Osteogenesis imperfecta – The child with fragile bones

Osteogenesis imperfecta, also known as brittle bone disease, is a hereditary disorder characterized by the weakness and fragility of bones. The name refers to the nature of the disease, where the tissues of the bones are unable to regenerate properly, leading to frequent fractures. OI encompasses a complex group of disorders that include various types of hereditary defects and are associated with severe abnormalities in bone metabolism. The term “brittle bone” indicates the nature of the disease, as the bones of affected individuals are as fragile as glass. This condition is relatively rare, with estimates suggesting that only one in 30,000 newborns is affected, regardless of gender.

The prevalence and symptoms of the disease exhibit diversity, as different subtypes of OI can cause varying degrees and types of symptoms. Due to the complexity of diagnosis and treatment, it is important to have a precise understanding of the disease so that patients can live with the best possible quality of life.

The Background of Osteogenesis Imperfecta

Osteogenesis imperfecta represents a disorder in the synthesis of collagen, particularly type I collagen. Collagen is the most important component of connective tissues, found in various tissues such as skin, blood vessels, and bones. The structure of bones consists of two main components: the organic matrix formed by collagen and the inorganic matrix containing calcium salts. The ratio of these two components is critical, as any deviation can result in weak and deformed bones. In the case of osteogenesis imperfecta, improper formation of the organic matrix leads to brittle bones, causing numerous problems.

Type I collagen consists of three protein strands in a spiral structure, where the COL1A1 and COL1A2 genes code for the alpha-1 and alpha-2 strands. Mutations in these genes cause amino acid substitutions, leading to improper construction of collagen. The classical classification of the disease distinguishes four categories, but recent research has uncovered an increasing number of genetic variations that also contribute to the development of the disease.

The Symptoms and Signs of the Disease

The most characteristic symptom of osteogenesis imperfecta is the deformation and brittleness of bones. Patients often experience deformities in long tubular bones, such as those in the limbs, which vary in severity depending on the subtypes. Spinal deformities are also common, resulting from damage to the vertebrae. Bone fractures are particularly frequent during infancy and puberty, and in the most severe subtypes, they can even occur in utero.

Other signs of the disease include disturbances in tooth development, known as dentinogenesis imperfecta, which results in translucent and fragile teeth. The skin is typically thin and has a soft texture, while joint laxity can also be observed. Additionally, hearing loss may be characteristic of various subtypes of the disease. The sclera (the white part of the eye) may appear bluish, indicating the thinness of the eye’s sclera and correlating with the severity of the bone formation disorder.

Cardiological problems are also common, as the reduced production of collagen can lead to thinner heart valves. In more severe cases, respiratory difficulties may arise, potentially leading to death in early childhood, although in most cases, patients’ lifespans do not significantly differ from the average.

Diagnosis and Treatment Options

The diagnosis of osteogenesis imperfecta is made through a combination of clinical symptoms and DNA testing. PCR techniques are used to detect mutations in the COL1A1 and COL1A2 genes, but since many other genes also play a role in the disease, diagnosis is not always straightforward. New technologies allow for the rapid examination of the complete sequence of all genes involved in the disease, which can aid in establishing an accurate diagnosis.

The goal of treatment is to increase the stability of bone tissue and prevent fractures. Although the disease is not curable, several medications and therapeutic approaches can help alleviate symptoms. Fluoride and bisphosphonates, which promote bone formation and inhibit bone resorption, show promising results. Surgical intervention may also be necessary, for instance, to correct bone deformities or to stabilize bones after fractures.

Rehabilitation is crucial for patients, as proper muscle strengthening and exercise increase bone stability, reduce the risk of fractures, and improve patients’ quality of life.

Prognosis and Prevention

Most patients with osteogenesis imperfecta reach adulthood, although they may have mobility limitations. The prognosis of the disease depends on its type and can be refined through genetic testing. In the mildest cases, the risk of fractures is increased, but this does not significantly affect lifespan. In the most severe subtypes, which can cause fractures even in utero, the risk of early mortality is higher.

Due to the hereditary nature of the disease, prevention is not possible, but genetic counseling before starting a family can help reduce the chances of having affected children. Analyzing family history and genetic classification are important steps in understanding and managing the risk of the disease.