How Osteogenesis Imperfecta Works

It's very easy for most of us to take our skeletal systems for granted. Like much of our anatomy, if it's working fine and isn't something we can fixate on in the mirror, then out of sight is truly out of mind. View a few photographs of decayed human remains, and you can quickly fall into the trap of perceiving our skeletons as fixed, permanent structures on which our flesh grows, lives and dies.

While the skeleton's main functions include supporting the body and protecting vital organs, our skeletal system is as much a living system as any other part of our anatomy. The red marrow inside our bones produces red blood cells. Yellow marrow stores fat, and the bone itself is home to various minerals. Your body constantly breaks down old bone cells and replaces them with new ones.


But, just as our bones are ruled by constant cellular activity, there are plenty of diseases, disorders and other conditions that can disrupt the intended process. One such condition is osteogenesis imperfecta (OI), Latin for "imperfectly formed bone."

Also known as brittle bone disease, OI is a genetic disorder. A person either inherits the condition from a parent or develops it spontaneously in the womb. OI disrupts the body's ability to form strong connective tissue. This, in turn, affects the body's ability to grow new bone tissue. Instead of creating strong, compact bones capable of withstanding normal stress, the cells of a person afflicted with OI produce weaker skeletal tissue. In addition to other symptoms, the bones can break easily under everyday levels of stress.

On the next page, learn exactly how OI leads to the production of brittle bones.


Osteogenesis Imperfecta Causes

UHB Trust/Stone/Getty Images

To understand how osteogenesis imperfecta affects the way skeletal tissue forms, it's important to understand how a normal human body grows new bone. The task largely falls to cells called osteoblasts, which create new bone tissue, while cells called osteoclasts break down old bone. This ongoing process is called bone remodeling.

Osteoblasts form new bones and increase the size of growing bones. This process is called ossificiation.


Think of workers constructing a building -- the process has a lot in common with the way osteoblasts build new bone. First, both need strong building blocks with which to form the finished product. Construction workers use bricks or concrete blocks to form walls. Osteoblasts form bone from inorganic mineral salts, mainly calcium carbonate and calcium phosphate. This is the reason a calcium-rich diet is important to maintain strong bones.

But you can't erect a building using only blocks and bricks. You need a metal framework to give it flexibility and tensile strength, the amount of stress a construction can endure without falling apart. An earthquake or strong wind could destroy a skyscraper, no matter the strength of the pieces, without a flexible steel framework. In bones, fibers of collagen, a protein produced by all vertebrates, supply this framework. Osteoblasts secrete these collagen fibers to form the framework and then initiate calcification -- calcium fills the flexible framework, providing strength.

In cases of OI, the body either creates poor-quality collagen or doesn't create enough of it. The resulting bones lack flexibility and tensile strength, making them far more susceptible to fracture than normal, healthy bones.

However, OI doesn't just affect bone tissue. Collagen also forms the framework for cartilage, teeth and various forms of connective tissue. Poor or too little collagen can also render these features brittle. Collagen shows up in sclera, the visible white portion of the eye. As a result, someone with OI may develop a blue or gray hue in this portion of his or her eyes. The condition can even lead to early hearing loss if the patient suffers a fractured stapes. The stapes, or stirrup, is one of the smallest bones in the body and plays a central role in transmitting sound waves to the eardrum.

OI is a genetic condition. Either a parent passes the gene on to his or her child or the genes mutate spontaneously. Doctors have identified eight types of OI, and six involve a dominant mutation. This means only one parent has to pass on the OI gene. Two additional varieties involve a recessive mutation, meaning both parents have to pass on the gene. While considered a rare condition, OI affects 20,000 to 50,000 people in the United States alone.

On the next page, we'll look at the different types of OI and the symptoms associated with each.


Types of Osteogenesis Imperfecta

© Mozart

The exact symptoms of osteogenesis imperfecta can vary greatly from person to person, even among people with the same variety of the disorder. Some patients experience just a few fractured limbs in the course of a lifetime, while others may experience hundreds. More extreme types can cause bone deformity or even death.

Doctors classify the eight types of OI based on when each type was discovered -- type I being the first and type VIII being the most recent. Types I-IV constitute the vast majority of diagnosed OI cases. Doctors link all four to dominant mutations in genes responsible for producing type-1 collagen.


Type I osteogenesis imperfecta is the mildest and most common variety. In addition to fragile bones, type I is frequently accompanied by blue sclarae, hearing loss, thin skin, loose joints, low muscle tone and brittle teeth. Type I patients may also develop scoliosis, a condition in which spine curvature leads to chronic back pain and difficulty breathing. Triangular faces are also common. Type I patients typically experience most of their fractures, about 40 breaks, before they enter puberty [source: Cleveland Clinic Center for Consumer Health Information].

On the other end of the spectrum, type II osteogenesis imperfecta is the most severe form of the disease. It occurs in 10 percent of OI patients and is frequently lethal. Most patients are stillborn or die shortly after birth due to respiratory problems. Type II usually occurs due to spontaneous gene mutation. Newborns typically have a small birth weight, underdeveloped lungs, fractures and bone deformities.

Patients with type III osteogenesis imperfecta tend to be short in stature with poor dental development and barrel-shaped ribcages. They also experience many of the symptoms associated with type I, including colored sclera, loose joints, poor muscle development, triangular faces and hearing loss. In addition, these people live with bone deformities that grow progressively worse with age. Spinal deformities and respiratory problems are also possible.

Type IV osteogenesis imperfecta is very similar, only less severe. Type IV patients tend to experience most of their fractures before puberty.

Four additional, less common varieties of the disease also exist. Type V and type VI are both similar to type IV; except it's unknown which collagen mutation causes these types. Researchers are also unsure if the gene is dominant with type VI, as with types I-V, or if it's actually recessive, meaning that it must be inherited from both parents to be passed on. Type V doesn't affect dental health, but does cause large calluses at the sites of fractures or surgeries. This type can also cause calcification of connective tissue in the forearm, restricting arm movement.

Doctors know of two exceedingly rare forms of recessive OI: type VII and type VIII. A mutation in the genes responsible for producing a cartilage-associated protein causes the condition. Type VIII patients frequently have small bodies, round faces and short limbs. Typically lethal, type VIII results in severe growth deficiency and very low mineral counts in an infant's bones.

Currently, there is no cure for OI. However, there are a number of treatments aimed at making life easier for those born with the condition. Learn about them on the next page.


Osteogenesis Imperfecta Treatment

© Asenova

Since there is no cure for OI, the main purpose of any treatment plan is to improve the quality of life for the patient. Though bone fractures can and will occur, the right preventive measures will keep these to a minimum. In most cases, the methods are nonsurgical and aimed at giving those with OI a maximum degree of mobility and independence.

Physical therapy

Muscle strength and bone mass can be increased through therapy (though patients can't overcome bone weakness). If properly tailored to an individual's symptoms and age, exercise can improve mobility and help prevent future fractures. Maintaining a healthy weight can also cut down on bone stress. Swimming is an ideal form of exercise for those with OI since it offers exertion without putting much stress on the limbs.



Good nutrition is very important for people with OI. A registered dietitian can help create a diet that both strengthens bones against fractures and decreases the time it takes for breaks to heal. Vitamin D and calcium are very important for ensuring bone strength, as are avoiding steroids and large amounts of caffeine or alcohol.

Surgical procedures

Doctors sometimes perform a surgery called rodding 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. Doctors sometimes perform surgery to stabilize the spine in cases that could lead to the development of scoliosis.


Aside from various medications used to treat the pain associated with bone fractures, doctors can prescribe bisphosphonates to help increase bone density. The drug slows down the rate at which osteoclasts break down old bone, with no effect on the osteoblasts building new bone tissue. Currently, doctors are experimenting with other similar medications, as well as human growth hormones and gene therapy.

There's more to living with OI than just exercise, diet, surgery and medication. In the next section, learn about some of the additional challenges people with OI face and how they work to overcome them.


Living with Osteogenesis Imperfecta


The challenges to daily life associated with osteogenesis imperfecta vary greatly from person to person, depending on condition type, severity of disease and the patient's age. The right balance of treatments can often help a person with OI live a reasonably normal life.

Parents of children with OI face a number of challenges. Care must be taken when handling a child with OI. However, parents also must not withhold physical affection or prevent the appropriate levels of exertion needed for the child to develop bone mass and muscle strength. Often, parents must deal with the fact that painful fractures may be unavoidable. In many cases, the number of breaks greatly diminishes after puberty ends.


False allegations of child abuse are frequent problems for these parents, especially when milder cases of the disorder go undiagnosed. Not only do bones break more easily for children with OI, but these children often bruise more easily due to their smooth, thin skin. School officials or law-enforcement officers unaware of the child's medical condition could easily misconstrue injuries sustained during normal, everyday activities as evidence of child abuse. To help prevent these false allegations, parents of children with OI should always keep documentation about their child's condition on hand and notify school officials.

Adults with milder cases of OI often face fewer fractures, but their symptoms still place limits on their lifestyles. The more rigorous the activity, the more likely it will result in injury. The more serious the fracture (or fractures), the more time the patient must spend recovering muscle mass lost from immobility. This also applies to pregnancy -- a pregnant woman with mild OI may experience few complications. Expectant mothers with type I and type IV may experience loose joints, reduced mobility, bone pain and dental problems. More debilitating forms of OI may lead to severe complications for the mother, including heart and lung difficulties and premature delivery.

Men with OI usually don't experience increased fractures as they age. Menopausal women, on the other hand, often suffer from osteoporosis, a condition in which both the calcium and collagen levels in bone decrease, resulting in less bone mass. Women with OI already have depleted or weak collagen levels, and osteoporosis only weakens their fragile bones further. To help combat these effects, doctors frequently prescribe menopausal women hormone replacement therapy or estrogen replacement therapy to increase hormone levels.

For more information on osteogenesis imperfecta and its support organizations, visit the links on the next page.


Lots More Information

Related HowStuffWorks Articles

More Great Links


  • American Academy of Orthapedic Surgeons. "Osteogenesis Imperfecta." August 2007. (April 25, 2008)
  • Brittle Bone Society. "Osteogenesis Imperfecta and Older People." March 1999. (April 25, 2008)
  • Cleveland Clinic Center for Consumer Health Information. "Osteogenesis Imperfecta." (April 25, 2008)
  • Columbia Orthopedics Pediatric Orthopedic Surgery. "Osteogenesis Imperfecta." (April 25, 2008)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases. "Osteogenesis Imperfecta." August 2007. (April 25, 2008)
  • Osteogenesis Imperfecta Foundation. "Child Abuse or Osteogenesis Imperfecta?" (April 25, 2008)
  • Osteogenesis Imperfecta Foundation. "OI Issues: Pregnancy." (April 25, 2008)
  • Osteogenesis Imperfecta Foundation. "Osteogenesis Imperfecta: A Guide for Medical Professionals, Individuals and Families Affected by OI." (April 25, 2008)
  • Tortora, Gerard J. and Sandra Reynolds Grabowski. "Principles of Anatomy and Physiology, Ninth Edition." John Riley & Sons. 2000.
  • U.S. National Library of Medicine and the National Institutes of Health. "Osteoblast and chrondroblast differentiation." PubMed. Aug. 17, 1995. (April 23, 2008)