Osteogenesis Imperfecta (OI) is a genetic bone disorder characterized by fragile bones that break easily. It is also known as “brittle bone disease.” The term literally means “bone that is imperfectly made from the beginning of life.” A person is born with this disorder and is affected throughout his or her life time.

For a summary of information about OI see Facts about OI.

For a detailed description of OI Types see Types of OI.

For a list of common myths about OI see Myths about OI.

OI Stories features stories about living with OI.

Osteogenesis imperfecta (OI) or Brittle Bone Disease is a complicated, variable and rare disorder. Its major feature is a fragile skeleton, but many other body systems are also affected. OI is caused by a mutation (change) in a gene that affects bone formation, bone strength and the structure of other tissues. It is a life-long disorder. OI occurs equally among males and females and in all racial groups. It is estimated that approximately 25,000 to 50,000 people in the U.S. have OI. With good medical management and supportive care, the majority of people who have OI will lead healthy, productive lives and can expect an average life span.

People with OI experience frequent broken bones from infancy through puberty. The frequency typically decreases in the young adult years but may increase again later in life. Respiratory problems including asthma are often seen. Other medical characteristics and issues include:

  • Bone deformity, and bone pain.
  • Short stature.
  • Spine curves.
  • Low Bone Density.
  • Loose joints, ligament laxity and muscle weakness are common.
  • Distinctive features of the skull including late closing fontanels, and head circumference greater than average.
  • Hearing loss may begin in the early 20s and by middle age is present in more than 50% of people with OI.
  • Brittle teeth (called dentinogenesis imperfecta or DI) are seen in 50% of people who have OI
  • Respiratory problems including asthma; may be aggravated by chest wall deformity and/or spine deformity.
  • Vision problems including myopia and risk for retinal detachment
  • Skin hyperlaxity; easy bruising.
  • Cardiac issues.
  • Fatigue.
  • Basilar Invagination a serious neurological problem is seen in some people with the more severe forms of OI.
  • Skin, blood vessels and internal organs may be fragile.

OI exhibits wide variation in appearance and severity.  Severity is described as mild, moderate, or severe. The most severe forms lead to early death. Clinical features (observable signs) such as fracture frequency, muscle strength or extraskeletal problems vary widely not only between types, but within types, and even within the same family. Some features are age dependent.

Since the 1970’s a list of numbered types has been used to describe the different forms of OI. The original list featured 4 Types. Today, as a result of recent research 15 Types of OI have been identified. Many people with OI do not fit clearly into one of the identified types and not all characteristics are seen in each person. A description of the more common OI Types follows. Understanding the individual’s OI Type provides a starting point for understanding the person’s health care needs. But due to all of the variable features, care for each person needs to be individualized.  

People with Type I OI, the mildest and most common form, may have only a handful of fractures or as many as several dozen fractures in a lifetime. They may have few obvious signs of the disorder. There usually is little or no bone deformity. Height is less affected than in other types of OI. People with Type I OI are often similar in height to other family members. Muscle weakness, joint laxity and flat feet are common. Dislocations and sprains may occur as well as fractures. Life expectancy appears to be average.

Type II OI is the most severe form. Infants are quite small and are usually born with multiple fractures, an unusually soft skull and an unstable neck. Limbs may be disproportionately small and legs may fall into a frog-like position. The head may be large for the size of the body. Almost all infants with Type II OI die at or shortly after birth, often due to respiratory problems. In the newborn period, it can be difficult to distinguish between Type II and severe Type III OI. This means that some children diagnosed clinically as Type II at birth may actually have Type III OI and have a longer life expectancy.

People with Type III OI are born with fractures. X-rays may reveal healed fractures that occurred before birth. Common signs include short stature, progressive long bone deformities, spinal curvature, and a barrel-shaped rib cage. People with Type III OI may have anywhere from several dozen to several hundred fractures in a lifetime. Surgical correction of long bone bowing and scoliosis is common. Life expectancy varies. Some people with Type III OI have severe, sometimes fatal, respiratory problems in infancy or childhood. Some children and adults with severe Type III OI may require supplemental oxygen. Some individuals succumb to respiratory problems in adulthood due to progressive rib cage and spine deformities. Other people with Type III OI will have a near-average life span.

Type IV OI is the moderate type of OI. The clinical picture can be similar to Type I OI or more like Type III OI. People with this form of OI may be somewhat shorter than others in their family, have frequent fractures that decrease after puberty, and have mild to moderate bone deformity. Life expectancy appears to be average.

Type V is moderate in severity and is similar to Type IV in appearance and symptoms. Identifying features include hypertrophic calluses that may form at fracture or surgical procedure sites and restricted forearm rotation due to calcification of the membrane between the radius and ulna.

Type VI is another moderate form and is similar to Type IV in appearance. This is an extremely rare form. It is distinguished by a characteristic mineralization defect that can be seen in biopsied bone.

For additional information on OI Types see the Fact Sheet section under “About OI/Publications” on this website

Osteogenesis imperfecta (OI) is a genetic disorder. Most cases (90 percent) are caused by a faulty gene that reduces either the amount or the quality of type 1 collagen throughout the body. These mutations are inherited in a dominant manner. The other 10 percent of cases are caused by mutations in other genes that are inherited in either a dominant or a recessive manner.

Children inherit two copies of each gene – one from each parent. When OI is caused by a dominant mutation only one copy of the OI gene mutation is necessary for the child to have OI. In the majority of cases, the gene is either inherited from a parent who has OI or results from a spontaneous new mutation occurring at the time of conception. In rare cases dominant OI can occur when a parent is mosaic for an OI mutation. This means that an OI causing mutation is present in a percentage of one parent’s cells, but does not cause any symptoms in the parent. For a child to inherit OI in a recessive manner, the gene mutation must come from both parents. In this situation, the parents do not have OI, but both carry the mutation in their genes.

A person who has dominant OI has a 50 percent chance of passing on the disorder to each of his or her children. An affected child will have the same mutation, and therefore the same type of OI, as the parent. However, the expression— the degree of severity, or number of fractures— may be different. Unaffected siblings of a child with dominant OI have no greater risk of having children with OI than anyone in the general population. Unaffected siblings of a child with recessive OI have a 67 percent chance of being a carrier for the recessive gene. Genetic testing is available for siblings.

Broken bones that occur from little or no trauma are often the first indication that an infant or child may have OI. Babies with moderate or severe forms of OI are often born with broken bones. Children with milder OI (Type I) often sustain their first broken bone as a result of normal activity—during a diaper change, while being lifted or burped, or when they begin standing and walking. Some very mild cases of OI Type I are not diagnosed until the teen or adult years.

OI remains primarily a clinical diagnosis. A physician, usually a geneticist, who is familiar with all types of OI, can often diagnose the condition based on the presence of fractures and other clinical features. A family history for the disorder and/or genetic testing can confirm a diagnosis. Additional blood and urine tests are often used to rule out other disorders such as Hypophosphatasia or rickets.

The more severe forms of OI can be diagnosed prenatally. Ultrasound can detect bowing, fractures, shortening or other bone abnormalities. But even when ultrasound is done by a highly qualified professional, it may not be possible to pinpoint the type of OI or differentiate between Type II or Type III.

There is no cure for OI, but there are ways to manage the symptoms. Despite the obstacles, many people who have OI lead productive and fulfilling lives well into their adult years. The goal of all treatment is to minimize fractures, enhance independent function, and promote general health. Medical care for children and adults who have OI involves an interdisciplinary team. This can include a primary care doctor, orthopedists, endocrinologists, geneticists, rehabilitation specialists, neurologists and pulmonologists. Treatment may include fracture care, physical therapy, surgical procedures, medications, life style features and mobility aides.

 

Fracture Care. Casting, splinting and bracing broken bones can help them heal properly. However long periods of immobility can further weaken bones and lead to muscle loss, weakness, and more fractures. Many orthopedists prefer to treat fractures with short term immobilization in lightweight casts, splints, or braces to allow some movement as soon as possible after the fracture.

 

Physical Therapy and Safe Exercise. Goals for physical therapy include expanding and maintaining function and promoting independence. A typical program includes muscle strengthening and aerobic conditioning. Physical therapy often begins in infancy to counteract the delay in motor skill development many children experience due to OI related muscle weakness. Adaptive devices may be needed. Occupational therapy can help with fine motor skills and selection of adaptive equipment for daily living. As a child with OI grows older and gains more independence, he or she will benefit from continued physical activity, such as adapted physical education. Adults with OI also benefit from safe, regular exercise to maintain bone and muscle mass. Swimming and water therapy are particularly well-suited for people with OI of all ages, as they allow independent movement with little fracture risk. Walking is also excellent exercise for those who are able (with or without mobility aids).

 

Surgery. Surgery may be needed to repair a broken bone, correct bone deformities such as bowing, stabilize the spine or repair tiny bones in the middle ear and improve hearing. Many children with OI undergo a surgical procedure known as rodding, in which metal rods are inserted into the long bones to control fractures and improve deformities that interfere with function. Both non-expandable and expandable rods are available.

 

Medications. Bisphosphonate drugs, which are currently approved by the Food and Drug Administration (FDA) to prevent and treat osteoporosis are used off label to increase bone density in children and adults with moderate and severe OI. Other drugs that were developed to treat osteoporosis are also used to prevent age-related bone loss in adults who have OI. Teriparatide (a drug based on the parathyroid hormone) is one of them. Treatments under study include growth hormone, and gene therapies. The search continues for a drug treatment that is specific for OI.

 

Healthy Lifestyle. People with OI benefit from a healthy lifestyle that includes safe exercise and a nutritious diet. Adequate intake of nutrients, such as Vitamin D and calcium is necessary to maintain bone health, however, extra-large doses of these nutrients are not recommended.

Maintaining a healthy weight is important since extra weight adds stress to the skeleton, heart and lungs and reduces the ability to move easily. In addition, people with OI should avoid smoking, second hand smoke, excessive alcohol or caffeine consumption and steroid medications, all of which reduce bone density.

 

Other Treatments that focus on OI related symptoms include:

  • Hearing aids
  • Crowns for brittle teeth
  • Supplemental oxygen for people with breathing problems
  • Mobility aids such as walkers, crutches, canes and wheelchairs
  • Never pull or push on a limb, or bend it into an awkward position not even to take an x-ray.
  • Use caution when inserting IVs, taking blood pressure, or performing other medical procedures to avoid causing injury.
  • Always dose medicines to the size, NOT the age of short statured adults.
  • When a fracture is suspected, minimize handling of the affected limb.
  • Respect the opinions, advice, or instructions provided by parents, children, and adults with OI. Based on experience they give good directions for the safest ways to lift, carry or reposition. Having dealt with dozens of fractures and medical procedures, even children have a good sense of when a bone is broken even before x-rays are taken.
  • Handle babies with extra care.
    • Lift a baby with OI by placing one hand under the buttocks and legs, and the other hand under the shoulders, neck and head.
    • Do not lift the baby from under the armpits.
    • Do not lift by the ankles to change a diaper; rather slide a hand under the buttocks.
    • Babies do not need to be kept on a pillow or soft surface. Encourage babies to explore independent movement.
    • Supporting infants in a variety of positions (e.g., side lying, stomach lying) develops muscles that will help with sitting and standing later on.

There is evidence that OI has affected people since ancient times. It has been recognized in an Egyptian mummy of an infant from about 1000 BC. The mummy is currently in the British Museum in London, England. A Viking leader who lived in the 9th century, Ivar Ragnarsson “Ivar the Boneless,” probably had OI. He is reported to have been a very wise leader and a very fierce warrior who had to be carried into battle on a shield because his legs were so soft. Case studies of people with fragile bones and hearing loss began appearing in medical literature in the 1600’s. The term “osteogenesis imperfecta” was used in medical literature beginning in the 1840’s. Early in the 20th century OI was identified as a condition people were born with rather than an illness they acquired later. Today, people who have OI are involved in every walk of life.

This article is based on the brochure, Introduction to Osteogenesis Imperfecta: A Guide for Medical Professionals, Individuals and Families Affected by OI. See the section of this website – “About OI/Publications” – for fact sheets, booklets and videos that provide additional information on many topics related to understanding, treating and living with OI.

 

Brittle Bone Disease Or Osteogenesis Imperfecta (OI) Is A Rare Heritable Condition Of Connective Tissue. It Is Characterized By Brittle Bones, Fractures And Extraskeletal Manifestations. Both Dominant And Recessive Patterns Of Inheritance Are Seen. The Most Common Mutations Affect The Quantity And/Or Quality Of Type 1 Collagen. The Number Of Symptoms And The Severity Of Symptoms Of OI Vary Greatly Among Patients And Range From Mild Forms With Few Exterior Signs To Very Severe Cases Where Life Expectancy Is Decreased. Variable Features Of OI Include Short Stature, Hearing Loss, Scoliosis, Dentinogenesis Imperfecta, And Cardiopulmonary Issues. In Addition, Skin, Blood Vessels And Internal Organs May Be Fragile.

Prevalence And Prognosis

It Is Estimated That 6-7 Per 100,000 People Worldwide Are Affected. This Translates To Approximately 50,000 People In The United States. OI Occurs Equally In Both Males And Females And In All Races And Ethnic Groups. Treatment Is Directed At Addressing Clinical Features And Improving Function. OI Is A Lifelong Condition. Respiratory Failure Is The Most Frequent Cause Of Death For People With OI, Followed By Accidental Trauma. The Most Severe Forms May Cause Death In Infancy. With Good Medical Management And Supportive Care, The Majority Of People Who Have OI Will Lead Healthy, Productive Lives And Can Expect An Average Life Span.

Inheritance Factors

The Majority Of Cases Of OI (Approximately 90%) Are Caused By Dominant Mutations In Genes That Encode For Type 1 Collagen. Other, Mostly Recessive, Forms Are Caused By Mutations That Affect The Collagen Pathway. A Few Additional Forms Have Been Identified That Do Not Have Mutations Related To Type 1 Collagen. Since The 1970s A List Of Numbered Types Has Been Used To Describe The Different Forms Of OI. A Type Chart And A Description Of Clinical Features By Type Are Included For Your Reference. OI Can Be Inherited Directly From An Affected Parent, Or Less Commonly Recessively From Both Parents.  In Some Cases, Parental Mosaicism Has Been Identified As An Additional Mechanism. Spontaneous Dominant Mutations May Be Responsible For 20-30% Of New Diagnoses. These New Mutations Do Not Appear To Be Caused By Poor Nutrition, Drinking Alcohol During Pregnancy, Exposure To Toxins In The Environment, Nor Are They Caused By An Action A Parent Should Have Taken.  Mutations Occur Randomly In Everyone.

Clinical Features

OI Exhibits Wide Variation In Appearance And Severity. Severity Is Described As Mild, Moderate, Severe Or Lethal (Causing Early Death). Clinical Features Vary Not Only Between Types But Within Types And Even Within Families. At Times, The Distinction Between Types May Not Be Clear. Children With Milder OI May Have Few Obvious Clinical Features. It Is Also Important To Recognize That Some Of The Listed Features Are Age Dependent. Besides Fractures, Clinical Features Include:

  • Bone deformity and bone pain
  • Short stature
  • Spine curves
  • Low bone density
  • Hearing loss (present in more than 50% of people with OI)
  • Brittle teeth, dentinogenesis imperfecta or DI, (present in 50% of people who have OI)
  • Respiratory problems including asthma; may be aggravated by chest wall deformity and/or spine deformity
  • Vision problems including myopia and risk for retinal detachment; tinted sclerae (seen in 50% of patients)
  • Loose joints, ligament laxity and muscle weakness
  • Skin hyperlaxity; easy bruising
  • Cardiac issues including mitral valve laxity
  • Fatigue
  • Distinctive features of the skull include wormian bones (60%), late closing fontanels, and head circumference greater than average

General Health Issues

OI Is A Lifetime Disorder And The General Health Care Needs Of Children And Adults Who Have OI Are Similar To Those Of People The Same Age In The General Population.

  • Typical childhood illnesses can be expected
  • Immunizations are not contraindicated and protection from flu and pneumonia is suggested
  • Information on reproductive health is necessary
  • Obesity should be prevented and/or treated
  • Illnesses seen in the general population including diabetes, heart disease and cancer occur
  • Mental health issues including depression, anxiety and coping with social stigma occur

General Care Issues

  • Higher baseline temperature is common; excessive perspiration may be observed
  • Small, fragile blood vessels can lead to difficulty drawing blood or establishing an intravenous line
  • When handling the patient support the spine and all limbs and do not pull or twist the torso or limbs
  • Blood pressure measurements should not be taken on an arm that is fractured or bowed
    • Patients often have anxiety about suffering a fracture from the cuff
    • Pediatric size equipment may be necessary for small adults
    • Manual cuffs are preferred to avoid and promptly relieve patient complaint about tightness
    • Use automatic cuffs with care and consider using the neonatal setting
    • Medication dose is usually based on the patient’s size, not age, in both children and adults
    • Limit exposure to substances that reduce bone density such as corticosteroids
    • Limit exposure to substances with side effects that lead to tendon rupture such as fluroquinolones.

References

Ben Amor IM, Glorieux FG, Rauch F. Genotype-Phenotype Correlations In Autosomal Dominant Osteogenesis Imperfecta. Journal Of Osteoporosis 2011.

Bober, MB (Ed.). (2013). Introduction To Osteogenesis Imperfecta: A Guide For Medical Professionals, Individuals And Families Affected By OI. Gaithersburg, MD: Osteogenesis Imperfecta Foundation.

Shapiro J, Byers PH, Glorieux FG, Sponseller PD (Eds.). (2014). Osteogenesis Imperfecta: A Translational Approach To Brittle Bone Disease 1st Edition. New York, NY: Elsevier Academic Press.

Attribution This Document Was Reviewed By Michael Bober, MD, PhD From Thomas Jefferson Medical College & A.I. DuPont Hospital For Children. February 2015.

 

Osteogenesis imperfecta (OI) is an uncommon (about 1/10,000 worldwide) inherited disorder caused by mutations in any of more than a dozen genes. Multiple types of OI, extreme range of severity, changes across the lifespan, in addition to dominant and recessive patterns of inheritance contribute to the complexity of OI. Identified mutations affect type I collagen genes or are in genes in the collagen or bone formation pathways. This contributes to the wide range of clinical features, beyond fragile bones, that are seen in OI patients.

Genetics and Inheritance Patterns of OI

OI is considered a “heritable” condition because it results from genetic changes. Most people with OI (>90%) have a mutation in one of the two copies of the genes (COL1A1 or COL1A2) that carry instructions for making type I collagen- the protein “scaffolding” of bone and other connective tissues. These mutations either reduce the amount of type I collagen made or alter the quality of the protein. The remaining individuals with OI have mutations in other genes and the inheritance pattern in those families may be either dominant or recessive.

A person’s genetic inheritance is composed of two copies of each gene. Each parent contributes only one of those two copies. If one altered copy of a gene is sufficient to cause a clinical condition, including OI, then the disorder can be transmitted from parent to child and the pattern of inheritance is called “dominant”. Both males and females are affected, and it is clearly transmitted from parents to their children in about 50% of the pregnancies. The first time a mutation appears in the family and it is referred to as a “new dominant mutation”. These usually occur in a single egg or sperm and then can be transmitted in subsequent generations. For the more severe forms of OI, the mutations commonly occur in this fashion and so may be seen only in the affected child who may not reproduce.

In some instances, when the affected child is born to unaffected parents one parent may have only some cells in which the mutation occurred, some of which are in the germ cells and can be transmitted. Those parents are considered to be mosaic for an OI mutation. This means that an OI causing mutation is present in a percentage of one parent’s cells, but does not cause any symptoms in the parent. The chance to have another child in that situation depends on the proportion of cells in the germ cells (sperm or eggs) that have the mutation. It would never be more than 50%.

In the last decade, it has been recognized that some individuals do not have mutations in COL1A1 or COL1A2 yet still have OI. In many of these individuals, it has been found that they have two altered copies of a gene, many involved in collagen processing or bone cell maturation. In these families, each parent has one copy of the altered gene and one copy of the normal copy and the condition is referred to as having “recessive inheritance”. The parents are asymptomatic and both must transmit the altered copy of the gene to have an affected child, a situation that will occur in about 25% of the pregnancies. For complete discussion about the inheritance pattern of OI and recurrence risks, parents are urged to consult with a medical geneticist or a genetic counselor.

A person who has a dominantly inherited form of OI has a 50% chance of passing on the disorder to each of his or her children. An affected child will have the same mutation, and therefore the same type of OI, as the parent. Although the expression- the degree of severity, or number of fractures- may be different among family members, the chance to have an affected child remains 50% with each pregnancy. Unaffected siblings of a child with dominant OI have no greater risk of having children with OI than anyone in the general population. Unaffected siblings of a child with a recessively inherited form of OI have a 67% chance of being a carrier for the recessive mutation but are not at risk to have an affected child unless they have children with another individual who is a carrier for a mutation in the same gene or someone who has OI as a result of two mutations in the same gene. For more information on dominant and recessive forms of OI, and mosaicism, please see the factsheet on Inheritance Patterns How OI Occurs in Families

Diagnosing Osteogenesis Imperfecta

Evidence of OI is often present at birth. In severe instances it can be seen on a prenatal ultrasound, beginning by 14 weeks of pregnancy. Milder forms might not be recognized until the child begins to walk. Unusually low bone density may lead to a young adult’s diagnosis. In the usual situation, the diagnosis of OI is suspected on clinical grounds and can be confirmed by DNA or biochemical testing. A physician, usually a geneticist, who is familiar with OI, can often make the diagnosis on the basis of the presence of fractures and other clinical features. A family history for the disorder and genetic testing can help confirm a diagnosis. Bone densitometry by itself is not diagnostic for OI but lower than expected scores suggest a need for further evaluation for OI and/or other skeletal disorders. Some of the clinical features that are considered in the diagnostic process include: bone density, spine deformity or fractures, tinted sclera (although this is seen outside of OI in children under age 18 months), wormian bones and other skull anomalies, delayed growth and excessive sweating.

Laboratory tests are available to confirm a diagnosis of OI. All forms of OI can be tested for by DNA-based tests using blood or saliva as a source of the DNA. Collagen/skin biopsy is no longer the first choice for testing. Because all genetic causes for OI have not yet been identified, a negative test does not exclude the diagnosis but should initiate reassessment. Test reports are frequently complex. Patients and families may need genetic counseling to understand them and their implications. For a list of laboratories that process OI genetic testing results, please see the factsheet on OI Testing Centers in the United States

Because OI is an uncommon disorder, affected individuals and/or their families may be unfamiliar with the condition. Information and support provided at the time of diagnosis will help them understand their OI and participate in making treatment decisions. Adults who receive a diagnosis may be relieved that some aspects of their medical history now make sense. They will need a plan to maintain general health as they age. Parents of a child with a new diagnosis will need information about treatments and fracture care and access to resources in their community for a child with a disability.

Prenatal Diagnosis

Prenatal testing can detect all forms of OI if the genetic alterations are known. They depend on the ability to obtain a DNA sample from the pregnancy and usually take a sample of the placenta by a process known as chorionic villus sampling (CVS) at about 10 weeks after pregnancy starts. Ultrasound can detect bowing, fractures, shortening and other bone abnormalities, but even experienced professionals may not be able to pinpoint the type of OI or differentiate between OI Type II (lethal), or OI Type III (severe) or other conditions, if neither parent is affected and there is no genetic information to assist in the diagnosis. Cells obtained through amniocentesis can be used for DNA analysis. A fetal MRI does not see bone well, but may offer useful information on other topics. Parents should always be advised as to risks for miscarriage associated with a pre-natal test. Whether one of the parents has OI or prenatal testing suggests the presence of OI symptoms in the fetus, it is recommended that the couples seek genetic counseling.

Postnatal Diagnosis

The diagnostic process begins with a clinical evaluation. If the clinical evaluation indicates the possibility of OI, genetic testing of the patient follows. Unless otherwise indicated, a test for the dominant form of OI is done first, followed by the test for recessive OI. Information about pregnancy and birth is informative since a breach position at birth is common among infants who have OI. For parents who have lost a child to a severe form of OI, testing will confirm the diagnosis and help determine the chance of future affected pregnancies.

Differential Diagnosis

A variety of disorders may present with recurrent fractures due to bone fragility–that is, not everyone with fractures has OI. Other causes of brittle bones include osteomalacia, disuse osteoporosis, disorders of increased bone density and defects of bone, such as fibrous dysplasia and tumors. In determining a cause for brittle bones, it is important to use history, physical examination, laboratory diagnostics and radiographic studies to hone the differential diagnosis. If the history and physical examination do not narrow the differential diagnosis sufficiently, then laboratory tests should be employed.

Child Abuse

The question of non-accidental injury versus osteogenesis imperfecta arises most often when infants and toddlers experience unexpected or unexplained broken bones. A child with a fragile skeleton may fracture during routine care. Toddlers pulling to stand and beginning to walk are also at risk for a fragility fracture. Children who have OI may fracture from little or no apparent trauma and can bruise easily. Bruises may give the impression of greater trauma. In the interest of providing appropriate medical care, when there are no signs of neglect the possibility of mild or moderate OI or a related bone disorder should be considered. An examination and evaluation by a physician who is experienced in diagnosing OI and other rare bone disorders is warranted. Besides OI, other conditions that feature fragile bones and bruising include Ehlers-Danlos syndrome, hypophosphotasia, disorders of vitamin D metabolism, disorders of copper metabolism, and premature birth. DNA or biochemical testing may be necessary.

References

Sutton VR. Differential Diagnosis of Osteogenesis Imperfecta in Children (253-266). In Shapiro JR. (Ed.). (2014). Osteogenesis Imperfecta: A Translational Approach to Brittle Bone Disease 1st edition. New York, NY: Elsevier Academic Press.

Bober MB (Ed.). (2013). Introduction to Osteogenesis Imperfecta: A Guide for Medical Professionals, Individuals and Families Affected by OI. Gaithersburg, MD: Osteogenesis Imperfecta Foundation.

Website- Information about and resources for genetic testing may be found on GeneTests (www.genetests.org) or the GTR: Genetic Testing Registry (http://www.ncbi.nlm.nih.gov/gtr/).

Treatments for Osteogenesis Imperfecta

Treatment for osteogenesis imperfecta (OI) is directed at managing the symptoms. A multidisciplinary approach to treatment is recommended for children and adults. The goal of all treatment is to minimize fractures, enhance independent function, reduce pain and promote general health. Current treatment approaches for the musculoskeletal aspects of OI include: physical therapy, fracture care, orthopedic surgery, medications to strengthen bones, and mobility equipment. Despite the obstacles they face, many people with OI are able to enjoy productive and fulfilling lives well into their adult years. A summary of treatment considerations based on OI Type (degree of severity) is included in the supporting documents.

Pediatric Treatment Summary

Medications

  • IV bisphosphonates (pamidronate (Aredia®) and zoledronate (Reclast®/Zometa®) to increase bone mass; may be started in neonatal period if infant can breathe on own.
  • Supplement with vitamin D and calcium as needed.

Physical and occupational therapy beginning in infancy

  • Both land and aquatic based programs.
  • To improve function, address joint laxity, and improve cardiopulmonary status.
  • To aid development of fine motor skills.
  • To identify appropriate mobility aids.

Surgery

  • To correct bowing of long bones; may involve osteotomies.
  • To insert rods (intramedullary rodding surgery) to support long bones.
  • To stabilize the spine.

    Adult Treatment Summary

    Medications

    • IV and oral bisphosphonates such as alendronate (Fosamax®), teriparatide (Forteo®) or other osteoporosis drugs to maintain bone mass.
    • Supplement with vitamin D and calcium as needed

    Physical and Occupational Therapy

    • To maintain mobility.
    • To adjust to physical changes due to injury and/or aging.

    Surgery

    • Joint replacement,
    • Fracture Repair,
    • Rod repair.

    Monitoring for Children and Adults

    In addition to monitoring for general health and when a patient is receiving drug therapy, regularly evaluate:

    • Lax joints.
    • Muscle strength.
    • Pain level changes; assess for a non-OI problem.
    • Spine curve progression.

    Fracture Care and Repair

    The effects of immobility are cumulative. Long periods of immobility further weaken bones and lead to muscle loss, weakness, and more fractures. Orthopedists who are familiar with OI recommend:

    • Cast or splint with lightweight materials for shortest term possible.
    • Limit use of the spica cast.
    • Avoid the use of plates or pins for surgical fracture repair.
    • Plan for rehabilitation services after fracture or surgery for people with all types of OI including Type I.
    • Acute Care for fractures
      • Immobilize for comfort;
      • Fracture may not be visible in first set of x-rays particularly in child with severe OI;
      • Address pain control
      • Address muscle spasms

    Rehabilitation and Safe Exercise

    Goals for physical and occupational therapy include expanding and maintain function, promoting independence and moving into community based recreational physical activity programs. A typical program includes muscle strengthening and aerobic conditioning that focuses on the individual’s needs. Physical therapy often begins in infancy to counteract delays in motor skill development. It may be needed across the life span in response to injury, surgery or aging. Older children and teens benefit from continued physical activity such as adapted physical education and appropriate recreational activities. Swimming and water therapy are particularly well-suited to people with OI of all ages as it allows independent movement with little fracture risk. Walking is also excellent exercise for those who are able with or without mobility aids.

    Orthopedic Surgery

    Surgery may be needed to repair a broken bone, correct bone deformities such as bowing, or stabilize the spine. Many children with OI undergo rodding surgery to insert metal rods into the long bones. For a discussion of IM Rodding, see the document Rodding Surgery. Issues related to orthopedic surgery for children and adults include positioning, thermal instability, anesthesia, and potential for excessive bleeding.

    Spine curves and fractures are seen in all types of OI including the milder forms. Onset of scoliosis and other curves is often earlier than in most children. Curves may continue to change during the adult years. Vertebral fractures are also seen across the life span. Recommendations include:

    • Monitor for scoliosis, kyphosis, and vertebral compression fractures.
    • Evaluate for curve starting at age 2-3 years in Type III OI or age 6-8 years in mild OI.
      • X-rays should be taken every 1-2 years, as observation alone may not be effective.
    • For people who cannot stand independently, a standard scoliosis exam should consist of a seated AP and lateral x-ray with a level pelvis, except in cases of pelvic obliquity.
    • If the person is able to stand independently, a standing x-ray with a level pelvis should be taken.
    • Surgery is generally recommended following progression to 60 degrees.
    • Factors to consider include age, balanced curve, leg length discrepancy, trunk imbalance, lung function and bone quality.
    • Use of an intermittent soft brace can be effective in mild Type I OI and may work for mild Type IV OI. It is not recommended for other Types of OI due to stresses placed on sternum.
    • Research into the role of exercise to improve or prevent scoliosis is ongoing.

    Medications

    At this time, there are no drug therapies specifically developed to treat OI in either children or adults. The drug therapies currently in use are based on medications developed to treat age-related osteoporosis or cancer-related bone loss in adults in the general population. Bone strengthening in an effort to reduce the frequency and seriousness of fractures is a key treatment issue for children and adults who have OI.

    Bisphosphonates: Bisphosphonate drugs which are currently approved by the US Food and Drug Administration to prevent and treat osteoporosis and bone complications of cancer have become a standard treatment to increase bone density in children with moderated and severe OI. There are many different types of bisphosphonates. The two that are most often prescribed for people with OI are pamidronate (Aredia®) and zolendronic acid (Reclast®).  Pamidronate has been studied the longest.  Bisphosphonate treatment has been shown to reduce pain, and increase bone mineral density in children. The effects of such treatment on fracture frequency and bone deformity are less clear, but there are studies that have shown reduction in fracture rates in treated children. Side effects include a drop in blood levels of calcium especially at the start of the treatment and delayed bone healing after osteotomies. The longer-term side effects of pamidronate treatment are not well known. Several different protocols are currently in use. When to start treatment, most effective dose, and how long to treat are issues that continue to be studied. In children, once bisphosphonate treatment is initiated, it is important to maintain it (often at a reduced maintenance dose) until growth plates are fused in order to protect the new bone formed during the growing process. Bisphosphonates do not build new bone, or improve the quality of existing bone. They do not address any of the non-skeletal features of OI.

    Zoledronic acid is a newer bisphosphonate that is given intravenously like pamidronate but only requires one 30-60 minute infusion every 6 months. It is as effective as pamidronate when the treatment is started; however the best dose for long-term treatment is not yet known. Alendronate (Fosamax®) is a bisphosphonate given orally. It has been shown to increase bone density but does not appear to have a significant effect on fracture rates or pain in children with OI. There is no evidence at this time of osteonecrosis of the jaw in children who have OI who are treated with the appropriate dose of a bisphosphonate. This problem has not been studied in adults with OI. See the supporting document Bisphosphonate Protocols for information on administering these drugs.

    Use of Bone Building Drugs for Adults with OI: Adults who have OI frequently are treated with bisphosphonates and other drugs developed to treat age-related osteoporosis. Adults may receive oral or intravenous bisphosphonates. Unlike the experience with children, treatment with bisphosphonates has not been shown to significantly decrease fractures in the OI adult. In addition in studies conducted on adults with osteoporosis, it has been noted that some individuals experience musculoskeletal pain due to bisphosphonate treatment. This is now mentioned as a warning on the product insert for most types of bisphosphonates. Bone building drugs are typically not prescribed to young adults.

    Teriparatide (Forteo®) is a medication that builds bone rather than preserving existing amount of bone like bisphosphonates. Teriparatide has been shown to increase bone mineral density and increase bone strength, but the effects on fracture are not clear. It appears that this form of treatment may be more beneficial to those with milder forms for OI. It is given as a daily injection. It has been approved by the US FDA as a treatment for osteoporosis in adults but it is not approved for use in children who are still growing.

    Growth Hormone Therapy has been studied as a treatment for children with OI. Although people who have OI are sometimes short in stature, this does not appear to be due to a lack of growth hormone. Studies indicate the some children with OI (moderate OI Type IV) respond to a daily injection with an initial increase in growth. Responders show changes in bone architecture and small increased in BMD; bone strength and growth are also positively affected. There is no data at this time regarding any effect on fracture rate

    Mobility Aids
    Correct sizing of aids – walkers, canes, crutches and wheelchairs—is important to mobility and to reducing use-related injuries. It is not unusual for children and adults to use different mobility aids depending on whether they are at home, or out in the community.

    Other Treatment
    Information Additional information about treatments for hearing loss, cardiac, vision, respiratory and other problems associated with OI can be found in the Non-Skeletal Issues section of the this website.  The sections on Pediatric and Adult Care cover treatment and management topics that are particular to either the child or the adult with OI.

     

    References

Non-skeletal Issues of Osteogenesis Imperfecta

Early definitions of osteogenesis imperfecta (OI) refer to a syndrome of fragile bones plus hearing loss. This suggests that the problems seen in people with OI include more than just brittle bones. In dominant OI, the mutation in type 1 collagen affects not only the skeleton but also the collagen-rich tissues in other organ systems. Like the skeletal manifestations, the non-skeletal clinical features vary in the degree of severity. In some instances, age is also a factor in severity. Research is needed to fully understand the prevalence and best approach to management of non-skeletal issues.

More detailed information and recommendations for many of the following topics is provided in the Supporting Documents for this section.

Dental Oral-Facial

OI affects the growth of both jaws and tooth development. In addition, about 50% of people with OI also have dentinogenesis imperfecta (DI). Regular dental care is recommended for all people with OI beginning within 6 months after the primary teeth erupt and continuing throughout life. Other common oral cavity problems related to OI include impacted teeth, anterior and posterior open and cross bites and skeletal Class III malocclusion.

Pulmonary

In people with severe forms of OI respiratory complications are a leading cause of death. Although respiratory problems are usually more severe in those with severe OI, the primary collagen defect affects lung tissue in all people with OI, including those with a mild phenotype. Altered lung tissue predisposes the person to respiratory infections.

Rates of asthma and pneumonia are higher in children and adults who have OI than in the unaffected population. Chest wall deformities, rib fractures, scoliosis, kyphoscoliosis, chest wall muscle weakness, limited mobility and the effects of gastrointestinal problems such as constipation and reflux all contribute to poor pulmonary function. Fatigue, breathlessness and wheezing are frequent symptoms. Manifestations can include asthma, recurrent pneumonia, exercise intolerance, and sleep apnea.

Hearing

Approximately 50% of adults with OI have a measurable hearing loss, which typically arises in the second or third decade of life. Bone quality and structural abnormalities of the ear bones — including visible deformities in the ossicles and inner ear– contribute to the loss. Environmental factors affecting hearing may cause a loss sooner than in the unaffected population. Most hearing loss in OI is mixed but conductive, and sensorineural types of loss are seen. Severity ranges from mild to profound. In addition, some people report tinnitus and vertigo. Treatments include hearing aids and/or surgery such as stapedectomy or cochlear implant. Physicians should be alert to dangers of ototoxins in this population.

Cardiovascular

The prevalence of cardiovascular problems among patients with OI is unknown. The most frequently reported cardiovascular issues are hypertension, and mitral valve prolapse. Heart valve problems are believed to develop over time. They are more of a concern for adults who have OI, but are infrequently seen in children. Cardiac surgery, including valve replacement, has been successful.

Neurological

Intelligence is typically normal in OI. People with all subtypes of OI may develop basilar impression (BI) over time, and those with severe OI (Type III) have a greater risk. Enlarged head circumference is seen in infants and children who have OI and may or may not be caused by hydrocephalus. Evaluation is required; shunting is possible

Vision

People with OI seem to experience the common refractive errors such as myopia, hyperopia or astigmatism at about the same rate as people in the unaffected population. More serious conditions like glaucoma and retinal detachment are seen in adults, but the incidence is unknown. Blue sclerae, a frequently described finding, may be associated with corneal thinning. Scleral thickness is normal in OI Type I but may be thin in other types of OI.

Connective Tissue: Blood Vessels, Skin, Tendons and Ligaments

  • Thin blood vessels and thin skin may cause people to bruise easily.
  • Skin may be stiffer and less elastic, increasing the risk for scarring.
  • Reduced muscle strength may be significant in those with moderate and severe forms of OI.
  • Joint laxity is common and contributes to frequent sprains and dislocations particularly of the ankles, hips, shoulders, thumbs and elbows.
  • Flat feet are common, particularly in Type I (the mildest type).
  • Hernias may be present at birth and occur more frequently in children with OI than in the general population.

Endocrine

  • People with more severe forms of OI are often short however growth hormones and other hormones are typically normal.
  • Excessive diaphoresis has been reported in individuals of all types of OI.
  • Young women with OI may start menstruating later than other women.

Gastrointestinal

  • Constipation is common in children and adults with OI.
  • Spine, hip and pelvic deformities contribute to constipation in severely affected children.
  • Treatments include diet, hydration, physical activity and medication.
  • Celiac disease, gluten sensitivity, and colitis are reported in children, teens and adults with all types of OI, but it is not clear if these are more common than in the general population.

Pain

People who have OI experience acute pain from an injury; surgical pain; and varying degrees of chronic pain. Back pain may be due to compression fractures of the spine or spine curves such as scoliosis or kyphosis. Some people may have pain without clear evidence of a fracture. Adequate pain management is essential to maintaining mobility and improving quality of life. People with OI feel the same level of pain as others but may complain less since they experience pain more often than others.

Shapiro J., Byers PH, Glorieux FG, Sponseller PD (Eds.) (2014). Osteogenesis Imperfecta: A Translational Approach to Brittle Bone Disease 1st edition. New York, NY: Elsevier Academic Press.

Care for Children Who Have OI

Care for children who have OI should be customized to meet the needs of each individual child. No two children with OI are exactly alike: the picture of OI varies greatly, not only between different types, but also within groups. Elements of a care plan will include:

  • Management of skeletal and non-skeletal issues;
  • Rehabilitation to enhance function and encourage development of maximum bone mass;
  • Nutrition counseling for health and weight control;
  • Surgical/hospital care that reflects knowledge of OI and respect for bone and tissue fragility;
  • Referrals to other specialists, including mental health professionals, as needed;
  • Attention to normal childhood diseases and immunizations;
  • Age appropriate information about reproductive health, and sexuality.

Interdisciplinary Care

Children benefit from coordinated interdisciplinary care from physicians familiar with OI. A number of medical centers across the United States and Canada have OI clinics and/or research programs, often as components of genetics or bone dysplasia centers. The OI Foundation maintains a “Clinic Directory” on its website. In other communities the parents and the primary care physician work together to create a network of health care providers for the child with OI. Clear and timely communication between all health care providers is important.

General Pediatric Care

The general health needs of children with OI are the same as other children. Typical childhood illnesses can be expected, but ear infections may occur more frequently. Children with all types of OI have a predisposition to respiratory infections; they may be more serious in children with OI Type III. Immunizations are not contra-indicated and are encouraged. Physicians with experience caring for children with OI suggest:

  • Titrate medication dosage to a child’s weight, not age, even with older children and teens.
  • Monitor the use of non-steroidal anti-inflammatory (NSAIDS) drug. Some have been linked to retarded bone healing after fracture.
  • Minimize the use of drugs that contain steroids because of negative effects on bone metabolism.
  • It is beneficial when PCP office personnel are trained in OI-specific safe handling techniques.

Monitoring

  • Routine screenings are needed for vision, hearing and dental care.
  • Spine checks for scoliosis and kyphosis beginning at age 2 years.
  • Bone density testing is recommended to help monitor changes over time.  A baseline test when a new course of treatment is started is informative along with a test approximately 6-12 months after a change in treatment.
  • Echocardiogram as a baseline heart valve screening during later teen years or early young adult.
  • Consult with an orthodontist no later than age 7 to assess jaw development, and presence of malocclusions or cross-bite.
  • Perform a baseline quantitative Pulmonary Function Test (PFT) on all children with OI at age 5 or when the child can cooperate, and again at maturity (age 20-25 years). If PFT is normal, repeat every 2 years.

Diet and Nutrition

Children with OI need a balanced diet containing adequate water, fiber, calcium and vitamin D calibrated to their age and size. Nutrition counseling for parent and child may be beneficial.

  • Slow weight gain is seen in infants and may not be failure to thrive.
  • Swallowing difficulties, reported in some toddlers, may require referral to an occupational or speech therapist, or a nutritionist who treats feeding disorders.
  • Small appetite is seen in children of all ages. Inactivity, pain, medications and depression are potential causes.
  • Constipation is seen in children of all ages and with all types of OI and can be recurrent. Short stature, inactivity, pelvic deformity and difficulty with hydration are contributing factors.
  • Weight control is important, as obesity places a strain on the fragile skeleton and can lead to loss of mobility. Hormonal changes related to puberty can contribute to unhealthy weight gain, especially in girls who have OI.

Mental Health

Living with OI presents emotional as well as physical challenges for the child, parents and siblings. Health care providers are encouraged to note signs of depression, substance abuse, and fearfulness, and to make referrals to mental health professionals. Children may experience low self-esteem and anxiety. Children with the milder forms of OI may struggle to cope with having a hidden disorder that can be misunderstood by their peers. Older children may become discouraged by the repeated need to re-learn mobility skills, receive painful therapies and miss out on activities with their peers due to fractures and reduced mobility. Relationships between siblings can be strained.

Development

OI does not affect a child’s ability to think and learn, but children with OI often demonstrate delays in meeting developmental milestones. These delays can be the result of repeated immobilizations after fractures, misalignment of the long bones and joints and the general hypotonia and ligamentous laxity common in OI. Interventions can include physical and occupational therapy, braces, use of adaptive equipment and mobility aides. Small-muscle development, especially in hands and fingers, is likewise affected. To the best of our current knowledge, the incidence of autism, hyperactivity and childhood cancers is believed to be similar to that seen in the unaffected population.

Growth

Mild to significant short stature and a slow growth rate occurs in OI. Hip and back pain due to poor alignment and leg length discrepancies occur in all types of OI and should be evaluated by an orthopedist and/or a gait specialist. Height and weight charts for the child with OI are available.

Other Pediatric Treatment Information

Additional information about treatment for the musculoskeletal issues associated with OI can be found under the Treatment Section of this website. Information managing hearing loss, cardiac, vision, respiratory and other non-skeletal issues associated with OI can be found in the Non-Skeletal Issues section.

References

Glorieux F. (2007) Guide to Osteogenesis Imperfecta for Pediatricians and Family Practice Physicians. Osteogenesis Imperfecta Foundation. Gaithersburg, MD.

Attribution Thank you to Dr. Francis Glorieux, Canadian Shriners Hospital for Children and McGill University in Montreal, Quebec, for reviewing this document. April 2015.

Adults Who are Affected by OI

Take Charge of Your Health

A Tool Kit of Materials for Adults who have OI and Their Doctors

For All Adults

 

For Teens and Young Adults

To Share with Your Doctors

NEW! The OI Foundation would like to bring your attention to a new publication-
A Recommendation from OI Experts- Treating the Adult with OI. A panel of experienced physicians, led by Dr. Jay Shapiro and Dr. Eric Orwoll, developed this recommendation to assist physicians in formulating pharmacological treatment plans for adults living with OI. This document was reviewed by the OI Foundation’s Medical Advisory Council and is available as a service to the OI community. The OI Foundation always recommends to consult with your local medical team and nearest OI Clinic about your personal treatment plan. Email Bonelink@oif.org or call (301) 947-0083 if you are looking for an OI clinic or a physician referral, or if you have any questions.

The Adult Health Initiative: Working to Improve the Health and Well-being of Adults with Osteogenesis Imperfecta.

The Adult Health Initiative is a multi-year effort sponsored by the OI Foundation. It is a series of research projects, publications, and outreach efforts to OI Adults and their Physicians. Long term goals for the Adult Health Initiative are to:

  • Increase knowledge about the health status, needs and health priorities of adults with OI
  • Encourage, and when necessary, self-fund studies specifically designed to improve the health of adults who have OI.
  • Equip adults who have OI and their health care providers with information they need to anticipate problems, and when possible prevent or minimize symptoms that are aggravated by time and age.


Activities and Resources

  • OIF website section for Medical Professionals has specific information on the health care needs of adults with OI. Adults are encouraged to review the new podcasts on OI. A link to them is under the Medical Professionals Tab.
  • Brittle Bone Disorders Consortium studies of specific adult OI issues including Quality of Life and Pregnancy for Women with OI.
  • Longitudinal Study of OI. This natural history study is continuing as a key project of the Brittle Bone Disorders Consortium and is collecting information about how OI changes during the years.
  • 2011 Adult Natural History Initiative Survey laid the foundation for identifying and prioritizing the health questions adults with OI are concerned about and how they compare to adults in the general population. Results from this survey have been published. (See the Research and Studies Tab for a link.)

 

Upcoming Research – Pulmonary Function

The OIF is preparing a series of studies related to breathing issues faced by adults with OI.

Summary: Health Information for Adults

Basics 

  • The general health needs of adults with OI are the same as in unaffected adults. OI may complicate treatment of various illnesses or injuries due to the fragility of the bones, the blood vessels and the internal organs.
  • Special health needs may include pulmonary (breathing issues) and a possible increased risk for heart valve problems.
  • Weight management, healthy diet, appropriate exercise and maintenance of bone mass are the corner stones of health management.

Issues to Keep Track of 

  • Routine screenings are needed for vision, dental, and hearing.
  • Obtain a baseline Quantitative Pulmonary Function Test (PFT) to monitor lung function.
  • Until there is more information on heart issues, a baseline echo-cardiogram is suggested for young adults along with blood pressure monitoring.
  • Talk with your doctor about post-menopausal changes to spine, joints, and signs of arthritis.
  • Monitor changes in pain level and discuss with your doctor potential for non-OI problems.

Taking care of your general health makes a difference.

  • Exercise as possible in a safe and regular manner.
  • Maintain healthy weight; extra weight is a strain on your skeleton and heart.
  • Follow a healthy diet with adequate numbers of calcium and vitamin D.
  • Monitor respiratory health especially if you have scoliosis or compression fractures of the spine.
  • Protect your hearing.
  • Take safety precautions; trauma from accidents is a leading cause of death.
  • Use seat belts in vehicles and wheelchairs.
  • Be alert to situations at home and away that could cause a fall.

Medicines

  • Talk with your doctor about adjusting the dose of medication to your weight and height, rather than age.
  • Monitor the use of NSAIDS due to link to delayed bone healing after fracture.
  • Minimize the use of drugs that contain steroids because of the negative effects on bone.
  • Discuss your risk of spontaneous tendon rupture seen in people with a connective tissue disorder when using antibiotics known as fluroquinolones (Cipro, Levaquin).

Resources for Adults with OI and their Physicians

  • Factsheets on many topics of interest to adults with OI are listed in the Information Center section of this website.
  • Information Center for Medical Professionals: Section on Adult Care.
  • Podcasts (See link on Medical Professionals Page).