627

8-131

Pictorial essay: Radiographic skeletal changes in Sickle cell

anemia
SV PHATAK, PK KOLWADKAR, MS PHATAK
Ind J Radiol Imag 2006 16:4:627-632
Keywords: Sickle cell Anemia
Introduction: - Sickle cell anemia is caused by production
of abnormal hemoglobin which binds with other abnormal
hemoglobin molecules within red blood cells and causes
rigid deformation of the cell. Due to this deformity of shape
there is impairment of passage of cell through small
vessels, sludging and congestion of vascular bed to be
followed by ischemia and infarction. Infarction is common
throughout the body in patients with sickle cell anemia
and involves bones, brain, lungs, kidneys, spleen and
liver. Finally as red blood cells are abnormal they are
removed from the circulation resulting into hemolytic
anemia. The normal human hemoglobin molecule consists
of 4 globin chains 2alpha and 2 beta chains. Abnormal
hemoglobin is usually result of abnormality in beta chains
and not in alpha chains. The beta globin chain is coded
to chromosome 11 on the short arm. Sickle cell
hemoglobin is formed (HbS) when the aminoacid valine
is substituted for glutamic acid at the sixth position of
beta chain which has far reaching effects on hemoglobin
reactions, RBC morphology and hemodynamics. The Hb
S beta chain has unusual propensity to bind with other
Hb S chains when deoxygenated resulting into twisted
ropelike structure composed primarily of two complete
hemoglobin molecule strands with binding between beta
chains process called polymerization. Polymerization is
responsible for sickled or banana shape and dehydration
of RBC 's in sickle cell anemia also appear to have
increased binding affinity for vascular endothelium. [1]
Discussion: -The skeletal system of patients with sickle
cell Anemia is remarkable for its lifelong preservation and
frequent expansion of red (cellular marrow)[1] The main
skeletal radiographic changes are seen in Sickle cell
anemia are caused by bone marrow hyperplasia, infarcts
and superadded infection. [2,3,4,5,6] Chronic anemia is
responsible for hyperplasia of bone marrow seen in long
bones as expansion in red bone marrow containing regions
caused by remodelling. This is best shown in 1st
metacarpal known as squaring of metacarpals, which is

seen around 6 months of age as genetically determined

HbS replaces fetal hemoglobin. Bone enlargement can
also be seen in distal femur causing Erlenmeyer flask
deformity. Changes induced by marrow hyperplasia are
nonspecific as these can also be seen in chronic iron
deficiency anemia, Hemoglobin E disease and
Thalassemia, where changes are severe that includes
extramedullary hematopoesis. [2] Marrow hyperplasia
leads to thinning and crowding of trabeculae causing
osteoporosis. In the diaphysis trabeculae becomes sparse
while remaining trabeculae are thickend. Metaphyseal
bone remains relatively dense. In cases of children
changes are most evident in long bones and small tubular
bones of hand and feet. In adolescence osteoporosis
disappears due to conversion of red marrow to yellow
marrow in extremities. Various patterns which are seen
in skull are diploic thickening, granular texture, lamination
of diploe and hair on end pattern. [7] Coarse granular or
stippled pattern is best seen in upper parietal region. It
may be first sign of developing bone marrow hyperplasia.
[8] Cranial vault thickens with most contribution from
diploic component and with resultant thinning of outer
table. In a normal person with thick skull all component
layers contribute to overall thickness. Presence of diploic
layer more than 2.5 times the combined thickness of inner
and outer table s suggests diseased state. Diploic
thickening is significant in frontal and parietal region and
does not involve squamous portion of temporal or occipital
bone. [7] Diploic thickening is nonspecific as it is also
found in other anemias like thalassemia, hereditary
sperocytosis and severe iron deficiency anemia [9]. It is
also seen in cases of Dilatin toxicity [10], after surgical
treatment of hydrocephalus [11], cyanotic congenital heart
disease [12] and pseudohypoparathyroidism [13]
Sometimes in-patients with thick diploe curvilinear dense
bone within lucent marrow parallal to inner table gives
appearance of onion skin. Hair on end appearance is also
observed as fine linear densities like spicules of bone
perpendicular to inner table. This is frequently seen in

From the IGMC and Mayo Hospital Nagpur. Consultant Radiologist, Amarjyoti x-ray and Sonography clinic, Wardha road,
Dhantoli Nagpur 12. Maharashtra State
Request for Reprints: Dr.Suresh V.Phatak M.D. (Radiology), Honorary Asst.Prof Radio-diagnosis, IGMC and Mayo Hospital
Nagpur. Consultant Radiologist, Amarjyoti x-ray and Sonography clinic, Wardha road, Dhantoli Nagpur 12. Maharashtra State
Received 22 August 2005; Accepted 10 August 2006

628

628 SV Phatak et al

IJRI, 16:4, November 2006

Fig1) Radiograph of hand and foot showing coarse trabecular

pattern and squaring of metacarpals suggestive of bone
marrow hyperplasia.

Fig4) Radiograph of DL spine lateral showing concave

depression of centrum involving upper and lower surfaces
confined to central part.

Fig2) Radiograph of lumbar spine showing coarse, striated

or lacy appearance of vertebrae due to marrow hyperplasia.

Fig3) Radiograph skull lateral showing thickend vault bones

with increased diploic component, pronounced in frontal and
parietal bones.

Fig5) Radiograph of lumbar spine showing concave

depression of centrum only on lower surface confined to
central part of L4 vertebra.

629
IJRI, 16:4, November 2006

Radiographic skeletal changes 629

Fig6) Radiograph of forearm showing rarefaction of radial

shaft with significant periosteal new bone formation and
linear cortical sequestration bone in bone appearance.

Fig9) Radiograph of shoulder showing conical epiphyseal

deformity of humerus suggestive of old growth retardation.

Fig7} Radiograph of both femurs showing marked thickening

of cortex with a linear dense shadow in subcortical region
suggestive of cortical infarct.

Fig8) Radiograph of forearm showing marked irregular

sclerosis of radial shaft, destruction of proximal end and
sequestration in proximal and distal shaft.

thalassemia. [7] In spine marrow hyperplasia is reflected

as coarse striated or lacy appearance of vertebra in
children and adults both and may involve the whole length
of spine [14] Compression deformity can also be a result
of hyperplasia of bone marrow. In simple flattening
rectilinear shape is preserved, only height to width ratio
is altered. For objective assessment of simple flattening
Diggs et al [15] determined normal adult height to width
ratio in first four lumbar vertebrae and found it to be 1.0:1.4
in AP view and 1.0:1.2 in lateral view. With true flattening

Fig10) Radiograph shoulder showing marked sclerosis of

humeral head with significant compression deformity and
inferomedial sublaxations ---osteonecrosis of head of
humerus.

measurements clearly exceed this ratio [16] Simple

flattening is seen in lower dorsal and lumbar region.
Occasionally non-compressible disc smoothly depress
end plate to create a concave deformity or a wedge shaped
deformity which is seen in dorsal spine. [7] Sometimes
persistent anterior vertebral notching is seen on lateral
projection. Riggs and Rockett described that this notch
is large in young children with sickle cell disease. [17]
The first appearance of ischemic insult usually comes in
sickle cell anemia in form of dactylitis called as hand foot
syndrome seen after 3 months of age usually between 618 months and uncommon after 6 yrs.with disappearance

630

630 SV Phatak et al

IJRI, 16:4, November 2006

Fig13) Radiograph pelvis showing destruction of right femoral

head with resultant flattening and sclerosis ---osteonecrosis
head of femur.

Fig11) Radiograph of shoulder showing severe compression

deformity and fragmentation of humeral head --osteonecrosis.
Fig14) Radiograph forearm showing severe osteoporosis
with pathological fracture of distal ends of both bones.

Fig12) Radiograph of hip showing patchy sclerosis of femoral

head with fragmentation and flattening and secondary
osteoarthritic changes-----osteonecrosis.

of red marrow from tubular bones. Soft tissue swelling

and periosteal reaction results if infarction is involving
medullary cavity. If there is compromise of periosteal
circulation diaphyseal cortical bone infarct seen with
areas of bone destruction and patchy areas of new bone
formation. Epiphysis and metaphysis is usually spared
by virtue of multivessel supply. It may involve one or
multiple bones. Feet are involved less than hand [2] When
the long bone involvement is not severe no radiological
findings are seen. In acute long bone infarct there is
only medullary infarction seen well on Radionuclide bone
scan, CT and MR can demonstrate medullary
abnormalities. [18] With severe involvement and
compromised periosteal circulation full thickness cortical
destruction with periosteal reaction can be visualized.
The periosteal reaction may actually become new cortex.
Infarct can heal completely or with fibrosis. Calcification
may or may not take place. Both full thickness or
endocortical long bony infarcts tend to spare metaphysis
due to collateral circulation. The classical site of long
bone infarct is metadiaphyseal segment of shaft [19]
Carpals and tarsal have blood supply by number vessels
rather than a single nutrient artery. Tarsals are involved
more than carpals. Radiologically destruction and
osteopenia is visualized. [20] Necrotic bone marrow is a
fertile site for secondary infection. Patients with sickle
cell anemia have immunologic deficiencies making them
susceptible to certain infections than other people. [21]
Staphylococcus aureus is a common offender [22] but
salmonella organisms also frequently involved. [23]

631
IJRI, 16:4, November 2006

Radiographic skeletal changes 631

as snowcap appearance and flattening and step like
depressions of subarticular cortex are seen eventually
secondary osteoarthritis develops. Shoulder is involved
less as compared to hip but radiological findings are
similar. In adult patients diaphyseal sclerosis is visualized
due to endo cortical sclerosis, cortical thickening and
medullary calcification. [2] Spine show evidence of
ischemic changes in form of vertebral sclerosis, massive
collapse of centra and central cupping of end plate. Like
other bones in body infarcts also occur in spine with clinical
presentation of recurrent attacks of back pain present
radiographically as small areas of increased density,
coalesce and produce diffuse vertebral density [15] It is

Fig15) Radiograph knee showing pathological fracture of

femur and deformed tibial epiphysis suggestive of old growth
retardation.

Growth disturbances are seen after acute diaphyseal

infarcts or osteomyelitis are due to deficiency in nutrient
artery circulation. To the central region of metaphyseal
side of growth plate. [24] Triangular or coned epiphysis is
probably due to metaphyseal deformity. Benign cyst or
malignant neoplasm may develop at the site of medullary
scarring from old infarcts. Fibrosarcoma, osteosarcoma
and fibrous histiocytoma are the most common of the
neoplasms [2]. Epiphyseal avascular necrosis is less
common before growth plate fusion when it occurs at the
hip before fusion capital femoral epiphysis and later femoral
head have a diffusely flattened or mushroom appearance
associated with widened femoral neck. [25] After growth
plate closure segmental involvement typically in weight
bearing anterosuperior portion of femoral head is seen.
Radiographic findings include a curvilinear lucency
beneath the subarticular cortex, the crescent sign later
on dense homogenous dome of appearance also known

FIG16 and B) Hand Foot Syndrome Radiographs of Hands

and Feet.
A----AP Radiograph both hands showing marked thinning
of cortex, minimal periosteal reaction in metacarpals,
generalized osteopenia, few streaks of dense bones in
metacarpals suggestive of infarcts.
B-----AP Radiograph feet showing marked osteopenia,
thinning of cortex, coarse trabecular pattern, and dense
streaks of new bone seen in metatarsals suggestive of
infarcts.

632

632 SV Phatak et al
seen in old patients with differentials including chronic
renal failure, carcinoma prostate, myelofibrosis and
fluoride intoxication. [7] Massive collapse of centra is
visualized in lower dorsal and lumbar region .It can involve
two or three contiguous vertebrae with narrow disc space.
Some of these lesions are produced in part by
osteomyelitis. [26] A very typical change is seen in
vertebral end plates of a vertebrae in many patients of
sickle cell anemia, causing a central cupping [27] A
concave depression is seen in both upper and lower
surfaces of centrum show a concave depression confined
to middle 50-60% of the endplate, located at or slightly
behind the midcoronal plane. The floor of the cup is flat
and cortical bone at its base has a more rectilinear and
angular contour as compared to curved or arcuate shape
of simple collapse. It represents bulky capital" H"[7] This
distinctive feature is seen on lateral view. Upper and lower
end plates are symmetrically involved but occasionally
confined to only one surface. [28] Exact mechanism of
this deformity is not known but said to be effect of chronic
local ischemia [26,29] Occasionally different pathological
conditions may show morphologically similar changes
like thalassemia major [30], gauchers disease [31],
homocystinuria [32], chronic renal disease [33]
paroxysmal nocturnal hemoglobinuria, alcoholism,
histiocytosis x with healing vertebra plana and young
woman on birth control pills. [7]
References: 1)

Gael Lonergan et al Sickle Cell Anemia Radiographics

2001;21:971-994
2) Stanley P.Bohrer Bone changes in extremities in sickle
cell anemia Seminars in Roentgenology vol XXII No.3
(July) 1987:176-185.
3) J.George Teplik, Marvin E Haskin Sickle cell disease In
Roentgenologic diagnosis, Volume II, 3rd edition
WBSaunders and company Philadelphia 1976:11481154
4) David Sutton Text book of Radiology Sickle cell anemia,
Reprint, E and S Livingstone Edinburgh and London
1971:127-129.
5) Grainger and Allisons Diagnostic Radiology a textbook
of medical imaging Sickle cell disease Churchill
Livingstone New York, Third edition Volume two
1997:1693-6.
6) Jack Edeikin, Philip J.Hodes The Anemias In Roentgen
diagnosis of diseases of bone Volume one, Asian
edition, Williams and Wilkins company Baltimore
1973:360-374.
7) Jack Reynolds: The skull and spine Seminars in
RoentgenologyVolXXII, no.3 (July) 1987:168-175.
8) Reynolds J: An evaluation of some roentgenographic
signs in sickle cell anemia and its variants South Med J
1962; 55:1123-1128.
9) Burko H, Mellins HZ, and Waston J: Skull changes of
iron deficiency anemia simulating congenital hemolytic
anemia AJR 1961; 86:447-452.
10) Kattan KR: Calvarial thickening after Dilantin medication
AJR 1970; 110:102-105.

IJRI, 16:4, November 2006

11) MoseleyJE, RobinowitzJG, DziadiwR: Hyperostosis cranii
ex vacuo Radiology; 1966:1105-1107.
12) Fellows KE, Rosenthal A: Extracardiac roentgenographic
abnormalities in cyanotic congenital heart disease AJR
1972; 114:371-379.
13) Cusmano
JP,
BakerDH,
Finby
N:
Pseudohypoparathyroidism Radiology 1956; 67:845853.
14) Carrol DS, EvansJW Roentgen findings in sickle cell
anemia Radiology 1949; 53:834-845.
15) Diggs LW, Pulliam HM, and KingJC the bone changes in
sickle cell anemia South Med J 1937; 30:249-259.
16) Golding JSR The bone changes in sickle cell anemia
Ann R coll Surg Engl 1956; 19:296-315.
17) RiggsW, RockettJF: Roentgen chest findings in
childhood sickle cell anemia AJR 1968; 104:838-845.
18) RaoVM, FishmanM, MitchellDG et al Painful sickle cell
crisis: Bone marrow patterns observed with MR imaging
Radiology 1986; 161:211-215.
19) BohrerSP: Acute long bone diaphyseal infarcts in sickle
cell disease Br J Radiol 1970; 43:685-697.
20) Bohrer SP: Fractures complicating bone infarcts and /or
osteomyelitis in sickle cell disease Clin Radiol1971;
22:83-88.
21) Barrett Connor E: Bacterial infections and sickle cell
anemia An analysis of 250 infections in 166 patients
and a review of literature Medicine1971; 50:97-112.
22) Sadat Ali, Sankaran kutty, KuttyK: Recent observations
on osteomyelitis in sickle cell disease Int orthop1985;
9:97-99.
23) AdeyokunnuAA,
HendrickseRG:
Salmonella
osteomyelitis in childhood A report of 63 cases seen in
Nigerian children of whom 57 had sickle cell anemia
Arch Dis Child 1980; 55:175-184.
24) Cockshott WP: Dactylitis and growth disorders Br.J Radiol
1965; 36:19-26.
25) Lee REJ, Golding JSR, Serjent GR The radiological
features of avascular necrosis of femoral head in
homozygous sickle cell disease Clin Radiol 1981;
32:205-214.
26) Borton CJ, Cockshott WP: Bone changes in Hemoglobin
Sickle cell disease AJR 1962; 88:523-32.
27) Reynolds J: The radiological feature of sickle cell disease
and related hemoglobinopathies Springfield: CC
Thomas 1965.
28) Martel W: A reevaluation of "Fishvertebra"sign in sickle
cell hemoglobinopathy. (Reviewers comment) Invest
Radiol 1968; 3:128-129.
29) Reynolds J: A reevaluation of the fish vertebra sign in
sickle cell anemia AJR 1966; 97:693-707.
30) Cassady JR, BerdonWE, and BakerDH: The typical spine
changes of sickle cell anemia in a patient of thalassemia
major (Cooleys anemia) Radiology 1967; 89:1065-68.
31) Hansen GC, GoldRH: Central depression of multiple
vertebral end plates: A "pathognomonic"sign of sickle
hemoglobinopathy in gauchers disease AJR 1977;
129:343-344.
32) WestrmanWP, GreenfieldGB, WongPWK:"Fish
vertebrae"homocystinuria and sickle cell disease
JAMA1974; 230:261-262.
33) Zitter FMH: central vertebral endplate depression in
chronic renal disease: Report of two cases AJR 1979;
132:809-811.