Osteogenisis Imperfecta (Oi)- Essay, Research Paper

Osteogenisis Imperfecta (OI)-

DEFINITION

Osteogenisis 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. Osteogenisis

imperfecta is still not completely understood, and while

there have been advances in diagnosing the disease,

treatment is still limited.

CAUSES

Osteogenisis 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)

SIGNS AND SYMPTOMS

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 a 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 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 are

found in 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 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.

DIAGNOSIS

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

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 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.

TREATMENTS

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 opthalmol-

ogists 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 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 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)

RECENT RESEARCH

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 were 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 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 part-

ially 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

strengthing 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

experi-

ence 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)

STATISTICAL DATA

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)

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:

754-756.

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.

Smith, et al. The Brittle Bone Syndrome London:

Butterworths, 1983.