What is the pathophysiology of sickle cell disease (SCD)?

Updated: Jul 24, 2019
  • Author: Ivan Ramirez, MD; Chief Editor: Felix S Chew, MD, MBA, MEd  more...
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Answer

The skeletal manifestations of sickle cell disease are the result of changes in bone and bone marrow caused by the chronic tissue hypoxia that is exacerbated by episodic occlusion of the microcirculation by the abnormal sickle cells. The main processes that lead to bone and joint destruction in sickle cell disease are infarction of bone and bone marrow, compensatory bone marrow hyperplasia, secondary osteomyelitis, and secondary growth defects. [6, 7, 8, 9, 10, 19, 11, 12, 13, 14, 15, 16]

When the rigid erythrocytes jam in the arterial and venous sinusoids of skeletal tissue, the resultant effect is intravascular thrombosis, which leads to infarction of bone and bone marrow. Repeated episodes of these crises eventually lead to irreversible bone infarcts and osteonecrosis, especially in weight-bearing areas. These areas of osteonecrosis (avascular necrosis/aseptic necrosis) become radiographically visible as sclerosis of bone with secondary reparative reaction and eventually result in degenerative bone and joint destruction.

Infarction of bone and bone marrow in patients with sickle cell disease can lead to the following changes: osteolysis (in acute infarction), osteonecrosis (avascular necrosis/aseptic necrosis), articular disintegration, myelosclerosis, periosteal reaction (unusual in the adult), H vertebrae (steplike endplate depression also known as the Reynold sign or codfish vertebrae) (see the first image below), dystrophic medullary calcification, and bone-within-bone appearance.

Skeletal sickle cell anemia. H vertebrae. Lateral Skeletal sickle cell anemia. H vertebrae. Lateral view of the spine shows angular depression of the central portion of each upper and lower endplate.
Skeletal sickle cell anemia. Chronic infarcts and Skeletal sickle cell anemia. Chronic infarcts and secondary osteoarthritis. Image shows advanced changes of irregular sclerosis and lucency on both sides of the knee joint reflecting numerous prior infarcts. The joint surfaces are irregular and the cartilages are narrowed due to secondary osteoarthritis.
Skeletal sickle cell anemia. Bone-within-bone appe Skeletal sickle cell anemia. Bone-within-bone appearance. Following multiple infarctions of the long bones, sclerosis may assume the appearance of a bone within a bone, reflecting the old cortex within the new cortex.

The shortened survival time of the erythrocytes in sickle cell (10-20 days) leads to a compensatory marrow hyperplasia throughout the skeleton. The bone marrow hyperplasia has the resultant effect of weakening the skeletal tissue by widening the medullary cavities, replacing trabecular bone and thinning cortices.

Deossification due to marrow hyperplasia can bring about the following changes in bone: decreased density of skull, decreased thickness of outer table of skull due to widening of diploe, hair on-end striations of the calvaria (see the images below), and osteoporosis sometimes leading to biconcave vertebrae, coarsening of trabeculae in long and flat bones, and pathologic fractures. [20, 21]

Skeletal sickle cell anemia. Expanded medullary ca Skeletal sickle cell anemia. Expanded medullary cavity. The diploic space is markedly widened due to marrow hyperplasia. Trabeculae are oriented perpendicular to the inner table, giving a hair-on-end appearance.
Skeletal sickle cell anemia. Detailed view of the Skeletal sickle cell anemia. Detailed view of the expanded medullary cavity in the same patient as in the previous image.

Patients with sickle cell disease can have a variety of growth defects due to the abnormal maturation of bone. The following growth defects are often seen in sickle cell disease: bone shortening (premature epiphyseal fusion) (see the image below), epiphyseal deformity with cupped metaphysis, peg-in-hole defect of distal femur, and decreased height of vertebrae (short stature and kyphoscoliosis).

Skeletal sickle cell anemia. Bone deformity. Image Skeletal sickle cell anemia. Bone deformity. Image shows shortening of the second and third metacarpals and phalanges with partial or complete early fusion of the growth plates due to osteonecrosis in infancy. Osteomyelitis is now superimposed the third metacarpal.

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