Glass Bone Disease - Causes, Symptoms and Therapy

Glass bones - Osteogenesis imperfecta

Osteogenesis imperfecta means "imperfect bone formation" and is colloquially referred to as vitreous bone disease. This rare hereditary disease is due to certain genetic defects that affect the collagen balance. This leads to disturbances in the connective tissue and bone metabolism in those affected. The consequence of deformable and easily fragile cooking is the guiding symptom, which stands behind the pictorial concept of glass bones. The treatment relies exclusively on symptomatic therapy methods to prevent and provide the best possible bone fractures.

contents

• Glass bones - Osteogenesis imperfecta
• A short overview
• definition
• symptoms
• causes
• diagnosis
• treatment
• Naturopathic treatment
• Current state of research

A short overview

The following overview lists the most important facts about the rare hereditary disease Osteogenesis imperfecta. Detailed information on the complex clinical picture can be found in the following article.

• definition: Osteogenesis imperfecta (vitreous bone, vitreous bone disease) refers to hereditary collagen malformation, which primarily causes connective tissue disorder. In particular, it comes in the disease to an imperfect bone formation, which manifests itself as the guiding symptoms of increased fractures and bone deformities.
• symptoms: In addition to the abnormally high susceptibility to spontaneous fractures and bone deformities, the disease causes a variety of other complex complaints. Typical symptoms include muscle weakness and blue sclera. The severity of the disease ranges from very mild forms to lethal manifestations.
• causes: Triggers are several gene mutations that are responsible for disorders in collagen formation (collagen type 1). Collagen is a major component of connective tissue and an important building block for bones and other structures and tissues. Therefore, not only disorders in the entire musculoskeletal system but also in many other areas of the body.
• diagnosisIn addition to a thorough anamnesis and clinical examination, X-ray examinations are primarily used in the diagnosis. If necessary, the diagnosis can be confirmed by genetic verification. Prenatal, more severe forms of disease are often detectable by prenatal ultrasound.
• treatment: Conventional treatment of symptoms is usually based on relatively new drugs (biophosphonates), orthopedic procedures and continuous physiotherapy. The therapy options are still in development. In addition, general measures for health promotion and osteopathic treatment can be consulted.
• Current state of research: Current research on the causes of illness (molecular genetics) and treatment options to expand the knowledge of this rare hereditary disease and ensure those affected the best possible care.

The vitreous bone disease is a rare hereditary disease in which different gene mutations cause very different manifestations. (Image: peterschreiber.media/fotolia.com)

definition

The medical term osteogenesis imperfecta (general abbreviation: OI) derives from the Greek and refers to an imperfect bone formation. In general parlance, however, the terms glass bones or vitreous bone disease are mostly used, which refer to the main symptom of increased bone fractures. First and foremost, however, the disease is a rare hereditary connective tissue disorder, which occurs due to various genetic defects and leads to collagen formation (collagen type I). Osteogenesis imperfecta occurs in about one in 20,000 births.

Classification and clinical features

A variety of different genetic defects and thereby disrupted collagen composition lead to this disease. Because of this, there are also different symptoms in those affected and the disease shows a large variability in severity and disease progression.

In 1979, a four-type classification was first introduced, subdividing various forms of disease and their clinical characteristics. The description of the types I to IV goes back to the Australian physician David Sillence. In these four forms, mutations of collagen type 1 encoding genes (COL1A1 or COL1A2) occur, which are responsible for more than 80 percent of the disease in Europe.

Ongoing new genetic and clinical findings have led to an expansion of this distribution. Currently, eleven types are described in which other genes and mutation forms are taken into account. However, only the types I to VI find a largely uniform use. To date, not all forms can be assigned, because the large number of causative genes makes a clear classification difficult. The extended classification is therefore still under discussion and there is still a need in the elucidation of unclassified forms of disease.

The common type I mild form is also known as Osteogenesis imperfecta tarda or Lobstein type, and the most severe type II lethal form is referred to as Osteogenesis imperfecta congenita or Vrolik type.

The classification according to Sillence describes the four most common types of osteogenesis imperfecta. (Image: heilpraxis.de/Original: Neokryuger / fotolia.com)

symptoms

Despite the high variability in the symptoms that occur, almost all cases of illness focus on the abnormally high innate susceptibility of the bones to fractures (osteopsathyrosis). The fractures occur due to reduced bone mass and lack of stability and elasticity without adequate trauma (spontaneous fractures).

In addition, there are (pronounced) skeletal deformities, especially the long bones in the extremities and the spine (scoliosis, kyphosis) and dwarfism.

In addition to these main symptoms, depending on their severity, the following additional symptoms may occur, among others:

• Muscle weakness, reduced muscle tension (hypotonia),
• distensible joints and ligaments,
• independent bone islands (switching bones) on the skullcap,
• blue sclera (leather skins of the eyes),
• hardness of hearing,
• myopia,
• heart problems,
• Pulmonary disorders (deformation of the rib cage),
• Discoloration and brittleness of the teeth (Dentinogenesis imperfecta),
• Tendency to hematomas,
• soft, translucent skin,
• triangular face with broad forehead and protruding ears.

In addition to bone fractures, skeletal symptoms often include deformities of the extremities and spine, such as scoliosis. (Image: tower_alia / fotolia.com)

disease

The many possible complaints and degrees of severity require individually very different courses of illness. In middle and severe disease processes, fractures and deformities on the extremities and the spine occur during the first months of life. Particularly critical are the growth phases to adolescence, during which fractures occur again and again under very little force.

But even before birth fractures, deformities and other abnormalities of the bones can occur. In the most severe form (type II), the disease is either preterm birth lethal or fatal in the first few months of life. Other serious forms may prevent the patient from standing and walking due to the frequency of fractures and possible bony obstruction.

On the other hand, if there is a mild form of the disease (type I), sufferers usually experience only a few fractures in their childhood and adolescence without further restrictions. Many forms of disease have in common that the fracture rate decreases significantly after the end of puberty.

In principle, there are no diminished life expectancy for the viable forms and under appropriate therapy applications.

causes

The rare hereditary disease is inherited predominantly autosomal dominant. An inheritance therefore takes place independently of the sex and the disease can manifest itself even if the corresponding genetic defect is located only on one of the 22 Autosomenpaare (body chromosomes). In addition, if neither parent has transmitted the disease, then a spontaneous mutation is the trigger.

The most common genetic mutations associated with this disease lead to quantitative or qualitative disorders in collagen formation. Mostly collagen type I is affected, which is often equated with the general concept of collagen. Collagens are the most common fiber-forming proteins (structural proteins, fiber proteins) with binding and supporting functions in different parts of the human body. Type I collagen is a major component of connective tissue. Likewise, it is an important building block for bones, cartilage, tendons, ligaments, teeth, and skin as well as the conjunctiva (conjunctiva). The disease affects not only the skeletal system, but the entire musculoskeletal system and all other structures that contain collagen type 1 to a certain extent.

Despite the clear cause of the gene mutation, this is not always genetically detectable, even with the latest methods.

More than 80 percent of those affected have a mutation of the collagen type 1 coding genes COL1A1 (see picture) or COL1A2. (Image: ibreakstock / fotolia.com)

diagnosis

The first clues in the diagnosis provide the patient survey (anamnesis), in addition to the typical symptoms of a familial occurrence of osteogenesis imperfecta is clarified. In addition, physical examinations, X-rays and laboratory examinations are used to rule out other possible skeletal disorders that occur in childhood (for example rickets and hypochondroplasia). Particular importance is attached to the exclusion of causative traumas for existing bone fractures. This may also become relevant in suspected cases of child abuse.

The radiograph reveals an increased transparency of the bones. The structures appear vitreous because there is too little shadowing bone substance. The outer layer is usually diluted in a line shape. Frequently a callus formation becomes visible. This is scar tissue, which widens and deforms the bone at the fracture site.

In addition, a bone density measurement can provide information about the disease, because in affected the bone density is significantly reduced. A reliable description of the bone structure and the muscle-bone interaction is possible via computed tomography, but this is not applicable to every person affected (minimum body size).

If symptoms of other structures and organs appear in addition to the symptoms on the skeleton, these are also clinically examined.

A validation and extension of the diagnosis provides a genetic examination, which is looking for causative gene mutations. Although it is not always possible to prove the disease and the underlying genetic defect, a possible identification is used in addition to the diagnosis and the further classification and elucidation of their own risk of transmission. If a genetic test has been performed, this does not mean at the same time that a reliable statement can be made about the individual characteristics or viability. Before birth, a cytogenetic examination is performed with the help of a pancreatic puncture (chorionic villus sampling).

In general, the more severe forms of vitreous bone disease in the womb can already be detected during prenatal ultrasound. Typical findings include shortened and deformed limb bones, rib fractures and occasionally callus formations.

To secure the diagnosis, a genetic proof can serve, but can not be provided in 100 percent of the cases. (Image: Eisenhans / fotolia.com)

treatment

So far, there are no possibilities for controlling the cause or cure of this hereditary disease. The symptomatic treatment is based on the three pillars of medical treatment, orthopedic treatment and physiotherapeutic treatment.

Medication

Intravenously administered bisphosphonates have proven to be a successful therapy option, especially in medium and severe cases in recent years. The drugs (eg neridronate and pamidronate) cause an increase in bone mass and an increase in bone strength. As a result, bone fractures and improved mobility are less common. The various bisphosphonates are still not approved for the treatment of osteogenesis imperfecta, which is why an application must be individually clarified. Only with the express consent of those affected can a so-called "individual therapeutic attempt" be made with these medicines. Close monitoring of efficacy and potential side effects is essential.

Contrary to some treatment concepts of other bone diseases, intake of vitamin D and calcium beyond the general recommendations does not make sense.

Orthopedic treatment

The most common symptoms of bone fractures and bone deformities usually require intensive orthopedic treatment. The aim of this form of therapy is primarily to maintain or restore the functionality and resilience of the skeletal system. Conservative measures for broken limb bones include, especially for very young children, special techniques of winding and storage. Furthermore, orthoses (for example rails) and plaster casts are used.

In more complicated cases, however, surgical interventions are necessary to prevent or correct fractures and deformities and to heal them. For operations in childhood and adolescence, consideration of the growth phases is of particular importance. This requires, if possible, the use of a telescopic nail system (Bailey or Fassier Duval nail). In this case, often after several targeted bone separations (osteotomies), two nested nail parts are introduced into the interior of the bone. The bone parts are thereby reconnected, and during growth, these nails slide apart along with the bone. So the bones can be stabilized over a long period of time.

For very young children, the bones may not yet have enough room for a telescopic nail. If this is the case, other aids are used, which may then have to be removed or replaced at a later date.

In severe cases and in complicated cases, surgical intervention is necessary to prevent or treat deformities and fractures. (Image: zharkovmarkfotolia.com)

Physiotherapeutic treatment

In order to prevent the risk of misalignments, malpositions and skeletal changes, individually coordinated physiotherapy is of great importance. But also in the rehabilitation after bone fractures a targeted physiotherapy is a central component of the therapeutic measures. The primary goal is to improve or increase flexibility and strengthen musculature. Every affected person should receive a regular and continuous physiotherapy treatment and support the other treatment measures.

If other areas of the body or organs are affected, such as the lungs or the heart, additional forms of therapy may be necessary.

Naturopathic treatment

The conventional medical procedures for the treatment of osteogenesis imperfecta can be supported by general, health promoting measures. As much as possible exercise, sports (swimming) and a waiver of cigarettes and alcohol have a positive effect.

Apart from the physiotherapeutic treatment also measures from the range of the Osteopathie can contribute to the relief of the complaints. A visit to the naturopath can also be helpful.

Current state of research

Although the disease has been known for a long time, the complex genetic foundations and widely varying disease characteristics require intensive research, especially in the area of ​​the causes of illness and the individual therapeutic options.

The Monthly Paediatrics Monthly Consensus Paper, published in 2017, mentions studies and research on the use of biophosphonates and other medicines, such as the effects of parathyroid hormone as a bone-building drug in adults. Also in the field of gene and cell therapy as a treatment option international studies are carried out.

Only recently was the change in collagen decrypted, most likely responsible for reduced bone resistance in vitreous bone disease.

Since this is a rare disease, there are still no defined guidelines for the care of those affected. In the continuing education journal "pädiatrie hautnah", German specialists who have long been caring for children and adolescents with osteogenesis imperfecta have summarized the current status of the disease. (tf, cs; updated on 17.12.2018)

Additional information:
German Society for Osteogenesis imperfecta (vitreous bone) Affected e.V..
Osteogenesis imperfecta - Information for sufferers and relatives