FREE ESSAY ON OSTEOGENESIS IMPERFECTA

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, laxity in the ligaments, and spinal deformities.(Binder,
386). Other collagen-containing skeletal 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 has been advances in diagnosing the disease,
treatment is still limited.
Osteogenesis imperfecta is the result of mutations in the genes that code 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 dramatic outcomes of similar glycine mutations in either the alpha 1 (I)
or the alpha 2(I) chains (Smith, 169).
The clinical signs can be caused from defective osteoblastic activity and defective
mesenchymal collagen (embryonic connective tissue) and its derivatives, such as sclerae,
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 worm like 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 karyotypes 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 death is usually from intracranial hemorrhaging 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 is 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 occurs leading to progressive and severe deformities.
Kyphoscoliosis (curvature of the spine) 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 (types I, III, and IV) can appear when the child begins to walk, and
decreases with age. The tendency of bone 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 increases the number of 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 almost translucent skin. Discolored (blue-gray or yellow-brown) and
malformed teeth which break easily and are cavity prone are found in most patients.
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 due
to the deformity of its canal in the skull. 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
noteworthy. 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 and
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 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 inserting 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 a
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 opthalmol-
ogists for vision and audiologists 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 is 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 sponsor 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 osteogenesis 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, 386-387).
Group A patients were the most severely involved. Most were basically sitters. The
majority was 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 of these groups all included posture exercises and active
range of motion and strengthening exercises. Group B had additional ROM and posture
exercises, as well as developmental exercises. Group C added coordination activities
(Binder, 388).
Conclusion, 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
mineralization. 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). 
Bibliography
1. Anderson, Kenneth N., 1994. Mosby's Medical, Nursing and Allied Health- 4th 
Edition (St. Louis: Mosby) pp. 112.
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Obstetricia et Gynecologica Scandinavica: v. 4. n. 72. 1994. Pp. 1-323.
3. Binder, Helga, MD, et al. Rehabilitation Approaches to Children With Osteogenesis
Imperfecta: A Ten-Year Experience Arch Phys Med Rehabil: v. 74. 1993. Pp. 386-390.
4. Isselbacher, et al. 1994. Harrison's Principles of Internal Medicine (New York: McGraw
Hill, 1994) pp. 2111-2113.
5. 5. Jackson, Debra B., and Saunders, Rebecca B. Child Health Nursing (Philadelphia:
J.B. Lippincott, 1993) pp. 1696-1699.
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Living: v. 72. 1992. Pp. 50-53.
7. Loeb, Stanley. 1993. Diseases (Bethelehem: Springhouse) pp. 754-756.
7. Paterson, Collin R. Clinical Variability and Life Expectancy in Osteogenesis 
Imperfecta Clinical Rhumatology: v. 14. 1995. Pg. 228.
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10. Smith, Roger. 1983. The Brittle Bone Syndrome (London: Butterworths) pp. 357.