Disease name: osteogenesis imperfecta.
Alias: brittle bone disease, primary bone fragility, periosteal dysplasia.
Location: Whole body.
Related symptoms: fever, abnormal body shape, hearing loss, reduced bone metabolism.
Pharmacological treatment: oyster calcium carbonate granules, children’s vitamin D calcium chewable tablets.
5: Osteogenesis Imperfecta Symptoms:
The disease is characterized by skeletal dysplasia, osteoporosis, increased fragility and malformation, blue sclera and hearing loss, but the clinical differences are very large. In severe cases, multiple intrauterine fractures and deaths occur, and symptoms are mild to school age. And can survive to the old age. The widely used clinical classification method is the four-type classification of Silence. Sillence et al. (1979) classified osteogenesis imperfecta into four types from the perspective of her genesis.
This type of typing has been recognized by the academic community. Type 1 is autosomal dominant, blue sclera, only mild bone deformity; type 2 is equivalent to the congenital type of the past; type 3 is severe, many cases show delayed intrauterine growth, fractures occur after birth, clinically Severe osteoarticular malformation, blue sclera in infancy, not significant after childhood, this type of patient can generally survive to adulthood; type 4 is autosomal dominant, but no blue sclera, moderate bone, and joint deformity, Although there is no intrauterine growth delay, the general development rate is slow and the body is short. Repeated fracture is a feature of osteogenesis imperfecta.
Traverse fractures and spiral fractures are the most common, and about 15% of fractures occur at the metaphysis. After fracture, there can be a large number of epiphyseal hyperplasia, most of which can heal, but often residual deformity. There are reports of a large number of bone dysplasia after 4 long bone fractures, leading to high discharge heart failure and a large number of bone hyperplasia caused by the septal syndrome. Nonunion of the fracture is easy to occur in the site of progressive deformity with progressive deformity, and type 3 is more than type 4. Localized atrophy or proliferative changes may occur.
At the age of 4, 70% of children with type I osteogenesis imperfecta can walk independently, and 1/3 of type 4 children can walk or climb, while type 3 children cannot stand alone at this time. At the age of 10, 80% of type 3 children can sit independently and 20% of children can walk a short distance. 50% of type 1 and type 4 children have dental defects, and more than 80% of type 3 children have incomplete tooth formation. It is not uncommon for congenital heart malformations to be in type 3. Individual cases suffer from hearing impairment due to otosclerosis. Recently, there have been reports of kidney stones, renal papillary calcification, and diabetes.
1: A slight injury to bone fragility can cause a fracture, and a severe patient presents with a spontaneous fracture. Congenital people have multiple fractures at birth. Most of the fractures are blue-branched, with less displacement, lighter pain, faster healing, and relying on subperiosteal ossification to complete the bone, which often leads to malformation. Long bones and ribs are good sites. The deformity caused by multiple fractures further reduces the length of the bone. After puberty, the fracture trend gradually decreases.
2: The blue sclera accounts for more than 90%. This is because the patient’s sclera becomes translucent and the color of the choroid below it can be seen. There is no abnormality in the thickness and structure of the sclera, and its translucency is due to the change in the properties of collagen fibers.
3: Deafness often occurs in 11 to 40 years old, accounting for about 25%. It may be due to ear canal sclerosis. The humeral foot plate attached to the oval window is fixed due to osteogenic rigidity, but some people think that it is the auditory nerve. In the end, it is caused by pressure.
4: Excessive joint relaxation, especially the wrist and ankle joint. This is due to the development of collagen tissue in tendons and ligaments. You can also have knee valgus and flat feet. Sometimes there are habitual shoulder dislocations and dislocation of the humeral head.
5: The muscles are weak.
6: Skull dysplasia with severe head and face deformity, the head has a skin sensation at birth. Later, the skull was broad, the parietal bone and occipital bone were prominent, and the two bulges bulged. The frontal bone was protruding, and the ears were pushed downward, and the face was inverted triangle. Some patients have hydrocephalus.
7: Tooth dysplasia Dentin cannot develop well, and both the deciduous teeth and the permanent teeth can be affected. The teeth are yellow or blue-gray, easy to lick and fall off early.
8: Gnomes. This is due to the development of a shorter period than normal, plus the healing of multiple fractures of the spine and lower extremities.
9: Increased skin scar width, which is also due to defects in collagen tissue.
The four main diagnostic criteria are:
1. Osteoporosis and bone fragility increase.
2. Blue sclera.
3. Dentin formation imperfect.
4. Premature otosclerosis.
Two of the above four items, especially the first two items, can be diagnosed. Combined with imaging studies to help diagnose. ‘Osteogenesis Imperfecta Treatment | Causes, Diagnosis, PPT’
6: Osteogenesis Imperfecta Testing:
The auxiliary examination methods for this disease are mainly X-ray examination and laboratory examination:
1, X-ray inspection:
X-rays are mainly characterized by bone deficiency and generalized bone sparseness.
1: The long bones are slender, the trabecular bones are sparse, semi-translucent, and the cortex is as thin as a pencil. The medullary cavity is relatively large, and cystic changes may occur in severe cases. Both ends of the bone are swollen and sinuous, and there are many old or fresh fractures. Some have been deformed and the backbone is bent. Some deformities are caused by muscle traction, such as hip varus, the arch of the femur and tibia. Some patients will form a rich spheroidal callus after the fracture. The number and scope of the patient will be misdiagnosed as osteosarcoma. In other patients, the cortical bone is thicker and is called “thick bone type.” Rare.
2: delayed calcification of the skull, thinning of the bone plate, bulging of the double tibia, wide front anterior, relatively dense rock bone, flat skull base. Calcium calcification is not good, and permanent tooth development is acceptable.
3: The vertebral body is thin, double concave, and the trabecular bone is sparse. The intervertebral disc is double convex and compensatory. There may be scoliosis or kyphosis.
4: The ribs are bent downward from the ribs, and multiple fractures are often seen. The pelvis is triangular and the pelvis becomes smaller.
5: joints: There are four main changes: one part of the patient may cause depression of the acetabulum and femoral head to the pelvis due to osteomalacia; 2 the intramedullary osteogenesis of the backbone may cause the bone to become thinner, but due to cartilage calcification and cartilage The osteogenesis is still normal, and the bone ends that make up the joints are relatively large; in most of the patients, there are many calcifications in the epiphysis. Maybe due to the non-absorption of intra-articular calcium in the cartilage ossification process; 4 pseudo-articular joint formation, due to multiple fractures, cartilage formation at the fracture, X-ray film looks like pseudo-articular formation.
6: Skeleton: There is a difference in bone damage between early-onset and late-onset osteogenesis. Early-onset patients showed multiple fractures of the long bones with osteophyte formation and skeletal deformation; late-onset patients had obvious osteoporosis, multiple fractures, long bone bending or short femur and thick “accordion”-like changes. The bone is too thin or the backbone is too thick, and the bone changes in a sac or honeycomb shape. Long cortical bone defects are rough. The ribs are thinner, the lower edge is irregular or the thickness is different, and the fingers are changed like peanuts. The alveolar plate absorbs. Scoliosis, vertebral body flattening, or increased vertebral body upper and lower diameter, can also be expressed as a small vertebral body, pedicle growth. The skull is thin, the seam is present, the front and rear are convex, and the occipital part is drooping. The metaphyseal ends of the long bones of the extremities have a majority of transverse dense lines, and the density of the periorbital cartilage discs is increased and uneven. MRI and CT examinations have found proliferative osteophyte formation in the lesions of osteogenesis imperfecta, sometimes resembling bone tumors.
2: Ultrasound examination:
Ultrasound examination of the fetal skeletal system can detect congenital bone development disorders early. The experience of Garjian et al. shows that three-dimensional ultrasound can obtain stereoscopic anatomical positioning, so it is superior to two-dimensional ultrasound examination, and the former is more likely to find deformities of the head, face, and ribs.
3: Laboratory inspection:
Generally normal, sometimes there may be an increase in blood phosphatase, which may be due to increased osteoblast activity after traumatic fracture. Very severe cases have a reduction in plasma calcium and phosphorus but are rare.
Patients with blood calcium, phosphorus and ALP are generally normal, a small number of patients with ALP can also be increased, urinary hydroxyproline increased, and some with amino acid urine and mucopolysaccharide urine. Two-thirds of patients had elevated serum T4. Due to the increase in thyroxine, there is a platelet aggregation disorder in leukocyte oxidative metabolism.
7: osteogenesis imperfecta diseases:
Some scholars believe that the key point in the diagnosis of this disease is the identification of achondroplasia.
Cartilage hypoplasia is a systemic symmetrical cartilage development disorder, mainly manifested as pygmy deformities with short limbs but the almost normal trunk. Characteristics of severe cartilage hypoplasia: the fetal head is enlarged, the double top diameter is widened; the rib is thick and short, the thoracic cage is narrow, but the lower thoracic cavity is relatively enlarged; the fetal abdomen is bulging and the abdominal circumference is enlarged; the fetal limbs are short and the long bone is short and long. More accompanied by bending, bone end enlargement; increased amniotic fluid volume. The limbs of these two malformed fetuses are short, but the osteogenesis is incomplete, the bone density is reduced, the cortex is thin, the bone is easily fractured, and the bone deformity and thoracic deformation are caused by the fracture, which is different from the dysplasia.
In addition, it should be noted that this disease can cause bone deformity, fracture, and osteophyte formation, so the X-ray diagnosis should be differentiated from osteosarcoma, rickets, abnormal bone fiber, and congenital pseudoarthrosis.
1. Delayed juvenile osteoporosis, general osteoporosis, vertebral biconcave deformation or flat vertebral body, and lateral kyphosis and easy fracture of the spine, similar to osteogenesis imperfecta; but the latter still has a large head The humerus on both sides, the base of the skull, the small triangle, the blue sclera, the multiple suture bones, and the family history are different from the former.
The diagnosis of type I OI is sometimes very difficult. Any type of OI may be thought of in patients with osteoporosis or severe osteoporosis during menopause.
2. Bone softening and rickets without bone fragile and easy to fold, no blue sclera. The front of the mineralization is blurred with a brush or cup, and the cartilage disk is widened. Bone softening is more common in pregnant women or lactating women, with bone pain, serum calcium and phosphorus are reduced.
3. Patients with vitamin C deficiency also have osteoporosis, but there may be bleeding points in the subcutaneous, intermuscular, and epithelial membranes. There may be severe pain and pseudos pasm, and calcification may occur after fracture healing.
4. Patients with osteosarcoma osteogenesis imperfecta can have a large number of osteophytes in the fracture. Most are benign. Only a few have erythrocyte sedimentation rate and elevated blood ALP, and bone biopsy can be identified if necessary.
5. Hyperactivity of the joints Joint relaxation and hyperactivity are one of the characteristics of OI and should be associated with other collagen-deficient diseases that cause this change, such as benign joint hyperactivity syndrome, Morquio syndrome, Ehlers-Danlos syndrome, Identification of Marfan syndrome, Larsen syndrome, and the like. In addition, a special type of OI can be expressed as Cole-Carpenter syndrome, or adolescent osteoporosis, Ehlers-Danlos syndrome, OI combined with primary hyperparathyroidism, OI with dentinogenesis imperfecta (DI), OI-like syndrome should be noted for identification.
8: osteogenesis imperfecta treatment:
The disease is a congenital disease with no special treatment. Mainly to prevent fractures, children should be strictly protected until the fractures are reduced, but the complications of long-term bed rest should be prevented. The treatment of the fracture is the same as normal. However, the fracture heals quickly and the fixation period can be short. In terms of correcting deformity, in recent years, some people have deformed long bones in many places, wear long intramedullary nails, correct the alignment line, and stay in the bone to prevent further fracture. If the cortex is too thin and surgery is difficult, allogeneic bone grafting can be used. For patients with hearing loss, patella resection can be performed. 50% to 70% of the sick children have scoliosis and can be protected by a stent. If scoliosis exceeds 60°, it should be corrected for spinal fusion. Estrogen can be applied to older women to reduce severe osteoporosis. Some people have tried to reduce calcium in the literature to treat this disease, but the effect is not certain.
1. Insufficient growth hormone growth is one of the clinical features of OI. Some OI patients have low GH/IGF-1 axis function. Growth hormone has a certain effect on OI, can increase the exchangeable calcium and calcium pool, increase the calcium content (more obvious for men), and is beneficial to bone mineralization. Growth hormone can promote collagen synthesis. After 12 months of treatment, the longitudinal growth rate of bone increases (no change in bone age) and the fracture rate decreases. This is because growth hormone can increase osteocalcin synthesis, promote mineralization, and increase BMD. Children with type III and IV OI (1 to 4 years old) have a growth stagnation period. Treatment with 0.1 ~ 0.5U / (kg • d) growth hormone, 6 days a week, 6 months after the increase in dose, many children with an increased linear growth rate of bone. Dutch scholars reported that the first batch of 20 children had satisfactory results in the mid-term treatment.
2. Cell replacement refers to the conversion of cells carrying a mutant gene by bone marrow transplantation with completely normal cells. Analysis of all bone tissue by polymerase chain reaction analysis revealed that the replacement was not successful. At present, it has not been clarified to what extent normal cells need to be able to alleviate clinical symptoms, and ideal treatment is still under investigation.
3. Bisphosphonate Plotkin and the like using a bisphosphonate (such as pamidronate, pamidronate) injection can improve the prognosis of patients with severe OI under 3 years of age. Each cycle of 3 days, a total of 4 to 8 cycles of treatment, the total dose of pamidronate was 12.4mg / kg, after treatment, BMD increased by 86% ~ 227%, Z value decreased from -6.5 ± 2.1 to -3.0 ± 2.1, The fracture rate is reduced.
1: Many children with OI are associated with long sagittal and/or coronal curvature: if the sagittal plane is more than 40°, it is easy to fracture. This degree of bending is often accompanied by a reduction in the amplitude of dorsiflexion. Parents should be informed that the child is at greater risk of fracture; surgery may require surgical intervention when bending more than 40°.
2: Back pain in children with OI: often presents multiple compression fractures of the chest and lumbar spine and/or scoliosis. Treatment includes hyperthermia and symptomatic treatment. Apparent pain can be applied to patients with obvious pain. Such as 1 calcitonin is effective for pain caused by fractures and osteoporosis. 2 non-steroidal drugs (such as ibuprofen sustained-release tablets, pyrroline, and indomethacin) and topical creams (such as indomethacin, Youmai cream, etc.). 3 Chinese medicine such as Sanqi, safflower plus frankincense, myrrh, and alcoholic beverages also have a certain effect.
3: Osteotomy orthopedics Some children have undergone multiple osteotomies during childhood to reduce the incidence of fractures and prevent lower limb flexion. Surgery can improve limb deformity and improve the quality of life of patients.
4: Treatment Prospects OI treatment hopes to use osteogenic stem cells and biomaterials for orthopedic repair. Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been tried to treat OI model animals. Patients with type I and IV OI can survive for a long time, while the main causes of death in type II and III patients are heart failure, respiratory or neurological damage, intracranial hemorrhage, and accidental trauma.
9: osteogenesis imperfecta prevention: