OSTEOGENESIS

IMPERFECTA

INTRODUCTION

Osteogenesis Imperfecta (OI) is also known as Brittle Bone Syndrome, or “Lobstein Syndrome” which is a genetic
bone disorder characterized by bones that break easily, often from little or no apparent cause. A classification system
of different types of OI is commonly used to help describe how severely a person with OI is affected. For example, a
person may have just a few or as many as several hundred fractures in a lifetime.

LOCAL INCIDENCE

The prevalence is reported at 6-7 per 100,000. According to the data available from the Philippine Osteogenesis
Imperfecta Support Group, as of December 2014 there are 56 diagnosed patients in Luzon and 11 in the Visayas
area. Since there is an absence of a formal national registry for OI, the true prevalence in the Philippines may be
underestimated. Based on the database of the Section of Genetics, Department of Pediatrics at the University of the
Philippines-Philippine General Hospital (UP-PGH), there are 68 clinically diagnosed patients as of December 2014.

However, only 41 are on regular follow-up. Of these 41, 6 have OI type 1, 18 have type III, 11 have type IV, and 6
have type V. The definitive treatment for OI is gene therapy. Investigations are underway to the applicability of this
therapy in humans. Medications seek to address the osteopenia that is present in osteogenesis imperfecta patients.
The goal is to increase bone strength, either by increasing the amount of bone protein matrix or by increasing bone
mineralization via a reduction in bone remodeling.

OBJECTIVES

 Introduce Osteogenesis Imperfecta (OI)

 Describe the Pathophysiology of Osteogenesis Imperfecta
 Determine the clinical manifestations of Osteogenesis Imperfecta
 Identify complications of OI
 Determine treatment/s for OI
 Determine the Medical and Surgical management of OI

DEFINITION

OI is caused by genetic defects that affect the body’s ability to make strong bones. In dominant OI, a person has too
little type I collagen or a poor quality of type I collagen due to a mutation in one of the type I collagen genes.
Collagen is the major protein of the body’s connective tissue. It is part of the framework that bones are formed
around. In recessive OI, mutations in other genes interfere with collagen production. The result in all cases is fragile
bones that break easily. People with OI are born with defective connective tissue, or without the ability to make it,
usually because of a deficiency of type-1 collagen. This deficiency arises from an amino acid substitution of glycine
to bulkier amino acids in the collagen triple helix structure. The larger amino acid sidechains create steric hindrance
that creates a “bulge” in the collagen complex. As a result, the body may respond by hydrolyzing the improper
collagen structure. If the body does not destroy the improper collagen, the relationship between the collagen fibrils
and hydroxyapatite crystals to form bone is altered, causing brittleness. Severely affected patients suffer multiple
fractures with minimal or no trauma, and infants with the worst form of OI die in the perinatal period. Mild forms of
OI may manifest with only premature osteoporosis or severe postmenopausal bone mineral loss.

ETIOLOGY

In OI due to qualitative defects of type 1 collagen, autosomal dominant mutations are found on either the COL1A1
or the COL1A2 gene. The mutations result in the production of a mixture of normal and mutant collagen chains.
Substitution of a larger amino acid (e.g., cysteine or alanine) for glycine results in abnormal helix formation, but
these chains can combine with normal chains to produce type 1 collagen. The type 1 collagen thus formed is
functionally impaired because of the mutant chain; this is the so-called dominant negative mechanism.

RISK FACTORS

The greatest risk factor is heredity. If one parent has osteogenesis imperfecta, a child has a 50 percent chance of
having the condition. The most common forms of osteogenesis imperfecta are inherited and can usually be traced
through the family. Less common forms are passed to children through recessive inheritance.

CLINICAL MANIFESTATIONS

Several clinical manifestations were studied, and included: hearing loss, cardiac diseases, pregnancy complications,
cerebrovascular manifestations, musculoskeletal manifestations, respiratory manifestations, vision impairment.
Although the characteristic features of OI vary greatly from person to person, even among people with the same type
of OI, and even within the same family. Not all characteristics are evident in each case. The majority of cases of OI
(possibly 85%- 90%) are caused by a dominant mutation in a gene coding for type I collagen (types I, II, III, and IV
in the following list). Types VII and VIII are newly identified forms that are inherited in a recessive manner. The
genes causing these two types have been identified. Types V and VI do not have a type 1 collagen mutation, but the
genes causing them, has not yet been identified. The general features of each known type of OI are as follows:

Type I

•Most common and mildest type of OI.

•Bones fracture easily. Most fractures occur before puberty.

•Loose joints and muscle weakness.

•Sclera usually has a blue or gray tint.

•Triangular face.

•Tendency toward spinal curvature.

•Bone deformity absent or minimal.

•Brittle teeth possible.

•Hearing loss possible, often beginning in early 20’s or 30’s.

•Collagen structure is normal, but the amount is less than normal.

Type II

•Most severe form.

•Frequently lethal at or shortly after birth, often due to respiratory problems.

•Numerous fractures and severe bone deformity.

•Small stature with underdeveloped lungs.

•Tinted sclera.

•Collagen improperly formed.

Type III
•Bones fracture easily. Fractures often present at birth, and x-rays may reveal healed fractures that occurred before
birth.

•Short stature.

•Sclera have a blue or gray tint.

•Loose joints and poor muscle development in arms and legs.

•Barrel-shaped rib cage.

•Triangular face.

•Spinal curvature.

•Respiratory problems (possible).

•Bone deformity, often severe.

•Brittle teeth possible.

•Hearing loss possible.

•Collagen improperly formed.

Type IV

•Between type I and type III in severity.

•Bones fracture easily. Most fractures occur before puberty.

•Shorter than average stature.

•Normal color sclera.

•Mild to moderate bone deformity.

•Tendency toward spinal curvature.

•Barrel-shaped rib cage.

•Triangular face.

•Brittle teeth possible.

•Hearing loss possible.

•Collagen improperly formed.

By studying the appearance of OI bone under the microscope, investigators noticed that some people who are
clinically within the type IV group had a distinct pattern to their bone. when they reviewed the full medical history
of these people, they found that groups had other features in common. They named these group Types V and VI OI.
The mutations causing these forms of OI have not been identified, but people in these two groups do not have
mutations in the type I collagen genes.

Type V

•Clinically similar to Type IV in appearance and symptoms of OI.

•A dense band seen on x-rays adjacent to the growth plate of the long bones.

•Unusually large calluses (hypertrophic calluses) at the sites of fractures or surgical procedures. (A callus is an area
of new bone that is laid down at the fracture site as part of the healing process.)

•Calcification of the membrane between the radius and ulna (the bones of the forearm). This leads to restriction of
forearm rotation.

•White sclera.

•Normal teeth.

•Bone has a “mesh-like” appearance when viewed under the microscope.

•Dominant inheritance pattern

Type VI

•Clinically similar to type IV in appearance and symptoms of OI.

•The alkaline phosphatase (an enzyme linked to bone formation) activity level is slightly elevated in OI type VI.
This can be determined by a blood test.

•Bone has a distinctive “fish-scale” appearance when viewed under the microscope.

•Diagnosed by bone biopsy.

•Whether this form is inherited in a dominant or recessive manner is unknown, but researchers believe the mode of
inheritance is most likely recessive.

•Eight people with this type of OI have been identified.

•Recessive Forms of OI

After years of research, two forms of OI that are inherited in a recessive manner were discovered in 2006. Both
types are caused by genes that affect collagen formation. These forms provide information for people who have
severe or moderately severe OI but who do not have a primary collagen mutation.

Type VII

•The first described cases resemble type IV OI in many aspects of appearance and symptoms.

•In other instances, the appearance and symptoms are similar to type II lethal OI, except infants had white sclera, a
small head and a round face.

•Short stature.

•Short humerus (arm bone) and short femur (upper leg bone)

•Coxa vera is common (the acutely angled femur head affects the hip socket).

•Results from recessive inheritance of a mutation to the CRTAP (cartilage-associated protein) gene. Partial function
of CRTAP leads to moderate symptoms while total absence of CRTAP was lethal in all 4 identified cases.

Type VIII

•Resembles lethal type II or type III OI in appearance and symptoms except that infant have white sclera.
•Severe growth deficiency.

•Extreme skeletal under mineralization.

•Caused by a deficiency of P3H1 (Prolyl 3-hydroxylase 1) due to a mutation to the LEPRE1 gene.
 PATHOPHYSIOLOGY

Autosomal Dominant
Inheritance

abnormally formed collagen or

too little collagen

Abnormal Collagen Molecule

released
Decreased quantity of fibroblasts

OSTEOGENESIS
IMPERFECTA
Increased serum alkaline
phosphatase levels

Thin collagen fibers Poor healing Increased susceptibility to Improper Bone deformity in
fractures deposition of ears
dentine

Choroid layers is Multiple fractures Deformed Interference with

exposed Short Deformed
limbs sound transmission
Thin skin Stature cranial Abnormal
structure tooth and
Bluish
enamel
Sclera development
Middle ear
deafness
DIAGNOSTIC PROCEDURES

In addition to a complete medical history and physical examination, diagnostic procedures for OI may include a
skin biopsy to evaluate the amount and structure of collagen or molecular (DNA) tests. However, this test is
complicated and not many qualified facilities are available to perform the procedure. It is not unusual for results of
the biopsy to take up to six months.
Additional diagnostic tests may include:
 X-ray
 Radiography
 Examination of the ear, nose, and throat (to detect hearing loss)
 Bone mineral density, as measured with dual-energy x-ray absorptiometry (DEXA)
 Prenatal ultrasonography
 Biochemical (collagen) or molecular (DNA) tests

Medical Management
 BISPHOSPHONATES
Nitrogen-containing bisphosphonates
Administered to increase bone mass and reduces incidence of fracture
Proven efficacy in reducing fracture rates in children
 TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION
 PHYSICAL THERAPY

Surgical Management

 Internal Fixation (Intramedullary Rod Replacement)

To help strengthen long bones against fracture and prevent or correct deformities.
This involves implanting metal rods to run along the lengths of the bones. To help growing children, these
rods can be expanded to keep pace with developing bones.
 Casting, bracing, or splinting of fractures
 Surgery for basilar impression. This procedure is reserved for cases with neurologic deficiencies, especially
those caused by compression of brain stem.
 Correction of scoliosis. Correction of scoliosis may be difficult because of bone fragility, but spinal fusion
injury may be beneficial in patients with severe disease.

Nursing Diagnosis and Management

 Risk for injury related to fragile bones.

• Modify environment as indicated to enhance safety.
 R: to prevent possible injury
• Refer the client to a physical therapist for exercise routines
R: to prevent disuse atrophy of muscle and loss of bone mass
 Impaired dentition related to genetic predisposition
• Provide a mouth care routine
R: Cleaning of teeth with a toothbrush and fluoride-containing toothpaste prevents the build-up of
plaque.
• Instruct the patient to rinse the mouth thoroughly
R: These measures help promote oral hygiene.
• Educate patient about the importance of oral hygiene.
R: Right knowledge helps prevent possible dental problems.
• Instruct patient to obtain regular dental checkups and follow ups
R: Regular dental checkups identify dental problems early.
 Impaired physical mobility
• Assess the functional ability of the client.
R: To plan Proper intervention suitable for client condition.
• Provide assistance for active and passive ROM exercises.
R: To improve mobility and functions of joints and strengthen muscles and increase bone density.
• Teach the use of physical aids.
R: Physical aids help to maintain upright ambulation

Complications

 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

REFERENCES

Elsevier, 2013 1st edition Osteogenesis Imperfecta a Translational Approach to Brittle Bone Disease

Lydia D. Thomson-Smith (2012) Osteogenesis Imperfecta Genetic Bone Disorder

Lynda Juall Carpenito-Moyet 12th Edition Handbook of Nursing Diagnosis

John F. Beary, III, MD (2021) Osteogenesis imperfecta: Clinical features and diagnosis Retrieved from:
https://www.uptodate.com/contents/osteogenesis-imperfecta-clinical-features-and-diagnosis#H2
Neil K. Kaneshiro, MD, MHA (2021) Osteogenesis Imperfecta Retrieved from:
https://medlineplus.gov/ency/article/001573.htm

https://www.hopkinsmedicine.org/health/conditions-and-diseases/osteogenesis-imperfecta

https://oisupportphilippines.wordpress.com/about-osteogenesis-imperfecta-oi/

https://www.genome.gov/Genetic-Disorders/Osteogenesis-Imperfecta