Jeremy Casson - An Architectural and Historical Journey Around Europe
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1.
2. A) General retardation in body growth.
B) Decrease in density at the zone of provisional
calcification.
C) Disorganization and "fraying" of spongy bone.
D) Slight axial widening at the growth plate.
1. Which of the following radiographic findings
represents the earliest specific change in rickets?
3. A) General retardation in body growth.
B) Decrease in density at the zone of provisional
calcification.
C) Disorganization and "fraying" of spongy bone.
D) Slight axial widening at the growth plate.
1. Which of the following radiographic findings
represents the earliest specific change in rickets?
4. • Most evident in active growth regions.
• Earliest change: Slight axial growth plate widening.
• Nonspecific features: Bony growth retardation.
• Growth plate changes: Deficient mineralization in provisional
calcification zone.
• Fraying and disorganization of the spongy bone occur at the
metaphyseal area.
RICKETS
5. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
2. In rickets, the "rachitic rosary" physical finding
develops at which of the following locations?
6. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
2. In rickets, the "rachitic rosary" physical finding
develops at which of the following locations?
7. A) Osteoid accumulation in the skull
B) Bulky growth plates at bone-cartilage
junctions
C) Ossified epiphysis center
D) Peripheral ossified nucleus rim
4. Which physical finding is characteristic of rickets?
8. A) Osteoid accumulation in the skull
B) Bulky growth plates at bone-cartilage
junctions
C) Ossified epiphysis center
D) Peripheral ossified nucleus rim
4. Which physical finding is characteristic of rickets?
9. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
• Rachitic Rosary – Swelling at the costochondral junctions of
the middle ribs.
• Harrison’s Groove – Semicoronal impression at the costal
attachment of the diaphragm.
RICKETS – PHYSICAL FINDINGS
12. A) Excess osteoid formation at the inner table.
B) Flattening of the frontal and parietal regions.
C) Strengthening of the calvaria.
D) Displacement of growth centers in the
diaphyses.
3. During the first months of life, the skull’s accommodation to
the rapidly growing brain in rickets is associated with:
13. A) Excess osteoid formation at the inner table.
B) Flattening of the frontal and parietal regions.
C) Strengthening of the calvaria.
D) Displacement of growth centers in the
diaphyses.
3. During the first months of life, the skull’s accommodation to
the rapidly growing brain in rickets is associated with:
14. • Head is particularly affected during the first months of life.
• Skull accommodates to the brain’s rapid growth.
• Craniotabes – develops from osteoid accumulation in the
frontal and parietal regions
RICKETS – PHYSICAL FINDINGS
15. A) Scoliosis development.
B) Strengthening of long bones.
C) Thickening of the skull.
D) Alignment of the spine.
5. With increasing age in rickets, what contributes to an overall
decrease in height?
16. A) Scoliosis development.
B) Strengthening of long bones.
C) Thickening of the skull.
D) Alignment of the spine.
5. With increasing age in rickets, what contributes to an overall
decrease in height?
17. • Scoliosis deveolopment Bending deformities in the long
bones Overall decrease in height
• Expansion of intervertebral discs Concave impressions on
vertebral endplates.
RICKETS – PHYSICAL FINDINGS
18. A) Saber shin deformity
B) Triradiate pelvis configuration
C) Basilar invagination in skull
D) Scoliosis development
6. Which deformity is an example of a musculotendinous
pull on the growth plate in rickets?
19. A) Saber shin deformity
B) Triradiate pelvis configuration
C) Basilar invagination in skull
D) Scoliosis development
6. Which deformity is an example of a musculotendinous
pull on the growth plate in rickets?
20. • Infancy and childhood: Long bone deformities at the
cartilage-shaft junctions and diaphyses.
• Bowing deformities of arms and legs
• Saber shin deformity – strong posterior pull of the Achilles
tendon on the calcaneus
RICKETS – PHYSICAL FINDINGS
21. A) Looser's lines (Milkman's pseudofractures)
B) Rachitic rosary
C) Craniotabes
D) Saber shin deformity
7. What is the term used for accumulations of osteoid that
strongly suggest osteomalacia?
22. A) Looser's lines (Milkman's pseudofractures)
B) Rachitic rosary
C) Craniotabes
D) Saber shin deformity
7. What is the term used for accumulations of osteoid that
strongly suggest osteomalacia?
23. 1. What is the finding pointed at by the arrow?
Looser’s zone; Pseudofracture
24. • Looser’s zones or pseudofractures – lucent areas that are
oriented at right angles to the cortex
• Spans the diameter of the bone incompletely
• Tend to occur in the axillary margins of the scapula, ribs,
pubic rami, etc.
• Bilateral and symmetrical
OSTEOMALACIA
25. A) Cystic fibrosis
B) Scleroderma
C) Peptic ulcer disease
D) Pancreatitis
8. Which gastrointestinal disorder can lead to rickets
or osteomalacia?
26. A) Cystic fibrosis
B) Scleroderma
C) Peptic ulcer disease
D) Pancreatitis
8. Which gastrointestinal disorder can lead to rickets
or osteomalacia?
27. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
• Gastrointestinal disorders are associated with intestinal
malabsorption and is the most common cause of vitamin D
deficiency in the United States.
• Conditions include scleroderma, sprue, celiac disease, regional
enteritis, and blind loop syndromes, among others.
GASTROINTESTINAL MALABSORPTION
28. A) Metaphyseal Chondrodysplasia (Type Schmid)
B) Hereditary Vitamin D-Dependent Rickets
C) Hypophosphatasia
D) Renal Osteodystrophy
9. Which condition presents with a "Rugger jersey" appearance
on radiographs?
29. A) Metaphyseal Chondrodysplasia (Type Schmid)
B) Hereditary Vitamin D-Dependent Rickets
C) Hypophosphatasia
D) Renal Osteodystrophy
9. Which condition presents with a "Rugger jersey" appearance
on radiographs?
30. 2. What is the term for this characteristic
finding in the spine? Rugger jersey;
Rugger jersey spine
3. This finding is frequently found in what
condition? Renal osteodystrophy; Uremic
osteodystrophy
31. • Bone disease associated with chronic renal failure.
• Two main mechanisms: secondary hypoparathyroidism and
abnormal vitamin D metabolism.
• Radiographic abnormalities are observed in both the bones
and soft tissues.
• Rickets – presenting feature and 1st indication of chronic renal
disease in children
RENAL OSTEODYSTROPHY
32. • Osteosclerosis are noted in uremic osteopathy and represents
excessive osteoid accumulation, and are characteristic in the
spine, subjacent to the cartilaginous plates – “Rugger jersey”
appearance.
RENAL OSTEODYSTROPHY
33. A) Weighing >1000g at birth
B) Born at 32 weeks of gestation
C) Weighing <1000g at birth or <28 weeks’
age of gestation
D) Born at 37 weeks of gestation
10. Which infants are most likely to be affected by neonatal
rickets (Metabolic Bone Disease of Prematurity)?
34. A) Weighing >1000g at birth
B) Born at 32 weeks of gestation
C) Weighing <1000g at birth or <28 weeks’
age of gestation
D) Born at 37 weeks of gestation
10. Which infants are most likely to be affected by neonatal
rickets (Metabolic Bone Disease of Prematurity)?
35. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
• Abnormal mineral homeostasis in low-birth weight premature
infants.
• Affects infants weighing <1000g at birth or <28 weeks’ age
of gestation.
• Bone disease appears around 12 weeks of age.
METABOLIC BONE DISEASE OF PREMATURITY
36. Multifocal areas of paravertebral
ossification in X-linked
hypophosphatemia are similarly
found in other conditions. Name at
least 1 condition: Diffuse Idiopathic
Skeletal Hyperostosis; DISH;
Ankylosing spondylitis; AS
37. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
• Familial vitamin D-resistant rickets
• Renal tubular phosphate loss
• Most common form
• Men>Women
• Characteristic in adulthood – generalized increase in bone
density, especially in the axial skeleton.
• Spinal changes may resemble those of AS or DISH
X-LINKED HYPOPHOSPHATEMIA
38. What is this condition
with characteristic axial
skeleton involvement?
Atypical Axial
Osteomalacia
39. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
• Spares the appendicular sites
• Dense, coarse trabecular pattern involving primarily the
cervical spine.
• All reported patients have been men.
ATYPICAL AXIAL OSTEOMALACIA
40. This image is of a 9-year-old boy with
shortening of all metacarpal bones. Diagnosis?
Pseudohypoparathyroidism; Albright’s hereditary
osteodystrophy
41. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
• Short stature, round face, short neck, and shortening of
metacarpal bones (particularly the 1st, 4th and 5th).
• Pseudopseudohypoparathyroidism – characteristic phenotype
+ normal blood chemistry values.
PSEUDOHYPOPARATHYROIDISM AND PSEUDO-PSEUDOHYPOPARATHYROIDISM
42. A) Osteosclerosis
B) Osteoporosis circumscripta
C) Ivory vertebra
D) Fish vertebrae
11. Which term is used to describe the initial phase of Paget’s disease in the
skull characterized by intense osteoclastic activity and resorption of bone
trabeculae?
43. A) Osteosclerosis
B) Osteoporosis circumscripta
C) Ivory vertebra
D) Fish vertebrae
11. Which term is used to describe the initial phase of Paget’s disease in the
skull characterized by intense osteoclastic activity and resorption of bone
trabeculae?
44. A) Active phase
B) Quiescent phase
C) Inactive phase
D) Osteoblastic phase
12. What phase of Paget's disease involves intense
osteoclastic activity and resorption of normal bone?
45. A) Active phase
B) Quiescent phase
C) Inactive phase
D) Osteoblastic phase
12. What phase of Paget's disease involves intense
osteoclastic activity and resorption of normal bone?
46. 7. In Paget’s disease, what is the
specific term for the cranial vault
appearance? OSTEOPOROSIS
CIRCUMSCRIPTA
8. In what stage of Paget’s
disease is this appearance found?
Osteolytic Stage; Osteolytic
47. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
• Initially begins with intense osteoclastic activity and bone
resorption Osteolytic form radiographically
• Appears as OSTEOPOROSIS CIRCUMSCRIPTA in the skull.
• Involves the frontal or occipital regions which may
progress to involve the entire skull.
PAGET’S DISEASE
48. A) Circular radiodense lesions
B) Ground-glass or washed-out
pattern
C) Smooth, even bone density
D) Cortical thickening
13. Which of the following is a radiographic feature
associated with the progression of osteolysis in Paget's
disease?
49. A) Circular radiodense lesions
B) Ground-glass or washed-out
pattern
C) Smooth, even bone density
D) Cortical thickening
13. Which of the following is a radiographic feature
associated with the progression of osteolysis in Paget's
disease?
50. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
PAGET’S DISEASE
• Stages involve an
1. Active osteolytic phase
2. An osteolytic, osteosclerotic, or both
3. Inactive osteosclerotic
• Diaphyseal involvement without epiphyseal involvement is
characteristic of Paget’s disease.
51. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
PAGET’S DISEASE
• Ground-glass or washed-out pattern –
observed in advancing osteolysis
• V- or wedge-shaped radiolucent area distinct
from the adjacent bone.
52. 14. Which of the following is a characteristic
radiographic appearance of Paget's disease in the
cranium?
A) "Cotton-wool" appearance in focal radiodense
areas.
B) Facial bone changes are common.
C) Basilar invagination is absent in all patients.
D) Cranial thickening is limited to the occipital
region.
53. A) "Cotton-wool" appearance in focal radiodense
areas.
B) Facial bone changes are common.
C) Basilar invagination is absent in all patients.
D) Cranial thickening is limited to the occipital
region.
14. Which of the following is a characteristic
radiographic appearance of Paget's disease in the
cranium?
54. 9. In what stage of Paget’s
disease is this cranial
involvement found?
Osteosclerosis;
Osteosclerotic;
Osteosclerotic Stage
55. • Cranial involvement in Paget’s disease range from typical
osteoporosis circumscripta to widespread sclerosis.
• Cotton-wool appearance in focal radiodense areas during the
inactive osteosclerotic stage.
• Cranial thickening especially in the frontal areas.
PAGET’S DISEASE
56. A) Picture frame vertebra.
B) Ivory vertebra.
C) Fish vertebra.
D) Paget's vertebra.
15. Which term is used to describe the vertebral body changes observed in
Paget's disease, characterized by enlarged, coarsened trabeculae and
condensation of bone along the contours of the vertebral body?
57. A) Picture frame vertebra.
B) Ivory vertebra.
C) Fish vertebra.
D) Paget's vertebra.
15. Which term is used to describe the vertebral body changes observed in
Paget's disease, characterized by enlarged, coarsened trabeculae and
condensation of bone along the contours of the vertebral body?
58. 9. What is the term for this
vertebral body appearance?
PICTURE-FRAME VERTEBRA;
PICTURE FRAME; PICTURE
FRAME VERTEBRA
59. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
PAGET’S DISEASE
• Picture-Frame vertebra – Condensation of the periphery of a vertebral
body
• It is a result of disorganized new cortical bone formation after
excessive osteoclastic activity causes the resorption of normal
bone.
60. A) Fish vertebra
B) Ivory vertebra
C) Cotton-wool appearance
D) Picture frame vertebra
19. What is the vertebral deformity seen due to the compression
of the affected vertebrae by the adjacent intervertebral disc?
61. A) Fish vertebra
B) Ivory vertebra
C) Cotton-wool appearance
D) Picture frame vertebra
19. What is the vertebral deformity seen due to the compression
of the affected vertebrae by the adjacent intervertebral disc?
62. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
PAGET’S DISEASE
• Fish vertebrae – biconcave deformities of
the vertebral bodies
• Occurs in metabolic disorders –
osteoporosis, osteomalacia and
hyperparathyroidism.
• Related to compression of affected
vertebrae.
63. A) Picture-frame vertebra
B) Vertical trabeculae
C) Ivory vertebra
D) Rugger-jersey spine
18. Which condition is characterized by a diffuse sclerosed
vertebral body, mimicking metastasis or lymphoma, and can
be seen in some Paget’s disease patients?
64. A) Picture-frame vertebra
B) Vertical trabeculae
C) Ivory vertebra
D) Rugger-jersey spine
18. Which condition is characterized by a diffuse sclerosed
vertebral body, mimicking metastasis or lymphoma, and can
be seen in some Paget’s disease patients?
65. A) Elbow joints.
B) Knee joints.
C) Costochondral junctions of middle ribs.
D) Hip joints.
IVORY VERTEBRA
66. A) Hyperostosis Frontalis Interna
B) Fibrous Dysplasia
C) Anemia
D) Skeletal Metastasis
16. Which disorder can be mistaken for Paget’s disease of the skull that
predominates in women and characterized by thickening of the inner table?
67. A) Hyperostosis Frontalis Interna
B) Fibrous dysplasia
C) Anemia
D) Skeletal Metastasis
16. Which disorder can be mistaken for Paget’s disease of the skull that
predominates in women and characterized by thickening of the inner table?
68. A) Osteoblastic metastasis
B) Hyperostosis Frontalis Interna
C) Fibrous Dysplasia
D) Skeletal Metastasis
17. What can mimic the cotton-wool radiodense lesions of
Paget’s disease of the skull?
69. A) Osteoblastic metastasis
B) Hyperostosis Frontalis Interna
C) Fibrous Dysplasia
D) Skeletal Metastasis
17. What can mimic the cotton-wool radiodense lesions of
Paget’s disease of the skull?
70. 11. This differential
diagnosis for Paget’s
disease involve
hyperostosis and calvarial
thickening in the frontal
region with characteristic
facial involvement.
Diagnosis? Fibrous
Dysplasia
71. • Calvarial hyperostosis as seen on Paget’s disease can be
confused with other conditions:
• Hyperostosis frontalis interna
• Fibrous dysplasia
• Sickle cell anemia
• Thalassemia
• Osteoblastic metastasis
CALVARIAL HYPEROSTOSIS
76. b. stapes
a. joints
c. 206
d. vertebrae
a. knee
d. bone marrow
b. 25
d. all of the above
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Editor's Notes
• Nonspecific features - o Body growth retardation o Osteopenia
• Changes at growth plate:
o Disordered hypertrophy zone cell growth o Deficient mineralization in provisional calcification zone
• Earliest change: Slight axial growth plate widening.
• Progression: Density decrease at provisional calcification zone; Further widening of growth plate; Irregular zone of provisional calcification
• Metaphyseal region: Spongy bone disorganization and fraying
• Metaphysis changes: Widening and cupping due to chaotic cartilage growth.
RICKETS
• Most evident in active growth regions
• Radiographically evident in these sites:
o Costochondral junctions of middle ribs
o Distal femur
o Proximal humerus
o Both tibial ends
o Distal ulna and radius
The bulky growth plates at the shaft bone-cartilage junctions of long bones and ribs explain some of the characteristic physical findings of rickets.
Swelling about joints is typical, and a “rachitic rosary” develops at the costochondral junctions of the middle ribs.
An additional semicoronal impression may be found at the costal attachment of the diaphragm (Harrison’s groove).
RICKETS
• Most evident in active growth regions
• Radiographically evident in these sites:
o Costochondral junctions of middle ribs
o Distal femur
o Proximal humerus
o Both tibial ends
o Distal ulna and radius
expansion of the anterior rib ends at the costochondral junctions
scurvy
the costochondral junction is more angular and has a sharper step-off (scorbutic rosary)
the sternum is usually found to be depressed
RICKETS
• Most evident in active growth regions
• Radiographically evident in these sites:
o Costochondral junctions of middle ribs
o Distal femur
o Proximal humerus
o Both tibial ends
o Distal ulna and radius
scurvy
the costochondral junction is more angular and has a sharper step-off (scorbutic rosary)
the sternum is usually found to be depressed
The deformities caused by rickets exhibit different patterns, depending on the child’s age when the disease develops.
The head is particularly affected during the first months of life.
During this period, the skull must accommodate to the most rapidly growing organ, the brain.
The rapid accommodation by the skull is associated with excess osteoid formation, particularly at the central margins and outer table. Resorption at the inner table continues.
The thin calvaria is subject to supine postural influences, resulting in posterior flattening.
Continued accumulation of osteoid in the frontal and parietal regions results in the squared configuration known as craniotabes.
With increasing age, the effects of weight bearing become prominent.
Scoliosis frequently develops and, coupled with bending deformities of long bones, results in an overall decrease in height.
The intervertebral discs expand, producing concave impressions on the vertebral endplates.
The skull shows basilar invagination, and intrusion of the hip and spine into the soft pelvis produces a triradiate configuration.
During infancy and early childhood, the long bones show the greatest deformity, both at the cartilage-shaft junctions and in the diaphyses.
The characteristic bowing deformities of the arms and legs can be related to the sitting position assumed by infants and children.
Bowing also is a result of displacement of the growth centers owing to asymmetrical musculotendinous pulls on the weakened growth plate.
For example, the saber shin deformity of the tibia results from the strong posterior pull of the Achilles tendon on the calcaneus.
A typical saber shin deformity of the tibia is associated with anterior bowing of the bone. The fibula is also involved.
Pseudofracture (arrow) in adult patient with X-linked hypophosphatemic osteomalacia occurring in a characteristic location in the proximal portion of the ulna. Note bowing of the ulna.
Looser’s zones or pseudofractures are lucent areas that are oriented at right angles to the cortex and span the diameter of the bone incompletely.
They tend to occur in characteristic sites, such as the axillary margins of the scapula, ribs, pubic rami, inner margins of the proximal ends of the femora, and ulnae (Fig. 42-7).
Pseudofractures typically are bilateral and symmetrical. Sclerosis often demarcates the intraosseous margins; new bone on the periosteal aspect suggests callus.
Looser’s zones are considered an insufficiency type of stress fracture.
Radiolucent areas similar to those of pseudofractures may be found in bones affected by Paget’s disease and fibrous dysplasia.
Disorders of the small bowel, hepatobiliary system, and pancreas associated with intestinal malabsorption are the most common causes of vitamin D deficiency in the United States.
Rickets and osteomalacia may develop in many small bowel malabsorptive states, including sprue, gluten-sensitive enteropathy (celiac disease) (Fig. 42-9), regional enteritis, scleroderma, and even unusual conditions such as multiple jejunal diverticula or stagnant (blind) loop syndromes.
Decreased absorption and excessive fecal loss of both vitamin D and (probably) calcium are contributory. Small intestinal bypass surgery, performed for intractable morbid obesity, and partial gastrectomy have also been associated with osteomalacia.
Malabsorption associated with pancreatic insufficiency, even when pronounced, is infrequently associated with osteomalacia. Children with cystic fibrosis, in contrast to those with other malabsorptive diseases, seldom develop rickets.
Areas of increased sclerosis subjacent to the cartilaginous plates (rugger-jersey spine) are demonstrated in a patient with chronic renal failure.
Renal Osteodystrophy (Uremic Osteopathy)
The bone disease associated with chronic renal failure results from multiple complex factors. Although the pathogenesis remains incompletely explained, two main mechanisms (probably acting in concert) are responsible: secondary hyperparathyroidism and abnormal vitamin D metabolism.
Secondary Hyperparathyroidism. Secondary hyperparathyroidism is noted consistently in untreated uremia occurring early in the course of the disease. Parathyroid hormone levels may be increased significantly and frequently are higher than the levels reached in primary hyperparathyroidism. The secondary hyperparathyroidism is provoked by hypocalcemia, which results from several different mechanisms; phosphate retention is the major factor.
Abnormal Vitamin D Metabolism. The singular importance of the kidney as the only organ capable of producing the physiologically active form of vitamin D, 1,25(OH)2 D, was emphasized earlier in this chapter. Loss of renal tissue in acquired renal disease therefore would be expected to be associated with low levels of 1,25(OH)2 D. The hyperphosphatemia of renal failure also inhibits 1,25(OH)2 D production.
Renal Osteodystrophy (Uremic Osteopathy)
The bone disease associated with chronic renal failure results from multiple complex factors. Although the pathogenesis remains incompletely explained, two main mechanisms (probably acting in concert) are responsible: secondary hyperparathyroidism and abnormal vitamin D metabolism.
Secondary Hyperparathyroidism. Secondary hyperparathyroidism is noted consistently in untreated uremia occurring early in the course of the disease. Parathyroid hormone levels may be increased significantly and frequently are higher than the levels reached in primary hyperparathyroidism. The secondary hyperparathyroidism is provoked by hypocalcemia, which results from several different mechanisms; phosphate retention is the major factor.
Abnormal Vitamin D Metabolism. The singular importance of the kidney as the only organ capable of producing the physiologically active form of vitamin D, 1,25(OH)2 D, was emphasized earlier in this chapter. Loss of renal tissue in acquired renal disease therefore would be expected to be associated with low levels of 1,25(OH)2 D. The hyperphosphatemia of renal failure also inhibits 1,25(OH)2 D production.
Abnormal mineral homeostasis with low serum levels of calcium and phosphorus is a well-recognized complication in low-birth-weight premature infants.
Radiographs may reveal evidence of rickets and osteomalacia.
Affected infants usually weigh less than 1000 g at birth or were less than 28 weeks’ gestation at birth. Although bone disease usually appears at about 12 weeks of age, it may develop later, particularly when prolonged parenteral nutrition is required.
The pathogenesis of the bone disease in prematurity can be related to a combination of nutritional, metabolic, and sometimes iatrogenic factors.
A premature infant’s requirements for calcium, phosphorus, and vitamin D are greater than those of an infant born at term.
This increased need may not be provided for in the diet. Human milk and standard infant formulas, which are adequate for term babies, have insufficient amounts of vitamin D, phosphorus, and probably calcium for premature infants.
Rickets and osteomalacia in these premature infants lead to significant morbidity from fractures, respiratory distress, and skeletal deformity.
A, Multifocal areas of paravertebral ossification are similar to those in diffuse idiopathic skeletal hyperostosis or ankylosing spondylitis. Abnormalities of both sacroiliac joints result from ossification of the anterior sacroiliac ligaments.
X-linked hypophosphatemia
(also known as familial vitamin D–resistant rickets) is the most common form of renal tubular rickets and osteomalacia. The classic syndrome is transmitted genetically as an X-linked dominant trait. Men are affected to a greater degree than women. The syndrome is characterized by lifelong hypophosphatemia that is secondary to renal tubular phosphate loss, decreased intestinal absorption of calcium, and normal serum levels of calcium. Patients typically are short, bowlegged, and stocky. The development and severity of rickets may differ among patients with the classic syndrome.
Radiographic features may allow for the specific diagnosis of this syndrome. In children, rachitic changes at the growth plates, in themselves nonspecific, may be only mild in degree. Osteopenia is not prominent. Bowing of long bones, particularly of the lower extremities, may occur, but deformity frequently is minimal.
With increasing age, the trabecular pattern becomes coarsened. Looser’s zones are more prevalent and can be complicated by complete fractures.
By adulthood, a generalized increase in bone density, especially in the axial skeleton, is characteristic. Enthesopathic calcification and ossification develop in the paravertebral ligaments, anulus fibrosus, and capsules of apophyseal and appendicular joints (Figs. 42-12 and 42-13). The spinal changes may resemble those of ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis. In contrast to ankylosing spondylitis, however, the sacroiliac joints in X-linked hypophosphatemia show no bone erosions. Narrowing of the spinal canal, which may relate to ossification of the ligamentum flavum, is common. In the pelvis, multiple sites of calcification may involve the acetabulum, iliolumbar ligaments, and sacroiliac ligaments (see Fig. 42-12B). The appendicular skeleton shows multiple sites of new bone formation at various muscle and ligament attachments. Separate small ossicles may develop around various joints, particularly those in the carpus (see Fig. 42-13).
X-linked hypophosphatemia and the various Fanconi’s syndromes produce rickets and osteomalacia principally by renal tubular phosphate loss. Two separate renal tubular mechanisms for phosphate resorption have been identified: a parathyroid hormone–sensitive component, which is responsible for about two thirds of the total net resorption, and an additional system, which is responsive to the serum calcium level. The parathyroid hormone–sensitive component is completely absent in male patients with Xlinked hypophosphatemia and is partially absent in female patients. Abnormalities in vitamin D metabolism also have been demonstrated in both X-linked hypophosphatemia and Fanconi’s syndromes.
A, Multifocal areas of paravertebral ossification are similar to those in diffuse idiopathic skeletal hyperostosis or ankylosing spondylitis. Abnormalities of both sacroiliac joints result from ossification of the anterior sacroiliac ligaments.
X-linked hypophosphatemia
(also known as familial vitamin D–resistant rickets) is the most common form of renal tubular rickets and osteomalacia. The classic syndrome is transmitted genetically as an X-linked dominant trait. Men are affected to a greater degree than women. The syndrome is characterized by lifelong hypophosphatemia that is secondary to renal tubular phosphate loss, decreased intestinal absorption of calcium, and normal serum levels of calcium. Patients typically are short, bowlegged, and stocky. The development and severity of rickets may differ among patients with the classic syndrome.
Radiographic features may allow for the specific diagnosis of this syndrome. In children, rachitic changes at the growth plates, in themselves nonspecific, may be only mild in degree. Osteopenia is not prominent. Bowing of long bones, particularly of the lower extremities, may occur, but deformity frequently is minimal.
With increasing age, the trabecular pattern becomes coarsened. Looser’s zones are more prevalent and can be complicated by complete fractures.
By adulthood, a generalized increase in bone density, especially in the axial skeleton, is characteristic. Enthesopathic calcification and ossification develop in the paravertebral ligaments, anulus fibrosus, and capsules of apophyseal and appendicular joints (Figs. 42-12 and 42-13). The spinal changes may resemble those of ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis. In contrast to ankylosing spondylitis, however, the sacroiliac joints in X-linked hypophosphatemia show no bone erosions. Narrowing of the spinal canal, which may relate to ossification of the ligamentum flavum, is common. In the pelvis, multiple sites of calcification may involve the acetabulum, iliolumbar ligaments, and sacroiliac ligaments (see Fig. 42-12B). The appendicular skeleton shows multiple sites of new bone formation at various muscle and ligament attachments. Separate small ossicles may develop around various joints, particularly those in the carpus (see Fig. 42-13).
X-linked hypophosphatemia and the various Fanconi’s syndromes produce rickets and osteomalacia principally by renal tubular phosphate loss. Two separate renal tubular mechanisms for phosphate resorption have been identified: a parathyroid hormone–sensitive component, which is responsible for about two thirds of the total net resorption, and an additional system, which is responsive to the serum calcium level. The parathyroid hormone–sensitive component is completely absent in male patients with Xlinked hypophosphatemia and is partially absent in female patients. Abnormalities in vitamin D metabolism also have been demonstrated in both X-linked hypophosphatemia and Fanconi’s syndromes.
Atypical axial osteomalacia. A dense, coarse trabecular pattern involves the cervical spine. The appendicular skeleton was normal.
Atypical axial osteomalacia is a rare condition in which the radiographic changes are characteristic.
Skeletal involvement is axial, with sparing of appendicular sites (Fig. 42-14). A dense, coarse trabecular pattern involves primarily the cervical spine but also is present in the lumbar spine, pelvis, and ribs. Looser’s zones have not been identified.
All reported patients have been men. Their general health is good, symptoms are minimal, and the biochemical findings are within normal limits. Biopsy of the involved areas demonstrates typical osteomalacia. Patients do not respond to vitamin D therapy.
Pseudohypoparathyroidism (Albright’s hereditary osteodystrophy) in a 9-year-old boy, demonstrating shortening of all metacarpal bones, particularly the fourth.
Parathyroid Gland Abnormalities
Because parathyroid hormone is a major stimulus to 1,25(OH)2 D production, the clinical syndromes of hypoparathyroidism, pseudohypoparathyroidism, and pseudopseudohypoparathyroidism are associated with abnormalities of vitamin D metabolism.
Pseudohypoparathyroidism and Pseudo-pseudohypoparathyroidism.
The term pseudohypoparathyroidism was introduced by Albright and associates to describe patients who had a characteristic phenotype consisting of short stature, round face, short neck, and shortening of metacarpal bones (particularly the first, fifth, and fourth) (Fig. 42-16), accompanied by low serum calcium and high serum phosphorus levels consistent with hypoparathyroidism. Administration of parathyroid hormone in these patients did not result in the normally expected increase in urinary phosphate levels, leading investigators to postulate the existing of an end-organ (kidney) unresponsiveness to parathyroid hormone. Subsequently, patients were described who had the characteristic phenotype of pseudohypoparathyroidism with normal blood chemistry values, and the term pseudo-pseudohypoparathyroidism was applied to this condition. The renal response to parathyroid hormone in this latter group of patients is normal.
Both pseudohypoparathyroidism (the classic syndrome is termed type I) and pseudo-pseudohypoparathyroidism have the same phenotype. The parathyroid glands are intrinsically normal. Parathyroid hormone levels are normal in pseudo-pseudohypoparathyroidism and elevated in pseudohypoparathyroidism; the latter is a consequence of the ineffective hormone action at the kidney, with secondary hyperphosphatemia and hypocalcemia. Patients have been reported who exhibit this same phenotype but who have true hypoparathyroidism. Parathyroid hormone levels are low, and they have a proper target-organ response to the administration of parathyroid hormone. These patients would be classified as having pseudo-pseudohypoparathyroidism.
To clarify the distinctions between these disorders, it has been proposed that the condition with the phenotypic changes originally described by Albright be termed Albright’s hereditary osteodystrophy (distinct from Albright’s syndrome, which consists of fibrous dysplasia, precocious puberty, and café au lait spots). Hypoparathyroid states should be classified as either true hormone-deficient or hormone-resistant forms. Patients with Albright’s hereditary osteodystrophy may exhibit target-organ (kidney and bone) unresponsiveness to parathyroid hormone (pseudohypoparathyroidism) or may exhibit a normal target-organ responsiveness (pseudo-pseudohypoparathyroidism with normal parathyroid hormone levels or pseudopseudohypoparathyroidism with true deficiency of parathyroid hormone) (see Chapter 46)
Osteolytic stage of Paget’s disease.
A, Cranial vault (osteoporosis circumscripta). The osteolytic bone usually commences in the frontal or occipital area of the skull. Its advancing edge (arrowheads) is well demarcated from adjacent normal bone.
Focal radiodense areas (arrow) are apparent within the areas of osteolysis. In some locations, involvement of a portion of the cranial vault creates beveled margins (open arrow).
An initial phase of intense osteoclastic activity with resorption of bone trabeculae may be detected on radiographs as an “osteolytic” form of the disease.
This imaging appearance is particularly common in the skull, where it is termed osteoporosis circumscripta.
Osteolysis in the cranial vault is observed most frequently in the frontal or occipital region and may progress to involve the entire skull.
The advancing radiolucent lesion may be sharply delineated from the adjacent normal bone. The osteolytic phase of Paget’s disease may be apparent elsewhere in the skeleton, particularly in the long bones and, less commonly, the pelvis, spine, and small bones of the hands and feet.
Osteolysis begins almost invariably in the subchondral regions of the epiphysis and subsequently extends into the metaphysis and diaphysis; occasionally, the disease may appear at both ends of an involved bone, but only exceptionally is Paget’s disease apparent in the diaphysis without involvement of the epiphysis.
When present, this latter feature typically occurs in the tibia. As the disease progresses, osteolysis may advance into the diaphysis as a V- or wedge-shaped radiolucent area, clearly demarcated from adjacent bone.
This appearance has been likened to a blade of grass or a flame. Within the area of radiolucency, the remaining trabeculae may appear thickened, although they are frequently obliterated, and a hazy “ground-glass” or “washed-out” pattern is observed. The involved bone is commonly enlarged or widened, and pathologic fractures may be evident.
B, Tubular bones. An advancing wedge-shaped radiolucent edge (arrowhead) is observed in the femur.
Osteolysis begins almost invariably in the subchondral regions of the epiphysis and subsequently extends into the metaphysis and diaphysis; occasionally, the disease may appear at both ends of an involved bone, but only exceptionally is Paget’s disease apparent in the diaphysis without involvement of the epiphysis.
When present, this latter feature typically occurs in the tibia. As the disease progresses, osteolysis may advance into the diaphysis as a V- or wedge-shaped radiolucent area, clearly demarcated from adjacent bone.
This appearance has been likened to a blade of grass or a flame. Within the area of radiolucency, the remaining trabeculae may appear thickened, although they are frequently obliterated, and a hazy “ground-glass” or “washed-out” pattern is observed. The involved bone is commonly enlarged or widened, and pathologic fractures may be evident.
B, Tubular bones. An advancing wedge-shaped radiolucent edge (arrowhead) is observed in the femur.
Figure 43–2. General stages of Paget’s disease: osteolytic and osteosclerotic stage. Cranial involvement showing extensive osteosclerosis is producing the “cotton-wool” appearance.
Cranium. Pagetic alterations of the skull (see Figs. 43–1 and 43–2) vary from typical osteoporosis circumscripta to widespread sclerosis. Focal radiodense areas exhibiting the “cotton-wool” appearance may be observed. Cranial thickening is occasionally extensive, particularly in the frontal regions, and both bone sclerosis and thickening may be distributed asymmetrically. In contrast to the exuberant facial changes that may be seen in fibrous dysplasia, extensive alterations of the facial bones are infrequent in Paget’s disease.
Basilar invagination is seen in about one third of patients with Paget’s disease of the skull, and it increases in frequency with progressive severity of the disease. Basilar invagination is characterized by upward protrusion of the foramen magnum and surrounding bone as a result of the effect of gravity and muscle pull. It may be associated with neurologic symptoms and signs. Additional clinical findings are related to impingement on other cranial nerves by the enlarging pagetic bone.
Cranium. Pagetic alterations of the skull (see Figs. 43–1 and 43–2) vary from typical osteoporosis circumscripta to widespread sclerosis. Focal radiodense areas exhibiting
the “cotton-wool” appearance may be observed. Cranial thickening is occasionally extensive, particularly in the frontal regions, and both bone sclerosis and thickening may be distributed asymmetrically. In contrast to the exuberant facial changes that may be seen in fibrous dysplasia, extensive alterations of the facial bones are infrequent in Paget’s disease.
Basilar invagination is seen in about one third of patients with Paget’s disease of the skull, and it increases in frequency with progressive severity of the disease. Basilar invagination is characterized by upward protrusion of the foramen magnum and surrounding bone as a result of the effect of gravity and muscle pull. It may be associated with neurologic symptoms and signs. Additional clinical findings are related to impingement on other cranial nerves by the enlarging pagetic bone.
Condensation of the periphery of a vertebral body—the “picture-frame” vertebra—is almost diagnostic of Paget’s disease.
It differs from the accentuated vertical trabeculae of hemangiomas and the rugger-jersey spine of renal osteodystrophy.
Some patients with Paget’s disease have diffuse sclerosis of an entire vertebral body—the ivory vertebra—which can simulate skeletal metastasis and lymphoma.
Condensation of the periphery of a vertebral body—the “picture-frame” vertebra—is almost diagnostic of Paget’s disease.
It differs from the accentuated vertical trabeculae of hemangiomas and the rugger-jersey spine of renal osteodystrophy.
Some patients with Paget’s disease have diffuse sclerosis of an entire vertebral body—the ivory vertebra—which can simulate skeletal metastasis and lymphoma.
Biconcave deformities termed “fish vertebrae” are identical to those occurring in metabolic disorders such as osteoporosis, osteomalacia, and hyperparathyroidism.
These deformities are related to compression of affected vertebrae by the adjacent intervertebral disc. Pagetic changes in the posterior elements may occur in conjunction with vertebral body abnormalities or as an isolated spinal manifestation of the disease.
With pediculate involvement, increased radiodensity may simulate osteoblastic metastasis. Sacral alterations are usually associated with involvement of additional areas of the pelvis.
Osteolytic features commonly predominate in the sacrum, and in such instances, a missed diagnosis is not infrequent (Fig. 43–6).
Fish vertebrae complicating osteoporosis must be differentiated from fish vertebrae in other disorders.
In osteomalacia, biconcave vertebral deformities have been reported to be smoother than those in osteoporosis and to involve the superior and inferior margins of the vertebral body with equal severity; adjacent vertebrae are affected to the same extent.
Fish vertebrae in Paget’s disease, hyperparathyroidism, renal osteodystrophy, and neoplasm also resemble those in osteoporosis, although additional characteristics of the underlying disease process are usually discernible.
C LEFT Note the homogeneous increase in radiodensity of the vertebral body, without osseous enlargement.
C RIGHT Ivory vertebral body: skeletal metastasis (carcinoma of the prostate). The entire vertebral body is radiodense and, on pathologic inspection, contains cartilaginous nodes.
Fibrous dysplasia. Characteristic hyperostosis and calvarial thickening can be seen in the frontal region. The facial bones are also affected.
Fibrous dysplasia may cause gross enlargement of the skull, although facial involvement is particularly characteristic.
In addition, fibrous dysplasia leads to focal involvement of the cranial vault, whereas Paget’s disease is often diffuse in distribution.
Both disorders produce diploic widening and can extend across suture lines.
Certain anemias, such as sickle cell anemia and thalassemia, produce thickening of the cranial vault and a radiating trabecular pattern (hair-on-end appearance).
The base of the skull is generally spared.
Osteoblastic metastasis can simulate the cotton-wool radiodense lesions of Paget’s disease.
Calvarial Hyperostosis
Paget’s disease of the skull can be confused with other disorders associated with calvarial hyperostosis,
including hyperostosis frontalis interna, fibrous dysplasia, anemia, and skeletal metastasis.
Hyperostosis frontalis interna predominates in women and produces thickening of the inner table of the frontal squama.
Fibrous dysplasia may cause gross enlargement of the skull, although facial involvement is particularly characteristic.
In addition, fibrous dysplasia leads to focal involvement of the cranial vault, whereas Paget’s disease is often diffuse in distribution.
Both disorders produce diploic widening and can extend across suture lines.
Certain anemias, such as sickle cell anemia and thalassemia, produce thickening of the cranial vault and a radiating trabecular pattern (hair-on-end appearance).
The base of the skull is generally spared.
Osteoblastic metastasis can simulate the cotton-wool radiodense lesions of Paget’s disease.
