1, what is the meaning of porcelain doll
Osteogenesis imperfecta, also known as brittle bone disease, the patient has an alias - "porcelain doll", a very graphic illustration of the characteristics of this disease: like a Porcelain dolls will be broken when they meet collision, osteogenesis imperfecta patients encountered a fall, collision, it is easy to fracture.
In terms of research on the treatment of osteogenesis imperfecta, Peking Union Medical College Hospital is synchronized with the international standard and is at the leading level in China. Recently, a reporter interviewed Prof. Li Mei of the hospital's Department of Endocrinology on related issues. Prof. Li Mei and her colleagues have been focusing on osteogenesis imperfecta since more than 20 years ago, and have carried out a lot of clinical and basic research.
Osteogenesis imperfecta hereditary disease
Li Mei introduced to the reporter that osteogenesis imperfecta is a kind of monogenic skeletal disease due to the mutation of the gene coding for type I collagen or the mutation of the gene related to the metabolism and assembly of type I collagen, which results in the reduction of the amount of type I collagen or structural abnormality, causing the decrease of bone density, the increase of bone brittleness, and the occurrence of recurrent fractures. Hereditary bone disease. The reason why bone has both a certain strength and a certain toughness is because of the large amount of collagen contained in it. More than 90% of the protein in bone is type I collagen, and osteogenesis imperfecta occurs when there is insufficient production of type I collagen or structural abnormalities.
Li Mei said, although osteogenesis imperfecta is a rare disease, but due to the large population in China, the disease is not uncommon in China, but there is a lack of epidemiological survey data. Epidemiological survey in the United States, 10,000 newborns in 1 to 1.5 suffered from osteogenesis imperfecta, relative to other rare diseases, its incidence rate is relatively high. This is because about 90% of osteogenesis imperfecta is inherited in an autosomal dominant manner, which means that if one parent carries the mutated gene, the child has a 50% chance of developing the disease. Another 10 percent are recessive, in which case the child has a 25 percent chance of developing osteogenesis imperfecta if both parents carry the gene that causes the disease.
What are the consequences of osteogenesis imperfecta? Li Mei said, because of the increased bone fragility, patients will repeatedly fracture under minor external forces, multiple fractures will lead to bone deformity, accompanied by pain, seriously affecting the patient's quality of life, and some patients can even be disabled. Patients with multiple fractures resulting in skeletal deformities may require surgical treatment, placing a heavy financial burden on the family.
Osteogenesis imperfecta varies in severity and prognosis according to its subtypes, which are categorized from a clinical point of view as type 1, type 2, type 3, and type 4. Type 1 is a mild form of the disease; type 2 is perinatally lethal, which means that it can lead to death soon after birth; type 3 is the most severe form of the disease among survivors; and type 4 is the one that has a degree of disease in between types 1 and 3. Type 1 is the most severe form of the disease because it is less severe, and the number of fractures is less than that in patients with the disease. Type 1 patients because the disease is relatively mild, the number of fractures is relatively small, height is less affected; type 3, type 4 because of the number of fractures, bone deformity will be more serious, short stature is more common. Li Mei said, foreign research shows that the vast majority of patients with type 1, 3, 4 life expectancy is basically the same as normal people. Unless there is a serious thoracic deformity, the patient may appear cardiopulmonary function is impaired, often in the lung infection induced, leading to heart failure and other conditions occur.
Actively using medication to increase bone strength
Li Mei pointed out that in the past, osteogenesis imperfecta was thought to have no treatment, but in recent years, with the depth of research, there is now significant progress in the diagnosis and treatment of the disease both at home and abroad. With treatment, patients' fracture rates will drop and their quality of life will improve significantly.
Because osteogenesis imperfecta is caused by a genetic mutation, the most effective method is to change the causative gene, but this method is still in the research stage, not used in clinical treatment. So, what about the clinic? Li Mei pointed out that it is to find ways to increase bone density, so that the amount of bone increased to improve the ability to resist fracture. Currently used at home and abroad there are two main categories of drugs: one is to inhibit bone resorption of drugs, that is, to reduce bone destruction; the other is to promote bone formation of drugs that can increase bone mass.
Li Mei said, inhibiting bone resorption of commonly used drugs are bisphosphonates, such drugs into the bone, so that bone osteoclasts in the bone activity decreases, the number of reduction in bone resorption, thus reducing bone resorption in favor of bone formation is greater than the bone resorption, and gradually make the patient's bone density increased. Peking Union Medical College Hospital has conducted a lot of clinical research in this area and has published several papers. They first used intravenous second-generation pamidronate and third-generation ibandronate, then second-generation oral alendronate, and third-generation intravenous zoledronic acid. Currently, alendronate and zoledronic acid are more commonly used. Alendronate is an oral preparation, which is more convenient to use; zoledronic acid is an intravenous preparation, but it is used only once a year, which reduces the trouble of repeated visits to the doctor and medication, and the compliance is better, and the cost is not too high. Li Mei tips, bisphosphonates into the body, 50% will go to the bones, 50% through the urine in its original form, so before treatment to check the kidney function, to see if it can be used.
The drug that promotes bone formation is teriparat, which can increase osteoblast activity, leading to increased bone mass. But Li Mei said, this drug is now used at home and abroad are relatively few, because the drug has no children's indications, can only be used for adults. At present, only individual application of bisphosphonates of adult patients with poor results in the trial of Teripat, mainly because of the high price of the drug.
Li Mei pointed out that in addition to these two types of drugs, patients should also use calcium and vitamin D, which are "raw materials" and nutrients to promote bone growth. For particularly serious, has affected the motor function of the serious bone deformity patients, but also for bone surgery. In addition, patients should be told to take special care not to fall, as falls significantly increase the risk of fracture. It is also important to strengthen functional exercises, get more sunlight, and improve muscle and body coordination. Immobilization for fear of fracture can lead to disuse osteoporosis, which in turn increases the risk of fracture, thus creating a vicious circle.
Early detection and standardized treatment
Li Mei said that for osteogenesis imperfecta, medication is a basic and important form of treatment, which should be carried out early. A Peking Union Medical College Hospital study of age groups found that the younger the patient was at the start of treatment, the faster the bone formation, the better the increase in bone density, and the more pronounced the decline in fracture rates. In addition, Li Mei pointed out that bisphosphonates do not need to be used for life. For people with mild conditions, such as type 1 and type 4, bone density can reach normal levels after an average of 4.5 years of medication, and can be discontinued for observation. patients with type 3, or those with autosomal recessive inheritance, need a longer period of time due to their more severe conditions. All patients need to choose an individualized treatment plan according to their condition, the growth of bone density, and the status of fracture incidence, and set the course of treatment according to the response to treatment.
So how is this disease detected early? Li Mei pointed out that the first is to look at the family history, most patients have a family history. The second is to look at the performance, in addition to easy fracture, osteogenesis imperfecta patients may also have blue sclera, dentinogenesis imperfecta, joint ligament laxity and other manifestations. For example, if parents find that their children have blue eyes and a history of fracture, they should be alerted and go to the hospital in time for examination. Third, measurement of bone density. Fourth, genetic testing. Genetic testing can not only identify whether the osteogenesis imperfecta, predict the severity of the disease, but also guide eugenics. Li Mei introduced, at present the Peking Union Medical College Hospital has been able to gene chip technology, clear osteogenesis imperfecta patients with disease-causing gene mutations.
Li Mei emphasized that osteogenesis imperfecta should be standardized diagnosis and treatment, otherwise the consequences are very serious. For example, some patients go for massage and other treatments, and fractures occur during the massage. Some patients only focus on surgical treatment, postoperative drug therapy did not keep up, and then there are repeated fractures after surgery. In addition, in the process of treatment, a number of indicators to monitor, on the one hand, can guide the treatment, on the other hand, can also bring confidence to the patient. (Reporter Yang Liuxiang)
2, brittle bone disease what performance
1, blue sclera: about 90% of the above. This is due to the patient's sclera becomes translucent, you can see the color of the choroid underneath it. There is no abnormality in the thickness and structure of the sclera, and its translucency is due to the change in the nature of collagen fiber tissue.
2, excessive laxity of joints: especially wrist and ankle joints. This is due to the developmental disorders of the collagenous tissue of tendons and ligaments. There can also be knee valgus, flatfoot. Sometimes there are habitual shoulder dislocation and radial head dislocation.
3, head and face deformity: severe cranial dysplasia, at birth the head has a sense of skin. Later, the skull is wide, the parietal and occipital bones protrude, the two temporal globular bulging, frontal bone protrudes forward, the ears are pushed downward, and the face becomes an inverted triangle. Some patients are accompanied by hydrocephalus.
4, dwarf: this is due to the development of a slightly shorter than normal, coupled with multiple fractures of the spine and lower limbs due to malformation healing.
5, increased width of skin scars: this is also due to defective collagenous tissue.
6, dental dysplasia: dentition can not be well developed, milk teeth and permanent teeth can be involved. The teeth are yellow or blue-gray, easy to caries and early loss.
7. Weak muscles.
8, deafness: often to the age of 11 to 40 years old, accounting for about 25%, may be due to sclerosis of the ear canal, attached to the stapes foot plate of the oval window due to osseous ankylosis and fixation of the cause, but some people think that the auditory nerve out of the skull base when the compression of the cause.
9, increased bone fragility: minor injuries can cause fracture, serious patients show spontaneous fracture. Congenital type has multiple fractures at birth. Most of the fractures are of the green branch type, with little displacement, mild pain, fast healing, relying on subperiosteal osteogenesis to complete, and thus often go unnoticed and cause deformity connection. The long bones and ribs are the most common sites. The deformity caused by multiple fractures further reduces the length of the bone. The tendency to fracture gradually decreases after puberty.