Incomplete osteogenesis

Osteogenesis imperfecta (osteogenesisimperfecta, Lobstein-Vrolik disease; Q78.0) is a hereditary disease characterized by increased bone fragility, most often caused by mutations in the type I collagen genes, due to dysfunction of osteoblasts, which leads to disruption of endosteal and periosteal ossification. The incidence in newborns is 7.2 per 10,000, with type IV being the most common.

Classification of osteogenesis imperfecta

Up to 8 types of genetic defects are described. According to the clinical picture, 4 types are distinguished.

Characteristics of types of osteogenesis imperfecta

Type	Inheritance	Localization of the defect	Clinical manifestations
IA (OMIM 166200) IB (OMIM 166240)	Autosomal dominant	COL1A1 gene on 17q21-q22 (collagen 1, a-1 polypeptide) COL1A2 gene on 7q22.1 (collagen I, a-2 polypeptide) The defect is not localized	Fragility of bones, blue sclera, absence of hearing loss, fractures most often in preschool age with the development of progressive deformations of long tubular bones Type A - without incomplete dentinogenesis Type B - with completed dentinogenesis
II (OMIM 166210) (OMIM 610854)	Autosomal recessive	HA- gene COL 1A / on 17q21-q22 (collagen I, a-1 polypeptide) Gene COL1A2 on 7q22.1 (collagen I, a-2 polypeptide) IV - CASP gene on Zp22 (cartilage-associated protein)	Perinatal-lethal type: multiple bone fractures occurring in utero or during childbirth, deformation of the femur, impaired bone formation of the skull of the "membranous" type, blue sclera, development of respiratory distress syndrome leading to perinatal death
III (OMIM 259420)	Autosomal recessive	Gene SOSH/on 17q21-q22 (collagen I, a-1 polypeptide)	Recurrent fractures of long tubular bones, often during childbirth, progressive skeletal deformity, joint hypermobility, normal sclera, unchanged hearing
IV (OMIM 166220)	Autosomal dominant	COL1A1 gene on 17q21-q22 (collagen I, a-1 polypeptide)	Fragility of bones with rare fractures leading to bone deformation, normal color of sclera, unchanged hearing Type A - without incomplete dentinogenesis Type B - with completed dentinogenesis

Depending on the onset of the disease, there are early (Vrolika, fractures occur in utero or immediately after the birth of the child) and late forms (Lobstein, fractures occur after the onset of walking).

What causes osteogenesis imperfecta?

One of the most common monogenic connective tissue diseases caused by mutations in the genes encoding the synthesis of a _x - and a ₂ -chains of type I collagen. Clinical polymorphism is due to the nature of the mutations: insertions, deletions, splicing and nonsense mutations - over 160 have been described in total. The most severe forms are observed in cases of glycine replacement with another amino acid; mutations of the a ₂ collagen gene proceed more favorably than a. Sporadic cases are not uncommon. Differentiation of osteoblasts is reduced, deposition of calcium and phosphorus salts is impaired, production is insufficient and resorption of bone substance is inhibited.

Symptoms of Osteogenesis Imperfecta

A typical sign is a tendency to fractures of tubular bones, ribs and collarbones with minimal trauma; the earlier the symptoms appear, the more severe the disease. Other anomalies: shortening and curvature of the limbs due to fractures, muscle atrophy, looseness or contractures of the joints, blue sclera, yellow-brown color of the teeth, deformations of the spine and chest, long-term non-closure of fontanelles and cranial sutures, predominance of the brain skull over the facial skull due to this, otosclerosis. Fractures heal well with the formation of bone callus. Fractures of the skull bones are uncommon. Children are often immobilized, lag behind in somatic development.

Diagnosis of osteogenesis imperfecta

Diagnostic criteria:

• increased bone fragility;
• blue sclera;
• yellow, "amber" teeth;
• otosclerosis.

Radiographic changes in the diaphyses of tubular bones: diffuse osteoporosis up to transparency of the bone, sharp thinning of the cortical layer, decrease in the diameter of the diaphyses with expansion of the metaphyses, reticular pattern of the spongy substance, multiple bone calluses, curvature under the influence of muscle traction. When determining the clearance of phosphates and calcium by creatinine, their renal reabsorption is reduced.

Differential diagnosis with various forms of rickets, hypophosphatasia, juvenile idiopathic osteoporosis, metaphyseal chondrodysplasia.

Treatment of osteogenesis imperfecta

Gentle lifestyle. Diet rich in protein, calcium, phosphorus and magnesium, vitamins C, E, B, B2 _, B6 _, dietary supplements containing amino acids (glycine, methionine, lysine, proline, glutamine). Massage, physiotherapy (inductothermy, electrophoresis with calcium salts on tubular bones).

There are 2 groups of drugs that affect bone remodeling: bone-forming drugs, the action of which is aimed at restoring lost bone mass (fluorides, calcitonin) and anti-resorptive drugs, which can slow down bone loss (calcium salts, vitamin D, bisphosphonates). As a rule, vitamin D is prescribed for a long time - cholecalciferol in therapeutic doses (up to 8-10 thousand IU) or alphacalcidol (1-1.5 mcg / day) and drugs containing calcium, carbonates (vitacalcin, calcium-D3-Nycomed, vitrum osteomag) or ossein-hydroxyapatite complexes (osteogenon, osteocare). The following groups of drugs can be combined with them.

• Calcitonin preparations (in the form of a nasal spray of 100-200 IU/day), treatment is accompanied by inhibition of the process of bone loss, an increase in its mineral density and a decrease in the incidence of fractures.
• Bisphosphonates (etidronic, pamidronic, alendronic, zoledronic acids) have significant antiresorptive activity. Etidronic acid is prescribed for a long time (10 mg/kg per day intravenously for 3-7 days per month or orally at 20 mg/kg in courses up to 30 days). When treating with pamidronic acid (0.5-1 mg/kg), the incidence of fractures decreases, the degree of bone mineralization increases, and bone pain decreases.

In osteogenesis imperfecta type 3, early initiation of treatment (from the 2nd month of life) with neridronate has a positive effect on growth and fracture rate. Initiation of use at 6 months leads to a decrease in fracture rate, but is not accompanied by an increase in osteocalcin and insulin-like growth factor.

In case of deformations, conservative therapy courses are conducted, preparing patients for surgical orthopedic treatment methods. The prognosis is poor in early forms. A common cause of death is infectious diseases associated with immobility.

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