Osteogenesis imperfecta (Osteogenisis Imperfecta), also known as brittle bone disease (Fragililis ossium), idiopathic osteopsathyrosis, and periosteal dysplasia, is characterized by fragile bones, blue sclera, deafness, and joint laxity. It is a congenital hereditary disorder caused by mesenchymal tissue hypoplasia and collagen formation impairment.

bubble_chart Etiology

The cause of the disease is unknown and is a congenital developmental disorder. The incidence is equal in males and females. It can be divided into two types: congenital and late-onset. The congenital type refers to onset in the uterus and can be further subdivided into fetal and infantile forms. The condition is severe, often leading to death or short-term mortality after birth. It is inherited in an autosomal recessive pattern. The late-onset type has a milder course and can be divided into childhood and adult forms. Most patients can survive long-term, and it is inherited in an autosomal dominant pattern. Over 15% of patients have a family history.

bubble_chart Pathological Changes

Extensive mesenchymal defects inhibit the maturation of collagen fibers. During endochondral ossification, the epiphyseal cartilage and calcified cartilage zones remain normal, but the metaphysis shows a scarcity of osteoblasts and osteoid tissue. The formed bone trabeculae are thin, sparse, and arranged longitudinally, with no intersecting trabeculae visible. Intramembranous ossification is also affected, with thickened bone membranes but thin cortices lacking a lamellar structure. The Haversian canals are enlarged, and the medullary cavities contain abundant fat and fibrous tissue. The bones are shorter than normal, with reduced circumference and club-shaped ends. The skull is very thin, displaying scattered irregular calcifications, and in severe cases, it resembles a membranous sac with delayed fontanelle closure. The skin and sclera also exhibit pathological changes.

1) Increased bone fragility: Minor injuries can cause fractures, and severe cases may present with spontaneous fractures. Congenital types may have multiple fractures at birth. Most fractures are greenstick-type, with minimal displacement, mild pain, and rapid healing, relying on subperiosteal bone formation, often going unnoticed and leading to malunion. Long bones and ribs are common sites. Repeated fractures further reduce bone length. The tendency for fractures gradually decreases after adolescence.

2) Blue sclera: Present in over 90% of cases. This occurs because the sclera becomes translucent, allowing the underlying choroidal color to show. The thickness and structure of the sclera are normal, but its translucency results from altered collagen fiber properties.

3) Deafness: Typically appears between ages 11–40, affecting about 25%. It may be due to otosclerosis, where the stapes footplate becomes fixed due to bony ankylosis at the oval window, though some attribute it to compression of the auditory nerve at the skull base.

4) Joint hypermobility: Particularly in the wrists and ankles, caused by developmental defects in the collagen tissue of tendons and ligaments. Other manifestations may include genu valgum, flat feet, and habitual shoulder or radial head dislocations.

5) Muscle weakness.

6) Craniofacial deformities: Severe cranial dysplasia may present as a "bag-like" skull at birth. Later, the skull becomes broad, with prominent parietal and occipital bones, bulging temporal regions, protruding frontal bones, downward-displaced ears, and an inverted triangular face. Some patients may have hydrocephalus.

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8) Dwarfism: Caused by slightly shorter growth combined with malunion from multiple fractures in the spine and lower limbs.

9) Wide skin scars: Also due to defective collagen tissue.

X-ray findings: Primarily show bone deficiency and generalized osteoporosis. ① In long bones: Thin and elongated, with sparse trabeculae and a translucent appearance. The cortex is pencil-thin, and the medullary cavity is relatively enlarged, sometimes with cystic changes. The ends of bones are club-shaped, with evidence of old or fresh fractures. Malunion may cause bending. Some deformities result from muscle traction, such as coxa vara or bowing of the femur and tibia. Excessive callus formation post-fracture may mimic osteosarcoma. Rarely, a "thick-bone" variant is seen. ② Skull: Delayed calcification, thinning of bone plates, bulging temporal bones, wide anterior fontanelle, dense petrous bones, and a flattened skull base. Primary teeth show poor calcification, while permanent teeth develop relatively normally. ③ Vertebrae: Thin and biconcave, with sparse trabeculae. Intervertebral discs compensate by bulging biconvexly. Scoliosis or kyphosis may occur. ④ Ribs: Curve downward from the costal angle, often with multiple fractures. The pelvis is triangular with a narrowed cavity.

bubble_chart Auxiliary Examination

Generally, everything is normal, but sometimes there may be an increase in blood alkaline phosphatase, which may be due to increased osteoblast activity after a fracture. In extremely severe cases, there may be a decrease in plasma calcium and phosphorus, but this is very rare.

Generally, it is not difficult. Sometimes it needs to be distinguished from severe rickets. Rickets manifests as widened and blurred epiphyseal cartilage, irregularity and indistinct boundaries from the metaphysis to the calcified cartilage area. The metaphysis itself appears cup-shaped and widened. Additionally, the bone rarefaction in other bones is significantly less pronounced than in osteogenesis imperfecta. Clinically, it should also be differentiated from achondroplasia, congenital hypotonia, hypothyroidism, and hyperparathyroidism, among others, but generally speaking, it is not difficult.

bubble_chart Treatment Measures

There is no specific treatment. The main focus is on preventing fractures by strictly protecting the child until the frequency of fractures decreases, while also avoiding complications from prolonged bed rest. Fracture treatment is the same as for normal individuals, but healing occurs more rapidly, allowing for shorter immobilization periods. In terms of correcting deformities, some recent approaches involve multiple osteotomies of the deformed long bones, inserting long intramedullary nails to realign the bones and leaving them in place to prevent refractures. If the cortex is too thin for surgery, allogeneic bone grafting may be used. For hearing loss, stapedectomy can be performed. 50–70% of affected children develop scoliosis, which can be managed with bracing. If the spinal curvature exceeds 60°, correction followed by spinal fusion is recommended. For elderly women, estrogen therapy may help reduce severe osteoporosis. Some studies have explored the use of calcitonin for treating this condition, but its efficacy remains uncertain.

bubble_chart Prognosis

Severe cases may die in the uterus or within one week after delivery, mostly due to intracranial hemorrhage or secondary infections. If they survive for one month, there is a possibility of long-term survival. During infancy, multiple fractures pose the primary challenge in management. After puberty, the frequency of fractures gradually decreases. Women tend to experience an increased incidence of fractures after menopause. Although fractures can heal normally, many cases develop pseudarthrosis due to delayed detection or improper treatment. Pelvic deformities may complicate childbirth. Neurological complications include hydrocephalus, dysfunction caused by cranial nerve compression, and spinal deformities that may lead to paralysis.