;  88 (5) 1117-1132 88(7): 1602 (note: dosage error in article text)
  • 35 Mont M A, Zywiel M G, Marker D R, McGrath M S, Delanois R E. The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review.  J Bone Joint Surg Am. 2010;  92 (12) 2165-2170
  • 36 Steinberg D R, Steinberg M E, Garino J P, Dalinka M, Udupa J K. Determining lesion size in osteonecrosis of the femoral head.  J Bone Joint Surg Am. 2006;  88 (Suppl 3) 27-34
  • 37 Zhao F C, Li Z R, Zhang N F et al.. Lesion size changes in osteonecrosis of the femoral head: a long-term prospective study using MRI.  Int Orthop. 2010;  34 (6) 799-804
  • 38 Wang J, Zhang L L, Wu G. Clinical study on interventional therapy with Chinese and Western medicine for avascular necrosis of femoral head [in Chinese].  Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007;  27 (9) 800-803
  • 39 Xiao K, Liu W, Lu W, Xu H, Sun H, Tang J. Effects of ligustrazine on bone marrow microvessel system in the early period of acute radiation injury in mice.  J Tongji Med Univ. 1997;  17 (1) 9-12 27

James F GriffithM.B.Ch.B. 

Department of Imaging and Interventional Radiology, Chinese University of Hong Kong

Shatin, New Territorics, Hong Kong SAR, China