Spring is coming, the birds are singing, and the flowers are blooming beautifully. However, the children are very sad and feel that their spring is still far away. Obviously 7 years old, can not walk, can not run, he was diagnosed with a rare hereditary bone disease - osteogenesis imperfection, which is what we commonly call "porcelain dolls". On the occasion of the 15th International Rare Disease Day (February 28), the endocrinologist of Peking Union Medical College Hospital will take you to understand this rare disease, let us embrace the difference and share the color of life!
About the author: Zhou Bingna
Master's degree student in the Department of Endocrinology, Peking Union Medical College Hospital, under the supervision of Chief Physician Li Mei.
Audit Expert: Li Mei
Deputy Director of the Department of Endocrinology, Peking Union Medical College Hospital, Chief Physician, Doctoral Supervisor. He is the chairman-elect of the Osteoporosis and Bone Mineral Salt Disease Branch of the Chinese Medical Association, the chairman-elect of the Osteoporosis and Bone Mineral Salt Disease Branch of the Beijing Medical Association, and the deputy editor-in-chief of the Chinese Journal of Osteoporosis and Bone Mineral Salt Disease.
Mingming's story
Obviously, the child is 7 years old, he can't walk, let alone run, what is wrong with this?
It turned out that Ming Ming was different from other children since he was a child, and his eyes were blue when he was born, and his joint ligaments were soft and loose. At the age of 2, his parents found that his teeth were thin and transparent, and since the age of 3, he would have repeated fractures under slight external force, and now, his limbs have been fractured more than 10 times. Due to multiple fractures, his thighs and calves were significantly bent, resulting in his inability to walk, and his study and life were also significantly affected.
Obviously what kind of disease, mom and dad have been very anxious, do not know how to treat, later, mom and dad took him to the department of endocrinology of Peking Union Medical College Hospital, the doctor inquired in detail about the condition, carried out a detailed physical examination, obviously completed the corresponding blood tests, bone X-rays, bone density tests, pathogenic gene mutation tests. Finally, the doctor told him that he was suffering from a rare hereditary bone disease , osteogenesis imperfecta, which is commonly known as "porcelain doll".
What kind of disease is osteogenesis imperfecta?
Osteogenesis imperfecta, also known as brittle bone disease, is a single-gene genetic disease, 85% to 90% is autosomal dominant inheritance, 10% to 15% is autosomal recessive inheritance or with X chromosome recessive inheritance. About one in ten (15,000 to 20,000) newborns suffer from osteogenesis imperfecta. Children with osteogenesis imperfecta often develop diseases from an early age, and often repeated fractures occur in the case of slight external force or no obvious external force, resulting in different degrees of bone bending deformities and activity disorders, which seriously affects the quality of life. Osteogenesis imperfecta can also present with extraskeletal manifestations such as blue sclera, dentin hypoplasia, lax joint ligaments, hearing loss, and heart valve lesions.
How does osteogenesis imperfecta harm strong bones?
The structure of normal bones is like a strong, well-arranged building, the collagen fibers in the bones are like the steel bars that support the building, and the minerals deposited around the collagen fibers, mainly including calcium and phosphorus, are like the cement wrapped around the building and supporting the steel bars. Collagen fibers mainly maintain the toughness of bones and structural integrity, and minerals mainly guarantee the hardness of bones.
When the genes encoding type I collagen fibers in the human body or genes involved in collagen modification, transportation, assembly and other processes are mutated, it will cause insufficient collagen fiber content or structural abnormalities, resulting in a significant reduction in bone mass, bone microstructural damage, and increased bone fragility, which in turn leads to repeated fractures in patients, causing osteogenesis imperfections.
If you have osteogenesis imperfecta, how can I treat it?
There is currently no radical cure for osteogenesis imperfecta caused by genetic mutations, but there are drugs that can alleviate disease symptoms, reduce fractures, and improve the quality of life of patients.
First of all, it is recommended that Mingming's parents should maintain a positive and optimistic attitude and bravely face the disease.
It is recommended to carry out regular exercises to enhance muscle strength and improve mobility; pay attention to avoid falls to prevent inducing fractures; develop a healthy lifestyle, pay attention to balanced diet, maintain a suitable weight, prevent body obesity, and avoid excessive load on the bones. More importantly, it is recommended to take an appropriate amount of calcium and vitamin D under the guidance of a doctor, while combining more effective therapeutic drugs, including bone resorption inhibitors and bone formation promoters.
There are two important types of cells in the bone, one is osteoblasts and the other is osteoclasts, as the name suggests, osteoblasts are to help form new bones, and osteoclasts are to promote the absorption of old bones. If the drug can promote the formation of new bone or reduce the resorption of old bone, it may increase bone mass and reduce the risk of fracture.
Related drugs and research results
Current studies have shown that bisphosphonates help inhibit osteoclast activity, reduce the absorption of bones, and increase bone strength. Clinical studies at Peking Union Medical College Hospital have shown that oral sodium alendronate tablets or intravenous infusion of zoledronic acid can help increase the bone density of the lumbar spine and hip in patients with osteogenesis imperfecta, reshape the compressed vertebral body in children, reduce the incidence of fractures, and reduce the risk of skeletal deformities.
In recent years, the targeted therapy drug for osteoclasts, disumab, can also specifically inhibit osteoclast activity, reduce bone mass loss in patients, increase bone density, and reduce the risk of fracture.
There is also a drug that promotes bone growth - teripate, which may increase the bone mass in patients with osteogenesis imperfecta, but there is no safety data on the use of teriparatide in children, so it cannot be used at present; for adult osteogenesis patients, teriparatide may have a certain efficacy, but large samples of clinical studies are needed to further clarify its efficacy and safety.
In addition, the new drug that promotes bone formation, the hard osteostatin monoclonal antibody, may also play a certain role in the treatment of osteogenesis imperfecta in the future, but clinical studies need to be carried out to confirm.
In the treatment process of the patient accepting the above drugs, it is recommended that under the guidance of the doctor, observe the serum bone conversion biochemical indicators and liver and kidney function, measure bone density, take bone X-rays, record the height growth rate to understand the efficacy and safety of the drug, and adjust the drug treatment plan and course according to the results.
If a patient with osteogenesis imperfecta has an unstable fracture, a fracture that has delayed healing or non-union, or a severe bone deformity, etc., causing the patient's limited mobility and seriously affecting the quality of life, on the basis of drug treatment, orthopedic surgery can be received to alleviate bone deformity and improve mobility and quality of life.
Obviously the follow-up treatment...
Later, with the help of an endocrinologist at Peking Union Medical College Hospital, Ming ming received proper treatment - intravenous infusion of zoledronic acid once a year. After 3 years, Mingming's bone density increased significantly, and fractures rarely occurred. Later, with the help of Concordia orthopedics, Ming Ming also underwent lower limb orthopedic surgery, and the operation was successfully completed, and Ming Ming's calf finally straightened. After another year of medication and rehabilitation, Ming was finally able to stand and walk.
If we are unfortunate enough to meet osteogenesis imperfecta, don't be afraid, let us face it bravely and strongly, and believe that medicine is constantly improving and developing. At present, there are many effective treatment drugs that can increase bone density and reduce the risk of fractures. Let us pluck up the courage to find the light in life with the doctors, continue to work hard, and move forward with determination.
The future will always be full of hope, after the harsh winter, we will surely usher in the spring blossoms!
bibliography:
Chinese Medical Association Osteoporosis and Bone Mineral Salt Disease Branch. Guidelines for the clinical diagnosis and treatment of osteogenesis imperfecta. Chinese Journal of Osteoporosis and Bone Mineral Salt Diseases,2019,12(1):11-23.
[2] ForlinoA, Marini J C. Osteogenesis imperfecta. Lancet, 2016, 387: 1657-1671.
Lü Fang,Li Mei. Research progress on new drugs for the treatment of osteogenesis imperfecta. International Journal of Pharmaceutical Research,2017,44(02):173-177.
[4] Lv F, Liu Y, Xu X, et al. Effects of long-term alendronate treatment on a large sample of pediatric patients with osteogenesis imperfecta. Endocr Pract, 2016, 22(12): 1369-1376.
Photo/Provided by The Department of Endocrinology
Editor/Hong Chengwei
Editor-in-Chief/Chen Mingyan
Producer/Wu Peixin