(BRITTLE BONE DISEASE)

 Definition:
◦ Osteogenesis imperfecta is a group of
phenotypically related disorders that are caused by
deficiencies in the synthesis of type 1 collagen.

 Hereditary mechanical insufficiency of bone,

ligament structures, sclera, and dentin
◦ prominent skeletal manifestations
◦ other anatomic structures rich in type I collagen
 joints, eyes, ears, skin, and teeth
 Mutations in the genes that code for the α1 and α2
chains of the collagen molecule

 Autosomal dominant

 2 Phenotypes
◦ Decreased amount of qualitatively
normal collagen -mild skeletal abnormalities.
◦ Abnormal polypeptide chains that cannot assemble
into a triple helix configuration - More severe or
lethal phenotypes
 Basic abnormality
◦ Too little bone, resulting in a type of osteoporosis
with marked cortical thinning and attenuation of
trabeculae
 Endochondral ossification- Normal
  Osteoid formation
  Periosteal bone formation
 Medullary contents- fatty & fibrous
 Deformities- due to fractures and bending
 Frail cancellous trabeculae
surrounded by persisting
cartilage tissue( D1) and
uncalcified osteoid (D2).

 fails to develop into stable

lamellar bone
 Four types

 Types I and IV
◦ more mild manifestations of disease
◦ persist into adulthood

 Types II and III

◦ more severe
◦ fracture in utero, during birth, or in early childhood
◦ high mortality rate
 Subtype Inheritan Collagen Defect Major Clinical Features
ce

OI I Postnatal AD Decreased synthesis Compatible with survival

fractures, pro-α1(1) chain
blue
sclerae Abnormal pro-α1(1) Normal stature
or pro-α2(1) chains Skeletal fragility
Dentinogenesis
imperfecta
Hearing impairment
Joint laxity
Blue sclerae
OI II Perinatal Most AR Abnormally short Death in utero or within
lethal pro-α1(1) chain days of birth

Some AD Unstable triple helix Skeletal deformity with

excessive fragility and
multiple fractures
?New Abnormal or Blue sclerae
insufficient pro-
α2(1)
 Subtype Inherita Collagen Defect Major Clinical Features
nce

OI III Progressive AD(75%) Altered structure Compatible with survival

deforming of pro-peptides
of pro-α2(1)

AR(25%) Impaired Growth retardation

formation of Multiple fractures
triple helix Progressive kyphoscoliosis
Blue sclerae at birth that
become white
Hearing impairment
Dentinogenesis imperfecta

OI IV Postnatal AD Short pro-α2(1) Compatible with survival

fractures, chain
normal Unstable triple Moderate skeletal fragility
sclerae helix Short stature
Sometimes dentinogenesis
imperfecta
 Most common.
 Acquired mutation
 People who have type 1 disease generally
reach normal height and have few obvious
skeletal deformities.
 Typically causes more fractures during
childhood than in adulthood
 Hearing loss is pronounced and begins early
in childhood
 Most rare and the most
severe
 Produces numerous
deformities of the skeleton
 Often fatal in infancy.
 Abnormal collagen
formation also profoundly
affects the lungs, causing
significant breathing
problems
Skeletal radiograph of a fetus with lethal
type II OI.
Numerous fractures, resulting in accordion-
like shortening of the limbs
 More severe than type 1 but less severe than
type 3.
 Fractures - most common before puberty.
 Hearing loss begins in early childhood and
often profound
 Produces obvious skeletal
deformities
 Fractures before birth are
common
 Also affects the lungs and
muscles
 Hearing loss begins in
early childhood and often
becomes complete by
adolescence.
 Osteoporosis
 Multiple fractures
 Bone deformity
 Poor skeletal development
◦ Dwarfing
◦ Broad skull
 Dental imperfections
(small, misshapen, and blue-
yellow teeth)
 Hearing loss
 Blue sclera
 Laxity of joints (hypermobility)
and flat feet
 Skin vulnerability
 Bowed legs and arms
 Kyphosis
 Scoliosis (S-curve spine)

 The most numerous fractures occur during

childhood when the bones are growing and thus
have lower mineral content.

 The risk for fracture is lifelong, however, and

may increase in women after menopause when
bone density naturally declines
 Hearing loss (common in type I and type III)
 Heart failure (type II)
 Respiratory problems and pneumonias due to
chest wall deformities
 Spinal cord or brain stem problems
 Permanent deformity
◦ Osteoporotic
◦ Thin cortex with bulbous ends
 Reassurance
 Protection from and prevention of injuries
 Vitamin D supplementation
 Multiple osteotomies
 Type I (mild OI)-normal lifespan.
 Type II (severe form) -death in 1st year of life
 Type III - wheelchair bound & shortened life
expectancy
 Type IV (moderately severe OI)- similar to
type I, braces or crutches to walk