BONE FORMATION IMPERFECT (osteogenesis imperfecta; grech, osteon bone + genesis origin, origin; synonym: inborn fragility of bones, periosteal dystrophy, pre-natal rickets, osteopsathyrosis, Vrolik's disease, Lobstein's disease) — the hereditary disease with preferential disturbance of process of an osteogenesis which is shown generalized osteoporosis, softness and the increased fragility of bones. Depending on weight patol, process, time of manifestation a wedge, signs is allocated by two forms: inborn and late O. of N.
The disease is inherited on autosomal dominantly type, however there are autosomal and recessive forms. Frequency of a disease 1: 40 000 — 60 000 childbirth. According to WHO data (1967), O.'s incidence of N of sibs (see. Proband ) makes 4,9% that indicates quite big prevalence of this pathology in families with the burdened heredity on this disease.
The etiology and a pathogeny
of N connect O. with disturbances of protein or mineral metabolism, depression of function of osteoblasts or increase in activity of osteoclasts. At O. N note normal or even the increased number of osteoblasts and osteocytes at usual quantity of osteoclasts, a sufficient mineralization and expressed to a basophilia) the main substance of a bone that demonstrates normal development of processes of rezorbtsionny modeling bones (see). A. V. Rusakov paid attention that the speech at O. of N goes not about changes of quantitative structure of cellular elements, and about their high-quality shifts funkts, activities. A large number of the osteoblasts having high proliferative activity is developed a little bone substance, quickly turning into osteocytes. The N differs in this O. from rickets, at Krom, on the contrary, trace amount of osteoblasts develops the considerable mass of the ossiform substance which is not exposed to a sufficient mineralization. High proliferative activity of osteoblasts causes good healing of bone changes at O. of N. So, Ramzer (L. R. Ramser, 1966) at a research of a piece of tissue of edge of sick O. of N by means of a tetracycline tag established that the speed of formation of a bone at this disease exceeds usual three times, however cross sectional dimension of an edge remains at the same time is twice less than normal. This fact demonstrates that the basic possibility of growth of a bone skeleton at O. of N is not broken. As a result of an excessive pliability of bones of a skull at O. of N they do not influence growth of the bodies concluded in them therefore there is an increase in an eyeglobe and the stretched and thinned sclera is appeared through by the retina giving it a blue shade; owing to an edema of ventricles the mass of a brain increases that gives to the head characteristic spherical shape. Explained with disharmony of growth of a bone framework of an inner ear and other bones of a skull also development of the progressing deafness at O. to N. This explanation is based that at O. the N is about local insolvency of mesenchymal system only of bone bodies. However nek-ry researchers showed that inferiority of a mesenchyma has more generalized character and is shown by weak products of collagen fibroblasts of skin, sheaves, covers of an eyeglobe, etc. Such position allows to combine big group of syndromes and diseases, to-rykh the general genetic defect of a mesenchyma with preferential defeat at each syndrome of these or those its segments is the cornerstone — bone formation imperfect, desmogenez imperfect (see), chondrogenesis imperfect (see), Marfana syndrome (see). N explain with weak formation of dentine in rudiments of teeth at O., e.g., imperfect development of the teeth which are very quickly exposed to caries.
Modern researches showed that at O. of N there is an insufficient development collagen (see). At O. the N produce preferential prekollagenovy fibers, to-rye are not exposed to maturing, or collagen of special qualitative structure. Histochemical researches demonstrate that collagenic fibers at O. N have unusually high content of proline and that such collagen oppresses in vitro processes of calcification though the defined svetooptichesk processes of a mineralization of a bone at O. of N remain not changed.
At O. N and at adults in bones find identical changes in children. Only scales, depth and localization of damage of bones are various.
Macroscopically find old accrete pre-natal fractures of edges and long tubular bones in combination with a pseudoarthrosis in newborns (see. Nearthrosis ) and fresh changes (see), arisen at the time of delivery. Accrete changes are well noticeable because of sharp deformation, a curvature of bones and existence of large cartilaginous callosities. Changes can be found macroscopically in all bones of a skeleton. An exception are feet and brushes, in bones to-rykh it is possible to find traces old and fresh microfractures only at careful microscopic examination.
Feature of the majority of changes is absence of extensive hemorrhages and perifocal inflammatory infiltration of soft tissues that generally and defines painlessness inherent to them. Changes of the bones of a skullcap representing quite often thin fibrous plate with the islands of a bone tissue concluded in it in the form of crossbeams are very characteristic. Such changes of bones of a skull are, as a rule, incompatible with life owing to heavy traumatization of a brain in labor.
At late O. N macroscopically define abundance of the old healed fractures of tubular bones and nearthroses, and also the considerable rachiocampsis, pelvic bones and extremities caused not only the wrong comparison of bone fragments in the course of healing of a change, but also adaptive reorganization of bones in the conditions of the changed static load. E.g., at impossibility in vertical position patients adapt to movement to move on all fours or on all fours that leads to considerable is bent a niya of tubular bones of top and bottom extremities, and also pelvic bones. Bones differ in unusual fragility and are easily knifed. On cuts of long tubular bones cortical substance is sharply thinned (fig. 1) therefore their marrowy cavity looks disproportionately wide. And. V. Rusakov paid attention to a peculiar shape of a skull at late O. of N: rather poorly developed its front part and large brain departments of spherical shape. These changes are quite often combined with expansion of side cerebral cavities, protrusion from eye-sockets of eyeglobes (bulging eye) and an unusual kruglogolovost in combination with an edema of cerebral cavities.
Microscopically at inborn and late O. N find the same changes: underdevelopment of the main substance (fig. 2) in all bones developing both on cartilaginous and on a connective tissue basis. Epiphyseal cartilages have normal structure, the zone of preliminary calcification of a cartilage and a zone of its rassasyvaniye have usual contours, however in the centers of petrification the insufficient osteogenesis is noted. Therefore in a subchondral zone the big spaces filled with gentle and fibrous fabric are formed. On primary bone structures in the field of metaphyses further there is a weak stratification of bone substance of the subsequent generation therefore the network of bone plates gains shirokopetlisty character. Underdevelopment of bone substance is noted also in a diaphysis (in zones of a periosteum and an endosteum). Therefore cortical substance is represented excessively thin and as if corroded wide central (gaversovy) channels. Cortical substance of a diaphysis of long tubular bones reaches 1 — 1,5 mm, on a bigger extent it consists only of the general plate delimiting a marrowy cavity from a periosteum. Marrowy cavities — with the thin bone crossbeams forming the shirokopetlisty network opening in many sites under a periosteum (see. Osteoporosis ).
Bones of a skullcap at inborn O. of N are formed by a connective tissue cover, the containing various size the islands of calcification and thin bone plates with wide spaces between them filled with nezhnovoloknisty connecting fabric. Bone crossbeams and their fragments are surrounded with correctly created osteoblasts. At late O. the N notes extraordinary thinning of the bones of a skullcap which microscopically have large cell structure with very poorly developed outside plates. Spaces between bone crossbeams are filled with nezhnovoloknisty connecting tissue and islands of myeloid marrow. In spongy substance of long and flat bones the degrowth of bone substance is also noted, and marrowy cavities are filled with fatty and myeloid marrow. In zones of old changes considerable growths of the fibrous and reticular fabric representing endosteal proliferata are found; also considerable growth of fibrous and hyaline cartilages is observed. In the field of not accrete fractures of long tubular bones (nearthroses) growth of the fibrous fabric connecting bone fragments, sharply atrofichny with corroded edges, is noted. Joint cartilages femoral and other bones at O. of N are much thinner normal, their surface remains smooth. Microscopically z them almost total absence of a hondromukoid is noted (see. Hondromukoproteida ). By means of methods of microradiography, X-ray diffraction and microscopy in the polarized light disorganization of collagen, and also the disorder distribution of crystals of mineral salts in it comes to light.
Electronic microscopically in a periosteum, skin, a sclera and a cornea of an eye find collagenic fibers 400 nanometers thick (it is normal of 1000 nanometers) and periodic striation of disks from 200 to 400 nanometers (it is normal of 640 — 700 nanometers).
The clinical picture
the Clinical picture depends on a form of a disease, age and specific features of the patient. Conducting a wedge, symptoms are fragility of bones, blue scleras and relative deafness, the progressing deafness, dropsy of a brain. Discoloration of enamel of teeth, looseness of joints, an atrophy of muscles is less often noted.
At inborn O. of N children are born weak, often impractical. Skin thin, pale, hypodermic cellulose is thinned. The general hypotonia, fractures which arose vnutriutrobno or at the time of delivery is characteristic. Changes are found in the field of a diaphysis of a femur, % of bones of a shin, a humeral bone and bones of a forearm more often, breasts, a clavicle and bodies of vertebrae are more rare. Soft and pliable bones of the head badly protect a brain at the time of delivery.
Many children perish from intracraneal hemorrhage as a result of a birth trauma. With age there is a disproportion of bones of a calvaria and the person. Teeth are cut through later than usual, gain yellow-amber color, quickly are exposed to caries and destruction. The relaxation of ligaments results in looseness of joints and dislocations.
At late O. of N the wedge, manifestations are less expressed. Fractures of bones are characterized by more high-quality current, shown by local morbidity and a small swelling. Changes can be full and incomplete, usually are subperiostal. Fragments are more often displaced at an angle, in the subsequent the arc-shaped curvatures (fig. 3) develop. Shift on length and width is observed seldom. Consolidation happens quickly to formation of a big bone callosity. After one change soon there is another, near earlier occurred. Total number of changes can reach from 5 to 20 and more.
Owing to preferential damage of long tubular bones the characteristic picture of a micromelia develops: extremities become disproportionately short at the normal sizes of the head and trunk. The normal sizes of brushes and feet are typical for O. of N, phalanxes never break, and bones of a shank and a metatarsus — only in the rare occurences. The base of skull, a backbone and a breast at O. of N do not break. By the period of puberty fragility of bones usually considerably decreases.
Changes of internals, and also c. N consider N of page and endocrine system for O. uncharacteristic. Casuistic cases of a hypergenitalism, early puberty and a hypertrichosis are described.
Diagnosis in typical cases does not cause difficulties and the wedge, a picture and data rentgenol, researches is based on data of the anamnesis.
Rentgenol, a picture reflects the main morphological and functional changes at O. of N. Thickness of all bones is less normal, cortical substance in them is sharply thinned. The marrowy cavity in this regard eccentric is increased in the diameter, contours by its places uneven. The spongy structure is rarefied and has shirokopetlisty, mesh, and sometimes and the wrong chaotic drawing, separate bone trabeculas are sometimes hardly visible. In the most hard cases the bone tissue on the gentle homogeneous shadow differs in nothing from surrounding soft tissues so the bone becomes available rentgenol, to definition only thanks to striolas of cortical substance.
On the roentgenogram of the patient from O. N define the multiple fractures of long tubular bones, usually symmetric, most often in the field of average departments of a diaphysis of bones of a hip and shoulder, shin and forearm (fig. 4). Many changes are visible also on the course of edges. Changes are more often full cross, is more rare partial, in the form of subperiostal breaks. Usually does not happen because of hypotonia of muscles of very big shift of fragments of a bone. And characteristic the angular shift of fragments in an average third of a hip and shoulder is more considerable, and the vertex of angle of shift is directed aside and up. Multiple fractures of big tubular bones lead to their considerable shortening and a curvature. Sometimes in them cross and wedge-shaped zones of reorganization meet. Deformation and a thickening are promoted by the old and fresher bone callosities reaching sometimes the big sizes. They usually have spherical shape and symmetrically cover the place of a change. Considerable calcification and ossification of a callosity at O. the N is not observed. If changes are located close from each other (e.g. if 5 and more changes of a diaphysis), then to a callosity of various prescription are at the same time visible and size merge together and the deformed bone takes a peculiar knotty form. Therefore it is sometimes observed paradoxical rentgenol, a picture, i.e. not extreme thinning of cortical substance of a bone, and a nek-swarm its thickening. Deformation is aggravated as a result of the so-called telescopic shift of the fragments moved each other like parts of the telescope. It is observed by hl. obr. on bones of a hip, a shoulder and only occasionally on bones of a shin and a forearm.
Bodies of vertebrae as a result of dystrophy of a bone tissue can take the biconcave form.
Since the endostosis at O. of N does not suffer, the epiphyseal centers are almost not changed and a little bit loosened. Secondary osteogene points (epiphyseal kernels of ossification) appear in time, but they are very transparent.
The picture of a skull is characteristic rentgenol. Against the background of a soft shadow of the arch the separate specks or only single mosaic, landkartoobrazny or roundish star-shaped islands of calcification or isolated, or merging with each other with uneven fringed regional contours appear. Stronger than others obyzvestvlen scales of an occipital bone. Cover bones of the arch are extremely thinned. Face bones are a little changed.
The differential diagnosis
X-ray inspection has crucial differential and diagnostic importance. It is necessary to exclude chondrodystrophia (see), edges it can be suspected because of the symptom of a micromelia, general for both diseases. On the roentgenogram it is easy to distinguish a normal proportional brush at O. of N from very characteristic shortened phalanxes at a chondrodystrophia Rickets (see) it is excluded on the basis of N of the epiphyseal centers, neizkhmenenny at O., while at rickets the main patol, changes are concentrated in rostkovy zones. The differential diagnosis is carried out also with nephrogenic osteopatiya (see. Osteopathy nephrogenic ), at to-rykh indicators of phosphorus-calcium exchange are changed. Lakes of N differentiate with various genetically caused diseases, napr, a syndrome Wang-der-Huve (see. Wang-der-Huve syndrome ).
Treatment, especially at an inborn form, ineffectively also consists in palliative actions: the sparing mode, prevention of changes and the prevention of deformations to lay down. gymnastics and massage, balneoterapiya. In a complex of treatment appoint Ural federal district, polyvitamins, spirit and oil solutions of vitamin D, drugs of calcium, phosphorus, salt to - that with pepsin, methandrostenolone (Nerobolum), a calcitonin.
A specific place is held by ortopedo-surgical treatment. Treatment patol, changes at patients with O. of N shall come down to careful reposition of fragments and reliable fixing by a plaster bandage before full consolidation of fragments. Terms of fixing in most cases do not differ from terms of fixing of extremities at usual changes (see). Is of great importance in prevention of formation of secondary deformations to lay down. prosthetics (see. Orthoses ). Operational methods of treatment are directed first of all to correction of heavy deformations of extremities and to recovery of the lost function. There is no uniform operational technique of treatment; in some cases apply osteoclasis (see), osteotomy (see) with use intra-and ekstraossalny fixers in the form of allotransplants (see. Bone plastics ) and a metal osteosynthesis (see. Osteosynthesis ); in nek-ry cases can be used distraktsionno-compression devices (see). Operational treatment is possible after execution of five years. As indications to operation serve the heavy deformations of the lower extremities which are not allowing to pick up orthoses, in to-rykh patients could move. In quality of training of the patient to operation the above-stated conservative treatment is carried out. The most reasonable technique of operational treatment is the technique offered by M. V. Volkov (1964), edges includes a decortication (department of a periosteum throughout the deformed bone together with thin islands of cortical substance), a segmented osteotomy and bone plastics by means of allotransplants on the faggot type. Operation is made under the general anesthesia in position of the patient on spin. Carry out premedication: atropine and Promedolum in the corresponding dosages depending on age of the patient. The section of skin is made on the convex party of a curvature, muscles move apart in the stupid way, longwise move apart a periosteum and a thin chisel make a decortication throughout the bent diaphysis of a bone, ate what at top of a curvature carry out a segmented osteotomy of a bone: depending on degree of a curvature cut Gigli's saw, a chisel, an ultrasonic saw from 2 to 5 segments. The axis of an extremity is corrected by movement and comparison of the segments strung on the cortical allotransplant or a metal core entered into a marrowy cavity, edges by means of the electric drill extends. In addition around segments podnadkostnichno stack long cortical allotransplants (5 — 7 pieces), to-rye fix circular catgut seams («faggot»). The wound is layer-by-layer sewn up; carry out an immobilization a circular plaster bandage before full consolidation of fragments. Consecutive reconstructive multi-stage operations allow to correct deformation of extremities then you recommend;] production of bezzamkovy orthoses, sometimes with the emphasis on a sciatic hillock. As a complication failure of union of a segment, i.e. formation of a nearthrosis and nek-paradise loss of correction is possible.
In these cases well proved distraktsionno-kompres-sionny an osteosynthesis, with pomdshchyyu to-rogo the axis of an extremity, its length is recovered and at the same time there is an union of fragments.
The remedial gymnastics is carried out carefully. From methods of massage preference is given to stroking and grinding. In the preoperative period apply to lay down. the gymnastics and massage directed to strengthening of muscles. In the postoperative period when the extremity is still fixed by a plaster bandage, appoint exercises of isometric character. Broad application is found by the physical exercises which are carried out in warm water. The main attention shall be directed to achievement of static function of standing in orthoses, working off of step movements of legs. The purpose of rehabilitation at O. of N is prevention of secondary deformations and improvement of labor skills.
Forecast at an inborn form adverse, children perish from intercurrent diseases. At a late form the forecast for life more favorable.
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A. V. Papayan (ped.); M. V. Volkov, JH. H. Nefedyeva (ORT.), H. K. Permyakov (stalemate. An.), S. A. Reynberg (rents.).