Indian Journal of Nuclear Medicine

: 2012  |  Volume : 27  |  Issue : 1  |  Page : 59--62

Skeletal scintigraphy manifestations of hematologic disorders

Shrikant V Solav, Ritu Bhandari, Pallavi Solav 
 Nuclear Medicine Services, Kothrud, Pune, Maharashtra, India

Correspondence Address:
Shrikant V Solav
Spect Lab, Nuclear Medicine Serives, K 2/1 Erandawana Co-op Society, Near Mhatre Bridge, Kothrud, Pune - 411 004, Maharashtra


Skeletal manifestations are common in hematologic disorders. Benign entities such as Sickle cell disease develop microvascular embolization causing skeletal crisis. Leukemia, acute myeloblastic or lymphoblastic may develop bone marrow infarcts. Compromised immunity makes them susceptible to secondary infection leading to osteomyelitis or septic arthritis. Exposure to steroids may lead to osteonecrosis in these cases. Presented here is an atlas of various scintigraphic skeletal manifestations encountered over the past 10 years, in hematologic disorders.

How to cite this article:
Solav SV, Bhandari R, Solav P. Skeletal scintigraphy manifestations of hematologic disorders.Indian J Nucl Med 2012;27:59-62

How to cite this URL:
Solav SV, Bhandari R, Solav P. Skeletal scintigraphy manifestations of hematologic disorders. Indian J Nucl Med [serial online] 2012 [cited 2020 Feb 28 ];27:59-62
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Full Text


Skeletal symptoms are common in day to day practice. Elderly patients with mineral deficiency, degenerative changes, osteoarthritis etc may account for a large proportion of these cases. However, young patients or grown up patients with progressive skeletal manifestations may be specifically evaluated to rule out some systemic conditions. Hematologic disorders may also present with such symptoms and critical review of bone scan in such cases may help in early settlement of diagnosis. Present study highlights some important hematologic condition in pictorial essay.

 Materials and Methods

Skeletal scintigraphy was performed in the presented cases using Technetium 99 m-methylene diphosphonate. A dose of 150-750 MBq was used depending upon the age. Imaging was performed three to 4 h post-radiopharmaceutical administration E-Cam or Symbia gamma camera (Siemens, Erlangen, Germany) systems using a low-energy high resolution collimator. Matrix size used was 512 × 512.

Three phases scanning was done in patients with clinically localizing symptoms. Images were interpreted using dicom studies.

 Cases and Discussion

Sickle cell anemia

Sickle cell anemia was first described in 1910. [1] It is an autosomal recessive hemoglobinopathy. Hemoglobin electrophoresis and chromatography studies have demonstrated substitution of thymine for adenine in the glutamic acid codon of DNA, which, results in substitution of valine for glutamic acid in the sixth position on the beta globin chain of hemoglobin molecule. [2],[3] The major genotypes are Sickle cell (SS homozygous), Sickle cell C (SC Sickle hemoglobin C), Sickle beta thalassemia disease. Sickle cell trait is seen in a small population. Diagnosis is made by demonstration of various migration pattern of normal and hemoglobin S during electrophoresis. The difference in migration patterns of normal and hemoglobin S seen during electrophoresis is due to substitution of valine for glutamic acid resulting in two fewer negative charges in the abnormal molecule.

When a cell repeated Sickles because of deoxygenation, its membrane is permanently altered. [4],[5] These end-stage cells are responsible for clinical manifestations of Sickle cell anemia such as recurrent painful episodes, chronic organ dysfunction and chronic hemolytic anemia. Gall stones, hemolytic jaundice, poorly healing ulcers of shin are some other complications.

Case 1

Illustration of avascular necrosis, cortical bone infarct, soft tissue infarct in Sickle cell anemia [Figure 1].{Figure 1}

Musculoskeletal manifestation is the most common cause of morbidity in Sickle cell anemia. [6] Painful crisis usually affects the meta-diaphyseal region and can involve multiple sites. Juxta-articular involvement may cause joint effusion. [7],[8] Onset is usually at 5 years and progress until 30 years. [9] Precipitating factors include fever, dehydration, infection, acidosis, hypoxia and pregnancy. [10]

Presented is a known case of hemolytic anemia with hip pain. Bone scan revealed features of osteonecrosis of head of the left femur, the long bones revealed linear cortical uptake at multiple sites suggestive of cortical infarcts. Spleen revealed soft-tissue localization because of recurrent microvascular infarcts.

Case 2

Illustration of infarct, remodeling in hemolytic anemia had a backache of 10-day duration at presentation. He was a known case of congenital hemolytic anemia. Bone scan revealed cold area in D12 vertebra suggesting infarction. The distal metaphysis of femur and proximal metaphysis of tibia appear to be expanded. This is a manifestation of persistence of hematopoiesis in long bones in view of recurrent hemolysis [Figure 2].{Figure 2}

Acute myeloid leukemia

Skeletal manifestations have been described in acute leukemia. These are osteolysis, osteopenia, metaphyseal bands, pathological fractures, osteosclerosis, periosteal reaction, mixed lysis-sclerosis. It has been suggested that unexplained persistent skeletal pain and radiologic alterations should be investigated for acute leukemia. [11] Massive periosteal reaction has been reported in a variant of acute myeloid leukemia. [12] Post-bone marrow transplantation graft versus host disease related myositis has also been reported. [13]

Osteonecrosis can occur because of steroids or chemotherapy (all trans-retinoic acid). Alterations in fat metabolism with vascular occlusion due to fat embolization, as well as microtraumata and osteoporosis are etiologic factors. Multifocal aseptic osteonecrosis has been reported in acute leukemia. [14],[15]

Plain radiogram is usually the first investigation to be performed. It is less sensitive in detecting early changes. Bone scintigram and magnetic resonance imaging show early changes with variable sensitivity and specificity. [16] Both early and delayed phase of bone scan must be acquired to increase the sensitivity of the test. [17]

Case 3

Illustration of cortical infarcts in acute leukemia. A 4-year-old boy presented with weakness in lower limbs. Plain radiograph was normal. Three phase bone scan showed diffuse uptake of tracer in the shaft of femur bilaterally suggesting cortical infarcts. Hematologic work up revealed acute myeloid leukemia [Figure 3].{Figure 3}

Case 4

Illustration of osteonecrosis of humeral head secondary to steroid treatment was a known case of T cell lymphoblastic leukemia, which had allographic stem cell transplant. He was on long-term steroid therapy and complained of pain in the shoulder joint bilaterally. Bone scan revealed diffuse increased tracer uptake in the head of humerus bilaterally suggesting osteonecrosis [Figure 4].{Figure 4}

Superselective angiographic study in patients at risk for osteonecrosis with steroid therapy has shown obliteration of branches of the superior retinacular arteries as well as failure of revascularization. [18],[19],[20]

Chronic myeloid leukemia

Chronic myeloid leukemia is a myeloproliferative disorder with clonal expansion of transformed primitive hematopoietic progenitor cells. It comprises 15% of all adult leukemias. The Philadelphia chromosome (Ph), which results from a translocation between the long arms of chromosomes 9 and 22, t (9; 22) (q34; q11), can be demonstrated in 90% of patients with chronic myeloid leukemia (CML).

The condition may be diagnosed incidentally in asymptomatic patients as there are two phases of the disease-an indolent benign (chronic) phase or the acute blast phase. Exposure to steroids can make the skeleton osteoporotic and susceptible to fractures.

Case 5

Illustration of osteoporotic collapse Early whole-body images show increased tracer pooling in the metaphysis of long bones as well as the dorsolumbar vertebrae. Delayed images show linear uptake in thoracic 12 vertebra suggesting osteoporotic collapse. In addition diffuse uptake in axial and appendicular skeleton indicating high turnover of minerals in the skeleton. This is related to diffusing bone marrow involvement or underlying metabolic bone disease [Figure 5].{Figure 5}


Skeletal manifestations in various hematologic disorders are described. Bone scan is a non-specific investigation. Any insult that interferes with osteoblastic activity of the skeleton will appear to be hot. However, critical evaluation of scintigrams along with judicious review of clinical manifestations can help in making the diagnosis of underlying hematologic disorders. Some of these are subtle and the interpreter must be aware of these to avoid delay in diagnosis and management.


The following persons helped immensely: Indrajeet Solao as technical expert in image editing, Ranjit Mahajan, Parag Deshmukh, Supriya Ghosh, Jai Ganesh, Deepanjali Gawade who acquired the scintiscans.


1Herrick JB. Peculiar elongated and Sickle-shaped red corpuscles in a case of severe anemia. Arch Int Med 1910;6:517-21.
2Ingram VM. Gene mutations in human haemoglobin: The chemical difference between normal and sickle cell haemoglobin. Nature 1957;180:326-8.
3Dean J, Schechter AN. Sickle-cell anemia: Molecular and cellular bases of therapeutic approaches (first of three parts). N Engl J Med 1978;299:752-63.
4Bertles JF, Milner PF. Irreversibly sickled erythrocytes: A consequence of the heterogeneous distribution of hemoglobin types in sickle-cell anemia. J Clin Invest 1968;47:1731-41.
5Eaton JW, Jacob HS, White JG. Membrane abnormalities of irreversibly sickled cells. Semin Hematol 1979;16:52-64.
6Vinchinsky EP, Lubin BH. Sickle cell anemia and related hemoglobinopathies. Pediatr Clin North Am 1980;27:429-47.
7Bohrer SP. Acute long bone diaphyseal infarcts in sickle cell disease. Br J Radiol 1970;43:685-97.
8Bohrer SP. Bone Ischemia and Infarction in Sickle Cell Disease. St. Louis: Warren H Greene, Inc; 1981.
9Sennara H, Gorry F. Orthopedic aspects of sickle cell anemia and allied hemoglobinopathies. Clin Orthop Relat Res 1978;130:154-7.
10Serjeant GR. Sickle Cell Disease. Oxford: Oxford University Press; 1985. p. 191.
11Sinigaglia R, Gigante C, Bisinella G, Varotto S, Zanesco L, Turra S. Musculoskeletal manifestations in pediatric acute leukemia. J Pediatr Orthop 2008;28:20-8.
12Ueda T, Ito Y, Maeda M, Fukunaga Y. Massive periosteal reaction a presenting feature of acute megakaryocytic leukemia. Pediatr Int 2007;49:1015-7.
13Oya Y, Kobayashi S, Nakamura K, Shimizu J, Murayama S, Kanazawa I. Skeletal muscle pathology of chronic graft versus host disease accompanied with myositis, affecting predominantly respiratory and distal muscles, and hemosiderosis. Rinsho Shinkeigaku 2001;41:612-6.
14Solarino G, Scialpi L, Bruno M, De Cillis B. On a case of multifocal osteonecrosis in a patient suffering from acute lymphoblastic leukemia. Chir Organi Mov 2008;92:119-22.
15Chan BK, Bell SN. Bilateral avascular necrosis of the humeral trochleae after chemotherapy. J Bone Joint Surg Br 2000;82:670-2.
16Warwick BJ, Caristo V, Hartin N, Ihsleish W, Perera C, van der Wall H. MRI-negative, bone scintigram-positive in early osteonecrosis of the knees. Clin Nucl Med 2006;31:750-3.
17Shalaby-Rana E, Majd M. (99m) Tc-MDP scintigraphic findings in children with leukemia: Value of early and delayed whole-body imaging. J Nucl Med 2001;42:878-83.
18Atsumi T, Kuroki Y. Role of impairment of blood supply of the femoral head in the pathogenesis of idiopathic osteonecrosis. Clin Orthop Relat Res 1992;277:22-30.
19Smith DW. Is avascular necrosis of the femoral head the result of inhibition of angiogenesis? Med Hypotheses 1997;49:497-500.
20Usher BW Jr, Friedman RJ. Steroid-induced osteonecrosis of the humeral head. Orthopedics 1995;18:47-51.