Brittle bone disease, a form of osteogenesis imperfecta that manifests as bone fragility, blue sclera, deafness, and joint laxity, is a congenital hereditary pain due to hypoplasia of mesenchymal tissue and impaired collagen formation. The incidence is equal in males and females. It can be divided into two types: congenital type and late type. The congenital type refers to the onset of the disease in utero and can be subdivided into fetal and infantile types. The disease is severe and most of them die, or die within a short period of time after delivery. It is autosomal recessive, while the late-onset form is milder and can be divided into pediatric and adult forms. The majority of patients survive for a long time and are autosomal dominant. 15% or more of patients have a family history. The fracture should be reset and fixed as usual. Nutritional care should be taken to avoid injury. Some literature claims that bisphosphonates can treat the disease. Brittle bone disease, a form of osteogenesis imperfecta, manifested by bone fragility, blue sclera, deafness, and joint laxity, is a congenital hereditary pain due to hypoplasia of mesenchymal tissue and impaired collagen formation. It has equal incidence in males and females. It can be divided into congenital type and late type. The congenital type refers to the onset in utero and can be subdivided into fetal and infantile types. The disease is severe and most of them die, or die within a short period of time after delivery. It is autosomal recessive, while the late-onset form is milder and can be divided into pediatric and adult forms. The majority of patients survive for a long time and are autosomal dominant. 15% or more of patients have a family history of the disease. There is no specific treatment for this disease. The fracture should be reset and fixed as usual. The patient should pay attention to nutrition and avoid injury. Clinical picture 1. Fractures: Fractures can be caused by minor injuries or daily activities. The fracture can join itself, but slowly. It may not occur again after the young age. 2. Blue eyes: Patients may have dark blue sclera, caused by the pigmented outgrowth of the ocular choroid. 3. Deafness: It is mostly seen in patients over 20 years of age and is caused by sclerosis of the small bones in the ear. About 25% of cases suffer from deafness. 4. Other: muscle weakness, joint laxity, short stature, incomplete calcification of mammary teeth as translucent, but normal intelligence. On X-ray examination, the whole body is found to be osteoporotic. The long bones were small and thick at both ends, and the cortex was extremely thin. The bones are often bent or poorly fractured, and the vertebral body is flattened and biconcave, and the intervertebral discs are enlarged and biconvex. Pathological changes Extensive mesenchymal defects cause fibrous inhibition of collagen maturation. During chondrogenesis, epiphyseal cartilage and cartilage calcification areas are normal, but osteoblasts and osteoid tissue are scarce in the epiphysis, and the bonelets formed are sparse and longitudinally arranged, with no crossed trabeculae visible. The process of intra-membranous ossification was also affected, with thickened periosteum but thin bone cortex and lack of lamellar structure of the canal, enlarged lumen of Harvard’s canal, and many fatty and fibrous tissues in the lumen, shorter bone than normal, thinner circumference, and expanded pestle-like ends. The skull is very thin, and irregular foci of calcification are scattered, and in severe cases they resemble a membrane bag, with delayed closure of fontanelle. Skin and sclera are also lesions. Pathogenesis Extensive mesenchymal defects inhibit the maturation of collagen fibers. During the process of chondrogenesis, the epiphyseal cartilage and cartilage calcification areas are normal, but osteoblasts and bone-like tissue are scarce in the epiphysis, and the bone microfibrils formed are sparse and longitudinally arranged, without crossed trabeculae visible. The process of intra-membranous ossification was also affected. The periosteum was thickened but the bone cortex was thin, and the laminae of the canal were missing, the lumen of Harvard’s canal was enlarged, and there was a lot of fat and fibrous tissue in the bone marrow cavity. The skull is very thin, and irregular foci of calcification are scattered, and in severe cases they resemble a membrane bag, with delayed closure of fontanelle. The skin and sclera also have lesions. Osteogenesis imperfecta is a typical example of genetic variation, which has been studied at the biochemical, cellular ultrastructural and molecular levels in recent years. 1, osteonectin and proteog1ycan are reduced, and proteog1ycan is separated from collagen fibers, and in severe cases, the cross* of proteog1ycan particles and collagen is reduced by 95.2%. 2, the collagen type in bone tissue changes, only type 1 collagen in normal bone tissue, less type 2, 3, 4. In osteogenesis imperfecta, there is a large amount of type 3 collagen in long bones. 3, epiphyseal growth plate hypertrophy, disturbed mineralization in the original mineralized area, broken small columns, and very poorly mineralized areas with biochemical alterations in the glucosaminoglycosamine (GAGS) matrix. Collagen molecular defects, GAGS alterations, and non-collagenous protein alterations are the main pathological alterations underlying osteogenesis imperfecta. 4, Periosteal thickening, defective microvascular formation, thickening of arterial and capillary walls, lumen blocked by proliferating endothelial cells and myocytes, high proliferation rate of periosteal cell cultures, increased intracytoplasmic phospholipids, smooth endoplasmic reticulum, and decreased lysosomes and rough endoplasmic reticulum. 5, apatite crystals, especially small apatite crystals decreased, the most significant in type 2, type 1 decreased in childhood, and improved after youth, while type 3 and 4 also decreased in youth, especially type 3 more obvious. 6. It was found that cultured cells from osteoblastic patients with bone defective cells did not respond to growth transfer factor (TGF-B), while for cultured cells from normal human bone demented cells, TGF-B increased alkaline phosphatase activity while stimulating collagen synthesis. This indicates that osteoblasts with osteogenesis imperfecta are in various degrees of end maturity Pathological manifestations: 1. Increased bone fragility can cause fractures with minor injuries, and severe patients show spontaneous fractures. The congenital type has multiple fractures at birth. Most of the fractures are cyanotic, less displaced, less painful, faster healing, and rely on subperiosteal osteogenesis to complete, thus often going unnoticed and causing deformed connections. The long bones and ribs are the preferred sites. The deformity caused by multiple fractures further reduces the length of the bone. After puberty, the trend of fractures gradually decreases. 2. Blue sclera accounts for about 90% or more. This is due to the fact that the patient’s sclera becomes translucent and the color of the choroid beneath 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 nature of the collagen fiber tissue. 3. Deafness often appears by the age of 11 to 40, accounting for about 25% of cases. It may be due to sclerosis of the ear canal and fixation of the stapes footplate attached to the oval window due to bony ankylosis, but it is also thought to be due to pressure on the auditory nerve as it exits the skull base. 4. Excessive joint laxity, especially in the wrist and ankle joints. This is due to impaired development of the collagenous tissue of the tendons and ligaments. There can also be knee valgus and flat feet. Sometimes there is habitual shoulder dislocation and radial head dislocation, etc. 5.Weak muscles. 6, head and facial deformity severe cranial dysplasia, in the birth of the head with a sense of skin. Later, the skull is broad, the parietal bone and occipital bone protrude, the two temporal bulbous expansion, the frontal bone protrudes, both ears are pushed down, and the face becomes an inverted triangle. Some patients are accompanied by hydrocephalus. 7.Dental dysplasia is not well developed, and both milk teeth and permanent teeth can be involved. The teeth are yellow or blue-gray, easy to decay and fall off early. 8.Dwarf. This is due to the slightly shorter development than normal, coupled with multiple fracture deformities of the spine and lower limbs healing. 9. increased width of skin scars, which is also due to defective collagen tissue. x-ray manifestations are mainly lack of bone and generalized bone sparseness. ① In the long bones, it shows elongation, sparse bone trabeculae, semi-translucent, and thin cortex like pencil drawing. The medullary cavity is relatively large and may be cystic in severe cases. The ends of the bones are dilated in a pestle shape, and multiple old or fresh fractures are seen. Some of them have been deformed and connected, with a curved backbone. Some deformities are due to pulling at the muscle attachments, such as hip inversion and bowing of the femur and tibia. In some patients, abundant globular scabs form after the fracture, which are so numerous and extensive that they can be misdiagnosed as osteosarcoma. Other patients have a thicker bone cortex, called “thick bone”. This is rare. (2) Delayed calcification of the skull, thinning of the bone plate, bulging of both temporal bones, wide anterior chimney, relatively dense rock bones, and flattening of the skull base. The mammary teeth are poorly calcified, but the permanent teeth are still well developed. (iii) The vertebral body is thin and biconcave, the trabeculae are sparse, and the intervertebral discs are biconvex and compensatory expanded. Scoliosis or retrognathism may be present. ④ Ribs are bent downward from the rib angle and multiple fractures are often seen. The pelvis is triangular in shape and the pelvic cavity becomes smaller. Diagnostic differentiation is usually not difficult. Sometimes it has to be distinguished from severe rickets. Rickets manifests as widened, blurred epiphyseal cartilage, irregular and poorly demarcated from the epiphysis to the calcified cartilage area. The epiphysis itself is cup-shaped and widened. In addition, the sparseness of other bones is less pronounced than in osteogenesis imperfecta. It should be clinically distinguished from chondrodysplasia, congenital muscle relaxation, hypothyroidism, and hyperparathyroidism, which are generally not difficult. There are many other causes of lower back pain, including congenital bone defects, degenerative disease, or bone deformities, which can be examined on x-ray, such as an oblique film showing the small intervertebral articular surfaces. Ruptured discs, ligament sprains and muscle tears are sudden onset and symptoms often begin within 24 hours of lifting heavy objects. Localized pressure and muscle spasm at specific sites are of interest, suggesting a lesion in the back itself rather than intrapelvic or retroperitoneal disease. CT scan or MRI may provide valuable images of longitudinal cavity deformation. fractures and fracture dislocations can be excluded by history, nature of trauma. x-ray, CT scan, bone scan (e.g., 99mTc pyrophosphate labeling). Chronic arthritis of the small posterior vertebral joints is usually associated with degenerative disc disease, the former with specific clinical manifestations and radiographic signs of osteoarthritis and the latter with signs of nerve root irritation. Hyperextension usually exacerbates the pain in the affected posterior small joints of the vertebral body, and the progressive onset of lower back pain in younger adults suggests underlying bone abnormalities such as anterior spinal displacement or spondylolisthesis (e.g., ankylosing spondylitis or sacroiliac arthritis); adolescent onset is highly suggestive of spondylolisthesis, with corresponding symptoms of pelvic and retroperitoneal disease without local signs in the low back. Tumors and infections are more difficult to diagnose and can resemble ruptured intervertebral discs; occupying tumors are often diagnosed by CT, MRI, or myelography. Cerebrospinal fluid examination does not always identify tumors from ruptured discs; both can have elevated cerebrospinal fluid protein levels, but this test is necessary in the diagnosis of cerebrospinal meningitis and other infections. Fibromyalgia can cause chronic lower back pain and stiffness as part of its limited (myofascial) or diffuse (fibromyalgia) symptoms. In addition. It is appropriate to confuse the disease It is usually not difficult. Sometimes to be distinguished from severe rickets. Rickets manifests as widened, blurred epiphyseal cartilage, irregular and poorly demarcated epiphysis to calcified cartilage area. The epiphysis itself is cup-shaped and widened. In addition, the sparseness of other bones is less pronounced than in osteogenesis imperfecta. It should be clinically distinguished from chondrodysplasia, congenital muscle relaxation, hypothyroidism, and hyperparathyroidism, which are generally not difficult to distinguish. Sometimes there may be an increase in blood alkaline phosphatase, which may be due to an increase in osteoblast activity after traumatic fracture. In very severe cases, there is a decrease in plasma calcium and phosphorus, but this is rare. Therapeutic measures No specific treatment is available. The main thing is to prevent fractures, to protect the child strictly until the fractures tend to decrease, but to prevent the complications of prolonged bed rest. The treatment of fractures is the same as in normal subjects. However, the fracture heals rapidly and the fixation period can be short. In the correction of deformities, in recent years, the deformed long bones have been truncated in several places, threaded with long intramedullary pins to correct the alignment, and left in the bone to prevent re-fracture. If the cortex is too thin and surgery is difficult, allogeneic bone graft can be used. In patients with hearing loss, stapedectomy can be done. 50% to 70% of children with scoliosis can be protected with a brace. If the scoliosis exceeds 60°, spinal fusion should be performed after correction. Estrogen can be applied to older women to reduce severe osteoporosis. Bisphosphonates have been tried in the literature to treat this disease. In the late 1980s, there were some reports of trials of calcitonin therapy, which can be administered via nasal mucosal absorption, and salmon calcitonin (sal咖ncalcitonin) was given for 2-12 months, but the results were not satisfactory, except for 4-5 months after administration. No further changes were observed, except for a slight increase in urinary transcalcitonin excretion at 4-5 months after administration. There was no change in bone mineral density before or after treatment. Huaux (1988) reported that in severe cases the application of APD [(3-amino-l-hydroxypropylidene)-l,l- biphosPhonate) treatment, and the epiphyseal bone density increased after treatment. In recent years, Chen Shu et al. reported that the combined application of rocalciferol and metacalciclopride in the treatment of osteogenesis imperfecta patients with painful symptoms, the symptoms were relieved after a few weeks of medication, and the bone density increased and the bone cortex thickened after 3 months. With the development of rehabilitation medicine, Gerber et al. (1990) introduced the concept of systematic rehabilitation for infants and children with osteogenesis imperfecta. Hydrotherapy under strict protection, practice sitting up straight and strengthen the pelvic and lower limb muscles. After being able to sit upright independently, they practice standing under the protection of long-legged stationery, and later practice walking under the protection of braces and with the help of a walking device. Letts et al. suggested that the child could wear a vacuum trouser orthosis to practice standing, which is comfortable, safe and can reduce the incidence of fractures. Bone density also increased after rehabilitation treatment. In order to fix the fracture and increase the strength of the fragile bone, percutaneous or trans-fracture end intramedullary pin treatment can be used in infancy to temporarily maintain the force line of the bone in line, when the pin penetration requirement is not necessarily completely through the medullary cavity, partly in the medullary cavity and partly beside the bone, which is also helpful, and replace the extendable intramedullary struts after 3-4 years of age. Multi-segment osteotomy intramedullary nail or extendable intramedullary rod orthopedics is a proven method of treating compound deformities due to osteogenesis imperfecta. It can correct multiple deformities in one stage, rationally rearrange the bone alignment, strengthen the fragile bone, and significantly improve the function. The surgery should not be selected for very serious cases, but for cases with the ability to regain standing and walking after the correction of limb deformity. Correct estimation to judge the actual state of the deformed bone is very important. The deformed backbone is not only angular and bowed, but often has severe torsion, and it is difficult to judge the width of the medullary cavity on ordinary x-ray plain film, and multiple segments are osteotomized to enlarge the medullary cavity. After recombination, what kind of intramedullary support is used to strengthen it, which must be fully prepared before surgery. There are two types of extendable intramedullary struts: Balley-Hunbow bars and Sheffield bars. The internal support placed must be of sufficient length. In the case of the femur, the distal end should pass through the laying board to a position equivalent to the adult intertrochanter and should be placed at or near the center of the arrow to provide the best internal support for the diaphysis and metaphysis. For bilateral femoral and tibial deformities, it is advisable to correct the bilateral femur first and then the bilateral tibia in stages. Simultaneous correction of ipsilateral femoral and tibial deformities is difficult to maintain postoperatively. The femur generally does not require bone grafting, and multiple tibial osteotomies in older children are best treated with bone grafting because of the possibility of nonunion. If the proximal femoral osteotomy line is too high, there is a possibility of hip inversion after surgery. The long postoperative bone healing time and adequate protection by reliable braces are essential. In 50% to 70% of cases of osteogenesis imperfecta with spinal deformity, a brace is available for protection. If the scoliosis exceeds 60°, it is very difficult to deal with and light material stationery is ineffective, spinal fusion can be carefully considered. Estrogen may be used in older women to reduce severe osteoporosis. Calcium lowering has been tried in the literature to treat this disease, but the efficacy is not certain. In patients with hearing loss, stapedectomy may be performed.