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Bone and joint complications in sickle cell disease

Alex George, MD, PhD
Michael R DeBaun, MD, MPH
Section Editors
Donald H Mahoney, Jr, MD
William Phillips, MD
Stanley L Schrier, MD
Deputy Editor
Jennifer S Tirnauer, MD


Sickle cell disease (SCD) is characterized by a marked heterogeneity in clinical and hematologic severity [1,2], with bone and joint problems being the most common manifestations. Pain caused by vaso-occlusive episodes may occur as often as every week, or individuals with SCD may go with long stretches of time without any pain events. Many individuals with SCD also suffer from the long-term consequences of vaso-occlusive pain episodes in the musculoskeletal system, such as avascular necrosis of the femoral heads or collapsed vertebral bodies, leading to a chronic state of pain in addition to the more acute painful episodes.

Bone and joint complications in SCD are discussed here. Other manifestations of SCD are discussed separately. (See "Overview of the clinical manifestations of sickle cell disease".)

The management of individuals with SCD is discussed separately in an overview topic and in individual topics on the treatment of specific disease manifestations. (See "Overview of the management and prognosis of sickle cell disease".)


Repeated vaso-occlusive pain episodes are the hallmark of sickle cell disease (SCD). Clinicians caring for children and adults with SCD refrain from using the term "sickle cell crises" when describing a vaso-occlusive pain episode because "crisis" does not appropriately depict the clinical situation.

Pain episodes can lead to bone infarcts, necrosis, and, over time, degenerative changes in marrow-containing bone. Pain episodes can occur in early infancy and into adulthood, and are a major cause of hospitalization in SCD. Among individuals with SCD in the United States, almost 90 percent of all visits to the emergency department are for painful episodes, as are almost 70 percent of all hospitalizations, with an average duration of 8 to 11 days for adults and 4 to 5 days for children. Similar numbers are found in individuals with SCD in the United Kingdom [3].

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Literature review current through: Nov 2017. | This topic last updated: Sep 13, 2017.
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  1. Platt OS, Thorington BD, Brambilla DJ, et al. Pain in sickle cell disease. Rates and risk factors. N Engl J Med 1991; 325:11.
  2. Platt OS. Easing the suffering caused by sickle cell disease. N Engl J Med 1994; 330:783.
  3. Ware MA, Hambleton I, Ochaya I, Serjeant GR. Day-care management of sickle cell painful crisis in Jamaica: a model applicable elsewhere? Br J Haematol 1999; 104:93.
  4. Darbari DS, Onyekwere O, Nouraie M, et al. Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemia. J Pediatr 2012; 160:286.
  5. Hebbel RP, Vercellotti G, Nath KA. A systems biology consideration of the vasculopathy of sickle cell anemia: the need for multi-modality chemo-prophylaxsis. Cardiovasc Hematol Disord Drug Targets 2009; 9:271.
  6. Michaels LA, Ohene-Frempong K, Zhao H, Douglas SD. Serum levels of substance P are elevated in patients with sickle cell disease and increase further during vaso-occlusive crisis. Blood 1998; 92:3148.
  7. Mollapour E, Porter JB, Kaczmarski R, et al. Raised neutrophil phospholipase A2 activity and defective priming of NADPH oxidase and phospholipase A2 in sickle cell disease. Blood 1998; 91:3423.
  8. Barbeau P, Woods KF, Ramsey LT, et al. Exercise in sickle cell anemia: effect on inflammatory and vasoactive mediators. Endothelium 2001; 8:147.
  9. Morris CR, Kuypers FA, Larkin S, et al. Patterns of arginine and nitric oxide in patients with sickle cell disease with vaso-occlusive crisis and acute chest syndrome. J Pediatr Hematol Oncol 2000; 22:515.
  10. Browne PV, Mosher DF, Steinberg MH, Hebbel RP. Disturbance of plasma and platelet thrombospondin levels in sickle cell disease. Am J Hematol 1996; 51:296.
  11. Brittain HA, Eckman JR, Swerlick RA, et al. Thrombospondin from activated platelets promotes sickle erythrocyte adherence to human microvascular endothelium under physiologic flow: a potential role for platelet activation in sickle cell vaso-occlusion. Blood 1993; 81:2137.
  12. Frenette PS. Sickle cell vaso-occlusion: multistep and multicellular paradigm. Curr Opin Hematol 2002; 9:101.
  13. Chiang EY, Frenette PS. Sickle cell vaso-occlusion. Hematol Oncol Clin North Am 2005; 19:771.
  14. Serjeant GR, Ceulaer CD, Lethbridge R, et al. The painful crisis of homozygous sickle cell disease: clinical features. Br J Haematol 1994; 87:586.
  15. Gelfand MJ, Daya SA, Rucknagel DL, et al. Simultaneous occurrence of rib infarction and pulmonary infiltrates in sickle cell disease patients with acute chest syndrome. J Nucl Med 1993; 34:614.
  16. Roger E, Letts M. Sickle cell disease of the spine in children. Can J Surg 1999; 42:289.
  17. Berger E, Saunders N, Wang L, Friedman JN. Sickle cell disease in children: differentiating osteomyelitis from vaso-occlusive crisis. Arch Pediatr Adolesc Med 2009; 163:251.
  18. Keeley K, Buchanan GR. Acute infarction of long bones in children with sickle cell anemia. J Pediatr 1982; 101:170.
  19. Resar LM, Oliva MM, Casella JF. Skull infarction and epidural hematomas in a patient with sickle cell anemia. J Pediatr Hematol Oncol 1996; 18:413.
  20. Rao SP, Miller S, Solomon N. Acute bone and joint manifestations of sickle cell disease in children. N Y State J Med 1986; 86:254.
  21. Alavi A, Heyman S, Kim HC. Scintigraphic examination of bone and marrow infarcts in sickle cell disorders. Semin Roentgenol 1987; 22:213.
  22. Rao S, Solomon N, Miller S, Dunn E. Scintigraphic differentiation of bone infarction from osteomyelitis in children with sickle cell disease. J Pediatr 1985; 107:685.
  23. Skaggs DL, Kim SK, Greene NW, et al. Differentiation between bone infarction and acute osteomyelitis in children with sickle-cell disease with use of sequential radionuclide bone-marrow and bone scans. J Bone Joint Surg Am 2001; 83-A:1810.
  24. Mankad VN, Williams JP, Harpen MD, et al. Magnetic resonance imaging of bone marrow in sickle cell disease: clinical, hematologic, and pathologic correlations. Blood 1990; 75:274.
  25. Shapiro BS, Dinges DF, Orne EC, et al. Home management of sickle cell-related pain in children and adolescents: natural history and impact on school attendance. Pain 1995; 61:139.
  26. Section on Hematology/Oncology Committee on Genetics, American Academy of Pediatrics. Health supervision for children with sickle cell disease. Pediatrics 2002; 109:526.
  27. Jacob E, Miaskowski C, Savedra M, et al. Changes in intensity, location, and quality of vaso-occlusive pain in children with sickle cell disease. Pain 2003; 102:187.
  28. Jacob E, American Pain Society. Pain management in sickle cell disease. Pain Manag Nurs 2001; 2:121.
  29. Benjamin LJ, Swinson GI, Nagel RL. Sickle cell anemia day hospital: an approach for the management of uncomplicated painful crises. Blood 2000; 95:1130.
  30. Kutlar A, Ataga KI, McMahon L, et al. A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease. Am J Hematol 2012; 87:536.
  31. Luo W, Campbell A, Wang H, et al. P-selectin glycoprotein ligand-1 inhibition blocks increased leukocyte-endothelial interactions associated with sickle cell disease in mice. Blood 2012; 120:3862.
  32. Uong EC, Boyd JH, DeBaun MR. Daytime pulse oximeter measurements do not predict incidence of pain and acute chest syndrome episodes in sickle cell anemia. J Pediatr 2006; 149:707.
  33. Bernini JC, Rogers ZR, Sandler ES, et al. Beneficial effect of intravenous dexamethasone in children with mild to moderately severe acute chest syndrome complicating sickle cell disease. Blood 1998; 92:3082.
  34. Miller ST, Wright E, Abboud M, et al. Impact of chronic transfusion on incidence of pain and acute chest syndrome during the Stroke Prevention Trial (STOP) in sickle-cell anemia. J Pediatr 2001; 139:785.
  35. Pegelow CH. Survey of pain management therapy provided for children with sickle cell disease. Clin Pediatr (Phila) 1992; 31:211.
  36. Darbari DS, Castro O, Taylor JG 6th, et al. Severe vaso-occlusive episodes associated with use of systemic corticosteroids in patients with sickle cell disease. J Natl Med Assoc 2008; 100:948.
  37. Vandy Black L, Smith WR. Evidence-based mini-review: Are systemic corticosteroids an effective treatment for acute pain in sickle cell disease? Hematology Am Soc Hematol Educ Program 2010; 2010:416.
  38. NHLBI 2002 Guidelines. http://www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf (Accessed on February 05, 2013).
  39. Styles LA, Vichinsky E. Effects of a long-term transfusion regimen on sickle cell-related illnesses. J Pediatr 1994; 125:909.
  40. Gill FM, Sleeper LA, Weiner SJ, et al. Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease. Blood 1995; 86:776.
  41. Stevens MC, Padwick M, Serjeant GR. Observations on the natural history of dactylitis in homozygous sickle cell disease. Clin Pediatr (Phila) 1981; 20:311.
  42. Bennett OM. Salmonella osteomyelitis and the hand-foot syndrome in sickle cell disease. J Pediatr Orthop 1992; 12:534.
  43. Webb DK, Serjeant GR. Haemophilus influenzae osteomyelitis complicating dactylitis in homozygous sickle cell disease. Eur J Pediatr 1990; 149:613.
  44. Wang WC, Ware RE, Miller ST, et al. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet 2011; 377:1663.
  45. Thornburg CD, Files BA, Luo Z, et al. Impact of hydroxyurea on clinical events in the BABY HUG trial. Blood 2012; 120:4304.
  46. Barrett-Connor E. Bacterial infection and sickle cell anemia. An analysis of 250 infections in 166 patients and a review of the literature. Medicine (Baltimore) 1971; 50:97.
  47. Bennett OM, Namnyak SS. Bone and joint manifestations of sickle cell anaemia. J Bone Joint Surg Br 1990; 72:494.
  48. Anand AJ, Glatt AE. Salmonella osteomyelitis and arthritis in sickle cell disease. Semin Arthritis Rheum 1994; 24:211.
  49. Neonato MG, Lu CY, Guilloud-Bataille M, et al. Genetic polymorphism of the mannose-binding protein gene in children with sickle cell disease: identification of three new variant alleles and relationship to infections. Eur J Hum Genet 1999; 7:679.
  50. Tamouza R, Neonato MG, Busson M, et al. Infectious complications in sickle cell disease are influenced by HLA class II alleles. Hum Immunol 2002; 63:194.
  51. Chambers JB, Forsythe DA, Bertrand SL, et al. Retrospective review of osteoarticular infections in a pediatric sickle cell age group. J Pediatr Orthop 2000; 20:682.
  52. Burnett MW, Bass JW, Cook BA. Etiology of osteomyelitis complicating sickle cell disease. Pediatrics 1998; 101:296.
  53. HOOK EW, CAMPBELL CG, WEENS HS, COOPER GR. Salmonella osteomyelitis in patients with sickle-cell anemia. N Engl J Med 1957; 257:403.
  54. Syrogiannopoulos GA, McCracken GH Jr, Nelson JD. Osteoarticular infections in children with sickle cell disease. Pediatrics 1986; 78:1090.
  55. Sadat-Ali M. The status of acute osteomyelitis in sickle cell disease. A 15-year review. Int Surg 1998; 83:84.
  56. Thanni LO. Bacterial osteomyelitis in major sickling haemoglobinopathies: geographic difference in pathogen prevalence. Afr Health Sci 2006; 6:236.
  57. Sankaran-Kutty M, Sadat-Ali M, Kutty MK. Septic arthritis in sickle cell disease. Int Orthop 1988; 12:255.
  58. Nistala K, Murray KJ. Co-existent sickle cell disease and juvenile rheumatoid arthritis. Two cases with delayed diagnosis and severe destructive arthropathy. J Rheumatol 2001; 28:2125.
  59. Umans H, Haramati N, Flusser G. The diagnostic role of gadolinium enhanced MRI in distinguishing between acute medullary bone infarct and osteomyelitis. Magn Reson Imaging 2000; 18:255.
  60. William RR, Hussein SS, Jeans WD, et al. A prospective study of soft-tissue ultrasonography in sickle cell disease patients with suspected osteomyelitis. Clin Radiol 2000; 55:307.
  61. Rao VM, Mitchell DG, Rifkin MD, et al. Marrow infarction in sickle cell anemia: correlation with marrow type and distribution by MRI. Magn Reson Imaging 1989; 7:39.
  62. Booz MM, Hariharan V, Aradi AJ, Malki AA. The value of ultrasound and aspiration in differentiating vaso-occlusive crisis and osteomyelitis in sickle cell disease patients. Clin Radiol 1999; 54:636.
  63. Milner PF, Kraus AP, Sebes JI, et al. Sickle cell disease as a cause of osteonecrosis of the femoral head. N Engl J Med 1991; 325:1476.
  64. Hawker H, Neilson H, Hayes RJ, Serjeant GR. Haematological factors associated with avascular necrosis of the femoral head in homozygous sickle cell disease. Br J Haematol 1982; 50:29.
  65. Adekile AD, Gupta R, Yacoub F, et al. Avascular necrosis of the hip in children with sickle cell disease and high Hb F: magnetic resonance imaging findings and influence of alpha-thalassemia trait. Acta Haematol 2001; 105:27.
  66. Worrall D, Smith-Whitley K, Wells L. Hemoglobin to Hematocrit Ratio: The Strongest Predictor of Femoral Head Osteonecrosis in Children With Sickle Cell Disease. J Pediatr Orthop 2016; 36:139.
  67. Milner PF, Kraus AP, Sebes JI, et al. Osteonecrosis of the humeral head in sickle cell disease. Clin Orthop Relat Res 1993; :136.
  68. Poignard A, Flouzat-Lachaniette CH, Amzallag J, et al. The natural progression of symptomatic humeral head osteonecrosis in adults with sickle cell disease. J Bone Joint Surg Am 2012; 94:156.
  69. Hernigou P, Galacteros F, Bachir D, Goutallier D. Deformities of the hip in adults who have sickle-cell disease and had avascular necrosis in childhood. A natural history of fifty-two patients. J Bone Joint Surg Am 1991; 73:81.
  70. Hernigou P, Habibi A, Bachir D, Galacteros F. The natural history of asymptomatic osteonecrosis of the femoral head in adults with sickle cell disease. J Bone Joint Surg Am 2006; 88:2565.
  71. Mont MA, Marulanda GA, Jones LC, et al. Systematic analysis of classification systems for osteonecrosis of the femoral head. J Bone Joint Surg Am 2006; 88 Suppl 3:16.
  72. Mitchell DG, Steinberg ME, Dalinka MK, et al. Magnetic resonance imaging of the ischemic hip. Alterations within the osteonecrotic, viable, and reactive zones. Clin Orthop Relat Res 1989; :60.
  73. Huo MH, Friedlaender GE, Marsh JS. Orthopaedic manifestations of sickle-cell disease. Yale J Biol Med 1990; 63:195.
  74. Baykul T, Aydin MA, Nasir S. Avascular necrosis of the mandibular condyle causing fibrous ankylosis of the temporomandibular joint in sickle cell anemia. J Craniofac Surg 2004; 15:1052.
  75. Mukisi Mukaza M, Manicom O, Fillipini P, Hernigou P. Elbow osteonecrosis in sickle cells anemia: a study of six cases. Orthop Traumatol Surg Res 2009; 95:82.
  76. Mankin HJ. Nontraumatic necrosis of bone (osteonecrosis). N Engl J Med 1992; 326:1473.
  77. Steinberg ME. Early diagnosis of avascular necrosis of the femoral head. Instr Course Lect 1988; 37:51.
  78. Garino JP, Steinberg ME. Total hip arthroplasty in patients with avascular necrosis of the femoral head: a 2- to 10-year follow-up. Clin Orthop Relat Res 1997; :108.
  79. Steinberg ME. Classification of avascular necrosis: a comparative study. Acta Orthop Belg 1999; 65 Suppl 1:45.
  80. Neumayr LD, Aguilar C, Earles AN, et al. Physical therapy alone compared with core decompression and physical therapy for femoral head osteonecrosis in sickle cell disease. Results of a multicenter study at a mean of three years after treatment. J Bone Joint Surg Am 2006; 88:2573.
  81. Mukisi-Mukaza M, Manicom O, Alexis C, et al. Treatment of sickle cell disease's hip necrosis by core decompression: a prospective case-control study. Orthop Traumatol Surg Res 2009; 95:498.
  82. Marker DR, Seyler TM, McGrath MS, et al. Treatment of early stage osteonecrosis of the femoral head. J Bone Joint Surg Am 2008; 90 Suppl 4:175.
  83. Martí-Carvajal AJ, Solà I, Agreda-Pérez LH. Treatment for avascular necrosis of bone in people with sickle cell disease. Cochrane Database Syst Rev 2012; :CD004344.
  84. Johannson HR, Zywiel MG, Marker DR, et al. Osteonecrosis is not a predictor of poor outcomes in primary total hip arthroplasty: a systematic literature review. Int Orthop 2011; 35:465.
  85. Al-Mousawi F, Malki A, Al-Aradi A, et al. Total hip replacement in sickle cell disease. Int Orthop 2002; 26:157.
  86. Kamath AF, Sheth NP, Hosalkar HH, et al. Modern total hip arthroplasty in patients younger than 21 years. J Arthroplasty 2012; 27:402.
  87. Hernigou P, Zilber S, Filippini P, et al. Total THA in adult osteonecrosis related to sickle cell disease. Clin Orthop Relat Res 2008; 466:300.
  88. Issa K, Naziri Q, Maheshwari AV, et al. Excellent results and minimal complications of total hip arthroplasty in sickle cell hemoglobinopathy at mid-term follow-up using cementless prosthetic components. J Arthroplasty 2013; 28:1693.
  89. Azam MQ, Sadat-Ali M. Quality of Life in Sickle Cell Patients After Cementless Total Hip Arthroplasty. J Arthroplasty 2016; 31:2536.
  90. Vichinsky EP, Neumayr LD, Haberkern C, et al. The perioperative complication rate of orthopedic surgery in sickle cell disease: report of the National Sickle Cell Surgery Study Group. Am J Hematol 1999; 62:129.
  91. Perfetti DC, Boylan MR, Naziri Q, et al. Does sickle cell disease increase risk of adverse outcomes following total hip and knee arthroplasty? A nationwide database study. J Arthroplasty 2015; 30:547.
  92. Daltro GC, Fortuna V, de Souza ES, et al. Efficacy of autologous stem cell-based therapy for osteonecrosis of the femoral head in sickle cell disease: a five-year follow-up study. Stem Cell Res Ther 2015; 6:110.
  93. Piuzzi NS, Chahla J, Jiandong H, et al. Analysis of Cell Therapies Used in Clinical Trials for the Treatment of Osteonecrosis of the Femoral Head: A Systematic Review of the Literature. J Arthroplasty 2017; 32:2612.
  94. Saito N, Nadgir RN, Flower EN, Sakai O. Clinical and radiologic manifestations of sickle cell disease in the head and neck. Radiographics 2010; 30:1021.
  95. Curran EL, Fleming JC, Rice K, Wang WC. Orbital compression syndrome in sickle cell disease. Ophthalmology 1997; 104:1610.
  96. Ganesh A, William RR, Mitra S, et al. Orbital involvement in sickle cell disease: a report of five cases and review literature. Eye (Lond) 2001; 15:774.
  97. Naran AD, Fontana L. Sickle cell disease with orbital infarction and epidural hematoma. Pediatr Radiol 2001; 31:257.
  98. Royal JE, Harris VJ, Sansi PK. Facial bone infarcts in sickle cell syndromes. Radiology 1988; 169:529.
  99. Ganesh A, Al-Zuhaibi S, Pathare A, et al. Orbital infarction in sickle cell disease. Am J Ophthalmol 2008; 146:595.
  100. Sadat-Ali M, Ammar A, Corea JR, Ibrahim AW. The spine in sickle cell disease. Int Orthop 1994; 18:154.
  101. Sarrai M, Duroseau H, D'Augustine J, et al. Bone mass density in adults with sickle cell disease. Br J Haematol 2007; 136:666.
  102. Marlow TJ, Brunson CY, Jackson S, Schabel SI. "Tower vertebra": a new observation in sickle cell disease. Skeletal Radiol 1998; 27:195.
  103. Westerman MP, Greenfield GB, Wong PW. "Fish vertebrae," homocystinuria, and sickle cell anemia. JAMA 1974; 230:261.
  104. Platt OS, Rosenstock W, Espeland MA. Influence of sickle hemoglobinopathies on growth and development. N Engl J Med 1984; 311:7.
  105. Bennett EL. Understanding growth failure in children with homozygous sickle-cell disease. J Pediatr Oncol Nurs 2011; 28:67.
  106. Al-Saqladi AW, Cipolotti R, Fijnvandraat K, Brabin BJ. Growth and nutritional status of children with homozygous sickle cell disease. Ann Trop Paediatr 2008; 28:165.
  107. Soliman AT, Bererhi H, Darwish A, et al. Decreased bone mineral density in prepubertal children with sickle cell disease: correlation with growth parameters, degree of siderosis and secretion of growth factors. J Trop Pediatr 1998; 44:194.
  108. Taddesse A, Woldie IL, Khana P, et al. Hypogonadism in patients with sickle cell disease: central or peripheral? Acta Haematol 2012; 128:65.
  109. Luporini SM, Bendit I, Manhani R, et al. Growth hormone and insulin-like growth factor I axis and growth of children with different sickle cell anemia haplotypes. J Pediatr Hematol Oncol 2001; 23:357.
  110. Buison AM, Kawchak DA, Schall JI, et al. Bone area and bone mineral content deficits in children with sickle cell disease. Pediatrics 2005; 116:943.
  111. Sadat-Ali M, Al-Elq AH, Sultan O, et al. Low bone mass due to sickle cell anemia: is it becoming a real issue? West Afr J Med 2008; 27:218.
  112. Goodman BM 3rd, Artz N, Radford B, Chen IA. Prevalence of vitamin D deficiency in adults with sickle cell disease. J Natl Med Assoc 2010; 102:332.
  113. Chapelon E, Garabedian M, Brousse V, et al. Osteopenia and vitamin D deficiency in children with sickle cell disease. Eur J Haematol 2009; 83:572.
  114. Arlet JB, Courbebaisse M, Chatellier G, et al. Relationship between vitamin D deficiency and bone fragility in sickle cell disease: a cohort study of 56 adults. Bone 2013; 52:206.
  115. Adewoye AH, Chen TC, Ma Q, et al. Sickle cell bone disease: response to vitamin D and calcium. Am J Hematol 2008; 83:271.