Osteogenesis Imperfecta
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What is osteogenesis imperfecta?
Osteogenesis imperfecta is a group of genetic disorders that mainly affect the bones. The term osteogenesis imperfecta means imperfect bone formation. People with this condition have bones that are brittle and easily broken. Multiple fractures are common, and in severe cases, can occur even before birth.
Researchers have identified several types of osteogenesis imperfecta. The types are often distinguished by their signs and symptoms, although their characteristic features overlap. Increasingly, specific bony changes and genetic factors are also used to define the different types of this condition.
Type I osteogenesis imperfecta, the mildest form of the condition, is characterized by bone fractures during childhood and adolescence that often result from minor trauma. Fractures occur less frequently in adulthood. People with this form of the condition typically have a blue or grey tint to the part of the eye that is usually white (the sclera) and may develop hearing loss in adulthood. Affected individuals are usually of normal or near normal height.
Osteogenesis imperfecta type II is the most severe form of the disorder. Infants with type II have bones that appear bent or crumpled and may fracture before birth. The chest is narrow, with a very small rib cage and underdeveloped lungs. Affected infants have short, bowed arms and legs; dark blue sclerae; hips that turn outward; and unusually soft and thin skull (calvarial) bones. Most infants with type II are stillborn or die shortly after birth, usually from respiratory failure.
People with type III osteogenesis imperfecta have very fragile bones that may begin to fracture before birth. In some cases, rib fractures can cause life-threatening problems with breathing. Bone abnormalities tend to worsen over time and often interfere with mobility. People with this form of the disorder have very short stature; their adult height may be less than 3 feet. Type III osteogenesis imperfecta is also associated with blue sclerae that lighten with age, hearing loss beginning in adolescence, and a disorder of tooth development called dentinogenesis imperfecta.
Osteogenesis imperfecta type IV is a moderate form of the disorder. About 25 percent of affected individuals are born with bone fractures; others may not have any broken bones until later in childhood or adulthood. Although the sclerae may have a bluish tint in infancy, adults with this form of the condition usually have white sclerae. Additional features of type IV osteogenesis imperfecta can include mild short stature, hearing loss, and dentinogenesis imperfecta.
Researchers have proposed several additional types of osteogenesis imperfecta, but in most cases the genetic causes of these types have not been determined.
How common is osteogenesis imperfecta?
This condition affects an estimated 6 to 7 per 100,000 people worldwide. Types I and IV are the most common forms of osteogenesis imperfecta, affecting 3 to 4 per 100,000 people. Types II and III are rarer, with an estimated incidence of 1 to 2 per 100,000 people.
What genes are related to osteogenesis imperfecta?
Mutations in the COL1A1, COL1A2, and CRTAP genes cause osteogenesis imperfecta.
Mutations in the COL1A1 and COL1A2 genes are responsible for about 90 percent of all cases of osteogenesis imperfecta. These genes provide instructions for making proteins that are used to assemble type I collagen, which is the most abundant protein in bone, skin, and other tissues that provide structure and strength to the body (connective tissues).
Most of the mutations that cause osteogenesis imperfecta type I occur in the COL1A1 gene. These mutations reduce the amount of type I collagen produced in the body, which causes bones to be brittle and fracture easily. The mutations responsible for osteogenesis imperfecta types II, III, and IV can occur in the COL1A1 or COL1A2 gene. These mutations typically alter the structure of type I collagen molecules. A defect in the structure of type I collagen weakens connective tissues, particularly bone, resulting in the characteristic features of osteogenesis imperfecta.
Mutations in the CRTAP gene are responsible for rare cases of osteogenesis imperfecta. This gene provides instructions for making a protein that is involved in processing collagen molecules. Mutations in this gene reduce the amount of CRTAP protein or prevent cells from producing any of this protein. As a result, collagen molecules cannot form as they should, weakening connective tissues and leading to the bone abnormalities found in osteogenesis imperfecta.
In cases of osteogenesis imperfecta without identified mutations in the COL1A1, COL1A2, or CRTAP gene, the cause of the disorder is usually unknown.
How do people inherit osteogenesis imperfecta?
Most cases of osteogenesis imperfecta have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition. Many people with type I or type IV osteogenesis imperfecta inherit a mutation from a parent who has the condition. Almost all infants with type II osteogenesis imperfecta have no history of the condition in their family. In these infants, the condition is caused by new (sporadic) mutations in the COL1A1 or COL1A2 gene. The disorder is not passed on to the next generation because affected individuals do not live long enough to have children.
Less commonly, osteogenesis imperfecta can have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means two copies of the gene in each cell are altered. Most often, the parents of a child with an autosomal recessive disorder are not affected, but each carry one copy of the altered gene. Some cases of osteogenesis imperfecta type III are autosomal recessive; these cases usually result from mutations in genes other than COL1A1 and COL1A2. Rare cases of osteogenesis imperfecta caused by mutations in the CRTAP gene also have an autosomal recessive pattern of inheritance.
Source: National Institutes of Health
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The National Coalition for Osteoporosis and Related Bone Diseases Briefed Congress on Action Plan for a National Vision for Bone Health
2009 JUN 1 - (NewsRx.com) -- The National Osteoporosis Foundation (NOF) in conjunction with the National Coalition for Osteoporosis and Related Bone Diseases held a briefing on Capitol Hill today to engage Congress in an action plan for making bone health a national priority and encourage lawmakers to sign on to the "Bone Health Promotion and Research Act." The proposed legislation would create a National Bone Health Program to enhance the activities of the Centers for Disease Control and Prevention (CDC) and augment educational activities on bone health at the national and state levels; establish an Osteoporosis and Related Bone Disease Advisory Committee to advise the CDC and the National Institutes of Health (NIH); expand and intensify research activities of the NIH on osteoporosis and related bone diseases; and authorize grants and cooperative agreements to facilitate the collection, analysis and reporting of data regarding osteoporosis. Representatives Shelley Berkley (D-1st-NV) and Michael C. Burgess (R-26th-TX) provided remarks for the briefing. "Promoting good bone health and increasing fracture prevention efforts among older Americans are two ways we can help bring the growth in healthcare spending down to sustainable levels," said Congresswoman Berkley. "The 'Bone Health Promotion and Research Act' and the 'Medicare Fracture Prevention and Osteoporosis Testing Act' will help us meet this goal and I will be working with my colleagues in Congress and the healthcare community to build support for the enactment of these important bills." "As a doctor for over 25 years serving the people of Texas, I know the importance of health education and disease prevention in improving the lives of Americans," said Congressman Burgess. "That's why we are proud to introduce this comprehensive bill for bone health promotion and research. It allows us to improve bone health and directly address osteoporosis as a major public health issue that affects an estimated 44 million Americans." The National Coalition for Osteoporosis and Related Bone Diseases, (the Bone Coalition) comprised of the National Osteoporosis Foundation, the American Society for Bone and Mineral Research, the Osteogenesis Imperfecta Foundation, The Paget Foundation and most recently the American Academy of Orthopaedic Surgeons, released in January 2009 a National Action Plan for Bone Health: Recommendations from the Summit for a National Action Plan for Bone Health with input from leaders of major health and public health organizations, health systems, academic institutions, industry, government and media. The report provides an action plan and agenda to advance bone health promotion and disease prevention for the nation. It is a direct result of the Summit for a National Action Plan for Bone Health held in June 2008 in Washington, D.C. Ethel Siris, M.D., immediate past president of NOF, professor of clinical medicine with the College of Physicians and Surgeons at Columbia University and director of the Toni Stabile Osteoporosis Center at the Columbia University Medical Center, New York-Presbyterian Hospital in New York, was joined by Henry Bone, M.D., director of the Michigan Bone and Mineral Clinic, chief of the Section of Endocrinology and Metabolism at St. John Hospital and Medical Center in Detroit, adjunct professor of the Division of Metabolism, Endocrinology and Diabetes, Department of Medicine at the University of Michigan, to address the four priority areas of the National Action Plan report: developing a bone health alliance; promoting bone health and disease prevention; improving diagnosis and treatment; and enhancing research, surveillance and evaluation. "Broken bones due to osteoporosis are more common in women than breast cancer, heart attacks and strokes combined," said Dr. Siris. "Osteoporosis and related fractures take a significant physical, emotional and economic toll on our nation. We urge Congress to support this national action plan for bone health, which includes improved patient access to care, and increased support for prevention, education and research programs for osteoporosis and related bone disease." "We must do better at recognizing and treating osteoporosis," said Dr. Bone. "It is essential that funding be restored for bone density testing for Medicare patients so they can be diagnosed before fractures occur, and we must increase awareness that a fragility fracture often signals an underlying bone disease and should lead to evaluation and treatment." Linda Johnson, an osteoporosis patient and health advocate, also spoke at the briefing about her long-standing battle with osteoporosis. "I've suffered several fractures because of osteoporosis. I developed stooped over posture and lost two inches in height, which means that my clothes no longer fit properly. My children were even afraid to hug me because I was so fragile. I was in pain and felt helpless and confused," said Ms. Johnson. "I continually talk to people about my experience and encourage them to exercise, eat a balanced diet and talk to their healthcare professional about their bones. Everyone, young and old, including healthcare professionals, needs to make bone health a priority." During National Osteoporosis Awareness and Prevention Month in May, we applaud Representatives Berkley and Burgess and all the Members of Congress who recognize better bone health and osteoporosis prevention, diagnosis and treatment as a major component of health reform. Keywords: Bone Disease, Genetics, Health Policy, Marketing and Licensing Agreements, Medicare, Orthopedics, Osteogenesis Imperfecta, Osteoporosis, Public Health, National Osteoporosis Foundation. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.
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