Osteogenesis Imperfecta (OI) is a genetic disorder affecting connective tissue. The disease is characterized by bones that fracture easily, often from little or no apparent trauma. There are now six types of OI that are recognized, with significant variability, not only between types but also within types and even within the same family affected by the same type of the condition. People suffering from OI are also likely to suffer from lax and unstable joints, skeletal malformations and postural imbalances, muscle weakness, growth impairment and other connective tissue-related problems. Other features common in people with OI include excessive perspiration, easy bruising, a high-pitched voice and thin, smooth skin.
Osteogenesis Imperfecta affects approximately one person in 20,000. Approximately 25 percent of children with OI are born into families with no history of the disorder. This is usually due to a spontaneous dominant mutation that takes place in the sperm or the egg prior to conception. There is equal frequency of occurrence among males and females and among all racial and ethnic groups. Life expectancy varies, with those most severely affected rarely surviving childbirth and some living into old age.
Individuals with Osteogenesis Imperfecta have a faulty gene that fails to instruct their bodies to manufacture sufficient type I collagen or else leads to the production of poor quality type I collagen. There are at least 10 identifiable types of collagen that are found in the connective tissues of the body and make up a large portion of the bones and cartilage. It is the substance that holds the tissues together, providing strength and mass to the bones. For a person with OI, either the amount of collagen being produced is too little or the quality being produced is poor. Either way, the bones of a person with OI are less dense and break easily.
Collagen rods are formed by a strict interactive arrangement of rigid collagen fibres. The collagen rods that make up OI bone do not give the skeleton full strength because the quantity or shape of the rods is abnormal. This is the result of a genetic defect affecting either the structure or numbers of collagen fibres. When a sufficient mutation occurs, a defective blueprint is produced that tells the cell to produce deformed collagen, resulting in bad collagen fibres. Although the body may still make some proportion of good collagen fibres, they are going to bind with defective fibres, leading to unstable collagen structures that are predisposed to damage. Between one half to three quarters of all collagen fibres that are formed are defective. The severity of OI is determined by the severity of the defect in collagen fibres and the consequent level of weakness in the collagen rods.
Although many people consider bones to be a solid structure made of minerals, it is the collagen proteins that act as the frame to which the minerals are deposited. If there is insufficient type I collagen or else a faulty version of type I collagen, then the supporting frame of the bone will be inefficient. This means that despite potentially optimal density of minerals, the unstable collagen framework results in the minerals not being able to add sufficient strength and rigidity to the bone, and it is therefore susceptible to frequent fractures from loads that would not apparently affect normal bone. Type I collagen is also important for the structure of other connective tissues, so it is not only bone that is affected by OI (although this is where the condition has its most noticeable effect).
Four Types of Osteogenesis Imperfecta
Type I is the most common and mildest form of Osteogenesis Imperfecta. People with Type I OI average nearly 40 fractures before puberty and a few fractures after puberty. As with all types of OI, the skeleton is predisposed to fractures, and there are likely to be various issues related to loose connective tissue. Unlike the other types of OI, Type I is due to a deficiency in Type I collagen, rather than a faulty version of the protein. These may include lax joints, easily bruising skin, muscle weakness and poor posture (scoliosis, in particular). Most fractures occur before or during puberty. Stature tends to be normal or close to normal, as compared with unaffected family members. The face may be triangular in form. The sclera (whites of the eyes) usually have a distinct blue, purple or gray tint. Any bone deformity itself is minimal, if present at all.
Because it is the mildest form, some individuals may seem to "grow out" of the condition following puberty. Although this may seem to be the case as the person stops experiencing fractures, those individuals will again become susceptible to fractures later in life and for women in particular following menopause. Many children with Type I OI are able to lead normal childhoods, taking part in many moderate impact and non-competitive sports and activities. Some children will participate in higher impact and even competitive sports, although this should not be recommended once a diagnosis of OI has been made.
Type II Osteogenesis Imperfecta is the most severe form of the disease. It affects approximately 10 percent of people with the condition. Type II OI is frequently lethal at or shortly after birth, often due to respiratory and/or cardiovascular problems. There have been a few cases of some individuals with this type of OI living into young adulthood. Infants are often premature or stillborn and are small for gestational age. Multiple fractures in the womb lead to a bowing and shortening of the long bones at birth. The rib cage is small and narrow, and palpation reveals a “beading” feel due to callus development from fractures in utero. The lungs are underdeveloped. The head is large for the small body size, with severe undermineralization. The sclerae are uniformly dark blue or gray. The numerous fractures and severe skeletal deformity is due to the improper formation of collagen.
Type III OI is the most severe type for people that survive past infancy. Type III OI affects 20 percent of the people who have the condition. It is common for a person with this type to have experienced 100 fractures by the time he or she reaches puberty. Multiple long bone fractures may be present at birth, but there would not be the severe thoracic malformation seen in people with Type II OI. Frequent long bone fractures combined with the stress of muscles on the bones through tendon attachments and disruption of the growth plates leads to bowing of the long bones and progressive malformation and short stature. Compression fractures of the vertebrae also occur frequently, and the short stature is often accompanied by kyphoscoliosis. Pectus carinatum (pigeon chest) and pectus excavatum (funnel chest) are also common. The face is often triangular, and the head is usually large for the body size. Diagnosis of Type III OI is usually at birth due to the presence of multiple fractures. The sclera may be normal or else tinted blue, purple or gray. The individual may also suffer from Dentinogenesis Imperfecta and hearing problems.
People with Type III O.I. often have a reduced life expectancy, although some are able to live into their sixties and seventies. Many people with Type III O.I. die due to pulmonary complications. These tend to happen around particular ages, in early childhood, teenage years, and thirties and forties. Some affected individuals may be able to live independently, whilst others require assistive devices, either general mobility devices or specific tools for some normal activities of daily living. Surgery may be required to support and to straighten bowed long bones. Alike all other types of O.I., the bones fracture easily, with fractures often occurring before and during birth. The joints are often loose and there is poor muscle development in the legs and arms.
The severity of Type IV Osteogenesis Imperfecta is between that of Type I and Type III. The bones fracture easily and most before puberty. The individual will tend to be shorter than average in stature, with loose joints and mild to moderate bone deformity. The spine may be curved with a barrel-shaped rib cage. The face tends to be triangular, and the individual may suffer from Dentiongenesis Imperfecta and/or hearing loss. The sclera are often white or near white. The diagnosis of Type IV OI is usually at birth but may not take place until later as fractures may not occur until the child is ambulatory. Bowing of the long bones may be present but to a lesser extent than Type III. Individuals with Type IV OI will have moderate to severe growth retardation, which is one of the factors that distinguish them clinically from Type I OI. Life expectancy is not affected. Research has also found that there are two other types of OI, Type V and Type VI, that were previously diagnosed as Type IV. Many of the clinical features are the same, and blood or skin tests are required to differentiate between them. From a healthcare professional’s perspective, it is only the manifestation of the condition that is important, with regards to susceptibility of fracture and related conditions.
Physical Complications Caused by Osteogenesis Imperfecta
Breathing problems are a huge concern for individuals that are severely affected by OI. Associated complications such as pneumonia represent a significant cause of death for those with Type II and Type III OI. Respiratory problems can affect anyone with OI, the extent of which will often be exacerbated by the presence of injury to the rib cage or a scoliosis. Muscle weakness and a deficiency of the other connective tissues around the thorax can also have a negative affect on lung function. This can then be compounded by other respiratory disorders such as bronchitis, asthma and decreased or inhibited chest capacity.
Some individuals with OI may suffer from a related heart valve abnormality. The most common of these complications is mitral valve prolapse, but even so, this is not as prevalent as other connective tissue disorders associated with OI. Individuals with OI may experience a higher than normal body temperature, excessive sweating and sensitivity to the effects of heat and cold. This has obvious implications in a training environment where there may be evidence of earlier than expected signs of fatigue. Because the entire cardiovascular system is made up of connective tissue, the entire system is therefore at risk of the effects of OI. Someone with OI may bruise more easily than someone without the condition as an effect of the increased fragility of the blood vessels. Frequent nosebleeds and profuse bleeding may also be experienced by some individuals following injury.
There are a number of neurological conditions that may affect someone with OI, but most of these will affect only those with the most severe forms of the condition. Individuals with Type III and Type IV OI may suffer from basilar invagination (BI), whereby there is increased pressure on the base of the skull from the spinal column. This can lead to headaches, tingling or numbness in the hands and feet and muscle weakness. BI does not necessarily become progressively worse over time, but it does need to be assessed by a neurologist should the symptoms occur.
Because the gastrointestinal tract is predominantly connective tissue, it too is susceptible to abnormalities in persons with OI. A decreased length of the chest cavity, which may affect breathing in the respiratory system, can also cause gastric acid reflux and chronic constipation. A short stature can contribute to the problem as can frequent use of medications, in particular pain medication. Medication and dietary factors can also increase the risk of kidney stones in individuals with OI.
It will be necessary to get recommendations and consent from any physicians and specialists working with the individual before you begin training a new client with OI. Osteogenesis Imperfecta is very much an individual condition. People of the same type of OI and even within the same family are all likely to be affected by the condition in very different ways. Differences between individuals could be in the number, type and location of fractures, differing joint mobility, hearing and dental problems and respiratory problems. Therefore, when working with a client with OI, it is detrimental to begin devising an exercise program based on any kind of assumptions whatsoever including personal experience of working with others with the condition. Over time, it will also be necessary to obtain continued feedback from other healthcare professionals regarding your client’s development.
Ideally, individuals with Osteogenesis Imperfecta should have their bone density measured on a yearly basis. For individuals who have a mild form of the condition and who stop experiencing fractures following puberty, they could perhaps have a lay off until they are once again at an increased risk for fractures. This would typically be for men in their 50s and for women post menopause, depending upon their physician’s advice. Bone densitometry is non-invasive and should be focused initially on the key fracture sites of the spine, hips and arms. This information will give you an idea of how the individual responds to training over time and at least initially may highlight areas of greater risk from fracture.
Because the weakness in the bones of people with OI is related to the collagen fibres rather than the mineral content directly, it is not appropriate to assume that sufficient density means that the individual is not at a greater risk of fracture than anyone else with similar bone mineral density (BMD). The lack of strength in OI bones comes from the structure of collagen, so even if there is adequate BMD, the minerals may not be positioned effectively to bear weight. The bone densitometry can be useful in highlighting very weak areas, but it is the composition and structure of the bone’s collagen and minerals that predetermine fracture risk rather than BMD alone.
The bone densitometry is also relevant to assessing fracture repair and the effectiveness of any treatments. There is, of course, radiation exposure with any bone densitometry, but units such as DEXA submit the patient to significantly less radiation than standard X-ray units. There is no merit in performing the assessment more than once a year as changes in bone will be too small for the measuring equipment to detect. It is worth being aware that postural abnormalities and body size can lead to misinterpretations of the bone densitometry as can the use of different machines for performing the assessments.
Individuals with Osteogenesis Imperfecta often have a number of musculoskeletal issues in addition to a history of fractures and increased likelihood of future fractures. Many people with OI will have muscular imbalances and malalignments including kyphosis and scoliosis. They may also suffer from increased joint laxity and mobility and joint deterioration, leading to joint weakness and instability, which may cause pain in the surrounding areas as well as increasing the risk of falls (and thereby increasing the risk of fractures). Lower back and hip pain can result from any of these factors including compression fractures of the vertebrae.
Because of the pain and any history of fractures associated with the condition of some bones and joints, it should be expected that many people would not be receptive to the idea of increasing activity. As we know, many degenerative conditions such as osteoporosis and muscular atrophy could progress through the individual’s reluctance for weight-bearing activity. In addition to treating the lack of bone strength and density, it is also important to consider other concerns for individuals with OI. Although the type of OI gives an idea of the severity of the condition on bone, it is probable that there are also collagen defects affecting the rest of the body. Someone with OI is also susceptible to issues with tendons, ligaments, muscles, joints, teeth, breathing, heart function, hearing and sight.
The healthcare team involved in the treatment and management of a patient with Osteogenesis Imperfecta could include the physician, orthopaedic consultant, endocrinologist, physical therapists, dieticians and possibly neurologists and pulmonologists. What is important for the physical therapist as well as everybody else involved in treatment is that they appreciate the value of this pool of knowledge and expertise. The first step when considering working with an individual with Osteogenesis Imperfecta is to build a picture of the extent of the condition and then seek to develop this through open communication and debate with other healthcare practitioners.