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Osteogenesis Imperfecta

Taylor Wells

Introduction

Osteogenesis Imperfecta (OI) is an inherited disease that causes weak bones that break

easily. Osteogenesis Imperfecta can also cause other problems such as weak muscles, brittle

teeth, respiratory problems, and hearing loss (“What Is Osteogenesis Imperfecta? Fast Facts: An

Easy-to-Read Series of Publications for the Public”). There are four main types of OI, there are

other types, but they are very rare. About 90% of patients have mutations in type I collagen

genes, which are called COL1A1 and COL1A2, but many other genes have been found to play a

role. OI occurs equally among all genders and racial groups. It occurs in about 1 in 10,000-

20,000 live births (Shaker). About 20,000 to 50,000 people in the United States have

Osteogenesis Imperfecta (“What Is Osteogenesis Imperfecta? Fast Facts: An Easy-to-Read Series

of Publications for the Public”).

Normal Bone Anatomy and Physiology

Bone is composed of support cells called osteocytes and osteoblasts, remodeling cells

called osteoclasts, and a matrix of collagen with salts deposited in the matrix. During life, the

bones undergo a vast amount of growth, modeling, and remodeling. Ossification, or

osteogenesis, is the process of formation of new bone by cells called osteoblasts. “The

structure of bone is constituted by inorganic component, consisting of hydroxyapatite, and

organic component, constituted by collagen and noncollagen structural proteins which include

proteoglycans, sialoproteins, gla-containing proteins, and 2HS-glycoprotein” (Kini). Bone matrix

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is primarily composed of type I collagen and it is associated with the elasticity and flexibility of

the bone (van der Kamp).

Cause of OI and Resulting Anatomy and Physiology

The four main types of Osteogenesis Imperfecta are caused by mutations in type I

collagen. Type I collagen is a rod-like structure formed from 2 COL1A1 and 1 COL1A1 subunits,

which requires post-translational modification (Shaker). These changes cause a reduced

amount of type I collagen produced in the body, which is what causes the bones to be brittle

and break easily (Osteogenesis imperfecta).

Increased fracture risk in people with OI could be from a combination of reduced bone

mass, decreased bone material quality, and the presence of bone deformity, in some

individuals. Low bone mass is a clinical characteristic of OI, and individuals with this disorder

tend to have vastly reduced areal bone mineral density (BMD). The reduced bone mass could

be a consequence of decreased bone size, decreased BMD, or both. Studies have measured

bone material properties, including strength, by using surgical bone specimens from long bone

diaphyses of children with OI. Bone material strength was lower than normal in these children.

Along with the decreased bone mass and reduced bone material quality, bone deformities in

the spine and in long bones are common in Osteogenesis Imperfecta. Children with severe OI

often have anterolateral bowing of the femur and anterior bowing of the tibia. (Shaker).

Signs/Symptoms Related to the Different Types of OI

The most common signs and symptoms of Osteogenesis Imperfecta include: short/small

body, loose joints, muscle weakness, muscle and joint pain, sclerae that appear blue/gray,
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curved spine, brittle teeth, hearing loss often occurring in the 20s-30s, and bone fractures and

breaks. Type I OI is the mildest and most common form. Individuals have obvious signs of the

disorder, such as blue sclerae and muscle and joint pain. These individuals are often similar in

height to their family members. They have a handful of fractures in childhood and up to a few

dozen fractures in their life; dislocations and sprains may occur. People with type I OI have an

average life expectancy. Type II OI is the most severe form. Infants are born small and are

usually born with broken bones. Their limbs are small and their head may be large for the size

of their body. Almost all infants born with type II OI die at or shortly after birth, often due to

respiratory problems (“Facts About Osteogenesis Imperfecta”).

Type III OI is the most severe type that does not cause death. Those with type III are

born with fractures. Common signs are short stature, spinal curvature, and a barrel-shaped rib

cage. Someone with type III OI may have anywhere from several dozens to several hundred

fractures in their lifetime. Some people have severe, and sometimes fatal, respiratory problems

in infancy or childhood. Individuals may require supplemental oxygen. Some individuals pass

because of respiratory problems in adulthood due to progressive rib cage and spinal

deformities. Other people with type III OI will have a near-average life span. Type IV

Osteogenesis Imperfecta is a moderate type of OI. People with this form are somewhat shorter

than others in their family, have frequent fractures that may decrease after puberty, and have

mild to moderate bone deformity. Life expectancy appears to be average for these individuals

(“Facts About Osteogenesis Imperfecta”).

Diagnosis of OI
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No single test can identify and confirm that a person has Osteogenesis Imperfecta. A

variety of methods are used such as family and medical history, a physical exam, x-rays, blood

and urine tests, and ultrasounds. A physician, usually a geneticist, that is familiar with all types

of OI can diagnose the condition based on the presence of fractures and other clinical features.

Looking at the individual’s family history and use of genetic tests can confirm the diagnosis.

Additional blood and urine tests are done to rule out other disorders such as Hypophosphatasia

or Rickets (“Facts About Osteogenesis Imperfecta”). The more severe forms of OI can be

diagnosed before a baby is born. Ultrasounds can detect bowing, fractures, shortening of

bones, and other bone qualities. This can detect the presence of Osteogenesis Imperfecta, but

cannot differentiate which form the infant has.

Treatments of OI

The goal of treatment is to minimize fractures, enhance independent function, and

promote general health. Treatments may include fracture care, physical therapy, surgical

procedures, medications, life style changes, and mobility aides. Casting, splinting, and bracing

broken bones help them heal properly; but long periods of immobility can lead to muscle loss,

weakness, and can increase risk of fractures once the cast is removed. Surgery may be used to

repair a broken bone, stabilize the spine, and correct bone deformities such as bowing. One

common surgery that individuals with OI undergo is called rodding. Rodding is where metal

rods are put inside long bones to strengthen them, fix bone malformations, and prevent future

bone malformations (“What Is Osteogenesis Imperfecta? Fast Facts: An Easy-to-Read Series of

Publications for the Public”). Biophosphate drugs, which are currently approved by the Food

and Drug Administration (FDA) to prevent and treat osteoporosis are used to increase bone
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density in children and adults with moderate and severe OI. There is no drug treatment that is

specific to OI (“Facts About Osteogenesis Imperfecta”).

Prevention of OI

A healthy life style helps prevent broken bones and maintain health in individuals with

OI. Exercise such as swimming, walking, and water therapy is recommended. Physical therapy is

also of great help to those with OI. Patients are advised to not smoke, drink a lot of alcohol and

caffeine, not to take steroid medicines, eat a balanced diet, and maintain a healthy weight.

Adequate intake of nutrients, especially calcium and vitamin D, is necessary to maintain bone

health; however, large doses are not recommended. Maintaining a healthy weight is very

important because extra weight adds stress to a person’s bones, heart, lungs, and reduces their

mobility (“Facts About Osteogenesis Imperfecta”).

Prognosis of Individuals with OI

Prognosis of someone with Osteogenesis Imperfecta varies greatly depending on the

number and severity of symptoms. “Respiratory failure is the most common cause of death,

followed by accidental trauma” (“Fast Facts on Osteogenesis Imperfecta”). Most children and

adults with OI can lead productive, normal, and successful lives.

Conclusion

Osteogenesis Imperfecta is an inherited disease that causes weak bones that break

easily. The four main types of OI are caused by mutations in type I collagen, specifically COL1A1

and COL1A2. These mutations cause a reduced production of type I collagen and is the cause of
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brittle and easily broken bones. OI is diagnosed using a variety of tests, such as x-rays,

ultrasounds, and blood and urine tests; family medical history, and physical exams done by a

geneticist. Treatments include medications, physical therapy, fracture care, surgery, and

mobility aides. The most important ways of preventing new fractures in patients with OI are life

style changes such as eating a healthy diet, maintaining a healthy weight, and exercise.

Individuals with OI can lead normal and average-length lives with proper care, treatment, and

prevention.
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References

Facts About Osteogenesis Imperfecta. (2015, August 1). Retrieved November 29, 2015, from

http://www.oif.org/site/PageServer?pagename=AOI_Facts

Fast Facts on Osteogenesis Imperfecta. (2015, August 1). Retrieved December 8, 2015, from

http://www.oif.org/site/PageServer?pagename=fastfacts

Kini, U., & Nandeesh, B. (2012). Physiology of Bone Formation, Remodeling, and Metabolism.

Retrieved November 8, 2015, from http://www.springer.com/978-3-642-02399-6

Osteogenesis imperfecta. (2013, April 1). Retrieved November 27, 2015, from

http://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta

Shaker, J., Albert, C., Fritz, J., & Harris, G. (2015, September 1). Recent Developments in

Osteogenesis Imperfecta. Retrieved November 15, 2015, from

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566283/

Sherry, D., & Pessler, F. (2015). Osteogenesis Imperfecta. Retrieved November 8, 2015, from

http://www.merckmanuals.com/home/children-s-health-issues/hereditary-connective-

tissue-disorders/osteogenesis-imperfecta

Van der Kamp, S. (2012, June 8). Genetics and Osteogenesis Imperfecta. Retrieved November 7,

2015, from

http://web.a.ebscohost.com.ezproxy.jccmi.edu/ehost/pdfviewer/pdfviewer?sid=94fd15

c9-5b21-4fab-b433-e0ba10b2a983@sessionmgr4001&vid=1&hid=4209
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What Is Osteogenesis Imperfecta? Fast Facts: An Easy-to-Read Series of Publications for the

Public. (2014, November 1). Retrieved November 29, 2015, from

http://www.niams.nih.gov/Health_Info/Bone/Osteogenesis_Imperfecta/osteogenesis_i

mperfecta_ff.asp