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Osteogenesis Imperfecta


Osteogenesis imperfecta (OI) is "a rare genetic disorder of
collagen synthesis associated with broad spectrum of
musculoskeletal problems, most notably bowing and fractures
of the extremities, muscle weakness, ligamentous laxity,
and spinal deformities." (Binder, 386). Other
collagen-containing extraskeletal tissues, such as the
sclerae, the teeth, and the heart valves are also affected
to a variable degree. OI has a "common feature of bony
fragility associated with defective formation of collagen
by osteoblasts and fibroblasts." (Smith, 1983, 13) This
disease, involving defective development of the connective
tissues, is usually the result of the autosomal dominant
gene, but can also be the result of the autosomal recessive
gene. Spontaneous mutations are common and the clinical
presentation of the disease remains to be quite broad.
(Binder, 386) 

OI is most commonly referred to as "brittle bones", but
other names include: fragilitas ossium, hypolasia of the
mesenchyme, and osteopsathyrosis. Osteogenesis imperfecta
is still not completely understood, and while there have
been advances in diagnosing the disease, treatment is still
Osteogenesis imperfecta is the result of mutations in the
genes for type I collagen. In the mild dominantly inherited
form of OI (type I), " a non-functional allele for the
alpha 1 (I) chain halves collagen synthesis," (Smith, 1995,
169) and is largely responsible for the inheritance. Single
base mutations in the codon for glycine causes lethal (type
II) OI by wrecking the formation of the collagen triple
helix. Types III and IV are the "less dram- atic outcomes
of similar glycine mutations in either the alpha 1 (I) or
the alpha 2(I) chains.(Smith, 1995, 169)
The clinical signs can be caused from defective
osteoblastic activity and defective mesenchymal collagen
(embryonic connective tissue) and its derivatives, such as
sclera, bones, and ligaments. The reticulum fails to
differentiate into mature collagen or the collagen develops
abnormally. This causes immature and coarse bone formation
and thinning. (Loeb, 755)
The signs and symptoms of OI vary greatly depending on the
type. The most commonly used classification is the Sillence
(type I to IV):
Type I is the mildest form of OI and is inherited as an
autosomal dominant trait. The sclerae(middle coat of
eyeball) is distinctly blue. Type I is broken down into IA
and IB -- the difference being whether dentinogenesis is
present. IA has a life expectancy nearly the same as the
general public. The physical activity is limited, and may
appear to have no disability at all. The bones have a
mottled or wormian appearance, forming small islands.
(Isselbacher, 2111)
Type II is lethal in utero or shortly there afterbirth. The
survivors live from just a few hours to several months. The
kayotypes of parents are usually normal. This type is
broken down into three subgroups: IIA is characterized by a
broad, crumpled femora and continuos rib beading, IIB by
minimal to no rib fractures, and IIC by a thin femora and
ribs with extensive fracturing. While in the uterus, there
is poor fetal movement, low fetal weight, poor ossification
of the fetal skeleton, hypoplastic lungs, the long bones of
the upper and lower limbs are shortened or deformed, and
the head is soft. Intrauterine fractures occur, and
parinatal death is usually from intracranial hemorrhage due
to vessel fragility or respiratory distress from pulmonary
hypoplasia. The bones and other tissues are extremely
fragile, and massive injuries occur in utero or delivery.
The ribs appear beaded or broken and the long bones
crumpled. (Isselbacher, 2111)
Type III and IV are intermediate in severity between types
I and II. Type III differs from I in its greater severity,
and from IV in that it increases in severity with age. It
can be inherited as either an autosomal recessive or
dominant trait. The sclerae is only slightly bluish in
infancy and white in adulthood, although the average life
expectancy is 25 years. Type IV is always dominant. With
types III and IV, multiple fractures from minor physical
stress occur leading to progressive and severe deformities.
Kyphoscoliosis may cause respiratory impairment and
predisposition to pulmonary infections. "Popcorn-like"
deposits of mineral appear on the ends of long bones.
(Isselbacher, 2111) 

The symptoms of OI tarde (types I, III and IV) can appear
when the child begins to walk, and lessens with age. The
tendency to fracture decreases and often disappears after
puberty. Later in life, particularly during pregnancy and
after menopause, more fractures occur. The bones are
usually slender with short, thin cortices and trabeculae
(fibers of framework), but can also be unusually thin.
(Smith, 1983, 136) Narrow diaphysis of the long bones
contributes to the fractures and bowing deformities.
Scoliosis is common. The haversian cells are poorly
developed. The bones lack minerals needed to form bone
matrix. Epiphyseal fractures (end of the bone) results in
deformities and stunted growth (dwarfism). Osteopenia, the
decrease in bone mass, is symptomatic.
Other signs of OI include hyperextensibility of the joints
-- double-jointedness-- and abnormally thin, translucent
skin. Discolored (blue-gray or yellow-brown) and malformed
teeth which break easily and are cavity prone. Patients
with OI have a triangular-shaped head and face, a
bilaterally bulging skull, and prominent eyes with a wide
distance between the temporal region. (Loeb, 755)
Hearing loss by the age of 30-40 is the result of the
pressure on the auditory nerve because of the deformity of
its canal in the skull, and the development of
otosclerosis. Recurrent epistaxis (nosebleeds), bruising
and edema (especially at the sight of fractures),
difficulty tolerating high temperatures and mild
hyperpyrexia are other symptoms. Thoracic deformities may
impair chest expansion and the ability to effectively
breath deeply and cough. (Loeb, 755) Patients are also more
susceptible to infection.
In assessing a patient, data is needed about the genetic
history and birth of the child, as well as a complete
development assessment from birth. Vital signs are taken,
and periods of increased heart and respiratory rate and
elevated body temperature are note-worthy. Skin should be
examined for color, elasticity, translucency, and signs of
edema and bruising. A description of position and
appearance of a child's trunk, extremities, and facial
characteristics should be noted. The height of the child in
terms of expected growth, signs of scoliosis or laxity of
ligaments, and range of motion of the joints are all
important. Sight and hearing should be tested since there
are sensory problems associated with OI. The appearance of
the sclerae and tympanic membranes and defects of primary
teeth and gums are important. (Jackson, 1699) 

X-rays usually reveal a decrease in bone density. "There is
no consensus, however, as to whether the diagnosis can be
made by microscopy of bone specimens." (Isselbacher, 2112)
DNA sequencing and incubating skin fiboblasts are two ways
help diagnose OI.
Prenatal ultrasonography is used to detect severely
affected fetuses at about 16 weeks of pregnancy. Diagnosis
of the lethal type II by ultrasound during the second
trimester of pregnancy is by the identification of
fractures of the long bones. Compression of the fetal head
is seen by ultrasound probe, and low echogeneity of the
cranium can be signs of skeletal dysplasia (faulty
development of the tissues). Diagnosis is confirmed by
postmortem examination including radiography and
biochemical studies of cultivated fibroblasts from the
fetus. (Berge, 321) Diagnosis by analyzing DNA sequencing
can be carried out in chronic villa biopsies at 8-12 weeks. 


There is no known treatment of OI at this time. Treatment
therefore is predominantly supportive and educational.
Because of multiple fractures and bruising, it is important
to diagnose this disease in order to prevent accusations of
child abuse. 

Treatment of fractures is often challenging because of
abnormal bone structure and laxity of the ligaments.
Splinting devices are used to stabilize the bones and to
protect against additional fractures. Treatment aims to
prevent deformities through use of traction and/or
immobilization in order to aid in normal development and
rehabilitation. Limb deformities and repeated fractures can
be corrected by intramedullary rods -- telescoping rods
that elongate with growth. After surgical placement of the
rods, extensive post- operative care is required because
greater amounts of blood and fluid are lost. (Loeb, 755) It
should be noted that the healing of fractures appear to be
normal. (Isselbacher, 2112) Braces, immobilizing devices
and wheelchairs are necessary.
Physical therapy is important in the treatment of OI. Bone
fracture density in unfractured bone is decreased when
compared with age-matched controls due to limited exercise,
so it is essential to stay as active as possible. Physical
therapy is also used for strengthening muscle and
preventing disuse fractures with exercises with light
resistance, such as swimming.
Regular dental visits are necessary to monitor the teeth.
Monitoring by opthalmologists for vision and audiologits
for hearing is also essential. Radiologists need to examine
the structure and density of the bones, and an orthopedist
is needed to set fractures and take care of other bone
related problems. 

Counseling and emotional support is needed for both the
patient and the family. It is important not to limit a
child because of his/her disabilities, and to realize that
many victims of this disease live successful lives. Debrah
Morris, a successful business woman, and active fighter for
disability rights and helping other patients of OI, says,
"If I had the choice to be anyone in the world, I would be
exactly who I am. The people I have met, the challenges I
have faced, the opportunities that I have been presented --
all are directly related to dealing with being a little
person with brittle bones." (Kasper, 53) 

Many of the symptoms of OI can be confused with those of a
battered child. X-rays are used to show evidence of old
fractures and bone deformities to distinguish the
difference. The Osteogenesis Imperfecta Foundation (OIF)
has a national support group that offers assistance to
families in this position and to increase public awareness.
The OIF has a medical advisory council, chapters, support
groups, regional meetings, biennial national conferences,
and parent contacts to help families feeling alone and
helpless. They also publish a newsletter, provide
literature and videos about OI, and sponsors a fund to
support research. 

Magnesium oxide can be administered to decrease the
fracture rate, as well as hyperpyrexia and constipation
associated with this condition. (Anderson, 1127) A
high-protein, high-carbohydrate, high-vitamin diet is
needed to promote healing. A growth hormone has also been
administered during childhood, and is shown to
substantially increase growth. Treatment with
bisphosphorates and related agents has been discussed to
decrease bone loss, but no controlled studies have been
done. (Isselbacher, 2113)
Since there is no cure for Oseogenesis Imperfecta,
appropriate and properly timed rehabilitation intervention
is of the utmost importance to ensure that the child is
able to function to the best of his/her ability in society.
A ten year study that was submitted in 1992 proves this.
25 of 115 children with severe OI were observed since birth
or infancy at the National Institutes of Health, MD and the
Skeletal Dysplasia Clinic at the Children's National
Medical Center in D.C. One was Type I, two Type II, nine
Type III, and thirteen Type IV. They were classified by
physical characteristics and functional capacity:
Group A consisted of those who were severely dwarfed with
large heads and marked bowing , contractures, and weakness
of extremities. The highest functional skill expected was
independent sitting. Group B was growth deficient, but with
a normal sized head. Femoral bowing, scoliosis, and
contractures of the hip flexors were characteristics; they
were expected to stand and/or ambulate with braces. Group C
was less growth deficient, and had good strength, but poor
endurance. They had marked joint laxity and poorly aligned
lower extremity joints, but were ambulators. (Binder,
Group A patients were the most severely involved and most
were basically sitters. The majority were totally dependent
in their self care. Group B had the potential to become at
least short-distance ambulators. These patients had
acquired the ability to move to sitting, but had
transitional moving problems, such as sitting to standing.
All were partially independent in their self care. Group C
had antigravity strength and 50% had good strength in their
extremities. All were physically active and
age-appropriately independent, but none were good
long-distance walkers. (Binder, 387-388)
Progressive rehabilitation for all these groups included
posture exercises and active range of motion and
strengthing exercises. Group B had additional ROM and
posture exercises, as well as Developmental exercises.
Group C added coordination activities. (Binder, 388)
"Management of patients with OI should address the child's
functional needs. Even though the degree of disability may
be severe, management should not be limited to orthopedic
procedures and bracing. Treatment planning should be
considered, but not totally based on genetic, anatomical,
and biochemical abnormalities. Our experience suggests that
clinical grouping based in part on functional potential can
be useful in the appropriate management of children with
OI."(Binder, 390) Independence was stressed in this study,
and even patients with limited sitting ability, upper
extremity function can be improved to at least minimal
independence in self-help skills. Potential ambulators
should be helped because, although their ability might not
progress past indoor ambulation, walking will make them
more independent and may result in increased bone

Poor joint alignment, poor balance, and low endurance can
all be improved with persistent, individualized physical
and occupational therapy. For best results, therapy should
be started as soon after birth as possible. Mainstreaming
school aged children is also important. All of this
together leads to "age-appropriate social development and
markedly improved independence and quality of life in the
majority of patients."(Binder, 390)
Osteogenesis Imperfecta is the most common genetic disorder
of the bone. It occurs in about 1 in 20,000 live births,
and is equally prevalent in all races and both sexes. The
Type I OI has a population frequency of about 1 in 30,000.
Type II has a birth incidence of about 1 in 60,000. Types
III and IV are less common and may be as high as 1 in
20,000. (Isselbacher, 2111) The occurrence of OI in
families with no history or blue sclerae is about 1 in
3,000,000 births.(Smith, 1995, 171) The recurrence risks in
families is estimated to be 6 to 10%, but is only estimated
because most couples choose not to have any more children.
15 to 20% of patients with OI do not carry the gene for
abnormal collagen, making many wonder if there is yet
another genetic problem undiagnosed at this time.(Smith,
1995, 172) 
Works Cited:
 Anderson, Kenneth N., ed. Mosby's Medical, Nursing and
Allied Health -- 4th Edition. St. Louis: Mosby, 1994: 112. 
Berge, L.N., et al. "Prenatal Diagnosis of Osteogenesis
Imperfecta" Acta Obstetricia et Gynecologica Scandinavica
4.74 (1995): 321-323.
Binder, Helga, MD, et al. "Rehabilitation Approaches to
Children With Osteogenesis Imperfecta: A Ten-Year
Experience" Arch Phys Med Rehabil 74 (1993): 386-390.
Isselbacher, et al. Harrison's Principles of Internal
Medicine New York: McGraw Hill, 1994: 2111-2113.
Jackson, Debra B., and Saunders, Rebecca B. Child Health
Nursing Philadelphia: J.B. Lippincott, 1993: 1696-1699.
Kasper, Rosemarie. "Osteogenesis Imperfecta: Brittle Bones,
Sturdy Spirit" Independent Living 7 (1992): 50-53.
Loeb, Stanley. Diseases Bethelehem: Springhouse, 1993:
Paterson, Collin R. "Clinical Variability and Life
Expectancy in Osteogenesis Imperfecta" Clinical Rhumatology
14.2 (1995): 228.
Slagboom, P.E. "Collagen Genes and Skeletal Disorders" The
Lancet 342 (1993): 1045-1046.
Smith, Roger. "Osteogenesis Imperfecta, Non-Accidental
Injury, and Temporary Brittle Bone Disease" Disease in
Childhood 72 (1995): 169-175.
Smith, et al. The Brittle Bone Syndrome London:
Butterworths, 1983.



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