is with the Department of Radiology and Nuclear Medicine, Wilford
Hall Medical Center, San Antonio, TX.
The skeletal system is dynamic --a center for many important
physiologic processes, including red blood cell production and
calcium and phosphorus metabolism. Maintenance of physiologic
homeostasis requires an adequate supply of minerals, hormones, and
vitamins. Metabolic bone diseases are characterized by disruption
of the normal physiologic activity of bones. Although some
metabolic bone processes are congenital and are detected early in
life, others are acquired and may not be detected until later in
adulthood. Despite the recent technological advances in computed
tomography (CT) and magnetic resonance (MR) imaging, conventional
radiography remains the primary imaging modality for the evaluation
of metabolic bone disease. This article will review some of the
more common metabolic bone processes seen at our institution.
Osteoporosis is defined as decreased bone mass (with normal
matrix mineralization) of the involved bone caused by either a
deficiency of osteoid production or an increased resorption of
bone. The illness may be characterized as follows: diffuse, as in
the elderly female who is not on hormone replacement therapy;
regional, involving a portion of the skeleton; or localized, eg,
following extremity disuse after cast placement for stabilization
of a fracture (Figure 1). The most frequent sites of involvement
are the spine, pelvis, and periarticular regions of the
appendicular skeleton. The spine is typically one of the earliest
sites to manifest with osteoporotic changes, which include
osteopenia, anterior wedging, cortical thinning with endplate
preservation, and biconcave vertebral bodies.
Rickets and osteomalacia
Faulty mineralization or calcification of bone matrix is termed
in children and
in adults. Patients usually present with nonspecific pain,
weakness, and bone deformities. Numerous causes include dietary
deficiencies of vitamin D or calcium, renal disease, enzymatic
defects, liver disease, and inadequate absorption of calcium or
Radiographic features include osteopenia, widened physes of the
long bones, and flaring or cupping of the metaphysis (Figure 2).
Long-standing disease leads to osseous softening, giving a bowed
appearance, which is most commonly seen in the tibia and femur.
Findings in the pelvis include protrusio acetabuli and coxa vera.
The majority of patients respond to vitamin D therapy and calcium
supplementation, if indicated.
Paget's disease is a condition of uncertain pathogenesis that is
characterized by disorganized bone remodeling and that
predominantly affects Caucasians or Northern Europeans.
Histologically, a mosaic appearance of osseous formation is
typical. Three phases of the disease have been described.
The acute or hot phase is seen radiographically as a radiolucent
area that has been described as "flame-shaped" when involving a
long bone and is termed
when the radiolucency contains geographic margins and involves the
skull. The mixed blastic-lytic phase, in which increasing
osteoblastic activity (evidenced by increasing sclerosis) coexists
with the ongoing osteoclastic activity, results in bone with a
mixed sclerotic and lytic appearance. It is during this middle
phase that trabecular coarsening, cortical thickening, and
generalized bony enlargement occur. The cool or quiescent phase, in
which smoldering osteoblastic activity remains, is manifested by
dense sclerosis of the affected bone (Figure 3). Complications of
Paget's disease include pathologic fractures and, rarely,
Calcium pyrophosphate dihydrate deposition
Calcium pyrophosphate dihydrate deposition disease (CPPD) is a
disorder characterized by calcium pyrophosphate crystal deposition
within articular cartilage (ie, knee menisci, triangular
fibrocartilage of the wrist, symphysis pubis), synovium, tendons,
capsule, and ligaments (Figure 4).
This disease of calcium metabolism is associated with a classic
triad of findings: cartilage calcification, pain, and joint
destruction. Other than by anatomic location, the joint destruction
of CPPD is difficult to distinguish from that of osteoarthritis.
Calcium pyrophosphate dihydrate deposition disease is frequently
associated with gout, hemochromatosis, and hyperparathyroidism.
Hemochromatosis is a rare disorder characterized pathologically
by tissue damage secondary to excessive iron deposition. Associated
morbidity can be significant, as commonly affected organs include
the heart, liver, pancreas, skin, and joints. The arthritis of
hemochromatosis is insidious in onset and may occur at any stage
during the course of the disease, rarely preceding the other
clinical features. Although hemochromatosis arthropathy
superficially resembles degenerative joint disease--also showing
joint space narrowing, subchondral sclerosis, and
osteophytosis--the distribution of findings (metacarpophalangeal
joints, wrists, elbows, and glenohumeral articulations)
distinguishes it from osteoarthritis.
Abnormalities are particularly frequent in the second and third
metacarpophalangeal joints, and peculiar hook-like osteophytes on
the radial aspect of the metacarpal heads are characteristic
Furthermore, there is symmetric loss of joint space, which is
unusual for osteoarthritis. The loss of joint space is associated
with subchondral bony eburnation and cyst formation. Currently, the
most effective treatment is vigorous phlebotomy. Death is certain
if the disease goes untreated.
Hemophilia A is a sex-linked deficiency or abnormality of a
plasma protein called factor VIII (FVIII),
which is seen in 1 of 5000 male births. Symptoms typically begin in
childhood in association with hemorrhage after minor trauma and
increase through adolescence. The initial episode of
intra-articular bleeding is accompanied by joint effusion. With
recurrent small bleeds or after a large bleed, periarticular
osteoporosis and regional soft-tissue swelling are commonly seen.
In adolescents, the hyperemic joint may lead to localized
accelerated growth and limb length discrepancies. Eventually,
osseous irregularity and erosion develop, accompanied by
subchondral cystic change (Figure 6). Synovial effusions are common
and may appear radiodense due to hemosiderin deposition. As osseous
erosions continue, joint space narrowing is seen with progressive
and symmetric cartilaginous destruction. Eventually, complete
obliteration of the joint space occurs, and secondary degenerative
signs, such as osteophytosis and eburnation, develop. With chronic
disease, muscle atrophy and joint contractures may develop.
Treatment for hemophilia typically involves some form of factor
replacement, depending on the severity of the disease. The pain and
swelling associated with joint injuries can be treated with
Hurler's syndrome is one of the autosomal-recessive
mucopolysaccharidoses and is caused by a deficiency of the
alpha-L-iduronidase enzyme, resulting in excessive accumulation of
Clinical manifestations include mental retardation, corneal
clouding, and organomegaly of the heart, spleen, and liver. A
common radiographic finding seen on the lateral view is an
oval-shaped vertebral body with rounded vertebral end plates.
Moreover, there frequently is a dorsolumbar gibbous deformity with
a bony projection extending off the anteroinferior aspect of the
vertebral body (Figure 7). Other findings include osteopenia and an
abnormally configured pelvis.
This hereditary disorder is the result of abnormal type I
collagen metabolism (quality or quantity, defect in bone matrix),
producing a congenital form of osteoporosis. Osteogenesis
imperfecta is characterized by early hearing loss, blue sclera,
osteoporosis, bone fragility, and defective dentition. Two forms
have been described, congenital (10%) and tarda (90%).
In general, the congenital form is much more severe and is
characterized by multiple fractures at birth. Only 20% of those
with the tarda form will have fractures at birth. Radiologic
findings usually include a thinned cortex, osteoporosis, and
osseous deformities (Figure 8). The main differential consideration
is nonaccidental trauma.
Sickle cell disease
The most common hemoglobinopathy, sickle cell disease, occurs
primarily in African Americans and people of Mediterranean descent.
It affects the skeleton by either causing marrow hyperplasia, which
replaces the marrow and trabecular bone,
or results in infarction of marrow and bone.
The most frequently affected bones are the long bones, skull, and
spine. Radiographic findings usually appear 10 to 14 days after
infarction and include a permeative medullary pattern, periosteal
new bone formation, and osteopenia. Chronic disease is manifested
by sclerosis and cortical thickening. Humeral or femoral head
avascular necrosis can occur and results in a patchy, sclerotic
pattern and head flattening in later stages (Figure 9). Other
findings may include diploic widening, fish vertebrae, and ischemic
Hypertrophic pulmonary osteoarthropathy
Hypertrophic pulmonary osteoarthropathy is a chronic
proliferative disease characterized by clubbing of the fingers and
toes, synovitis, and painful periostitis of long and tubular bones.
The exact mechanism is unknown. This disease is a manifestation of
pulmonary disease and is often associated with bronchogenic
carcinoma. Radiographic findings include periosteal new bone
involving the diaphysis of the tibia, fibula, radius, ulna,
humerus, femur, and other long and tubular bones (Figure 10).
The differential diagnosis includes primary osteoarthropathy,
thyroid acropachy, and venous stasis.
This hereditary disease in patients of Mediterranean descent is
characterized by deficient production of beta-hemoglobin chains and
can result in a chronic microcytic anemia. In an attempt to
compensate for the anemia, the marrow activity increases
significantly, thereby producing the characteristic radiographic
changes. Long and tubular bones have an expanded appearance and can
be associated with cortical thinning and trabecular coarsening
(Figure 11). Calvarial changes include dipoploic expansion with a
"hair-on-end" appearance to the skull trabeculae. Moreover, there
is widening and flattening of the vertebral body, resulting in
vertebral plana. The ribs are osteopenic and widened, with an
occasional "rib-within-rib" appearance. Extramedullary
hematopoiesis is common, manifesting as a soft-tissue, paraspinal
Metabolic bone disease is often detected or suggested on
conventional radiography. This article has briefly reviewed a
variety of metabolic processes with osseous manifestations,
including osteoporosis, rickets/osteomalacia, Paget's disease,
CPPD, hemochromatosis arthropathy, hemophilic arthropathy, Hurler's
syndrome, osteogenesis imperfecta, sickle cell disease,
hypertrophic pulmonary arthropathy, and beta-thalassemia.
Familiarization with the characteristic radiographic findings of
these entities is important for effective diagnosis and treatment.