Osteogenesis Imperfecta

OSTEOGENESIS IMPERFECTA (imperfect ossification), a rare disease first described by Vrolik (1849). The numerous other names proposed for this disease—fragilitas ossium, osteopsathyrosis congenita (Klebs, Hochsinger and others), malacia myeloplastica (Recklinghausen), ostitis parenchymatosa chronica (Schmidt and Wagner), osteomalacia congenita (Jurgens), dystrophia periostalis (Porak and Durant) and others—did not find general recognition. The main clinical manifestation of the disease consists in the appearance of multiple fractures in various parts of the skeleton, especially in the long tubular bones and ribs. Cracks, tears, and fractures of the bones in O. i. usually occur already during the intrauterine period, and the child is born with multiple, sometimes literally countless fractures, some of which are already healed. If fractures do not form intrauterinely, they usually occur for the slightest reasons in the very near time after birth. The presence of multiple fractures of long tubular bones, some of which are incorrectly united, often causes the deformation of the limbs that is frequently observed in O. i. The patho-anatomical changes underlying the clinical picture consist in the insufficient production of bone tissue from the bone-forming elements of both the internal periosteum (endosteum) and especially the external periosteum. As for the epiphyseal cartilage of the tubular bones, there are no special changes in this regard, although in some cases the cartilage cells take a more elongated form, and the cartilage appears insufficiently differentiated; sometimes a decrease in the thickness of the columnar layer of cartilage cells and a decrease in the volume of the preparatory zone of cartilage ossification are also noted. The main microscopic changes consist in the insufficient formation of bone substance both of the cortical layer and of the spongy substance of the bones, and in various cases a predominance of the disturbance of either enchondral or periosteal ossification is noted; periosteal ossification is sometimes disturbed so sharply that this gives some authors grounds to treat O. i. as a predominantly periosteal dysplasia. The cortical layer of tubular bones is poorly developed, consisting of separate, loosely connected underdeveloped bone lamellae; in places it may be completely absent, and then the bone marrow comes into direct contact with the periosteum. The architecture of the spongiosa of tubular bones is disturbed. The bone trabeculae are arranged in an unsystematic manner, and their number is reduced. The bone trabeculae themselves are small, underdeveloped, and often contain remnants of cartilage. The bone cells are of irregular, angular shape and are poor in processes. The number of osteoblasts is usually reduced, their arrangement is often disorderly, and they appear as small low cells. There are no phenomena of intensified bone resorption noted. The calcium content in the bone substance is usually not reduced; therefore, the formation of osteoid substance is not noted. The bone marrow is of the ordinary type or, in places, of a fibrous appearance. The described histological changes are responsible for the excessive thinness, delicacy, and brittleness of the bones. Among other changes caused by the underdevelopment of the bony skeleton, one must note the extreme softness of the skull cap, which is explained by its sharp underdevelopment; the skull cap is often formed by connective tissue with only small bone lamellae embedded in it. The bones of the skull base usually do not present special changes. In addition to changes in the bony skeleton, sometimes a disturbance in the formation of dentin in the tooth primordia and teeth is noted. Sometimes a weak development of supportive connective tissue throughout the body is also noted. As for internal organs, deviations from the norm are usually not noted. The child's general nutrition is usually quite satisfactory, often even somewhat excessive compared to the norm. Children with O. i. are usually born prematurely, and in pronounced cases of the disease they are either already born dead or die shortly after birth. However, there are cases of survival of children with congenital O. i. for several months and even years. The disease is more common in the female sex. The etiology of the disease is still unclear. Attempts to explain the disease by a disorder of the functions of the internal secretion glands (thyroid, parathyroid, etc.) have no sufficient basis. Syphilis plays no role. In recent years, attempts have been made to cause O. i. experimentally by giving pregnant animals excessive doses of vitagol, which causes a severe disturbance of calcium metabolism. The offspring of these animals exhibit bone changes similar to those in O. i. These data still do not explain the etiology of O. i., since in the first place, in O. i. the metabolism, particularly the salt metabolism, does not present gross deviations from the norm, and in the second place, in O. i. cases of twins are known (Miiller, Kuznetsov), from one of which the infant was completely healthy. The most widespread view is that O. i. is a developmental defect expressing the underdevelopment of all derivatives of the mesenchyme (Bauer and others). The sudden appearance of O. i. in healthy families is explained by the mutation of the corresponding genes. However, it is not possible to trace the hereditary transmission of O. i., since children with O. i. are usually nonviable, and the genealogical line is thus interrupted at the very beginning. The majority of authors consider O. i. identical with idiopathic osteopsathyrosis (see); cases are known of children with O. i. being born to parents suffering from osteopsathyrosis (the Zurnelle case). In the survival of children with congenital fractures in O. i., the boundary between the latter and osteopsathyrosis blurs. Treatment—see Osteopsathyrosis.