Osteogenesis imperfecta
Osteogenesis imperfecta, commonly known as brittle bone disease, is a rare genetic disorder characterized by fragile bones that break easily. This condition, affecting approximately 6 to 7 in 100,000 people worldwide, results from a genetic defect that leads to a deficiency in collagen, a crucial protein that provides structure to bones. Patients with osteogenesis imperfecta experience imperfect bone formation, resulting in multiple and recurrent fractures, often occurring without significant trauma. In addition to bone fragility, individuals may exhibit symptoms such as bluish sclera (the white part of the eyes), thin skin that bleeds easily, frequent nosebleeds, and dental deformities.
There are eight recognized types of osteogenesis imperfecta, with Types I and IV being the most common, ranging from mild to severe manifestations of the disorder. While there is currently no cure, treatment options aim to enhance bone density and strength through medications, hormonal therapies, and physical therapy, particularly low-impact exercises. The long-term outlook for individuals with this condition varies; some may require mobility aids and experience a high incidence of fractures, while others may lead relatively active lives with fewer complications as they age. Advances in research offer hope for future gene therapies that could address the underlying genetic causes of this disorder.
Osteogenesis imperfecta
ALSO KNOWN AS: Brittle bone disease
ANATOMY OR SYSTEM AFFECTED: Bones, ears, ligaments, musculoskeletal system, spine, teeth
DEFINITION: A genetic disorder of variable severity that results in frequent bone breaks
CAUSES: Genetic defect resulting in collagen deficiency
SYMPTOMS: Imperfect bone formation, multiple and recurrent fractures, bluish sclera of eyes, thin skin that bleeds easily, frequent nosebleeds, elevated body temperatures
DURATION: Chronic
TREATMENTS: Hormonal therapy, exercise
Causes and Symptoms
Osteogenesis imperfecta, a rare genetic disorder occurring in approximately 6 to 7 in 100,000 people globally, affects the formation of collagen, which in turn alters bone formation, as provides the foundation for mineralization of developing and healing bone. As the name implies, patients with this disorder have imperfect bone formation, resulting in multiple, recurrent fractures.
Bones are composed of a complex including strands of cross-linked collagen. Collagen is produced by chondrocytes in newly forming bone. Osteoblasts then add the mineral matrix (calcium salts), which forms a complex with collagen to create bone. Children with osteogenesis imperfecta do not produce collagen molecules that allow for a well-organized, strong, stable structure. Fractures can take place without outside stresses such as those occurring in a fall. Normal muscle contractions can produce enough force in some children to induce a bone break.
The long-term outcome of the disease is variable. The most severely affected infants die from complications of lung disease. Patients with less severe disease usually survive but have fractures of their long bones. Most breaks occur between the ages of two and three and again during puberty, between ten and fifteen. From late adolescence through the adult years, the fracture incidence drops unless the patient becomes pregnant, is nursing, or becomes inactive.
There are eight types of osteogenesis imperfecta. Types I and IV are the most common. In Type I osteogenesis imperfecta, the mildest form, the person's collagen is normal, but there is not enough of it, and bones break fairly easily. Type II is the most severe; the person does not have enough collagen, and the collagen they do have is not formed properly. This type of osteogenesis imperfecta affects bone development during and results in bone fractures before birth. Because of the malformation of bony tissues and frequent fractures, patients do not grow normally, have numerous bone deformities, and may die in infancy. The other types of the disease present variations on these symptoms.
Other tissues with abundant collagen are also affected in severe cases of osteogenesis imperfecta. Because these tissues include tendons and ligaments, joints become more mobile and less stable. The small in the are similarly affected, resulting in otosclerosis, in which the stiffen and do not allow the normal transition of sound from the to the inner ear. Thus, patients have hearing difficulties and subsequent language delays. Because the white parts of the eyes (the sclera) are composed mainly of collagen, these patients tend to have bluish sclera. They also have thinner skin that bleeds easily. Epistaxis (nosebleeding) is likewise common and difficult to control. Patients may have deformed teeth, as tooth development is also affected. They tend to have elevated body temperatures, causing them to sweat excessively. It is important to note that the nervous system, and thus the intelligence, of children with osteogenesis imperfecta is not affected.
Treatment and Therapy
There is no known cure for osteogenesis imperfecta. Drug therapies include a class of drugs called bisphosonates, such as alendronate (Fosamax), which have been shown to increase bone density and are also used to treat similar conditions like osteoporosis. Treatment with growth hormones also seems to stabilize the bone matrix by stimulating bone-forming cells (osteoblasts) and inhibiting the cells that break down bone tissue (osteoclasts). This is likely why patients tend to improve during and after puberty, since levels of these hormones naturally rise.
Physical therapy, especially involving low-impact exercise like swimming, is another standard treatment. A healthy diet rich in calcium and vitamin D is encouraged, as is an active lifestyle, as exercise strengthens bones. Activities with a high potential for fractures, however, should be avoided. If fractures occur, orthopedic specialists may place metal in the long bones when repairing a fracture to help prevent deformities. Adaptive aids such as crutches, braces, or wheelchairs may also be needed.
Perspective and Prospects
Unfortunately, the for some children with osteogenesis imperfecta is poor, and many are confined to wheelchairs as adults. Others are more fortunate and have relatively few fractures after adolescence.
Some advancements in the understanding of osteogenesis imperfecta have occurred using techniques to help identify the errors in collagen formation. It is hoped that these data will result in future gene therapies.
Bibliography
Green, Morris. Pediatric Diagnosis: Interpretation of Symptoms and Signs in Infants, Children, and Adolescents. 6th ed. Philadelphia: W. B. Saunders, 1998.
Hay, William W., Jr., et al., eds. Current Diagnosis and Treatment in Pediatrics. 21st ed. New York: Lange Medical Books/McGraw-Hill, 2012.
Jones, Kenneth Lyons. Smith’s Recognizable Patterns of Human Malformation. 7th ed. Philadelphia: Saunders/Elsevier, 2013.
Jovanovic, Milena, et al. "Osteogenesis Imperfecta: Mechanisms and Signaling Pathways Connecting Classical and Rare OI Types." Endocrine Reviews, vol. 43, no. 1, pp. 61-90, Feb. 2022, doi.org/10.1210/endrev/bnab017. Accessed 7 Apr. 2024.
Kliegman, Robert M., and Waldo E. Nelson, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia: Saunders/Elsevier, 2011.
Larsen, Laura, ed. Childhood Diseases and Disorders Sourcebook. 3d ed. Detroit, Mich.: Omnigraphics, 2012.
Osteogenesis Imperfecta Foundation. http://www.oif.org/.
Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Osteogenesis Imperfecta. San Diego, Calif.: Icon Health, 2002.
Smith, Nathalie. "Osteogenesis Imperfecta." Health Library, November 26, 2012.
Van De Graaff, Kent M., and Stuart I. Fox. Concepts of Human Anatomy and Physiology. 5th ed. Dubuque, Iowa: Wm. C. Brown, 2000.
Yu, Hongjie, et al. "Pathogenic Mechanisms of Osteogenesis Imperfecta, Evidence for Classification." Orphanet Journal of Rare Diseases, vol. 18, no. 234, 9 Aug. 2023, doi.org/10.1186/s13023-023-02849-5. Accessed 7 Apr. 2024.