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Imaging Findings of Metabolic
Bone Disease1
Connie Y. Chang, MD
Daniel I. Rosenthal, MD
Deborah M. Mitchell, MD
Atsuhiko Handa, MD
Susan V. Kattapuram, MD
Ambrose J. Huang, MD
Abbreviation: SD = standard deviation
RadioGraphics 2016; 36:1871–1887
Published online 10.1148/rg.2016160004
Content Codes:
From the Division of Musculoskeletal Imaging and Intervention, Department of Radiology (C.Y.C., D.I.R., S.V.K., A.J.H.), and the
Pediatric Endocrine Division, Department of
Pediatrics (D.M.M.), Massachusetts General
Hospital, 55 Fruit St, Yawkey 6E, Boston, MA
02114; and the Department of Radiology, St.
Luke’s International Hospital, Tokyo, Japan
(A.H.). Presented as an education exhibit at the
2015 RSNA Annual Meeting. Received January
21, 2016; revision requested February 26 and
received March 25; accepted April 15. For this
journal-based SA-CME activity, the authors,
editor, and reviewers have disclosed no relevant
relationships. Address correspondence to
C.Y.C. (e-mail: [email protected]).
1
©
RSNA, 2016
SA-CME LEARNING OBJECTIVES
After completing this journal-based SA-CME
activity, participants will be able to:
■■Identify the most common metabolic
bone diseases.
the imaging findings related
to the most common metabolic bone
diseases.
Metabolic bone diseases are a diverse group of diseases that result
in abnormalities of (a) bone mass, (b) structure mineral homeostasis, (c) bone turnover, or (d) growth. Osteoporosis, the most
common metabolic bone disease, results in generalized loss of bone
mass and deterioration in the bone microarchitecture. Impaired
chondrocyte development and failure to mineralize growth plate
cartilage in rickets lead to widened growth plates and frayed metaphyses at sites of greatest growth. Osteomalacia is the result of
impaired mineralization of newly formed osteoid, which leads to
characteristic Looser zones. Hypophosphatasia is a congenital condition of impaired bone mineralization with wide phenotypic variability. Findings of hyperparathyroidism are the result of bone resorption, most often manifesting as subperiosteal resorption in the
hand. Renal osteodystrophy is the collection of skeletal findings observed in patients with chronic renal failure and associated secondary hyperparathyroidism and can include osteopenia, osteosclerosis,
and “rugger jersey spine.” Hypoparathyroidism is most commonly
due to iatrogenic injury, and radiographic findings of hypoparathyroidism reflect an overall increase in bone mass. Thyroid hormone
regulates endochondral bone formation; and congenital hypothyroidism, when untreated, leads to delayed bone age and absent, irregular, or fragmented distal femoral and proximal tibial epiphyses.
Soft-tissue proliferation of thyroid acropachy is most often observed
in the hands and feet. The findings of acromegaly are due to excess
growth hormone secretion and therefore proliferation of the bones
and soft tissues. Vitamin C deficiency, or scurvy, impairs posttranslational collagen modification, leading to subperiosteal hemorrhage
and fractures.
©
RSNA, 2016 • radiographics.rsna.org
■■Describe
■■Discuss
the most common causes of
these metabolic bone diseases.
See www.rsna.org/education/search/RG.
Introduction
Metabolic bone disease encompasses a diverse group of diseases that
diffusely affect the mass or structure of bones by an external process.
These diseases have many causes, from genetic disorders, to nutritional deficiencies, to acquired conditions. The imaging manifestations are also varied, and the same disease process can have a wide
range of skeletal findings (1). The purpose of this article is to review
the radiographic findings of numerous metabolic bone diseases,
including osteoporosis, rickets and osteomalacia, hypophosphatasia,
hyperparathyroidism, renal osteodystrophy, hypoparathyroidism,
hypothyroidism, hyperthyroidism, acromegaly, and scurvy.
MULTISYSTEM/GENERAL
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TEACHING POINTS
■■
Osteoporosis is the most common metabolic bone disease.
■■
Rickets is the interruption of orderly development and mineralization of growth plates.
■■
Osteomalacia is inadequate or abnormal mineralization of osteoid in cortical and trabecular bone.
■■
In 95% of patients with hyperparathyroidism, skeletal findings
are most readily recognized in the hand.
■■
Renal osteodystrophy refers to the complex of findings observed in the setting of chronic renal insufficiency. These include the findings of osteomalacia (and rickets in children)
and secondary hyperparathyroidism.
Osteoporosis
Osteoporosis is defined as a condition characterized by diminished but otherwise normal bone.
An osteoporotic state may arise either when bone
formation is inadequate or when bone resorption
exceeds bone formation. Osteoporosis may be
a local phenomenon (as in disuse osteoporosis)
or a generalized condition. The imaging features
depend to some degree on the rate at which osteoporosis develops.
Osteoporosis is the most common metabolic
bone disease, affecting 13%–18% of women older
than 50 years and 1%–4% of men older than 50
years (2–5). In the years prior to reliable quantification of bone mass, a patient was considered
to have osteoporosis only when a nontraumatic
fracture had occurred. With the development
of quantitative computed tomography (CT),
dual-energy photon absorptiometry, and, later,
dual-energy x-ray absorptiometry, reliable measurement methods became available, leading to a
change in the definition.
Osteoporosis results in substantial morbidity
and mortality, primarily through fractures. Worldwide, one osteoporotic fracture occurs almost every 3 seconds, which results in 9 million fractures
each year (6). One-third of women older than 50
years and one-fifth of men older than 50 years
will have an osteoporotic fracture (7–9). The three
most common fracture locations are the forearm,
the hip, and the spine (Fig 1) (10). Severe osteoporosis may prevent detection of nondisplaced
fractures, and CT or magnetic resonance (MR)
imaging may be helpful for diagnosis if the patient
has severe pain and a normal radiograph.
Clinically, osteoporosis is a state of low bone
mass and microarchitectural deterioration leading
to increased bone fragility. In 1994, the World
Health Organization defined osteoporosis as a
bone mineral density that is 2.5 or more standard
deviations (SD) less than that of a young healthy
adult (T-score of –2.5 or less) as measured with
dual-energy x-ray absorptiometry for postmeno-
radiographics.rsna.org
pausal women and for men older than 50 years
(11,12). This definition was a radical “rebranding” of several concepts. In science and medicine, an individual is usually considered to have
an abnormal result if his or her result is 2 SD
away from the mean of his or her age- and sexmatched norm, which is measured by the z score.
However, for predicting fracture risk, it is more
meaningful to compare an individual’s bone mineral density to that of a young healthy individual
prior to the occurrence of bone loss than to that
of an age- and sex-matched norm. The T-score
therefore compares the patient’s bone mineral
density to that of a young healthy reference
population and is therefore an absolute quantity,
not a relative one. This definition has led to some
confusion because of the fact that an individual
can have a normal T-score and yet may still have
osteoporosis. The World Health Organization also
defined osteopenia as a mild form of osteoporosis.
Primary osteoporosis takes slightly different forms in men and women. Traditionally,
these forms were separated into types I and II,
although these distinctions have not been used
in the endocrine literature for many years. After
menopause, estrogen deficiency results in a
period of accelerated bone loss, chiefly manifest
in cancellous (trabecular) bone, but cortical
bone loss also plays an important role (13). Men
experience a more linear pattern of bone loss.
Typically, by about 80 years of age, the two sexes
are equivalent (2,10,14).
Several disorders can interfere with bone
formation or promote bone resorption, leading
to secondary osteoporosis. Hypogonadism and
the resultant acceleration of bone resorption are
observed in conditions that include hyperprolactinemia; disorders of energy imbalance such
as anorexia nervosa and the female athlete triad
(disordered eating, osteoporosis, and amenorrhea); primary gonadal failure, as in Turner
syndrome or Klinefelter syndrome; and hypothalamic or pituitary dysfunction. Hyperthyroidism and hyperparathyroidism are additional
causes of accelerated bone resorption, whereas
growth hormone deficiency interferes with bone
formation. Hypercortisolism, whether iatrogenic
from exogenous glucocorticoids or from Cushing syndrome, is another important cause of low
bone mineral density (2,15). Regional osteoporosis can also occur because of inflammatory
arthropathy, immobilization, transient osteoporosis of large joints, or complex regional pain
syndrome (2,16,17).
In weight-bearing bones with little cortical
bone, such as the vertebral bodies, which are
composed of only about 5% cortical bone and
95% trabecular bone, the vertical weight-bearing
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Chang et al 1873
Figure 1. Distal radius fracture in an 81-year-old man with a history of prostate cancer,
chronic renal insufficiency, and osteoporosis who fell at a restaurant. (a, b) Posteroanterior (a) and lateral (b) radiographs of the left wrist show a comminuted, impacted,
dorsally angulated intra-articular fracture (arrow) of the distal radius, acquired positive
ulnar variance, and an ulnar styloid fracture (circle on a). (c, d) Radiographs of the left
femoral neck (c) and left proximal humerus (d) show that the same patient also fractured his left femoral neck (arrow on c) and left proximal humerus (circle on d).
trabeculae are thicker, and the horizontal trabeculae are thinner and are preferentially lost early
in the disease (Fig 2). Recent work has demonstrated that bone strength is related to structure
as well as bone mineral density (18–21). Reduction of horizontal trabeculae results in a loss of
load-bearing capacity greater than the loss of
horizontal trabecular bone cross-sectional area
because of the important role that the horizontal trabeculae play in laterally supporting the
vertical trabeculae. For example, a 50% loss of
horizontal trabecular bone cross-sectional area
results in a 75% loss of load-bearing capacity
(18–21). Three-dimensional analysis of CT and
MR imaging data has shown striking changes in
the shape and connectivity of the trabeculae that
make up cancellous bone (22).
Rickets and Osteomalacia
Rickets is the interruption of orderly development and mineralization of growth plates. Osteomalacia is inadequate or abnormal mineralization
of osteoid in cortical and trabecular bone. Prior
to growth plate fusion, rickets and osteomalacia
coexist. Rickets occurs as a result of hypophosphatemia. Any problem in the bone mineralization pathway, including insufficient calcium or
phosphate levels, abnormal pH, or the presence
of inhibitors of mineralization, can result in
osteomalacia (Fig 3). Causes of rickets and osteomalacia are listed in Table 1 (23–25).
The radiographic findings observed in rickets
are listed in Table 2 and illustrated in Figure 4.
Rachitic manifestations are most prominent at
the sites of greatest growth, including the knee
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Figure 2. Patterns of trabecular bone loss in osteoporosis. (a) Radiograph and diagram show normal mineralization of the vertebra
of a 17-year-old girl. Note the fine meshwork pattern of trabecular bone. (b) Radiograph and diagram show osteoporosis of the
vertebra of a 57-year-old man. There is preferential loss of the horizontal trabecular bone, with increased prominence of the vertical
trabeculae. (c) Radiograph and diagram show osteoporosis of the vertebra of an 82-year-old woman. Note the marked loss of vertical
and horizontal trabecular bone, resulting in large gaps between the vertical trabeculae.
Figure 3. Diagram of the calcium homeostasis
pathway. Ingested calcium is absorbed in the gastrointestinal tract, and vitamin D is either absorbed
in the gastrointestinal tract or generated from 7-dehydrocholesterol through exposure to UV light
(UVB). Vitamin D is further processed in the liver and
kidney, where it is converted to its fully active form,
which promotes calcium absorption in the gut. Parathyroid hormone acts on the bones and the kidneys
to increase serum calcium levels, and high serum
calcium levels in turn suppress parathyroid hormone
secretion. Parathyroid hormone, calcium, and phosphorous also modulate vitamin D metabolism in
the kidney (21). 25(OH)D = 25-hydroxy-vitamin D,
1,25-(OH)2D = 1,25-dihydroxy-vitamin D.
(distal femur and proximal tibia), distal tibia,
proximal humerus, distal radius and ulna, and
the anterior rib ends of the middle ribs. The findings are observed on the metaphyseal side of the
growth plate because unmineralized osteoid is
concentrated along the metaphyseal side of the
growth plate. Failure of mineralization leads to
disorganized chondrocyte growth, and hypophosphatemia leads to impaired apoptosis of hypertrophic chondrocytes, which results in excessively
long cartilage cell columns and the radiographic
findings of widening of the growth plate and cupping and fraying of the metaphyses (23–26).
Decreased bone mass is frequently observed
in osteomalacia; however, it is not an essential
feature in the diagnosis because an inability to
mineralize newly synthesized osteoid does not
imply that there is low bone mass of the skeleton.
The presence of large quantities of unmineralized
osteoid can sometimes be observed as indistinct
ill-defined trabecular bone, because osteoid on
the surface of the trabeculae is intermediate in
density between that of bone and that of marrow,
sometimes giving the impression of a “poor-quality” radiograph.
Looser zones are another distinctive feature
of osteomalacia. They occur late in the overall
course of the disease (Fig 5). Looser zones are
the result of deposition of unmineralized osteoid
at sites of stress or along nutrient vessels. These
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Chang et al 1875
Table 1: Causes of Rickets and Osteomalacia (Partial List)
Category of Rickets and Osteomalacia
Inadequate vitamin D (synthesis or diet)
Malabsorption
Abnormal vitamin D metabolism
Vitamin D resistance
Other cases (rare)
Causes
Poor nutrition, poor sunlight exposure
Pancreatic insufficiency, small bowel disease, rapid intestinal transit
Liver disease, chronic renal failure, nephrotic syndrome, vitamin D–
dependent rickets type I, medications that accelerate degradation
of vitamin D or metabolites
Vitamin D–dependent rickets type II
Dietary calcium deficiency, X-linked phosphatemic rickets, tumorinduced osteomalacia (unregulated secretion of fibroblast growth
factor 23)
Table 2: Radiographic Findings of Rickets
Body Part
Extremity
Chest
Skull
Active Rickets
Healing Rickets
Widened growth plate; irregularity and osteoWidened growth plate (especially distal femopenia along metaphyseal side of growth plate;
ral), mild metaphyseal cupping, sclerosis
flared, frayed, or fractured metaphysis; bowing;
along metaphyseal side of growth plate,
fracture
bowing
Rachitic rosary, bell-shaped thorax
…
Flat occiput, widened sutures, squared appear…
ance of skull, basilar invagination
zones can occur with no or minimal trauma, are
often bilateral and symmetric, and appear as
transverse lucent bands oriented at right angles
to the cortex that only span a portion of the bone
diameter. Although known as pseudofractures,
Looser zones are a type of insufficiency fracture,
with locations and appearances modified by
abnormal repair mechanisms, and Looser zones
are typically painful. Some of the common locations of Looser zones are similar to those of stress
fractures, such as the inner margin of the femoral
neck or the pubic rami. However, Looser zones
also occur in non–weight-bearing bones, which
are atypical locations for stress fractures, such as
the lateral aspect of the femoral shaft at the level
of the lesser trochanter, the ischium, the iliac
wing, and the lateral scapula (23,24).
Hypophosphatasia
Hypophosphatasia is a rare genetic disorder
caused by mutations in the gene that encodes
tissue-nonspecific alkaline phosphatase, resulting
in accumulation of pyrophosphate, an inhibitor
of bone mineralization. The skeletal findings of
hypophosphatasia resemble those of rickets and
osteomalacia. The clinical spectrum of disease varies widely, and it can be roughly categorized into
the following four clinical phenotypes of decreasing severity: perinatal (Fig 6), infantile, childhood
(Fig 7), and adult (27). In the perinatal form,
mineralization can be remarkably poor, with entire
segments of the spine not depicted (absent) on
radiographs. In the infantile and childhood forms,
there can be craniosynostosis; and in the childhood form, characteristic “tongues” of lucency
extend from the growth plate to the metaphysis. Skeletal findings can improve after enzyme
replacement therapy with asfotase alfa, a recently
developed recombinant tissue-nonspecific alkaline
phosphatase (Fig 8) (23,24,28).
Hyperparathyroidism
Hyperparathyroidism is a pathologic state of elevated parathyroid hormone concentrations, which
causes increased bone resorption. Primary hyperparathyroidism is a state of autonomous parathyroid hormone secretion by the parathyroid glands
and lack of feedback inhibition by serum calcium.
Primary hyperparathyroidism is usually caused
by a parathyroid adenoma, but in approximately
10% of cases, it is a result of four-gland hyperplasia, and in extremely rare cases, primary hyperparathyroidism is due to parathyroid carcinoma
(29). Secondary hyperparathyroidism is more
common than primary hyperparathyroidism and
is a response to low serum calcium levels. The
most common cause is chronic renal failure, in
which chronically elevated serum phosphate levels depress the serum calcium level, which leads
to compensatory hyperplasia of the chief cells of
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Figure 4. Nutritional rickets and femoral fracture in the setting of parental neglect of a 3-year-old girl. (a) Anteroposterior radiograph of the skull shows a partially patent frontal suture (arrow). (b) Posteroanterior radiograph of the chest shows wide and rounded
anterior rib ends (circles). This finding is often called a “rachitic rosary” because the chain of rounded rib ends resembles rosary beads
at physical examination. (c) Posteroanterior radiograph of both hands shows diffuse osteopenia, age-indeterminate fractures of several metacarpals (solid arrows), and cupped fragmented frayed metaphyses of the distal radii and ulnae (ovals). A peripheral rim of
bone along the metaphysis (dashed arrow) occurs by membranous ossification. (d) Anteroposterior radiograph of both knees shows
a fracture of the patient’s right distal femur (black arrow), as well as age-indeterminate fractures of her right tibia and both fibulae
(dashed white arrows). The metaphyses are fragmented, frayed, and fractured (solid white arrows). (e) Anteroposterior radiograph
of both lower extremities obtained 2 years later than a–d shows diffuse osteopenia, bowing of the tibiae and fibulae, flared metaphyses, and widening of the growth plates with sclerosis and irregularity on the metaphyseal side. Transverse sclerotic metaphyseal bands
(arrows) parallel to the growth plate reflect periods of intermittent adequate mineralization followed by poor mineralization. (Images
courtesy of Ok-Hwa Kim, MD, Ajou University, Seoul, Korea.)
the parathyroid gland. Renal insufficiency also
affects parathyroid hormone metabolism, further increasing the serum parathyroid hormone
levels. Secondary hyperparathyroidism can also
be observed in vitamin D deficiency and dietary
calcium deficiency (30).
In 95% of patients with hyperparathyroidism,
skeletal findings are most readily recognized in
the hand (31). The pathognomonic subperiosteal
bone resorption in hyperparathyroidism begins at
the radial aspects of the middle phalanges of the
middle and index fingers as lacelike irregularity
and at the distal phalangeal tufts as acro-osteolysis (Fig 9). In later stages, the resorption can appear similar to scalloping or “periosteal reaction”
(pseudoperiostitis) (30). Subperiosteal resorption
can also be observed in the ribs, lamina dura
(bone that surrounds the tooth sockets), humerus, femur, and upper medial tibia.
Trabecular, intracortical, endosteal, subchondral, and subligamentous or subtendinous bone
resorption can also occur. In the skull, bone
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Chang et al 1877
Figure 5. Tumor-induced osteomalacia in a 41-year-old man presenting with acute left hip pain after a fall down stairs, who had a
history of multiple fractures during the previous 10 years. Lateral radiograph of the thoracic spine (a) and anteroposterior radiographs
of the left forearm (b) and pelvis (c) show generalized osteopenia, vertebral body fractures (arrows on a), and multiple Looser zones
(arrows on b, c). The patient later underwent left total hip arthroplasty, and a fibroblast growth factor 23–secreting mesenchymal
tumor was found in the specimen from resection, a finding that led to the diagnosis of tumor-induced osteomalacia.
Figure 6. Hypophosphatasia in a newborn boy who presented when his mother was transferred to the hospital after sudden onset of labor. No Apgar scores are available. Knowing the
poor prognosis, the parents did not wish further resuscitation, and the newborn died 35 minutes
after birth. The alkaline phosphatase level was less than 5 IU/L (normal range for age, 150– 420
IU/L). Prenatal ultrasonography (US) disclosed short femoral length (–5 SD at 23 weeks; –7 SD
at 33 weeks) (images not shown). (a) Anteroposterior skull radiograph shows severe calvarial
ossification defects, with only small residual islands of bone in the frontal (dashed white arrows)
and parietal (solid white arrows) regions. The skull base and the facial bones (black arrows) are
only partially ossified. (b) Anteroposterior radiograph shows abnormal ossification in the axial
and appendicular skeleton, including thin clavicles (white arrowheads) and ribs (solid white arrows); absent cervical, thoracic, and lumbar vertebral bodies (rectangles); small scapulae (dashed
white arrows) and ilia (black arrowheads), absent ischia and pubic bones (oval); tonguelike metaphyseal ossification defects of the long bones (black arrows); and absent ossification of the
short tubular bones in the hands and feet. (Images courtesy of Gen Nishimura, MD, St. Luke’s
International Hospital, Tokyo, Japan.)
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Figure 7. Hypophosphatasia in a 6-year-old
girl with short stature
(–4.72 SD). (a) Lateral
radiograph of the skull
shows craniosynostosis,
resulting in brachycephaly (short anteroposterior
dimension of the skull)
with a “beaten-copper”
appearance of the calvaria (arrows). (b) Posteroanterior chest radiograph shows generalized
osteopenia with a coarse
trabecular pattern of all
of the depicted bones,
broad anterior rib ends
(*), and pseudofractures
(arrows) in the right and
left seventh ribs. (c) Anteroposterior radiograph
of the right femur shows
irregular
metaphyses
and wide growth plates
(solid arrows) and pseudofractures of the medial
aspect of the femoral
neck and the distal femur (dashed arrows).
(d) Anteroposterior radiographs of both lower
legs show wide growth
plates (arrows). Note
mild bowing of the tibiae
and fibulae and healing
fractures (circles) of both
fibulae. (Images courtesy
of Gen Nishimura, MD,
St. Luke’s International
Hospital, Tokyo, Japan.)
resorption is described as a salt-and-pepper appearance and can lead to decreased differentiation between the inner and outer tables of the
skull (Fig 10a). Trabecular resorption results in a
smudgy appearance of the trabeculae. Intracortical resorption is also described as cortical tunneling (Fig 10b) and is often a prominent feature of
hyperparathyroidism. Endosteal resorption may
lead to cortical thinning and may obscure the
corticomedullary junction.
Subchondral resorption can affect any joint,
leading to a widened and irregular appearance.
In the hands, subchondral resorption most often
begins along the distal interphalangeal joints and
progresses to the metacarpophalangeal and proximal interphalangeal joints. Subchondral resorption can also occur along the acromioclavicular
joint, more pronounced along the clavicular side.
In the sacroiliac joint, subchondral resorption is
more pronounced at the iliac side and may simulate an inflammatory or infectious arthritis (Fig
11a). Sternoclavicular joint resorption tends to
affect both sides of the joint equally. Subligamentous or subtendinous resorption also can occur
anywhere but most often occurs at the calcaneus,
clavicle (Fig 11c), greater and lesser tuberosities
of the humerus, greater and lesser trochanters of
the femur, anterior inferior iliac spine, and ischial
tuberosity (Fig 11b) (29–32).
Brown tumors, also known as osteoclastomas,
are lytic lesions that result from the parathyroid
hormone–driven activation of osteoclasts. Brown
tumors are generally solitary but can be multifocal and are at risk for pathologic fracture. Brown
tumors commonly involve the facial bones (Fig
12), ribs, pelvis, and femora and can have a large
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Chang et al 1879
Figure 8. Hypophosphatasia in a neonate with a low serum alkaline phosphatase level (5 IU/L) who had
short femoral length at prenatal US (images not shown). (a) Anteroposterior radiograph shows abnormal
ossification in the axial and appendicular skeleton, with a thin calvaria, thin clavicles and ribs, small vertebral bodies, small scapulae and ilia, stunted ends of the long bones, and poor ossification of the short
tubular bones in the hands. (b) Posteroanterior chest radiograph obtained at the age of 6 months, after
administration of recombinant enzyme replacement therapy, shows a remarkable increase in the ossification of the ribs, clavicles, scapulae, vertebrae, and long bones. The ends of the ribs and long bones are
broader than normal because of the accumulation of osteoid in patients with hypophosphatasia. (Images
courtesy of Gen Nishimura, MD, St. Luke’s International Hospital, Tokyo, Japan.)
Figure 9. Hyperparathyroidism in a
15-year-old boy presenting with minor trauma to his left hand. His calcium
level was 12.2 mmol/L (normal range,
8.5–10.2 mmol/L). Radiograph of the
left hand shows a mildly angulated fifth
metacarpal fracture (circle). There is resorption of the distal phalangeal tufts
(solid arrows), a finding consistent with
acro-osteolysis. Subperiosteal resorption
is depicted along the distal radial aspects
of the middle phalanges of the index and
long fingers (dashed arrows).
Renal Osteodystrophy
associated soft-tissue component. Treatment of
hyperparathyroidism may also lead to resolution
of brown tumors. Brown tumors were originally
described with primary hyperparathyroidism but
are now more common in patients with chronic
renal insufficiency and secondary hyperparathyroidism (Fig 13) (30,33,34).
Renal osteodystrophy refers to the complex of
findings observed in the setting of chronic renal
insufficiency. These include the findings of osteomalacia (and rickets in children) and secondary
hyperparathyroidism. In any given patient, the
findings of one or the other may predominate.
In patients with chronic renal insufficiency,
radiographs may show a diffuse increase in bone
radiodensity, a finding that is seen more often
in the axial skeleton, which has more trabecular
bone than cortical bone (Fig 14). The etiology of
this diffuse osteosclerosis is not well understood,
although it probably reflects the anabolic effect
of parathyroid hormone. Despite the increased
radiodensity, the bone is structurally weak and
prone to stress fractures (35). The spine often
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Figure 10. Chronic renal insufficiency and secondary hyperparathyroidism in a 65-year-old woman.
(a) Lateral radiograph of the skull
shows innumerable punctate lucent and radiodense foci, findings
consistent with a salt-and-pepper
appearance. (b) Posteroanterior
radiograph of the right index finger shows resorption (solid arrow)
along the radial aspect of the middle phalanx and cortical tunneling
(dashed arrow) of the proximal
phalanx.
Figure 11. Chronic renal insufficiency and secondary hyperparathyroidism in a 50-year-old man.
(a) Anteroposterior radiograph of the sacroiliac joints shows subchondral resorption (arrows), which
is more pronounced along the iliac bones. (b) Anteroposterior radiograph of the pelvis shows subtendinous resorption at the right hamstring (solid arrow) and adductor origins (dashed arrows) on the
ischial tuberosity. (c) Anteroposterior radiograph of the right clavicle shows subchondral resorption
(circle) along the distal clavicle and subligamentous resorption (arrows) at the clavicular attachment of
the coracoclavicular ligament.
demonstrates a characteristic striped appearance
(alternating bands of increased density along the
endplates and decreased density in the central portion of the vertebral body), which is also known as
the rugger jersey spine (Fig 15) (30,34,36).
In addition to renal osteodystrophy, renal
insufficiency may result in various soft-tissue
manifestations, especially after renal transplantation or a prolonged period of hemodialysis.
When present, soft-tissue deposits of calcium
hydroxyapatite, calcium pyrophosphate dihydrate,
and calcium oxalate typically occur around large
joints (Fig 16), but such deposits can occur in
any soft tissues and can be life threatening in the
heart, lungs, stomach, and kidney. Monosodium
urate crystals can also be deposited in the soft
tissues. All crystal deposition can lead to bursitis
and synovitis and responds to therapy with antiinflammatory agents (30,37).
Amyloid deposition can occur in patients
undergoing long-term hemodialysis and is due
to b2-microglobulin deposition in bone and soft
tissues, including cartilage, joint capsules, ligaments, tenosynovium, muscles, and intervertebral
disks. This deposition can lead to carpal tunnel
syndrome in as many as 31% of patients. Amyloid deposition in joints leads to a destructive
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Figure
12. Primary
hyperparathyroidism in a 43-year-old
woman presenting to the emergency department with acute
and chronic jaw pain 1 year after
extraction of a mandibular granuloma. (a) Axial CT image through
the mandible shows a lytic lesion
(*) with a large soft-tissue component, a finding consistent with a
brown tumor. (b) Radionuclide
image of the parathyroid gland
obtained after administration of
technetium 99m sestamibi shows
increased uptake in the neck (circle), a finding consistent with a
parathyroid adenoma.
Figure 13. Renal osteodystrophy
in a 28-year-old woman with nephrotic syndrome and end-stage
renal disease who was undergoing
treatment with dialysis. Anteroposterior radiographs of both knees
show diffuse osteosclerosis (*), a
finding often observed in patients
with end-stage renal disease, although osteosclerosis is typically
more common in the axial skeleton. Lytic lesions (circles) are depicted in both lateral femoral condyles, findings that are consistent
with brown tumors.
Figure 14. Renal osteodystrophy
in a 60-year-old man after he underwent renal transplantation for
glomerulonephritis.
Anteroposterior radiograph of the lumbar
spine shows diffusely increased radiodensity of the depicted bones.
Hypoparathyroidism
arthropathy (Fig 17). Renal transplantation can
arrest progression but does not reverse dialysisrelated amyloid arthropathy (30,38–43).
Hypoparathyroidism is most commonly an
acquired disorder caused by iatrogenic injury to
the parathyroid glands during thyroid surgery or
excision of the parathyroid glands or, more rarely,
during wide excision of a head and neck cancer.
Hypoparathyroidism may also result from autoimmune disease or genetic causes (eg, DiGeorge
syndrome) (44,45). End-organ insensitivity to parathyroid hormone is called pseudohypoparathyroidism and has different radiographic findings. Hypoparathyroidism that is due to genetic causes usually
manifests in childhood, but the clinical spectrum
varies widely, and in some cases, hypoparathyroidism may not be detected until adulthood (46,47).
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Figure 15. Renal osteodystrophy
in a 28-year-old woman with nephrotic syndrome and end-stage
renal disease who was undergoing treatment with dialysis. Lateral
radiograph of the lumbar spine
shows alternating bands of sclerosis along the endplates (dashed
arrows) and areas of lucency centrally (solid arrows). This pattern
is known as rugger jersey spine, a
finding named for the pattern of
the jerseys worn by rugby players
(shown at right).
Figure 16. Secondary hyperparathyroidism in a
57-year-old woman with renal failure and a parathyroid hormone level of 1313 pg/mL. (a) Lateral
radiograph of the left forearm shows soft-tissue calcification (arrows) in the dorsal soft tissues of the forearm.
(b) Axial nonenhanced CT image through the level
of the external auditory canal shows soft-tissue calcification (arrows) in both pinnae. (c) Anteroposterior
radiograph of the right knee shows chondrocalcinosis
(arrows) of the medial and lateral menisci. (d) Axial
nonenhanced CT image through the level of the pubic
symphysis shows calcification with fluid-fluid levels (arrows) in and around the pubic symphysis, as well as
erosions of both pubic bones (circles).
Radiographic findings of hypoparathyroidism
reflect an overall increase in bone mass, including
generalized or localized osteosclerosis and thickening of the calvaria, with a narrowed diploic
space. In rare cases, spinal ossification similar in
appearance to the enthesitis observed in psoriatic
arthritis can occur (47–51).
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Chang et al 1883
Figure 17. Amyloid arthropathy in an 83-year-old man with polycystic kidney disease who had undergone
treatment with hemodialysis for 18 years. (a) Lateral frog-leg radiograph of the left hip shows a large erosion
(arrows) along the superolateral femoral head. The joint space is only mildly narrowed, and there is minimal proliferative change of the bone. (b) Axial contrast material–enhanced CT image of the left hip shows the erosion
(arrow) along the superolateral femoral head, with only mild joint space narrowing and minimal bone proliferative change. There is mineralized soft tissue within the erosion, consistent with amyloid deposition.
Table 3: Radiographic Findings of Acromegaly
Body Part
Hands
Feet
Skull
Radiographic Findings
Spade-shaped tufts, tubulation of phalangeal shafts, exostoses, widened joint spaces, sesamoid
enlargement
Heel pad thickness > 25 mm in men and > 23 mm in women, skin thickening, tendon insertion
ossification, sesamoid enlargement
Thick skull bones; enlarged sella; frontal bossing; prominence of frontal and maxillary sinuses, supraorbital ridge, and zygomatic arch; prognathism (protrusion of jaw); enlargement of the mandible
Hypothyroidism
Hypothyroidism may be congenital, which leads to
severe skeletal abnormalities and delayed development, or it may be acquired, which results in
relatively mild skeletal abnormalities, if any. Acquired
hypothyroidism may occur after surgery or after
treatment (radioactive iodine therapy) or may be due
to glandular atrophy, acute or chronic (Hashimoto)
thyroiditis, infiltrative diseases such as amyloidosis or
lymphoma, therapy with certain medications, iodine
deficiency, or a pituitary disorder resulting in a deficiency of thyroid-stimulating hormone (52).
In children, there is delayed skeletal development,
often with absent, irregular, or fragmented distal
femoral and proximal tibial epiphyses (Fig 18)
resembling multiple epiphyseal dysplasia. Dental
development may also be delayed (52–54).
Hyperthyroidism
Hyperthyroidism is most commonly due to
oversecretion of thyroid hormone by the thyroid
gland diffusely (Graves disease) or focally (single
or multiple adenomas). The most common skel-
etal manifestation of hyperthyroidism is osteoporosis. As many as 1% of patients with Graves
disease may have thyroid acropachy, which
usually occurs after treatment, when the patient’s
condition becomes euthyroid or hypothyroid.
Radiographic findings of thyroid acropachy
are best observed in the hands and feet, in which
clubbing, periostitis, and soft-tissue swelling may
be seen. The periostitis is greatest along the radial
margins of the metacarpal, metatarsal, and middle
and proximal phalangeal diaphyses. Soft-tissue
swelling may also be seen in the pretibial region.
Exophthalmos, which is the result of thyroid-stimulating hormone receptor–stimulating antibodies
of Graves disease stimulating proliferation of the
retro-orbital fibroblasts, may be depicted on skull
radiographs or head CT images (52).
Acromegaly
Acromegaly is due to excess growth hormone
secretion from the anterior lobe of the pituitary.
The radiographic findings of acromegaly are listed
in Table 3 and shown in Figure 19 (47).
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Figure 18. Congenital hypothyroidism in a 12-year-old boy with short stature and developmental delay. (a) Oblique radiograph of the right hand shows ossification centers of only the capitate (arrowhead), hamate (arrow), and radius (circle). The
bone age is estimated at 1.5 years. (b) Lateral radiograph of the lumbar spine shows hypoplastic vertebral bodies. L1 has a
bullet-shaped vertebral body (arrow). (c) Anteroposterior radiograph of the pelvis shows mild flaring of the iliac bones with
shallow acetabula (solid arrows). The femoral capital epiphyses (dashed arrows) are small and fragmented. (d) Anteroposterior
radiograph of the right knee shows small and irregular distal femoral and proximal tibial epiphyses (arrows). (e) Posteroanterior radiograph of the left hand obtained after 2 years of thyroid hormone replacement therapy shows interval ossification of all
of the carpal ossification centers. The bone age remains delayed but has progressed to approximately 9 years (patient age, 14
years). (f) Anteroposterior radiograph of the right knee obtained after 2 years of thyroid hormone replacement therapy shows
maturation of the epiphyses but residual irregularity of the tibial and femoral epiphyses (arrows). (Images courtesy of Ok-Hwa
Kim, MD, Ajou University, Seoul, South Korea.)
Scurvy
Scurvy is a nutritional deficiency of vitamin C,
a required cofactor for hydroxylation of many
proteins, including collagen. At one time the
scourge of all ocean-going seamen, scurvy is now
exceedingly rare. Vitamin C deficiency results in
abnormal collagen production, leading to vascular
fragility and abnormal bone matrix, especially in
areas of greatest growth, such as the distal femur,
proximal tibia and fibula (Fig 20), distal radius
and ulna, proximal humerus, and distal rib ends.
The bones are diffusely osteopenic, and there are
thin cortices, especially in the epiphyses. Along the
growth plates, there is decreased and disorganized
cartilage proliferation, resulting in an irregular
appearance of the growth plate along the metaphyseal side. A dense band along the metaphyseal
side of the growth plate in the zone of provisional
calcification (Frankel line) represents the sclerotic
provisional zone of calcification. Peripheral extension of the zone of calcification results in a pointed
contour of the metaphyses known as “beaking.”
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Figure 19. Acromegaly in a 30-year-old man who
was 6 ft 7 in (201 cm) tall, had a history of diplopia for many years, and was later found to have
a growth hormone–secreting pituitary adenoma.
(a) Sagittal CT image of the head obtained near
the midline shows thick frontal bones (solid arrows)
and an enlarged sella (dashed arrows). (b) Posteroanterior radiograph of the right hand shows spadeshaped distal phalangeal tufts (circles). (c) Lateral
radiograph of the calcaneus shows an enlarged
heel pad (double-headed arrow) and thick plantar
skin (arrows).
Figure 20. Scurvy in a 10-year-old boy with autism
spectrum disorder presenting with nutritional deficiency
and an undetectable peripheral blood concentration of
vitamin C. Anteroposterior radiograph of the left knee
shows osteopenia, periosteal elevation and reaction
(solid black arrows), metaphyseal beaking (solid white
arrows), irregular appearance of the growth plate along
the metaphyseal side (*), thin cortices, especially in
the epiphyses (dashed black arrows), and dense bands
along the metaphyseal side of the physes in the zone of
provisional calcification (Frankel line [arrowhead]) with
an adjacent lucent line called the Trummerfeld zone, or
“scurvy line” (dashed white arrow).
Fragility of the trabeculae in this region results
in subepiphyseal “corner” fractures (Fig 21a). A
lucent line adjacent to the Frankel line called the
Trummerfeld zone, or scurvy line, reflects accumulation of hemorrhage in this zone, which tends
to fracture. Subperiosteal hemorrhage results in
periosteal elevation and periosteal reaction. At MR
imaging, bone marrow is heterogeneous on T1and T2-weighted MR images, and subperiosteal
hemorrhage can be seen as periosteal elevation
with increased subperiosteal T1 and T2 signal
intensity (Fig 21b) (55–57).
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Figure 21. Scurvy in a 4-year-old boy
with speech delay, a history of difficulty
walking for 1 month, and a serum vitamin
C level of 0.08 mg/dL (normal range, 0.2–
2.0 mg/dL). (a) Anteroposterior radiograph of both knees shows diffuse osteopenia, Frankel lines (arrowheads), Trummerfeld zones or scurvy lines (dashed
arrows), widening of the growth plate
(solid arrows), and subepiphyseal corner
fracture (circle). Because of the metaphyseal lucent bands, the patient was initially
thought to have leukemia or metastases,
but the findings from histopathologic
examination of the specimen from bone
marrow biopsy were normal. (b) Coronal
T2-weighted fat-suppressed MR image of
both distal femoral metadiaphyses shows
heterogeneously increased T2 signal intensity in the marrow (*) and around the
bone (arrows). (Images courtesy of Gen
Nishimura, MD, St. Luke’s International
Hospital, Tokyo, Japan.)
Conclusion
Metabolic bone diseases are a heterogeneous
group of disorders that diffusely affect the bones.
Understanding the underlying mechanism of the
diseases helps the radiologist to also understand
the radiographic findings and to make a correct
diagnosis.
Acknowledgments.—The authors thank Gen Nishimura, MD,
St. Luke’s International Hospital, Tokyo, Japan, and Ok-Hwa
Kim, MD, Ajou University, Seoul, Korea, for sharing their
cases and thank illustrator Susanne Loomis, Massachusetts
General Hospital, Boston, Mass, for her illustrations.
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TM
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