MARBLE DISEASE [synonym: Albers-Schoenberg's disease, inborn family osteosclerosis, family fossil of bones, generalized fragile (brittle) osteosclerosis] — seldom found inborn disease of dysplastic character which is shown a diffusion osteosclerosis of the majority of bones of a skeleton.
M. it is for the first time described on the basis rentgenol, pictures H. E. Albers-Schon-berg in 1904 and 1907 and bears his name. In the USSR the first works devoted to M., H are published in 1929 — 1930 by M. B. Kopylov, M. F. Runova. M. Kudryavtseva. Publications, as a rule, have descriptive character and do not open a being of a disease, a cut remains obscure. M. meets in all age groups. It is widespread equally on all continents, equally among men and women.
Etiology it is unknown. In most cases M. has family character and passes from father to son though in literature the arising M. is repeatedly described sporadic. at people with not burdened heredity.
Pathogeny it is a little studied. M. V. Volkov carries it to diseases of dysplastic character, i.e. to congenital anomalies of development, to-rykh the growths of a bone which are forcing out the hemopoietic fabric are the cornerstone patol. A. V. Rusakov would put M. in one row with an oyeteomiyelodisplaziya though communication between them is not absolutely clear. Gerstel would consider M. as result of disturbance of interaction three various funkts, parts of a skeleton: basic, endosteal and hemopoietic devices. The lack of coordination between them leads, according to A. V. Rusakov, to vicious formation of skeletogenous fabric and to insufficiency of myelogenetic fabric.
The dysplasia of a skeletogenous mesenchyma is expressed in education finktsionalno to a defective bone with accumulation in bone system of excess amount of the calciphied, very fragile, easily breaking bone substance. Myelogenetic fabric develops in insufficient quantity.
M.'s division. is defined on high-quality and malignant forms by extent of involvement of this or that derivative primary mesenchyma. When defeat only of a skeletogenous mesenchyma prevails, would speak about high-quality option M., to-ry proceeds only with an osteosclerosis and often long time does not give any a wedge, manifestations. If the myelogenetic mesenchyma also is involved in process, then heavy anemia — malignant option of a course of a marble disease develops, at Krom the wedge, symptoms are early shown.
The main changes at M. are localized in a bone tissue and have universal character. Bones at M. very heavy, are hardly sawn, but easily break up. The type of the femoral and humeral bones having the club-shaped thickenings respectively in the lower and upper thirds arising owing to more rough osteogenesis in these sites is very typical. On a cut long tubular bones have no marrowy cavity; instead of it the compact substance replacing spongy substance and flat bones (a backbone, clavicles, bones of a skull) is visible. In long tubular bones compact substance can sometimes alternate with the sites consisting of more porous bone substance, a cut has an appearance of the grayish and reddish ring or a belt going across a longitudinal axis of a bone (tsvetn. fig. 1). The belt of depression of substance of a bone indicates suspension of processes of an excess osteogenesis at a certain stage of a disease. Macroscopically it is possible to find changes from cortical substance both long tubular, and flat bones. The continuity of cortical substance is broken by places and in it instead of compact the spongy structure is found. Owing to such peculiar reorganization the surface of a bone stops being smooth, taking a rough, spongy form (tsvetn. fig. 2). Cortical substance of a bone has character of a dense (compact) bone or turns into a spongy bone with the marrowy spaces containing preferential unripe hemopoietic fabric (so-called medullization of cortical substance). Medullization represents the compensatory phenomenon in response to disappearance of marrowy spaces. In bones of a skull medullization can be a source epidural, and sometimes and subdural hemorrhages (tsvetn. fig. 3). Vicarious hemopoiesis takes place in a spleen and in limf, nodes, to a lesser extent in a liver that is followed by a splenomegaly and increase limf, nodes.
In some, especially tyazheloprotekayushchy cases, the centers of a hemopoiesis in kidneys are observed (tsvetn. fig. 4), pararenal cellulose.
At microscopic examination it is found out that patol, the excess osteogenesis goes in all bones of a skeleton as in an epiphyseal cartilage (a rostkovy zone), and on the course of a diaphysis. The periosteal osteogenesis is very seldom observed. In marrowy spaces in nek-ry cases find the thick bedded structures which are located around capillaries and representing patol, osteons. In other cases marrowy spaces are executed by a lamellar bone tissue with numerous arc-shaped lines of pasting. Beams from an unripe coarse-fibered bone tissue meet. In a splenial the number of osteoblasts, their distribution in a bone tissue uneven is reduced. The phenomena of a resorption of a bone are almost not observed. Marrowy spaces are sharply narrowed, executed by fibroretikulyarny fabric. Only it is possible to meet in places sites of marrow. In a zone of an endostosis the main substance of a cartilage is not exposed to a resorption as it takes place in fiziol, conditions, and gives an osteogenesis, at first in the form of roundish islands (fig. 1), and then wide bone crossbeams, at the edges to-rykh the remains of the main substance of a cartilage are visible. In process of removal from an epiphyseal cartilage substance of a bone gets a lamellar structure (fig. 2).
In nek-ry cases of M. it is possible to find a diffusion parenchymatous craw with increase in weight of a thyroid gland by 3 times and a hyperplasia of parathyroids. At microscopic examination the hyperplasia of S-cells of a thyroid gland connected with products of thyrocalcitonin came to light. Thyrocalcitonin promotes adjournment of calcium and phosphorus in bones and causes a hypocalcemia, leads edges to a secondary compensatory hyperplasia of parathyroids. These changes testify to value of a hyperplasia of S-cells in a pathogeny of a marble disease.
From c. the N of page is found a moderate nanocephalia, hydrocephaly, an atrophy of nervous conductors (preferential visual and preddverno-cochlear nerves). In kidneys changes in a basal membrane of balls and dystrophy of an epithelium of collective renal tubules are noted. The septicaemia or a septicopyemia as a complication of the osteomyelitis developing because of fragility of bones, patol, changes and their infection is often stated.
A clinical picture
V. Mac-Kyyuzik would allocate two forms M. One of them — autosomal and recessive, edges is called also malignant form. Another — autosomal and dominant — is rather good-quality. The malignant form comes to light very much early, sometimes in addition in uterine or at early children's age. At it all skeleton is surprised, a hemopoiesis is sharply broken (sm:.). Main a wedge, manifestations of the second form are changes (see) and osteomyelitis (see). It comes to light rather late, sometimes even at people of mature or advanced age.
Clinical signs of a disease are very various and depend on age of the patient, sharpness of a disease; anemia, falloff of visual acuity or a blindness at newborns or babies, osteomyelites, especially a mandible, fractures of bones is observed.
Patients with M. in most cases low growth, are a little infantile, hypodermic cellulose is poorly developed. Sick M. children cannot long go, teeth at them appear very late, easily drop out, are surprised caries. External outlines of extremities do not change or change a little at the expense of a thickening of epiphyseal and metafizarny departments of long tubular bones.
The deformations of bones caused by disturbances of enchondral growth are quite characteristic; deformations front and a neurocranium, edges and a thorax, a rachiocampsis, varus deformations of extremities, etc. can be referred to them; pelvic bones and even shovels can be surprised.
A disease the majority of bones of a skeleton is surprised, but degree of manifestation of process in different bones is not identical. Process in the bones forming a base of skull and in long tubular bones is most expressed: in femoral (is more often in distal departments), in tibial, fibular and humeral (in proximal). Are frequent patol. fractures of long tubular bones. Though sick M.' bones. are sharply condensed, they are withdrawal pains that is explained by features of their very tectonics, edges are lost funkts, by character because of chaotic filling of bone structures. The sclerous thickening of bones of a base of skull can lead to narrowing of its openings and channels, most often the visual channel. In this regard at children with M. the atrophy of optic nerves with the progressing loss of sight can develop. Much less often other cranial nerves are surprised.
At the easily current forms at adult M. can remain undetected or to be accidentally found at a X-ray analysis of bones.
Due to «replacement» of marrow by shapeless bone masses at patients anemia, usually hypochromia develops (see. Iron deficiency anemia ), is more rare normokhromny and extremely seldom Hyperchromic. Often the anisocytosis, a poikilocytosis, Polikhromatofiliya and Eritroblastoz is defined. In hard cases, hl. obr. at children, changes of the hemopoietic device develop suddenly, quickly progress and become a proximate cause of death; in other cases, a thicket at adults, anemia keeps for years. Content of calcium and phosphorus of blood is close to norm. Quite often increase limf, nodes, a liver and a spleen that is connected with development in these bodies of the extramedullary centers of a hemopoiesis. The extramedullary centers of a hemopoiesis which are also revealed on openings in the form of flat protrusions of dark red color under a periosteum of nek-ry bones, under a firm meninx are described that in these cases can remind subdural hematomas.
Diagnosis establish on the basis of data of clinic and rentgenol, inspections, a cut gives very characteristic picture of changes of almost all bones, including vertebrae (see. Marble vertebra ). The marble disease received the name in connection with the person rentgenol, a picture of the epiphyseal ends of long tubular bones and ossicles, to-rye give on roentgenograms the intensive homogeneous continuous shadow reminding marble without border between compact and spongy substances. Rentgenol, a research allows to define prevalence of process in bones of a skeleton, to specify character patol, changes, to track a current patol, process and to reveal possible complications (patol. changes, disturbance of enchondral growth of a skeleton etc.). Along with it rentgenol, the research allows to distinguish the family, asymptomatically proceeding M.'s cases.
Radiological changes find in bones of a skull, a basin, in vertebrae, proximal departments of a femur, edges, is more rare — in bones of upper extremities, brushes and feet. The form and the sizes of bones remain usually normal. In some cases the frequent club-shaped thickening of metafizarny departments of long tubular bones is observed. The structure of bones is sharply changed. Instead of the usual trabecular, mesh drawing of a bone get homogeneous density, and the greatest intensity of compact bone substance is noted in subcortical departments and on border of an epiphysis and metaphysis, and also on the course of a rostkovy zone of an apophysis (fig. 3). As a result of the uneven growth of a skeleton the struck departments acquire the peculiar drawing formed in parallel by the located strips and half rings. In bones of a skull first of all the bones having a cartilaginous origin are surprised. Along with a sclerosis of a bone tissue narrowing of channels is noted, through to-rye there pass cranial nerves, paranasal sinuses are obliterated. A peculiar form is taken by bodies of vertebrae, the central part to-rykh is brightened up, and on the course of the closing plates dense wide strips (fig. 4) are formed. Rates of an endostosis of a skeleton are quite often broken that is shown in delay of emergence of kernels of ossification and a sinostozirovaniye of an epiphysis in bones of brushes and feet.
Patol, fractures of bones most often arise in subtrochanterian area of a femur, is more rare in other tubular bones and edges. Plane of a change, as a rule, cross or kosopoperechny (fig. 5). Splintered changes meet more seldom. Shift of fragments usually insignificant.
Differential diagnosis in typical cases of M. it is not difficult. During the comparison low-expressed or atypical rentgenol, changes the differential diagnosis is carried out with osteopoikilosis (see), melocheostosis (see), and also with osteosclerotic anemia and a myelofibrosis (see. Osteomyelofibrosis ); more rare with leukoses (see) and lymphogranulomatosis (see), effects of lead poisoning, phosphorus, especially fluorine. To remind M. according to roentgenograms some forms of a disease of Pedzhet can (see. Pedzheta disease ), osteoplastic multiple metastasises, especially prostate cancer. It is necessary to consider that at children's age the osteosclerosis can be caused by medicinal therapy of inborn syphilis, and also at a hypervitaminosis of A and D.
Treatment and Forecast
symptomatic treatment. The temporary and unstable effect, and anemia at patients from actively current M. give hemotransfusions. progresses. The made attempts of surgical expansion of visual channels at patients with damage of optic nerves were unsuccessful in connection with irreversibility of the developing changes of optic nerves. Treatment patol, changes at patients with M., as a rule, conservative.
The forecast at a malignant form adverse. M. is the heaviest. proceeds at early children's age.
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H. E. Makhson; T. E. Ivanovskaya (stalemate. An.); M. K. Klimova (rents.).