Osteogenesis Imperfecta: Difference between revisions

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== Definition/Description ==
== Introduction ==
[[File:1024px-X ray for osteogenesis imperfecta.jpeg|alt=|Figure 1. X-ray of osteogenesis imperfecta.|thumb]]
Osteogenesis imperfecta (OI) is a "heterogeneous group of [[Congenital and Acquired Neuromuscular and Genetic Disorders|congenital]], non-sex-linked, [[Genetic Disorders|genetic disorders]]".<ref name=":0" /> It affects the production or processing of type 1 collagen, and therefore, impacts [[Connective Tissue Disorders|connective tissue]] and [[bone]].<ref name=":0" /><ref name=":2">Subramanian S. StatPearls Publishing LLC.; Treasure Island, FL, USA: 2021. Osteogenesis Imperfecta.</ref> 


Osteogenesis imperfecta (OI) is a rare genetic disorder of the synthesis of collagen that affects bone and connective tissue that can also be referred to as brittle bone disease. OI can occur by both inheritance and spontaneous genetic mutation andhas been linked to over 150 genetic mutations that all take effect on the genes COL1A1 and COL1A2. These are the&nbsp;genes that make up type I collagen. The mutation can either cause collagen production that is too low, or cause abnormal polypeptide chains that are unable to properly form type I collagen. There are four primary types of osteogenesis imperfecta that are described by the Sillence Classification of Osteogenesis Imperfecta.<ref name="Goodman">Goodman CC, Fuller KS. Pathology: Implications for the Physical Therapist. 3rd edition. St. Louis, Missouri: Saunders Elsevier, 2009.</ref>  
It is also referred to as "brittle bone disease". Individuals with OI are susceptible to fractures and reduced bone density.<ref name=":2" /> They may present with [[osteoporosis]] and blue sclera (i.e. the white part of the eye), and their teeth and hearing can be affected.<ref name=":0">Osteogenesisi Imperfecta. Available from: https://radiopaedia.org/articles/osteogenesis-imperfecta-1 (Accessed, 15/10/ 2021).</ref> It can also impact mobility and an individual's ability to perform activities of daily living.


"Sillence Classification of Osteogenesis Imperfecta
OI can have a negative effect on the social and emotional well-being of young people with this condition and their families. Adopting a coordinated, [[Multidisciplinary Team|multidisciplinary team]] approach helps to ensure that children with OI can "fulfill their potential, maximizing function, independence, and well-being."<ref>Marr C, Seasman A, Bishop N. Managing the patient with osteogenesis imperfecta: a multidisciplinary approach. Journal of multidisciplinary healthcare. 2017; 10:145.</ref>
== Epidemiology ==
OI is a rare condition. The estimated incidence is approximately 1 in every 15,000 to 20,000 births.<ref name=":2" /> It affects males and females equally, and there are no differences in terms of race / ethnic group.<ref name=":0" />


'''<u>Type I (most common form)</u>'''<br>  
== Aetiology ==
OI usually occurs secondary to mutations in the ''COL1A1'' and ''COL1A2'' genes, but there have been diverse mutations related to OI identified more recently.<ref name=":2" />


*Mildest form of OI
== Pathology ==
*Mild to moderate fragility without deformity
In OI, the synthesis of type I collagen is affected. Type I collagen forms the main protein of the extracellular matrix of many of our tissues, including our skin, bones, tendons, skin and sclerae.<ref name=":0" /><ref name=":2" />
*Most fractures occur before puberty
== Clinical presentation ==
*Associated with blue sclerae, triangular face, hearing loss (beginning in twenties or thirties), easy bruising<br>
[[Image:X-ray OI.jpg|Image of OI X-ray. This picture is included courtesy of gghjournal.com.|alt=|thumb]]There are four major clinical features that characterise OI, but each individual's presentation varies depending on their type of OI.<ref name=":0" /><ref name=":1" />  


[[Image:Blue sclera.jpg|center|This picture is included courtesy of img.tfd.com.]]<u>'''Type II'''</u><br>  
# Osteoporosis / bone fragility
#* fractures
#* bone deformities
# Discoloration of the sclera (white of the eye)
#* may be blue or gray in colour
# Dentinogenesis imperfecta
#* discolouration of teeth (e.g. blue-gray / yellow-brown colour)
#* translucent and weakened teeth
#* can affect baby and adult teeth<ref>Dentiogenesis Imperfecta. Available from: https://medlineplus.gov/genetics/condition/dentinogenesis-imperfecta/ (Accessed, 15/10/2021).</ref>
# Hearing impairments


*Most severe form of OI (perinatal lethal)
OI can also cause laxity of ligamentous, joint [[Hypermobility Syndrome|hypermobility]], short stature and individuals are prone to bruising.<ref name=":0" />
*Stillbirth or death during infancy or early childhood
== Types of OI ==
*Extreme fragility of connective tissue
There are at least eight different types of OI, but three types are said to be easily distinguished.<ref name=":0" />
*Multiple in utero fractures
*Usually intrauterine growth retardation
*Severe bone deformity
*Soft, large cranium
*Micromelia: long bones crumpled and bowed; ribs beaded&nbsp;


<u>'''Type III'''</u>  
* Type I:<ref name=":1" />
** The most common and mildest type of OI
** Around 50% of children with OI have Type 1 OI
** Individuals have few fractures / deformities
** Have half the amount of normal collagen
** Blue sclera
** Generalised osteoporosis
** Joint hyperlaxity
** Conductive hearing loss
** Dentinogenesis imperfecta<ref name=":4">Eskay, K. Paediatric Conditions: Down Syndrome, Duchenne Muscular Dystrophy, Osteogenesis Imperfecta and Arthrogryposis Multiplex Congenita. Plus. 2023</ref>
* Type II:<ref name=":1" /><ref name=":2" />
** The most severe type of OI - it is a lethal condition, usually within weeks of birth
** Causes severe disruption of the "qualitative function" of the collagen molecule<ref name=":2" />
** Infants with Type II OI present with very short arms and legs, small chest and they have delayed ossification of the skull
** There may be fractures at birth, low birth weight and under-developed lungs
* Type III:<ref name=":1" />
** Children who have severe clinical signs tend to have Type III OI
** They tend to present with moderate to severe fragility of bones, coxa vera, they may have slightly shorter arms and legs, and have arm, leg, and rib fractures
** Infants may have a larger head, a triangular-shaped face, changes in their chest and spine (scoliosis), and difficulties with breathing and swallowing
** May also have frontal bossing (i.e. prominent forehead), basilar invagination, short stature
** Symptoms vary in each infant<ref name=":1">Osteogenesis Imperfecta. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/osteogenesis-imperfecta (Accessed,  15/10/2021).
</ref>


*Moderately Severe &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;&nbsp;&nbsp;
* Types IV to VIII are not common and vary in terms of their severity<ref name=":0" />
*Progressive deformities
** Shorter in statue
*Scoliosis
** Frequent fractures that decrease after puberty
*Triangular face, large skull
** Mild to moderate bone deformity
*Severe osteoporosis
** Average life expectancy<ref name=":4" />
*Severe fragility of bones; usually in utero fractures
== Diagnosis ==
*Factures heal with deformity and bowing
The following diagnostic tests may be recommended:<ref name=":1" />
*Associated with tinted sclerae (blue, purple, or grey)
*Extremely short stature
*Usually wheelchair bound by teenage years


[[Image:Lg wyse family.jpg|center|This picture of the Wyse family is included courtesy of the Agape Family Life House website agapeflh.org.]]
# [[X-Rays|X-rays]]: able to show weakened / deformed bones,  fractures
# [[Laboratory Tests|Lab tests]]: including blood, saliva, skin and gene testing
# Dual Energy X-ray Absorptiometry scan (DXA or DEXA scan): to investigate softening of bone
# Bone biopsy (taken at the hip)


<u>'''Type IV'''</u><br>  
== Prognosis ==
Prognosis is variable depending on the type of OI.<ref name=":2" />  


*Variable but usually milder course; normal or near-normal lifespan
# Age of onset of long bone fractures is a prognostic indicator for ambulatory ability.
*Mild to moderate skeletal fragility and osteoporosis (more severe than type I)
# Survival: Location and severity of fractures, and appearance of the skeleton on radiography are significant indicators for survival.
*Associated with bowing of long bones
# The type of OI is the most important clinical indicator for ability to ambulate. Early achievement of motor milestones is associated with the ability to walk independently when the type of OI is not known.<ref>Engelbert RH, Uiterwaal CS, Gulmans VA, Pruijs H, Helders PJ. Osteogenesis imperfecta in childhood: prognosis for walking. J Pediatr. 2000 Sep;137(3):397-402.</ref>
*Barrel-shaped rib cage
*Bones fracture easily before puberty; some children improve at puberty
*Light or normal sclerae; may or may not have moderately short stature and joint hyperextensibility"<ref name="Goodman" />


<br>  
== Complications ==
Complications associated with OI vary depending on the type of OI, but they can affect most body systems. They may include the following:<ref name=":2" /><ref name=":1" />


Below is a documentary from the Discovery Channel titled "Children of Glass" courtesy of Youtube.com.  
* Respiratory infections eg. [[COVID-19|COVID 19]], [[pneumonia]]
* Cardiac issues eg. [[Cardiac Valve Defects|cardiac valve defects]]
* [[Nephrolithiasis (Kidney Stones)|Kidney stones]]
* Tumour (osteogenic sarcoma)
* Joint conditions
* Basilar invagination
* Eye conditions and vision loss
* Malignant hyperthermia


{{#ev:youtube|TpAMTOud3bw}} {{#ev:youtube|GTpSxlPzC8k}} {{#ev:youtube|L2f8fz6vzoI}} {{#ev:youtube|QvbY7XqyMz8}}
== Treatment ==
Treatment focuses on the prevention of deformities and fractures and the maintenance of independence.<ref name=":1" />
=== Team Approach ===
OI should be managed with an interdisciplinary team that may include primary care physician, orthopedist, geneticist, nutritionist, social worker, and psychologist, physiotherapists, occupational therapists. Pulmonologists may be involved in the care of individuals who have scoliosis that impacts pulmonary function.<ref name=":3">OI foundation [https://oif.org/wp-content/uploads/2019/08/PT_guide_final.pdf Physical and Occupational Therapists Guide to Treating Osteogenesis Imperfecta] Available:https://oif.org/wp-content/uploads/2019/08/PT_guide_final.pdf (accessed 15.10.2021)</ref>


== Prevalence  ==
Management options include:<ref name=":0" /><ref name=":1" />


Currently it is estimated that there are around 30,000 to 50,000 people in the United States living with osteogenesis imperfecta. The majority of kids with osteogenesis imperfecta inherit the genetic mutation from one of their parents. A parent that carries the OI genetic mutation has a 50% chance of passing this defect to their children. Around 25% fall in the category of children who have had spontaneous gene mutation leading to the diagnosis of OI.<ref name="Goodman" /> Osteogenesis imperfecta type I is the most common and has been found to be the type for around 50% of the people that have OI.<ref name="Kennedy">Kennedy Krieger Institute. About Osteogenesis Imperfecta. http://www.osteogenesisimperfecta.org/about-osteogenesis-imperfecta.php. Website updated: 2010. Website accessed: March 1, 2010.</ref> The incidence for OI in the United States is about 1 in 20,000 people<ref name="Goodman" /> and around 6 to 7 in 100,000 people worldwide.<ref name="NIH">National Institute of Health. Genetics Home Reference - Osteogenesis Imperfecta. http://ghr.nlm.nih.gov/condition=osteogenesisimperfecta. Website updated: 2007. Website accessed: March 2, 2010.</ref><br>
* surgery to help prevent fractures and to correct deformities (including intramedullary rods with osteotomy)


== Characteristics/Clinical Presentation  ==
* fracture care - casts tend to be made from the lightest material possible, movement of the affected area is encouraged as soon as possible
* bisphosphonates to strengthen bones and prevent fractures where possible
*[[The influence of human growth hormone (HGH) on physiologic processes and exercise|growth hormone]] therapy<ref name=":0" />
* treatment for dental issues - including capping teeth, braces, etc
*[[Assistive Devices|assistive devices]]<ref name=":1" />


Due to the different classifications, a patient with osteogenesis imperfecta can present anywhere from appearing normal with fractures that occur occasionally, to someone very small in stature with deformities to both the spine and long bones throughout the body.<ref name="Goodman" /> The clinical presentation of patients with OI is easier to picture when broken down into the four primary classifications.<br>  
== Rehabilitation ==
Therapists should remember the following when working with individuals with OI and their families:<ref name=":3" />  


<u>'''Type I'''</u><br>
* Listen and respect individuals with OI and their families.


*Due to only 50% of the collagen being produced, the patient's bones are predisposed to fracture. Most fractures in this classification occur before the child reaches puberty.<ref name="Goodman" /><br>
* Set goals that are realistic, achievable, and incremental.
*Lax Joints<br>
* Weakness affects movements in OI - individuals with OI do not tend to have other neurological issues such as impaired coordination, sensation or cognition.
*Low muscle tone<br>
* Individuals with OI may be fearful of fractures and this can significantly impact movement. It can be useful to:
*Tinted sclerae that may appear to be slightly blue, grey, or purple<br>
** establish safe movement patterns
*Possible scoliosis<br>
** encourage self-confidence
*Stature should not be affected much, if at all<br>
** optimise strength
*Possible hearing loss that usually occurs in the third or fourth decade of life<br>
* Expect success - with the appropriate environment and equipment, most individuals with OI can perform most activities of daily living, including self-care, school and work.
*Triangular shaped face<br>
*Very mild to no bony deformities<br>
*Teeth may be brittle and easily broken<ref name="OIF">Osteogenesis Imperfecta Foundation. OI: Guide for Medical Professionals, Individuals, and Families. http://www.oif.org/site/PageServer?pagename=Guidefor. Website updated: 1999. Website accessed: March 1, 2010.</ref><br>


'''<u>Type II</u>'''<br>  
Enhancing strength and function is essential for health and wellbeing and bone health. Rehabilitation approaches include:<ref name=":3" />


*Due to only 20% of the normal amount of collagen being produced due to malformation, this is the most severe type of OI.<ref name="Goodman" />
# [[Therapeutic Exercise|Exercise]], including [[weight bearing]] activities (braces may be needed)
*Usually results in stillbirth or death occurring in the early years of childhood. There have been a few people with type II OI that have survived into young adulthood.  
# Low-impact activities such as [[Aquatherapy|swimming]] (precautions must be defined)
*Respiratory problems that can lead to death[[Image:Deformed Long Bone X-ray.jpg|right|This picture is included courtesy of MyPACS.net]]  
# Care with safe handling and encouraging changes in body positions / postures throughout the day to help strengthen muscles / prevent deformities
*Severe bone deformities<ref name="OIF" />
# Prescribing appropriate adaptive equipment (e.g. [[Canes|cane]], [[Walkers|walker]], manual or power [[Wheelchair Fitting|wheelchair]]).
*Multiple in utero fractures
# Adapting the environment as needed (e.g. at work, home, school)
*Soft, large cranium
Individuals with OI might require intermittent or long-term rehabilitation for the following reasons:
*Micromelia: long bones that are crumpled and bowed; ribs beaded"<ref name="Goodman" />
# They have delays or weakness in motor skills
# They have had a fracture, surgery or injury
# They are experiencing fear of movement and are trying new skills and activities
# They are transitioning to a new stage of life etc, and need to get used to a new environment or train for a specific activity of daily living<ref name=":3" />
'''Key Principles of Therapeutic Strategies'''


<u>'''Type III'''</u>  
When designing a rehabilitation programme for OI, it is necessary to engage in an appropriate task analysis. The following are useful points to consider:<ref name=":3" />


*Very short stature
* Skill progression - develop and progress gross motor skills (reaching, sitting etc) if they are delayed / difficult, particularly for individuals with severe OI. Skills may need to be retrained in adults after injury. 
*Triangular face
* Using preventive positioning, protective handling and active movement with gradual progression can help to facilitate motor skill development safely. 
*Easily fractured bones
* Hydrotherapy can be useful for motor skill development and for individuals with fear of movement. 
*Scoliosis
* It is vital to ensure that an individual has appropriate equipment and assistive devices.
*Tinted sclerae that may appear to be slightly blue, grey, or purple
* Encourage healthy living to promote general health.
*Barrel-shaped chest
*Teeth may be brittle and easily broken
*Possibility of problems with respiration
*Possible hearing loss
*Increased joint laxity<ref name="OIF" />
*"Severe osteoporosis
*Fractures heal with deformity and bowing [[Image:Deformed Bones X-ray.jpg|This picture is included courtesy of uhrad.com]]
*Large skull
*Usually in utero fractures
*Usually wheelchair bound by teenage years"<ref name="Goodman" />


<u>'''Type IV'''</u>  
== Children of Glass ==
The following videos include excerpts from the Discovery Health documentary on the genetic brittle bone disorder "Osteogenesis Imperfecta" .
<div class="row">
  <div class="col-md-6"> {{#ev:youtube|TpAMTOud3bw|300}} <div class="text-right"><ref>Bublitz Videos. Children of Glass - (Part 1 of 4). Available from: http://www.youtube.com/watch?v=TpAMTOud3bw [last accessed 27/8/2020]</ref></div></div>
  <div class="col-md-6"> {{#ev:youtube|GTpSxlPzC8k|300}} <div class="text-right"><ref>Bublitz Videos. Children of Glass - (Part 2 of 4). Available from: http://www.youtube.com/watch?v=GTpSxlPzC8k [last accessed 37/8/2020]</ref></div></div>
</div>
<div class="row">
  <div class="col-md-6"> {{#ev:youtube|L2f8fz6vzoI|300}} <div class="text-right"><ref>Bublitz Videos. Children of Glass - (Part 3 of 4). Available from: http://www.youtube.com/watch?v=L2f8fz6vzoI [last accessed 27/8/2020]</ref></div></div>
  <div class="col-md-6"> {{#ev:youtube|QvbY7XqyMz8|300}} <div class="text-right"><ref>Bublitz Videos. Children of Glass - (Part 4 of 4). Available from: http://www.youtube.com/watch?v=QvbY7XqyMz8 [last accessed 27/8/2020]</ref></div></div>
</div>
== Resources ==


*More severe than type I and less severe than type III
* [https://oif.org/wp-content/uploads/2019/08/PT_guide_final.pdf Physical and Occupational Therapists Guide to Treating Osteogenesis Imperfecta]
*Short stature that is not as extreme as type III
*Barrel shaped chest
*Scoliosis
*Sclera are normal
*Triangular shaped face
*Teeth may be brittle and fracture easily
*Skin may be thin and smooth
*Possible hearing loss
*Bruises easily
*High pitched voice
*May perspire excessively<ref name="OIF" />
*"Mild to moderate skeletal fragility and osteoporosis
*Associated bowing of long bones
*Bones fracture easily before puberty; some children improve at puberty
*Joint Hyperextensibility"<ref name="Goodman" />
 
<br>
 
== Associated Co-morbidities  ==
 
*Joint hypermobility<br>
*Hearing impairment/Loss
*Excessive diaphoresis
*Cardiovascular complications
*Scoliosis
*Pectus deformity
*Metabolic defects
*Atrophy of muscles
*Multiple fractures
*Delayed developmental motor skills
*Spinal and long bone deformities
*Shortened stature<ref name="Goodman" />
 
== Medications  ==
 
<u>'''Past Pharmacological Treatment Options'''</u><br>
 
The following medications have been not been proven be effective for OI in controlled trials.<br>
 
*Anabolic Steroids
*Vitamin D
*Vitamin C
*Sodium Fluoride
*Magnesium Oxide
*Flavanoids
*Calcitonin
 
<u>'''Current Pharmalogical Treatment'''</u><br>
 
*Growth Hormone - This is used to improve bone metabolism and to improve growth for statural purposes.<br>
*Bisphosphonates - These are used to "promote bone mineral accretion while at the same time reducing bone turnover."<ref name="Antoniazzi">Antoniazzi F, Mottes M, Franschini P, Brunelli PC, Tato L. Osteogenesis Imperfecta Practical Treatment Guidelines. Paediatr Drugs; 2(6): 465-488. 2000.</ref><br>
 
<br>
 
== Diagnostic Tests/Lab Tests/Lab Values  ==
 
The diagnosis of osteogenesis imperfecta generally begins with the physician's findings during an examination. Physicians may find evidence of skeletal deformities accompanied by multiple past fractures that have healed using x-rays or bone scans. Wormian bodies, which are irregularly shaped islands of bone found in the wide sutures on skull radiographs of patients with OI, may also be present.<ref name="Goodman" /> Other ways to help confirm the diagnosis of OI include a history of osteogenesis imperfecta in the family, a skin biopsy, DNA testing, and ultrasound imaging before the child is born. Although OI is not always passed down from the parents, this would help the physician come to a conclusion because if one of the parents have OI, they have a 50% chance of passing this along to their child. A skin biopsy is used to determine if there is enough type I collagen or if the collagen is abnormal. DNA testing is accomplished by means of a blood test that is examined to locate the genetic mutation. Ultrasound imaging can be used to help diagnose OI before the child is born. The more severe the type of OI, the earlier ultrasound imaging can detect the fractures and deformities. By 14-16 weeks, type II OI is usually possible to diagnose. Type III OI is possible to diagnose around 16-18 weeks gestation. Types I and IV are generally not diagnosed with ultrasound.<ref name="OIF" /><br>
 
[[Image:X-ray OI.jpg|center|This picture is included courtesy of gghjournal.com.]]
 
== Causes  ==
 
Osteogenesis imperfecta is a genetic disorder that can be caused by inheritance from a parent with OI, or a random genetic mutation. The genetic disorder in most cases is passed from one of the parents to the child through autosomal dominant inheritance.<ref name="Goodman" /> This means that one copy of the mutated gene in each cell is enough to cause the osteogenesis imperfecta. This type of inheritance is usually the cause for most people with type I or type IV OI. Random mutation of the COL1A1 or COL1A2 gene may also occur. These children have no family history of OI and tend to have either type II or type III osteogenesis imperfecta, which are more serious. The least common way that osteogenesis imperfecta is caused by autosomal recessive inheritance. This is when each cell has two copies of the mutated gene. This cause occurs by two people that are carriers of the mutated gene passing one copy each to a child. This cause usually results in a child with type III OI.<ref name="NIH" /><br>
 
[[Image:Sean.jpg|center|This image of Sean Stephenson is included courtesy of http://26.media.tumblr.com.]]
 
== Systemic Involvement  ==
 
<u>'''Gastrointestinal'''</u>
 
*Constipation that may be caused due to pelvic asymetry in more serious forms of OI.
*Difficulties swallowing solid foods in more serious forms of OI.<ref name="Nutrition">Osteogenesis Imperfecta Foundation. OI Issues: Nutrion. http://www.oif.org/site/PageServer?pagename=Nutrition. Website updated: 2007. Website accessed: April 5, 2010.</ref>
 
<br><u>'''Cardiac'''</u>
 
*Heart valve problems such as aortic valve insufficiency, aortic aneurysm, mitral valve regurgitation, and mitral valve prolapse.<ref name="NIAMS">National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteogenesis Imperfecta: A Guide for Nurses. http://www.niams.nih.gov/Health_Info/Bone/Osteogenesis_Imperfecta/nurses_guide.asp#PTOT. Website updated: 2005. Website accessed: April  4, 2010.</ref>
 
<br><u>'''Respiratory'''</u>
 
*Restrictive pulmonary disorder is common in people with severe forms of OI.
*Pulmonary complications due to rib fractures, weakness of the muscles in the chest wall, chronic bronchitis, pneumonia, asthma and heart valve disorders.
 
<br>
 
<u>'''Neurological'''</u>
 
*Basilar invagination of the base of the skull may occur in OI patients in the adult years and cause complications with the brain stem.
 
<u>'''<br>Renal'''</u>
 
*Kidney stones have at times been associated with osteogenesis imperfecta.<ref name="NIAMS" /> <br>
 
<br>
 
<u>'''Integumentary'''</u>
 
*Patients with OI may have thin skin.
*Excessive diaphoresis may be apparent.
 
<br>
 
'''<u></u>'''
 
'''<u>Metabolic</u>'''
 
*Elevated serum pyrophoshate<br>
 
*Decreased platelet aggregation
 
<br><u>'''Auditory'''</u><br>
 
*Hearing loss/impairment is a common occurence in patients with OI. This can occur from deformity of the bony auditory structures.<ref name="Goodman" /> This can also be caused by a fracture of the stapes bone.<ref name="Stapes">ALbahnasawy L, Kishore A, O’Reilly BF. Results of stapes surgery on patients with osteogenesis imperfecta. Clin. Otolarygol; 26: 473-476. 2001.</ref><br>
 
<br>
 
<u>'''Vision'''</u><br>
 
*Sclera may be blue, purple, or grey tinted.
*Vision loss can occur.<ref name="Kennedy" />
 
<br>
 
<u>'''Musculoskeletal'''</u>
 
*Muscular atrophy
*Joint hypermobility<br>
*Multiple fractures<ref name="Goodman" /><br>
 
<br>
 
<u>'''Pain'''</u>
 
*"It is a myth that patients with osteogenesis imperfecta feel less pain than patients without OI."<ref name="NIAMS" /><br>
 
== Medical Management (current best evidence)  ==
 
The current best evidence for the medical management of osteogenesis imperfecta can depend on the form of OI and the severity its effect has been on the patient. With multiple fractures to long bones causing deformity of the bones, it can be impossible in some patients to achieve any weight bearing for ambulation. To best help with the gross deformation of the structure of long bones there is a surgical intervention that is called rodding. This procedure is most often performed in the femurs and tibiae. Rodding consist of realigning the long bone and inserting an intermedullary metal rod. This will promote the bone to hear to appear more like a normally shaped long bone and will improve the chances of the child to be able to functionally bear weight and improve chances of self ambulation.<ref name="Antoniazzi" /> Rodding does not help to improve the fragility of the long bones and further medical treatment is still needed.
 
Bisphosphonates such as Pamidronate are used to decrease the amount of bone resorption. Studies have found that children with OI that are given Pamidronate intravenously every one to four months have shown decreases in bone pain, an increased sense of well being, and rise in vertebral bone mass. It has been found that the child's vertebrae can regain a normal shape and size. Studies found that these Pamidronate infusions lead to a significant decrease in fractures and can improve a person's functional mobility. The uses of other bisphosphonates, such as Alendronate and Olpadronate, have also shown to make some improvements. There is not much evidence supporting the use of one bisphosphonate over another, but intravenous Pamidronate has been the one to show the most improvement with bone pain. Studies have also found that the use of bisphosphonates can impede the healing of osteotomy sites from the procedure of rodding. Bisphosphonates are not a cure for OI but need to be used in addition to physical therapy and orthopedic care.<ref name="Francis">Francis GH. Treatment of Osteogenesis Imperfecta: Who, Why, What?. Hormone Research; 68(5):8-11. 2007.</ref><br>
 
With research continuing in the areas of allogenic bone marrow transplantation there has been positive findings showing increased bone mineral content and new bone formation. There is also research being done in the area of gene therapy.<ref name="Goodman" />
 
== Physical Therapy Management (current best evidence)  ==
 
Physical therapy management for osteogenesis imperfecta can help prevent disuse atrophy of muscle and disuse loss of bone mass. It has also been found that physical therapy can strengthen muscles and even increase bone density in patients with OI.<ref name="Goodman" /> Physical therapy may also help cardiovascular fitness, mental alertness, improved sleep, weight control, ability to fight infection, decrease the chance of certain cancers, and improve activities of daily living. Physical therapy should begin as soon as the child begins to show signs of muscular weakness or motor skills are being accomplished later than other children of the same age.<ref name="NIAMS2">National Institute of Arthritis and Musculoskeletal and Skin Diseases.  Exercise and Activity: Key Elements in the Management of OI. http://www.niams.nih.gov/Health_Info/Bone/Osteogenesis_Imperfecta/exercise_activity.asp. Website updated: 2009. Website accessed: April 5, 2010.</ref>
 
Physical therapy intervention should include light resistance exercises to strengthen the hips and the core. A combination of hip extension, hip abduction, spinal musculature strengthening, and an aquatic exercise program twice a week has been found to increase the patient's ability to achieve an upright position and ambulate. Positioning is important in the care of children with OI. Neutral positioning of the head, trunk, and extremities with the hips in extension is the correct positioning. In more severe cases the prone position should be avoided.
 
Physical therapy management may also include the selection and adaptation of ambulation devices that are safe and beneficial to the patients. Adaptive equipment, even powered wheelchairs, may be essential for the child to have as much independence as possible.<ref name="Goodman" /> &nbsp;
 
== Dietary Management ==
 
Many resources have stated the importance of nutrition for patients with osteogenesis imperfecta. Patients with OI need to get adequate amounts of calcium, vitamin D, and vitamin C. Calcium is needed to develop peak bone mass and help prevent bone loss. Vitamin D is responsible for helping the body to absorb calcium and may also be involved proper functioning of the immune system. Low levels of Vitamin D may also have a role in chronic pain. Vitamin C is involved in the production of healthy connective tissues, and assists in the healing of wounds and fractures which is very important for patients with OI.
 
Calcium is found in dairy products and other foods such as broccoli, kale, dried beans, nuts, and soy products. Vitamin D is mainly absorbed from sunlight through the skin but can also be found in fortified foods and dietary supplements. Vitamin C is found in many fruits and Vegetables such as citrus fruits, cantaloupe, strawberries, sweet potatoes, tomatoes, and bell peppers.<ref name="Nutrition" />
 
== Differential Diagnosis  ==
 
The differential diagnosis for osteogenesis imperfecta can be grouped into stages of life that the differential diagnoses occur.<br>
 
<u>'''<br>'''</u>
 
<u>'''Prenatal/Neonatal'''</u>
 
*"Thanatophoric dysplasia
*Jeune dystrophy
*Achondroplasia
*Camptomelic dysplasia
*Chondrodysplasia punctata
*Chondroectodermal dysplasia (Ellis–van Creveld syndrome)
*Nonaccidental injury
*Menkes kinky-hair syndrome
*Menkes Kinky Hair Disease<br>
*Hypophosphatasia"<br>
 
<br>
 
<u>'''Preschool/Childhood'''</u><br>
 
*"Pyknodysostosis
*Hajdu-Cheney syndrome
*Osteopetrosis
*Vitamin D–resistant rickets
*Osteochondromatosis<br>
*Secondary osteoporosis (immobilization)
*Rickets
*Scurvy
*Leukemia
*Cushing syndrome
*Nonaccidental injury"
 
<br>
 
<u>'''Adolescence/Adulthood'''</u>
 
*"Mafucci syndrome
*Homocystinuria
*Albright hereditary osteodystrophy
*Wilson disease"<ref name="Emedicine">Emedicine. Osteogenesis Imperfecta: Differential Diagnosis &amp; Workup. http://emedicine.medscape.com/article/1256726-diagnosis. Website updated: 2008. Website accessed: April 5, 2010.</ref>
 
<br>
 
Milder forms of osteogenesis imperfecta may not be diagnosed early and can often be mistaken for child abuse by physicians.<ref name="Gahagan">Gahagan S, Rimsza ME. Child Abuse or Osteogenesis Imperfecta: How Can We Tell?. Journal of Pediatrics; 88(5): 987-992. 1991.</ref>
 
== Case Reports<br>  ==
 
*[http://www.seibertdc.com/Content-2/Case+Study.html Yochum TR, Kulbaba S, Seibert RE. Osteogenesis Imperfecta in a Weightlifter. Journal of Manipulative and Physiological Therapeutics; 25: 334-339. 2002.]<br>
*[http://www.cfp.ca/cgi/reprint/51/12/1655 Strevel EL, Adachi JD, Papaioannou A, McNamara M. Case Report: Osteogenesis Imperfecta Elusive Cause of Fractures. Canadian Family Physician; 51: 1655-1657.2005.]<br>
*[http://www.kjm.keio.ac.jp/past/53/4/251.pdf Iwamoto J, Takeda T, Sato Y. Effect of Treatment With Alendronate in Osteogenesis Imperfecta Type I: A Case Report. The Keio Journal of Medicine; 53 (4): 251–255. 2004.]<br>
*[http://www.atcs.jp/pdf/2002_8_1/51.pdf Aoki T, Kuraoka S, Ohtani S, Kuroda Y. Aortic Valve Replacement in a Woman with Osteogenesis Imperfecta. Annals of Thoracic and Cardiovascular Surgery; 8(1): 51-53. 2002.]
 
== Recent Related Research (from [http://www.ncbi.nlm.nih.gov/pubmed/ Pubmed])  ==
<div class="researchbox">
<rss>http://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1L9ANQ88k4eLMqhxcVtT2R_ZmVbEwB2cTbUsBrc</rss>
</div>
== Resources <br>  ==
 
*http://www.oif.org<br>
*http://www.genome.gov/25521839
*http://www.osteogenesisimperfecta.org
*http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html
*http://ghr.nlm.nih.gov/condition=osteogenesisimperfecta<br>
*http://www.brittlebone.org<br>
 
== References<br>  ==


==References==
<references />  
<references />  


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Latest revision as of 11:20, 25 April 2023

Genetic_DisordersOriginal Editors - Barrett Mattingly from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Barrett Mattingly, Lucinda hampton, Jess Bell, Admin, Uchechukwu Chukwuemeka, Robin Tacchetti, Kim Jackson, Kirenga Bamurange Liliane, Dave Pariser, WikiSysop, Meaghan Rieke, Anna Fuhrmann, 127.0.0.1, Heidi Johnson Eigsti, Elaine Lonnemann and Wendy Walker  

Introduction[edit | edit source]

Figure 1. X-ray of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a "heterogeneous group of congenital, non-sex-linked, genetic disorders".[1] It affects the production or processing of type 1 collagen, and therefore, impacts connective tissue and bone.[1][2]

It is also referred to as "brittle bone disease". Individuals with OI are susceptible to fractures and reduced bone density.[2] They may present with osteoporosis and blue sclera (i.e. the white part of the eye), and their teeth and hearing can be affected.[1] It can also impact mobility and an individual's ability to perform activities of daily living.

OI can have a negative effect on the social and emotional well-being of young people with this condition and their families. Adopting a coordinated, multidisciplinary team approach helps to ensure that children with OI can "fulfill their potential, maximizing function, independence, and well-being."[3]

Epidemiology[edit | edit source]

OI is a rare condition. The estimated incidence is approximately 1 in every 15,000 to 20,000 births.[2] It affects males and females equally, and there are no differences in terms of race / ethnic group.[1]

Aetiology[edit | edit source]

OI usually occurs secondary to mutations in the COL1A1 and COL1A2 genes, but there have been diverse mutations related to OI identified more recently.[2]

Pathology[edit | edit source]

In OI, the synthesis of type I collagen is affected. Type I collagen forms the main protein of the extracellular matrix of many of our tissues, including our skin, bones, tendons, skin and sclerae.[1][2]

Clinical presentation[edit | edit source]

Image of OI X-ray. This picture is included courtesy of gghjournal.com.

There are four major clinical features that characterise OI, but each individual's presentation varies depending on their type of OI.[1][4]

  1. Osteoporosis / bone fragility
    • fractures
    • bone deformities
  2. Discoloration of the sclera (white of the eye)
    • may be blue or gray in colour
  3. Dentinogenesis imperfecta
    • discolouration of teeth (e.g. blue-gray / yellow-brown colour)
    • translucent and weakened teeth
    • can affect baby and adult teeth[5]
  4. Hearing impairments

OI can also cause laxity of ligamentous, joint hypermobility, short stature and individuals are prone to bruising.[1]

Types of OI[edit | edit source]

There are at least eight different types of OI, but three types are said to be easily distinguished.[1]

  • Type I:[4]
    • The most common and mildest type of OI
    • Around 50% of children with OI have Type 1 OI
    • Individuals have few fractures / deformities
    • Have half the amount of normal collagen
    • Blue sclera
    • Generalised osteoporosis
    • Joint hyperlaxity
    • Conductive hearing loss
    • Dentinogenesis imperfecta[6]
  • Type II:[4][2]
    • The most severe type of OI - it is a lethal condition, usually within weeks of birth
    • Causes severe disruption of the "qualitative function" of the collagen molecule[2]
    • Infants with Type II OI present with very short arms and legs, small chest and they have delayed ossification of the skull
    • There may be fractures at birth, low birth weight and under-developed lungs
  • Type III:[4]
    • Children who have severe clinical signs tend to have Type III OI
    • They tend to present with moderate to severe fragility of bones, coxa vera, they may have slightly shorter arms and legs, and have arm, leg, and rib fractures
    • Infants may have a larger head, a triangular-shaped face, changes in their chest and spine (scoliosis), and difficulties with breathing and swallowing
    • May also have frontal bossing (i.e. prominent forehead), basilar invagination, short stature
    • Symptoms vary in each infant[4]
  • Types IV to VIII are not common and vary in terms of their severity[1]
    • Shorter in statue
    • Frequent fractures that decrease after puberty
    • Mild to moderate bone deformity
    • Average life expectancy[6]

Diagnosis[edit | edit source]

The following diagnostic tests may be recommended:[4]

  1. X-rays: able to show weakened / deformed bones, fractures
  2. Lab tests: including blood, saliva, skin and gene testing
  3. Dual Energy X-ray Absorptiometry scan (DXA or DEXA scan): to investigate softening of bone
  4. Bone biopsy (taken at the hip)

Prognosis[edit | edit source]

Prognosis is variable depending on the type of OI.[2]

  1. Age of onset of long bone fractures is a prognostic indicator for ambulatory ability.
  2. Survival: Location and severity of fractures, and appearance of the skeleton on radiography are significant indicators for survival.
  3. The type of OI is the most important clinical indicator for ability to ambulate. Early achievement of motor milestones is associated with the ability to walk independently when the type of OI is not known.[7]

Complications[edit | edit source]

Complications associated with OI vary depending on the type of OI, but they can affect most body systems. They may include the following:[2][4]

Treatment[edit | edit source]

Treatment focuses on the prevention of deformities and fractures and the maintenance of independence.[4]

Team Approach[edit | edit source]

OI should be managed with an interdisciplinary team that may include primary care physician, orthopedist, geneticist, nutritionist, social worker, and psychologist, physiotherapists, occupational therapists. Pulmonologists may be involved in the care of individuals who have scoliosis that impacts pulmonary function.[8]

Management options include:[1][4]

  • surgery to help prevent fractures and to correct deformities (including intramedullary rods with osteotomy)
  • fracture care - casts tend to be made from the lightest material possible, movement of the affected area is encouraged as soon as possible
  • bisphosphonates to strengthen bones and prevent fractures where possible
  • growth hormone therapy[1]
  • treatment for dental issues - including capping teeth, braces, etc
  • assistive devices[4]

Rehabilitation[edit | edit source]

Therapists should remember the following when working with individuals with OI and their families:[8]

  • Listen and respect individuals with OI and their families.
  • Set goals that are realistic, achievable, and incremental.
  • Weakness affects movements in OI - individuals with OI do not tend to have other neurological issues such as impaired coordination, sensation or cognition.
  • Individuals with OI may be fearful of fractures and this can significantly impact movement. It can be useful to:
    • establish safe movement patterns
    • encourage self-confidence
    • optimise strength
  • Expect success - with the appropriate environment and equipment, most individuals with OI can perform most activities of daily living, including self-care, school and work.

Enhancing strength and function is essential for health and wellbeing and bone health. Rehabilitation approaches include:[8]

  1. Exercise, including weight bearing activities (braces may be needed)
  2. Low-impact activities such as swimming (precautions must be defined)
  3. Care with safe handling and encouraging changes in body positions / postures throughout the day to help strengthen muscles / prevent deformities
  4. Prescribing appropriate adaptive equipment (e.g. cane, walker, manual or power wheelchair).
  5. Adapting the environment as needed (e.g. at work, home, school)

Individuals with OI might require intermittent or long-term rehabilitation for the following reasons:

  1. They have delays or weakness in motor skills
  2. They have had a fracture, surgery or injury
  3. They are experiencing fear of movement and are trying new skills and activities
  4. They are transitioning to a new stage of life etc, and need to get used to a new environment or train for a specific activity of daily living[8]

Key Principles of Therapeutic Strategies

When designing a rehabilitation programme for OI, it is necessary to engage in an appropriate task analysis. The following are useful points to consider:[8]

  • Skill progression - develop and progress gross motor skills (reaching, sitting etc) if they are delayed / difficult, particularly for individuals with severe OI. Skills may need to be retrained in adults after injury.
  • Using preventive positioning, protective handling and active movement with gradual progression can help to facilitate motor skill development safely.
  • Hydrotherapy can be useful for motor skill development and for individuals with fear of movement.
  • It is vital to ensure that an individual has appropriate equipment and assistive devices.
  • Encourage healthy living to promote general health.

Children of Glass[edit | edit source]

The following videos include excerpts from the Discovery Health documentary on the genetic brittle bone disorder "Osteogenesis Imperfecta" .

[9]
[10]
[11]
[12]

Resources[edit | edit source]

References[edit | edit source]

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Osteogenesisi Imperfecta. Available from: https://radiopaedia.org/articles/osteogenesis-imperfecta-1 (Accessed, 15/10/ 2021).
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Subramanian S. StatPearls Publishing LLC.; Treasure Island, FL, USA: 2021. Osteogenesis Imperfecta.
  3. ↑ Marr C, Seasman A, Bishop N. Managing the patient with osteogenesis imperfecta: a multidisciplinary approach. Journal of multidisciplinary healthcare. 2017; 10:145.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 Osteogenesis Imperfecta. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/osteogenesis-imperfecta (Accessed, 15/10/2021).
  5. ↑ Dentiogenesis Imperfecta. Available from: https://medlineplus.gov/genetics/condition/dentinogenesis-imperfecta/ (Accessed, 15/10/2021).
  6. ↑ 6.0 6.1 Eskay, K. Paediatric Conditions: Down Syndrome, Duchenne Muscular Dystrophy, Osteogenesis Imperfecta and Arthrogryposis Multiplex Congenita. Plus. 2023
  7. ↑ Engelbert RH, Uiterwaal CS, Gulmans VA, Pruijs H, Helders PJ. Osteogenesis imperfecta in childhood: prognosis for walking. J Pediatr. 2000 Sep;137(3):397-402.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 OI foundation Physical and Occupational Therapists Guide to Treating Osteogenesis Imperfecta Available:https://oif.org/wp-content/uploads/2019/08/PT_guide_final.pdf (accessed 15.10.2021)
  9. ↑ Bublitz Videos. Children of Glass - (Part 1 of 4). Available from: http://www.youtube.com/watch?v=TpAMTOud3bw [last accessed 27/8/2020]
  10. ↑ Bublitz Videos. Children of Glass - (Part 2 of 4). Available from: http://www.youtube.com/watch?v=GTpSxlPzC8k [last accessed 37/8/2020]
  11. ↑ Bublitz Videos. Children of Glass - (Part 3 of 4). Available from: http://www.youtube.com/watch?v=L2f8fz6vzoI [last accessed 27/8/2020]
  12. ↑ Bublitz Videos. Children of Glass - (Part 4 of 4). Available from: http://www.youtube.com/watch?v=QvbY7XqyMz8 [last accessed 27/8/2020]
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