2. Osteogenesis imperfecta
2
It is genetically heterogeneous group of collagen
disorders.
It is also known as brittle bones disease/
fragilitas ossium.
It results from a defect of type I collagen
production (major protein of bone matrix) that
leads to congenital osteopenia with increased
bone fragility, low bone mass, and other
connective tissue manifestations like dental
abnormalities, lax joints, thin skin.
It is a heritable condition of connective tissue.
3. Osteogenesis imperfecta
3
It occurs in 1:20,000 to 1:60,000 of live births.
It occurs with equal frequency among males and
females and across races and ethnic groups.
The hallmark feature of OI is fragile bones that
fracture easily.
Classical clinical triad of OI is fragility of bone, blue
sclera, and deafness (due to ankylosis of ossicles &
osteosclerosis) .
OI affects both bone quality and bone mass.
In some people, height, hearing, skin, blood vessels,
muscles, tendons, and teeth may also be affected.
4. Osteogenesis imperfecta
4
It is probably the most common form of skeletal
dysplasia requiring substantial orthopaedic care.
Although the disease is usually apparent at birth or in
childhood, more mild forms of the disease may not
become apparent until adulthood, when affected
individuals may present with insufficiency fractures and
osteopenia.
In the more severely affected fetuses antenatal
diagnosis may often be made in the second trimester
on the basis of shortened long bones with multiple
fractures.
The thorax tends to be short but not narrow.
5. Osteogenesis imperfecta
5
Pathophysiology
In most cases, OI is caused by a dominant mutation in
the COL1A1 or the COL1A2 genes that encode type I
collagen.
Fewer than 10 percent of OI cases are believed to be
caused by recessive mutations in other genes in the
collagen pathway.
Here is the production of abnormal collagen I
molecules as well as a decrease in the production of
normal collagen I molecules. This results from
mutations in the loci coding for pro-α 1 and pro-α 2
chains which form the helical structure of collagen 1.
6. Radiographic features
Radiographic features vary according to the type
of disease and its severity and include
osteopenia and fractures, which may heal with
florid callus formation, mimicking
osteosarcoma.
Bones are thin and under-tubulated (gracile),
normal in length or shortened, thickened and
deformed by multiple fractures.
Intra-sutural (Wormian) bones can be identified
on skull radiographs.
6
7. Radiographic features
In severe forms of osteogenesis imperfecta the
diagnosis may be made before birth by
detailed ultrasound in the second trimester.
Diagnostic features include cranial
enlargement, reduced echogenicity of bone
and deformity and shortening of limb bones
as a result of intrauterine fractures.
7
8. Classification of Osteogenesis imperfecta
8
The classification of osteogenesis imperfecta is
that devised by Sillence et al in 1979 and modified
in 1986.
The important characteristics in this classification
include
blue sclera
severity of the disorder &
the mode of inheritance (dominant, recessive,
sporadic/new mutation)
However accurate classification is difficult
because of phenotypic overlap.
9. Osteogenesis Imperfecta
9
Two forms:
Congenita-Life expectancy short.
Tarda-Life expectancy is normal
Types: 4 types
Osteogenesis Imperfecta Type I
Osteogenesis Imperfecta Type II
Osteogenesis Imperfecta Type III
Osteogenesis Imperfecta Type IV
10. Osteogenesis Imperfecta-Type I
10
A mild form of this condition (occurs in 70% cases).
It has autosomal dominance inheritance.
Sclera becomes blue.
Bone fragility mild.
Fracture rates in childhood diminish with increasing
skeletal maturity only to increase again in middle life,
particularly in postmenopausal women
Stature is normal or only mildly reduced.
Deafness occurs in adult life.
People suffering from it can expect to live as long as
any normal individual.
11. Osteogenesis Imperfecta- Type I
11
Subdivision:
Group A: No dental involvement but presence of
minor skeletal changes.
Group B: Subjects with dentinogenesis imperfecta &
more severe skeletal changes.
Osteoporosis occurs with cortical thinning with
bowed thin gracile long bones.
In 10% fractures are seen at birth.
Most fracture occurs in young children.
Wormian bones are seen in skull.
12.
13.
14.
15. Osteogenesis Imperfecta Type II
15
It is generally estimated to be the most severe type of
OI.
Individuals with Osteogenesis Imperfecta Type 2
generally die within the first year of their life.
Sclera are blue.
Overall bones are grossly demineralised with thin
cortices.
Numerous healing or healed fractures are seen at
birth despite protection of amniotic fluid. Fractures
are occurs during delivery.
16. Osteogenesis Imperfecta Type II
16
Sub types:
Type 2A: The long bones are bowed, short and broad.
Numerous fractures are seen. The ribs are broad with
continuous beading.
Type 2B: The long bones are as in Type 2A, but the ribs
show no beading or less beading.
Type 2C: The long bones are thinned, shows numerous
fractures and the ribs too are thin & beaded.
19. OI type II in a fetus.
There are fractures in all
the long bones.
Multiple fractures are
present in the ribs,
leading to shortened ribs
with a characteristically
“ beaded ” appearance.
Also there is poor
ossification of the skull
20.
21. Osteogenesis Imperfecta- Type III
21
This occurs in 15% of the patients, is a severe and
progressively deforming type & is usually due to new
mutation.
Affected individuals suffer from multiple fractures that
start from the initial years of their life result in bowing.
Overall bones are demineralised. Vertebral compression
is seen and a kyphoscoliosis results. The long bones are
osteoporotic and thin.
Sclera may be blue at birth but are usually normal in
adolescence.
In skull ossification is poor, sutures are wide and
wormian bones persists.
It also has association with dentinogenesis imperfecta.
22.
23.
24. Osteogenesis Imperfecta- Type IV
24
It is a mildly severe form of this disorder and is
similar to Type I. However, Osteogenesis Imperfecta
Type 4 sufferers need crutches and braces to walk.
Life expectancy is close to normal or completely
normal.
This types constitutes 5%.
Sclera-normal.
Fractures are seen at birth 30% and bony fragility is
mild.
Subtypes: 2
4A with no dental lesion
4B with dentinogenesis imperfecta
25.
26. Osteogenesis Imperfecta and Eyes
26
The reduced functioning of Type I collagen leads to
the thinning of the sclera and consequent showing
of the underlying veins through the whites of eyes.
Blue Sclera is one of the major symptoms of OI and
helps in the diagnosis of the disorder.
These are also an important component of teeth,
ligaments and whites of the eyes (sclera).
28. Osteogenesis Imperfecta and Genetics
28
This condition typically results from a genetic mutation.
Medical research has been able to establish that the
genetic defect causing OI runs in families.
Type I of OI is a dominant inherited condition arising due
to mutations on chromosome 17 in the COL1A1 gene,
on chromosome 7 in the COL1A2 gene. This leads to
reduced manufacture of normal collagen.
This protein is a major constituent of the connective
tissues located within the bone
Hence OI chiefly characterized by symptoms like multiple
bone fractures, blue sclerae
29. Osteogenesis Imperfecta Diagnosis
29
Physical examination of the sclera of the
eyes is usually enough to diagnose this
condition( bluish tinge). The condition is also
diagnosed with the help of other methods,
such as
DNA blood testing for gene defects has an
accuracy of 60-94%.
Prenatal DNA mutation analysis can be
performed in pregnancies with risk of OI to
analyze uncultured chorionic villus cells.
30. Osteogenesis Imperfecta Diagnosis
30
Prenatal ultrasonography: Most useful in
evaluating OI types II and III by 2nd trimester.
Findings include bowing, shortening and
angulation of the long bones due to fractures
and easy visualization of intracranial
structures due to decreased ossification of the
skull vault.
3 important US criteria of specific diagnosis of
OI-type-II:
• a) FL greater than 3SD below the mean,
• b)Demineralization of calvarium,
• c) Multiple fracture within a single bone.
31. USG
D, Osteogenesis imperfecta type I. Isolated femoral fracture with acute angulation
(arrow).
F, Osteogenesis imperfecta type IIA. Bowed femur with multiple discontinuities
representing fractures.
32. OI Diagnosis-Plane radiography
32
Obtain a radiographic skeletal survey after birth.
Generalized osteoporosis is present
In milder forms (Types I & IV)–Thin and gracile bones
with thin cortices. Skull vault may be normal.
In the more severe forms (types 2 and 3)-The bones
are thick and short with multiple fractures and
hyperplastic callus formation.
The skull is osteopenic and multiple wormian bones
are present. Multiple rib fractures may cause the bones
to become broad and deformed.
Platyspondyly and scoliosis are often present
33. Management
Genetic counseling is necessary for
couples who have a family history of
Osteogenesis Imperfecta (OI) and are
considering pregnancy.
Physiotherapy, rehabilitation, and
orthopaedic surgery are the mainstay of
treatment for patients with osteogenesis
imperfecta.
In recent years, biphosphonate therapy
has been used with success.
35. Battered baby syndrome:
Alternative name Child abuse/Non accidental trauma.
A young child, often under age 3, who has been
repeatedly and severely neglected by caretakers.
Battered children have signs of multiple episodes of
trauma—e.g., subdural haematomas, fractures,
bruises in various stages of healing—often with failure
to thrive and chronic malnutrition.
Fractures are usually metaphyseal. Multiple rib
fractures, fracture of scapula, sternum, vertebra, tibia,
metacarpal associated with intracranial injuries
(subdural haematomas).
Urinary hydroxypoline is not elevated.
36. Idiopathic juvenile osteoporosis:
Patient typically presents before puberty (8-
13 years) and have osteoporosis (lumbar &
thoracic vertebrae) that is progressive initially
and later stabilizes.
Vertebral compression fracture and
characteristically metaphyseal fractures
specially of lower limb bones occur.
39. Osteogenesis imperfecta. Results from genetic
mutations causing abnormalities in Type I collagen, and
resulting in osteoporosis and low-trauma fractures
(brittle bone disease). The different types vary in clinical
presentation and severity.
Frontal view of the femora in an infant showing reduced
bone density and marked deformity due to multiple
fractures.
Lateral spinal radiograph in a 30-year-old man showing
reduced bone density and end-plate fractures of all
vertebrae. There is also evidence of a metallic pin in a
previous hip fracture. Osteoporosis is much less
common in men than in women, and more likely to be
related to secondary causes, especially excess alcohol
intake.
40. Radiological Features of Rickets
Radiological changes: Result from loss of orderly maturation
and mineralization of cartilage cells at the growth plate.
These changes predominate at the sites of bones which are
growing most active. These sites are – around the knee, the
wrist (particularly the ulna) , the anterior ends of the middle ribs,
the proximal femur and the distal tibia, and depend on the age of
the child.
Changes at growth plate and cortex
Widening of physis (earliest change)/growth plate.
loss of normal zone of provisional calcification adjacent to
metaphysis.
Irregular metaphyseal margins (Fraying)
Splaying and cupping of the metaphysis.
Indistinct cortex because of uncalcified subperiosteal osteoid.
Some expansion in width of the metaphysis results in the
swelling around the ends of the long bones .
Rachitic rosary.( This expansion and cupping of the anterior
ends of the ribs)
Looser’s zone is uncommon on children
Hinweis der Redaktion
(Source-Denhart-233)Stroke:
3rd leading cause of death in United States (after heart disease+ cancer); 2nd leading cause of death due to cardiovascular disease in U.S.; 2nd leading cause of death in patients >75 years of age; 450,000 new cases per year; 160 new strokes per 100,000 population per year; leading cause of death in Orient.
Table 21.1 Causes of osteoporosis
Senile and postmenopausal statesMedication Glucocorticoids HeparinEndocrine states Hyperthyroidism Hyperparathyroidism Cushing's disease Acromegaly Pregnancy Diabetes mellitus HypogonadismDeficiency states Scurvy Malnutrition Calcium deficiencyAlcoholismChronic liver diseaseMalignant disease Myelomatosis Leukaemia Lymphoma MastocytosisOsteogenesis imperfectaIdiopathic condition
Wormian bones are ossicles located in the sutures or fontanelles and may be associated with multiple
conditions, such as
Pyknodysostosis,
Osteogenesis imperfecta,
Cleidocranial dysplasia,
Hypothyroidism, and
Trisomy 21.
Hypophosphatasia
LETHAL SKELETAL DYSPLASIAS
Thanatophoric Dysplasia
Achondrogenesis
Osteogenesis Imperfecta
Hypophosphatasia
Campomelic Dysplasia
Short-Rib Polydactyly Syndromes
Other Dysplasias
The majority of lethal skeletal dysplasias, including thanatophoric dysplasia, achondrogenesis, and osteogenesis imperfecta type II, can be diagnosed solely on the basis of prenatal ultrasound.
Net: Osteogenesis Imperfecta Definition
Medical researchers define Osteogenesis Imperfecta as an acquired hereditary disorder that makes sufferers extremely vulnerable to bone fractures. It is a congenital condition that causes extreme fragility of the bones in the body of an affected person.
This disease is more commonly known as “Brittle Bone Disease” or simply “OI”.
This condition is more common in premature infants and also in twins.
Osteogenesis Imperfecta in infants is characterized by occurrence of fractures in the first year of life, especially in the first six months after birth. However, fractures may continue for a full year in some cases. Osteogenesis Imperfecta is almost asymptomatic in babies with symptoms emerging only in the later months. Infants who suffer from this condition may have his or her parents as well as relatives suffering from collagen abnormalities.
In rare cases, however, the general signs of fracture may not be apparent. The fracture is not discovered until some months or years later when an X-ray examination is conducted for some other reason.
: Sutton-(2)-1062
OI is an autosomal dominant disease which means that possessing even one copy of this impaired gene can make a person suffer from this condition. Most sufferers acquire this gene from any of his or her parents.
In some cases however, OI may also arise as a result of new mutations in genes. Any person with this genetic flaw has a 50% chance of giving birth to an offspring who may be born with OI.
Coxa vara: When angle between neck & shaft is less than normal. (Normal angle at 1 year: 148 degree, at 5year 135 degree, ay elderly 120 degree)
Causes of acquired coxa vara:
Fibrous dysplasia,
Rickets.
OI.
Cleidocranial dysplasia.
Perthes disease.
Following slipped epiphysis.
Indication of BMD:
1. All PM lady with fracture.
All PM lady with 1/more risk factors.
All PM lady more than 65 years of age.
Source: (Pocket Primer on Rheumatic disease-199) World Health Organization Criteria for the Diagnosis of Osteoporosis
Normal: BMC or BMD not more than 1 standard deviation below peak adult bone mass
T-score > –1
Osteopenia: BMC or BMD that lies between 1 and 2.5 standard deviations below peak adult bone mass
T-score between –1 and –2.5
Osteoporosis: BMC or BMD value more than 2.5 standard deviations below peak adult bone mass
T-score ・ –2.5
Severe osteoporosis: BMC or BMD value more than 2.5 standard deviations below peak adult bone mass and the presence of one or more fragility fractures
T-score ・ –2.5 plus fragility fracture
World Health Organization criteria for the diagnosis of osteoporosis based on bone mineral content (BMC) or bone mineral density (BMD) measurements. These criteria can be applied to either the central or peripheral skeletal measurement sites.
Source: Imaging rheumatology-David:
Source: Imaging of rheumatology-The incomplete fracture (Looser's zone or Milkman's pseudofracture) is the classical finding in osteomalacia
Four main types,7 ranging in severity from forms that are lethal in utero or the perinatal period (type II), through severe deforming types with multiple fractures (types III and IV) to milder variants in which there may sometimes be only slightly increased fracture risk, verging on normality (type I). The cardinal features of all types of osteogenesis imperfecta (OI) reflect a reduction in the quantity of normal collagen matrix.
Type I collagen is not only the major structural protein in bone but also in many associated soft tissues, such as tendons and ligaments. Consequently, extraskeletal features are also common.
The most common congenital skeletal dysplasias are achondroplasia, osteogenesis imperfecta (OI), and thanatophoric dysplasia (TD).
Generalized conditions resulting in weak bones include osteogenesis imperfecta, osteopetrosis, neurofibromatosis, fibrous dysplasia, rickets, renal osteodystrophy, scurvy, hyperparathyroidism, Cushing’s syndrome, cytotoxic drugs, and disuse atrophy because of neurological or other disabling conditions resulting in generalized demineralization.
The most common metabolic disorders of bone are:
1. Osteoporosis, in which there is a deficiency of bone mass leading to insufficiency (low-trauma) fractures;
2. Rickets and osteomalacia, in which there is a defective mineralization of bone osteoid ( Fig. 49.2B ) due to vitamin D deficiency, hypophosphataemia, lack of alkaline phosphatase or calcium, or severe acidaemia; and
3. Hyperparathyroidism, in which a tumour or hyperplasia of the parathyroid glands causes increase in parathyroid hormone production and stimulation of osteoclasts.
4. Other metabolic bone disorders include osteogenesis imperfecta, hyperphosphatasia and osteopetrosis ( Fig. 49.2C ). Paget's disease is not strictly a metabolic bone disease, since it can be monostotic or polyostotic and does not involve the entire skeleton, but because it involves increased bone turnover ( Fig. 49.2D ) it is often included in this group of disease[19
The cardinal features of all types of osteogenesis imperfecta (OI) reflect a reduction in the quantity of normal collagen matrix. There is reduced bone density, increased fracture risk, and a variable tendency to bone deformity and short stature.
Causes of osteoporosis: (CDA SHOT)
A-Acromegaly
D-DM
C-Cushing’s syndrome
S-Steroid.
H-Haemocysteinurea.
O-Osteogenesis imperfecta.
T-Turner’s syndrome.
I-Idiopathic of young adult.
S-Scurvy
H-Haemochrommatosis.
E-Ehler Danlos syndrome.
R-Rheumatoid arthritis.
M-Marfan syndrome.
A-Addisons disease.
The cardinal features of all types of osteogenesis imperfecta (OI) reflect a reduction in the quantity of normal collagen matrix. There is reduced bone density, increased fracture risk, and a variable tendency to bone deformity and short stature.
Causes of osteoporosis: (CDA SHOT)
A-Acromegaly
D-DM
C-Cushing’s syndrome
S-Steroid.
H-Haemocysteinurea.
O-Osteogenesis imperfecta.
T-Turner’s syndrome.
I-Idiopathic of young adult.
S-Scurvy
H-Haemochrommatosis.
E-Ehler Danlos syndrome.
R-Rheumatoid arthritis.
M-Marfan syndrome.
A-Addisons disease.
Source: Imaging rheumatology:
Table 21.3 Causes of increased bone density
Cortical and trabecular boneOsteopetrosisCarbonic anhydrase II deficiencyDysosteosclerosisPycnodysostosisCortical bone (predominantly)Autosomal dominant osteosclerosisDiffuse idiopathic skeletal hyperostosisEndosteal hyperostosis (van Bucham's disease and sclerosteosis)Hypertrophic osteoarthropathyPachydermoperiostosisProgressive diaphyseal dysplasia (Engelmann's disease)Trabecular bone (predominantly)Dyplastic: osteomesopyknosisHaematological: mastocytosis, myelofibrosis, polycythaemia vera, sickle cell diseaseMetabolic: fluorosis, hyperparathyroidism, renal osteodystrophy, X-linked hypophosphataemic rickets, vitamin D toxicityNeoplastic disorders: metastatic disease; myeloma, lymphoma, leukaemia
Source: Net.-Above
Source: Imaging rheumatology-David
Silence type I to IV
Type-I: 70% of total case, bone density reduced 60% of normal, mild short stature & variable bone fragility. Fracture rates in childhood diminish with increasing skeletal maturity only to increase again in middle life, particularly in postmenopausal women. Indeed, the fracture rate in patients is approximately seven times that of the general postmenopausal population.
Type-II:
This is the most severe form of osteogenesis imperfecta, lethal in utero or the perinatal period.
Along with thanatophoric dysplasia, it is the most common form of short-limbed lethal dwarfism.
The infant is disproportionately short with deformed limbs. The skull is deformed and soft with deep grey-blue sclerae.
The diagnosis can be confirmed by whole-body radiography, which distinguishes it from other forms of lethal short-limbed dwarfism.
Mineralization of the skull is grossly defective and there are multiple fractures.
Type III :
This type is associated with severe fracture tendency, severe short stature, and progressive deformity and disability.
Phenotypically, there is a small degree of overlap with type II OI.
Multiple fractures at birth are typical and deformity affects the bones of the skull, the limbs, the spine, chest, and pelvis (Fig. 22.4).
In the long limb bones, cartilage islands can spread from the epiphyses across the growth plate into the metaphysis and diaphysis giving the appearance of popcorn bone (Fig. 22.5).
Severe kyphoscoliosis may develop and early death from respiratory infections is common. The sclerae are often blue in infancy but may become normal later in childhood
Type IV:
This is intermediate in severity between types I and III OI.
Stature is reduced (often <5th percentile) and a degree of bone deformity is usually present, although this is variable in severity.
The sclerae are typically of normal hue after infancy. This variant is most likely to be caused by mutations in COL1A2.
Hyperplastic callus may develop after fracture or corrective surgery for deformity mimicking sarcomatous change.
Source: Net.-Above
Source: Imaging rheumatology-David Translucent teeth are found in dentinogenesis imperfecta.
Silence type I to IV
Type-I: 70% of total case, bone density reduced 60% of normal, mild short stature & variable bone fragility. Fracture rates in childhood diminish with increasing skeletal maturity only to increase again in middle life, particularly in postmenopausal women. Indeed, the fracture rate in patients is approximately seven times that of the general postmenopausal population.
Type I
This is the mildest and most prevalent form of the disease and may only become apparent in adulthood.
There is a history of fractures, generally dating back to childhood.
In children the fractures may become radiographically and clinically apparent as the child becomes more active (5+ years), and may take the form of overt fractures or micro-fractures involving the metaphyses.
In infancy these features may resemble those found in non-accidental injury
Type-II:
This is the most severe form of osteogenesis imperfecta, lethal in utero or the perinatal period.
Along with thanatophoric dysplasia, it is the most common form of short-limbed lethal dwarfism.
The infant is disproportionately short with deformed limbs. The skull is deformed and soft with deep grey-blue sclerae.
The diagnosis can be confirmed by whole-body radiography, which distinguishes it from other forms of lethal short-limbed dwarfism.
Mineralization of the skull is grossly defective and there are multiple fractures.
Type III :
This type is associated with severe fracture tendency, severe short stature, and progressive deformity and disability.
Phenotypically, there is a small degree of overlap with type II OI.
Multiple fractures at birth are typical and deformity affects the bones of the skull, the limbs, the spine, chest, and pelvis (Fig. 22.4).
In the long limb bones, cartilage islands can spread from the epiphyses across the growth plate into the metaphysis and diaphysis giving the appearance of popcorn bone (Fig. 22.5).
Severe kyphoscoliosis may develop and early death from respiratory infections is common. The sclerae are often blue in infancy but may become normal later in childhood
Type IV:
This is intermediate in severity between types I and III OI.
Stature is reduced (often <5th percentile) and a degree of bone deformity is usually present, although this is variable in severity.
The sclerae are typically of normal hue after infancy. This variant is most likely to be caused by mutations in COL1A2.
Hyperplastic callus may develop after fracture or corrective surgery for deformity mimicking sarcomatous change.
Blue or grey sclerae are present in two thirds of all patients with osteogenesis imperfecta but mild variants of the disease with normal sclerae are well recognized.
Overt dentinogenesis imperfecta is seen in about half of patients with osteogenesis imperfecta.
Type-I
The differential diagnosis can usually be resolved by the presence of associated extraskeletal manifestations of osteogenesis imperfecta (blue sclerae, dentinogenesis imperfecta), or evidence of a family history of the condition, so that bone biopsy for diagnosis is infrequently required. Affected patients are short in stature, only 10% being of normal height, with joint laxity, blue sclerae and presenile hearing loss. Transmission is by autosomal dominant trait. Radiologically the bones are usually reduced in radio-density, although some patients may have normal bone density. Bones may be thin and under-tubulated (gracile), or modelled normally. Vertebral fractures often occur in the fourth decade. When scoliosis is present, it is mild.
Wormian bone-Intra sutural bone
Where worminan bone is found?
Ans: Pyknodysostosis,
Cleidocranial dysostosis,
Menke's syndrome,
Osteogenesis imperfecta and
Prader Willi syndrome.
Source: Sutton
In Type-I OI: Extra-articular features are also common and include:
blue or grey sclerae;
premature complete arcus;
hyperelasticity of the skin;
hypermobility of the joints;
abnormal bruising and scars;
dentinogenesis imperfecta with opalescent dentine;
deafness due to fragility of the auditory ossicles;
dilatation of the aortic and mitral valves.
Source: Imaging rheumatology-David
Scoliosis is uncommon but multiple vertebral fractures are common in Type I OI.
Biconcave vertebral bodies(fish vertebrae)
Source: Net.-Above
Source: Imaging rheumatology-David
Silence type I to IV
Type-I: 70% of total case, bone density reduced 60% of normal, mild short stature & variable bone fragility. Fracture rates in childhood diminish with increasing skeletal maturity only to increase again in middle life, particularly in postmenopausal women. Indeed, the fracture rate in patients is approximately seven times that of the general postmenopausal population.
Type-II:
This is the most severe form of osteogenesis imperfecta, lethal in utero or the perinatal period.
Along with thanatophoric dysplasia, it is the most common form of short-limbed lethal dwarfism.
The infant is disproportionately short with deformed limbs. The skull is deformed and soft with deep grey-blue sclerae.
The diagnosis can be confirmed by whole-body radiography, which distinguishes it from other forms of lethal short-limbed dwarfism.
Mineralization of the skull is grossly defective and there are multiple fractures.
Other complications include brain and spinal cord injury. Radiologically, multiple fractures are present with a characteristic ‘concertina’ deformity of the lower limbs.
The ribs may appear ‘beaded’ due to multiple rib fractures, which can occur in utero. The cranial vault is severely under-mineralized and may be distorted by moulding, with Wormian bones in the occipital and parietal region.
Type II(lethal perinatal)
Platyspondyly is present. Histology reveals defective endochondral ossification at the epiphyses, which appear disorganized with persistent islands of calcified cartilage and under-mineralized bone. There is defective transformation of woven bone to lamellar bone in both the cortical and trabecular skeletal components. Formation of membrane bone is also deficient, accounting for the marked calvarial thinning.
Type III :
This type is associated with severe fracture tendency, severe short stature, and progressive deformity and disability.
Phenotypically, there is a small degree of overlap with type II OI.
Multiple fractures at birth are typical and deformity affects the bones of the skull, the limbs, the spine, chest, and pelvis (Fig. 22.4).
In the long limb bones, cartilage islands can spread from the epiphyses across the growth plate into the metaphysis and diaphysis giving the appearance of popcorn bone (Fig. 22.5).
Severe kyphoscoliosis may develop and early death from respiratory infections is common. The sclerae are often blue in infancy but may become normal later in childhood
Type IV:
This is intermediate in severity between types I and III OI.
Stature is reduced (often <5th percentile) and a degree of bone deformity is usually present, although this is variable in severity.
The sclerae are typically of normal hue after infancy. This variant is most likely to be caused by mutations in COL1A2.
Hyperplastic callus may develop after fracture or corrective surgery for deformity mimicking sarcomatous change.
Child abuse is differentail diagnosis of OI. In child abuse metaphyseal corner fracture is common. The sclera and teeth are normal in many patients with OI. A family history is often not present. Keys to distinguishing OI from child abuse if no other stigmata of OI are present include the following points:
The type of fracture is of diagnostic significance; although any type of long bone fracture can occur in OI, certain types are rare; metaphyseal corner fractures, which are common in child abuse, are rare in OI
Source: Sutton-1125
Source: Imaging rheumatology-Davd
Source: Paediagric imaging manual-143
Source: Net.-Above
Source: Imaging rheumatology-David
Silence type I to IV
Type-I: 70% of total case, bone density reduced 60% of normal, mild short stature & variable bone fragility. Fracture rates in childhood diminish with increasing skeletal maturity only to increase again in middle life, particularly in postmenopausal women. Indeed, the fracture rate in patients is approximately seven times that of the general postmenopausal population.
Type-II:
This is the most severe form of osteogenesis imperfecta, lethal in utero or the perinatal period.
Along with thanatophoric dysplasia, it is the most common form of short-limbed lethal dwarfism.
The infant is disproportionately short with deformed limbs. The skull is deformed and soft with deep grey-blue sclerae.
The diagnosis can be confirmed by whole-body radiography, which distinguishes it from other forms of lethal short-limbed dwarfism.
Mineralization of the skull is grossly defective and there are multiple fractures.
Type III :
This type is associated with severe fracture tendency, severe short stature, and progressive deformity and disability.
Phenotypically, there is a small degree of overlap with type II OI.
Multiple fractures at birth are typical and deformity affects the bones of the skull, the limbs, the spine, chest, and pelvis (Fig. 22.4).
In the long limb bones, cartilage islands can spread from the epiphyses across the growth plate into the metaphysis and diaphysis giving the appearance of popcorn bone (Fig. 22.5).
Severe kyphoscoliosis may develop and early death from respiratory infections is common. The sclerae are often blue in infancy but may become normal later in childhood.
Type III (severe progressive)
Affected patients tend to be wheelchair bound because of the progressive deformities resulting from fractures. Complications include progressive pulmonary insufficiency through distortion of the thorax. Radiologically, the bones may be slender or broad due to recurrent fractures. Epiphyses are abnormal, with expansion and islands of calcified (‘popcorn’) cartilage[73]. As with other forms of osteogenesis imperfecta, the incidence of fracture declines following puberty.
Type III (severe progressive)
This is inherited as an autosomal recessive trait.
Fractures are usually present at birth and involve the long bones, clavicles, ribs and cranium, leading to deformity.
Although size at birth is normal, growth retardation is evident in the first year of life and many affected patients only reach 0.9–1.2 m (3–4ft) in height. As growth proceeds, increasing deformity of the calvaria occurs, with associated facial distortion, malocclusion and mild prognathism, basilar invagination, and progressive hearing loss. Sclerae are blue at birth, but this diminishes with age, and sclerae are white in adults. Vertebral fractures occur at an early age and contribute to the progressive and severe kyphoscoliosis which develops during childhood.
Type IV:
This is intermediate in severity between types I and III OI.
Stature is reduced (often <5th percentile) and a degree of bone deformity is usually present, although this is variable in severity.
The sclerae are typically of normal hue after infancy. This variant is most likely to be caused by mutations in COL1A2.
Hyperplastic callus may develop after fracture or corrective surgery for deformity mimicking sarcomatous change.
Fetuses with the lethal autosomal recessive form of osteogenesis imperfecta, OI type II, lack skull ossification and demonstrate multiple angulated long bone fractures.
Source: Net.-Above
Source: Imaging rheumatology-David
Silence type I to IV
Type-I: 70% of total case, bone density reduced 60% of normal, mild short stature & variable bone fragility. Fracture rates in childhood diminish with increasing skeletal maturity only to increase again in middle life, particularly in postmenopausal women. Indeed, the fracture rate in patients is approximately seven times that of the general postmenopausal population.
Type-II:
This is the most severe form of osteogenesis imperfecta, lethal in utero or the perinatal period.
Along with thanatophoric dysplasia, it is the most common form of short-limbed lethal dwarfism.
The infant is disproportionately short with deformed limbs. The skull is deformed and soft with deep grey-blue sclerae.
The diagnosis can be confirmed by whole-body radiography, which distinguishes it from other forms of lethal short-limbed dwarfism.
Mineralization of the skull is grossly defective and there are multiple fractures.
Type III :
This type is associated with severe fracture tendency, severe short stature, and progressive deformity and disability.
Phenotypically, there is a small degree of overlap with type II OI.
Multiple fractures at birth are typical and deformity affects the bones of the skull, the limbs, the spine, chest, and pelvis (Fig. 22.4).
In the long limb bones, cartilage islands can spread from the epiphyses across the growth plate into the metaphysis and diaphysis giving the appearance of popcorn bone (Fig. 22.5).
Severe kyphoscoliosis may develop and early death from respiratory infections is common. The sclerae are often blue in infancy but may become normal later in childhood
Type IV:
This is intermediate in severity between types I and III OI.
Stature is reduced (often <5th percentile) and a degree of bone deformity is usually present, although this is variable in severity.
The sclerae are typically of normal hue after infancy. This variant is most likely to be caused by mutations in COL1A2.
Hyperplastic callus may develop after fracture or corrective surgery for deformity mimicking sarcomatous change.
Type IV (moderately severe)
This is inherited as an autosomal dominant trait and can vary in severity.
It is sometimes confused with either type I or type III. There is generally more severe osteopenia and more extensive bone deformity than in type I.
The sclerae are blue in children, and although this may persist into adulthood, they may also fade to white.
Individuals are short in stature, with abnormal moulding of the calvaria and basilar invagination in a high proportion of patients.
Bones in the axial and appendicular skeleton are osteoporotic and dysplastic, resulting in scoliosis and deformity, particularly of the pelvis. Joint laxity can result in dislocation, particularly of the ankle or knee.
Source: Greinger’s
SourcePaediatric imaging manual-143)
Fracture I-10% (Premature arcus senility, Mild short stature, easy brusibility) II-100% (Short trunk, lethal perinatal, Connective tissue fragility short angulated limb), III-50% (Limb shortening, frontal boosing, Pulmonary HTN, Triangular facies) , IV-Rarely, usually in infacncy(Mild angulation, shortening, No bleeding diathesis).
Site of Type I collagen: Bones, Dentin, Sclera, Dermis, Tendon.
Rumak:
Osteogenesis Imperfecta Types I, III, IV—Nonlethal Types Osteogenesis imperfecta type I is a mild, “tarda’’ variant inherited in an autosomal dominant manner as a result of mutation in the COL1A1 (on chromosome 17) or COL1A2 (on chromosome 7) and possibly in other collagen genes.
OI type I is a generalized connective tissue disorder characterized by bone fragility and blue sclerae. The bones are of normal length, and only 5% present at birth with fractures. Most fractures occur from childhood to puberty. There is progressive hearing loss in approximately 50% of type I cases.
Type III has a heterogeneous mode of inheritance. This is a nonlethal, progressively deforming variety of OI that often spares the humeri, vertebrae, and pelvis. Rib involvement is variable. The blue sclerae will normalize, and there is no associated hearing impairment. Protrusio acetabuli may be seen in type III OI.
Type IV is an autosomal dominant form of OI. It is the mildest form, involving isolated fractures. The sclerae are blue at birth but normalize over time. There is no associated hearing impairment.
Net. Osteogenesis imperfecta (OI and sometimes known as brittle bone disease, or "Lobstein syndrome"
classification of osteogenesis imperfecta: - note that there is a wide variety in the OI phenotype, but all share in osseous fragility and propensity for fracture; - diff dx: - juvenile osteoporosis - rickets - battered child syndrome - leukemia; - abundant frx callus may be mistaken for osteosarcoma;
Causes of Type-2 collagen disease:
Achondrogenesis.
Hypochondrogenesis.
Spondyloepiphyseal dysplasia congenita.
Net.
Net.
Net.
Source: The most reliable sonographic sign of demineralization is increased compressibility of the calvarium.
This finding is typically present in osteogenesis imperfecta type II, achondrogenesis, and hypophosphatasia.
Platyspondyly: congenital flattening of the vertebral bodies.
Greinger-
Senile osteoporosis: Fracture usually occurs at neck of femur, vertebrae, distal radius, kyphosis may be present.
Source: Board review-611
Perkins’ line is a vertical line from the lateral edge of the acetabulum to Hilgenreiner’s line– the femoral epiphysis should lie medial to this line.
Hilgenreiner’s line is a horizontal line passing through the triradiate cartilage (superolateral margin) – the femoral head should lie below this.
Acetabular index/angle(slop of acetabular roof):Angle that lies in between Hilgrenreiner’s line & a line drawn from most superolateral ossified edge of acetabulum to superolateral margin of triradiate cartilage. It should be less than 30 degrees. It is more 30 degree strongly suggests dysplasia
Van Rosen’s line is drawn up the femoral shafts, with the hips abducted at 45 degrees, and this should point into the acetabulum.
Shenton’s curved line: It is formed by the inferior surface of superior pubic ramus(top of obturator foramen) medial surface of proximal mwtaphysis to the level of lesser trochanter. Disruption of the line DDx-Coxa valga.
Central edge angle of wiberg: Angle subtended by one line drawn from acetabular edge to centre of femoral head+ second line perpendicular to the line connecting centres of femoral heads. Less than 25 degree suggests femoral instability.
According to AKD: Angle between neck & shaft-125 degree in adult & 160 degree in childreen. Forward tilt of head & neck 15 degree in adult & 35 degree in newborn.
Ossification of triradiate cartilage-Starts at 12 years and completes at 20years.
Ossification of HIP bone: Primary OC: 3 {(1 for ileum, 1 for ischium, 1 for pubis) ossifying ishium & pubis fuses at 7-8years} Secondary OC: 5 2 for ilac crest, 2 for acetabulum, 1 for anterior superior iliac spine.
Ossification centre for femur:
Primary OC: 1 for shaft (starts at 7week of IUL) .
Secondary OC: 4 (1 for head-6 months of age, 1 for greater trochanter-4 years of age, 1 for lesser trochanter-12 to 14 years of age
and 1 for lower end of femur-9 months of age).
Epiphysis derived from secondary ossification centres fuses with diaphysis after puberty (head fuses in female at 14 year & in male 17 year,
distal end in female 16 year and in male 18 year, Lesser trochanter fuses soon after puberty and greater trochanter fuses after lessser
trochanter)