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Osteogenesis imperfecta (OI) is a group of genetic disorders that cause weak bones because of a defect or deficiency in type I collagen, a protein that’s a major structural component in bones and connective tissue.
It’s also called “brittle bone disease” because people affected by it can often get numerous fractures for seemingly no apparent reason. You might also hear OI referred to as glass bone disease, Lobstein disease, osteopsathyrosis, Vrolik’s disease, and Porak-Durante disease.
In severe types of OI, people can get bone fractures before they’re born and die shortly after birth. You may have heard of osteogenesis imperfecta from M. Night Shymalan’s Unbreakable films.
One of the main characters, Elijah Price aka Mr. Glass, portrayed by Samuel L Jackson, suffers from type I osteogenesis imperfecta. As he puts it, “It’s a genetic disorder. I don’t make a particular protein very well, and it makes my bones very low in density… very easy to break.”
Types of osteogenesis
OI is divided into different types based upon genetic characteristics as well as what symptoms are present.
Type I: This is the most common and mildest form of OI. The genetic defect in type I OI causes a normal collagen structure, but less than normal amounts of collagen are made.
This is in contrast to all other forms of OI, where there is still not enough collagen, but also the collagen that’s made has a weaker structure. The severity of disease in people with Type I osteogenesis imperfecta varies from person to person (Plotkin, 2004).
Some people will have only a few fractures over their lifetimes, and others will have numerous bone breaks. They will also have loose joints, muscle weakness, a triangular face, and a blue tint to the whites of their eyes (also called blue sclera).
They are at greater risk for brittle teeth and hearing loss that starts in their 20s or 30s. Typically, people with type I OI will grow to a normal height and have a normal lifespan.
Type II: This is the most severe form of OI, with most infants suffering life-threatening complications shortly after birth. Infants born with OI type II will have low birth weight, abnormally short arms and legs, severe bone deformities, extremely fragile bones, and numerous fractures at birth.
Because of deformities in how their chest and rib cage develops, the lungs of these infants will be small, causing breathing problems that may be fatal. In the United States, many children with OI type II are diagnosed prenatally (during the pregnancy) by ultrasound and DNA analysis.
Many parents choose not to carry the pregnancy to term. Even with medical therapy, 20% of babies born with OI type II are stillborn, and 90% die within four weeks (Van Dijk, 2014).
Type III: This form of osteogenesis imperfecta is progressive and deforming. People with type III OI have brittle, fragile bones. Like in type II, infants born with type III OI can have fractures at birth.
As these children grow up, they can develop deformities from numerous fractures, causing short stature, curving of the spine (scoliosis), and abnormalities in the skull. In severe cases, people with type III OI may require wheelchairs or mobility scooters to get around. Life expectancy in type III OI is lower than in healthy people.
Type IV: People with OI type IV have fragile bones, though not as brittle as those in type II and type III OI. Most fractures in type IV OI happen before puberty. People with OI type IV can have a normal lifespan, though they may experience some bone deformities, and their height is usually shorter than average.
Types V through VIII: These newly-identified types of osteogenesis imperfecta have mutations in genes other than collagen. Type V, VI, and VII resemble type IV in terms of disease severity, while type VIII resembles type III.
Who is at risk for osteogenesis imperfecta
Osteogenesis imperfecta affects 1 in 10,000–20,000 infants born worldwide. It’s a rare disease; only 20,000-50,000 people in the United States have it. Because it’s a genetically inherited disorder, the only true risk factor is who you’re related to (Lim, 2017).
Many people affected by osteogenesis imperfecta, especially a subtype that’s mild, have a relative with OI. In other people, it’s a new genetic mutation that developed. This is called a de novo mutation, and unfortunately, there’s no way to prevent it.
How is osteogenesis imperfecta diagnosed?
Your healthcare provider can diagnose osteogenesis imperfecta by first doing a complete history and physical exam.
They might suspect that a person has osteogenesis imperfecta if they have a history of frequent fractures without major injuries associated with them, along with finding a blue tint to the whites of their eyes (blue sclera), hearing loss, loose joints, or poor teeth.
A family history of osteogenesis imperfecta or frequent fractures is also important for a healthcare provider to know about. X-ray scans are also very helpful in identifying past and current fractures, as well as any deformities in the bone. It can help differentiate OI from other reasons that bones can be fragile, including rickets (vitamin D deficiency).
A special type of X-ray called a DEXA (dual-energy X-ray absorptiometry) scan is important to assess how dense your bones are. Finally, genetic testing of a blood or skin sample can confirm osteogenesis imperfecta and help identify what subtype it is.
After diagnosis, you might be asked to meet with a clinical geneticist to help you figure out whether other members of your family need to be tested and what the risk is of passing the disease onto your children.
Treating osteogenesis imperfecta
There is, unfortunately, no cure for OI. However, there are treatments available that can improve bone strength, reduce the risk of fracture, and make life a little bit easier:
- Bisphosphonates: These medications reduce the rate of bone breakdown. They’re widely used to make bones stronger in osteoporosis and work in the same way for osteogenesis imperfecta. Clinical trials have shown these medications to be effective in increasing bone mineral density in people with osteogenesis imperfecta (Dwan, 2014).
- Surgery: Surgery can be an important treatment option. One important surgical technique to treat osteogenesis imperfecta is called “rodding,” in which a metal rod is inserted into a long bone to stabilize broken bones and strengthen and straighten curved bones (Georgescu, 2013).
- Braces and splints: Wearing braces and splints can provide support for people with OI. This can be an effective way to decrease pain and make sure joints are properly aligned.
- Physical therapy: Experts agree that physical therapy to improve mobility and maintain strength can improve independence and quality of life in people with OI (Mueller, 2018).
- Experimental therapies: In addition to the more proven options, researchers have been testing other therapeutics that may offer hope for the future of osteogenesis imperfecta. Growth hormone, when combined with bisphosphonate medications, has been shown in small studies to be helpful in improving growth and bone density in children with OI (Antoniazzi, 2010). Cell transplantation and gene therapy have also been tested in small trials, and although both treatments are in very early stages, they show promise for the future of this bone disorder.
If you or your family member is struggling with osteogenesis imperfecta, the Osteogenesis Imperfecta Foundation is a great resource for finding support.
- Antoniazzi, F., Monti, E., Venturi, G., Franceschi, R., Doro, F., Gatti, D., … Tatò, L. (2010). GH in combination with bisphosphonate treatment in osteogenesis imperfecta. European Journal of Endocrinology, 163(3), 479–487. doi: 10.1530/eje-10-0208, https://www.ncbi.nlm.nih.gov/pubmed/20592128
- Dwan, K., Phillipi, C. A., Steiner, R. D., & Basel, D. (2014). Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database of Systematic Reviews, (7), CD005088. doi: 10.1002/14651858.cd005088.pub3, https://www.ncbi.nlm.nih.gov/pubmed/25054949
- Georgescu, I., Vlad, C., Gavriliu, T. S., Dan, S., & Pârvan, A. A. (2013). Surgical treatment in Osteogenesis Imperfecta – 10 years experience. Journal of Medicine and Life, 6(2), 205–213. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23904885
- Lim, J., Grafe, I., Alexander, S., & Lee, B. (2017). Genetic causes and mechanisms of Osteogenesis Imperfecta. Bone, 102, 40–49. doi: 10.1016/j.bone.2017.02.004, https://www.ncbi.nlm.nih.gov/pubmed/28232077
- Mueller, B., Engelbert, R., Baratta-Ziska, F., Bartels, B., Blanc, N., Brizola, E., … Semler, O. (2018). Consensus statement on physical rehabilitation in children and adolescents with osteogenesis imperfecta. Orphanet Journal of Rare Diseases, 13, 158. doi: 10.1186/s13023-018-0905-4, https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0905-4
- Osteogenesis Imperfecta Foundation. (2020). Osteogenesis Imperfecta Foundation. Retrieved from https://oif.org/
Paterson, C. R., Ogston, S. A., & Henry, R. M. (1996). Life expectancy in osteogenesis imperfecta. BMJ, 312, 351. Retrieved from https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2350292&blobtype=pdf
- Plotkin, H. (2004). Syndromes with congenital brittle bones. BMC Pediatrics, 4, 16. doi: 10.1186/1471-2431-4-16, https://bmcpediatr.biomedcentral.com/articles/10.1186/1471-2431-4-16
- Van Dijk, F. S., & Sillence, D. O. (2014). Osteogenesis imperfecta: Clinical diagnosis, nomenclature and severity assessment. American Journal of Medical Genetics Part A, 164(6), 1470–1481. doi: 10.1002/ajmg.a.36545, https://www.ncbi.nlm.nih.gov/pubmed/24715559
Dr. Chimene Richa is a board-certified Ophthalmologist and Senior Medical Writer/Reviewer at Ro.