osteogenesis imperfecta

Background This rare disease affects the major connective tissues of the body. Overall, there is a decrease in bone mass and increase in bone brittleness. Patients present with a blue sclera, dental abnormalities, progressive hearing loss, and a positive family history. Classification of Osteogenesis Imperfecta TYPE I II III IV

INHERITANCE CHARACTERIZATION AD AD OR AR AD OR AR AD

Mild fragility without deformity, short stature Perinatal lethal Severe, progressive deformity Skeletal fragility and osteoporosis, bowing

OUTLINE Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/Immunohistochemistry/Electron Microscopy Differential Diagnosis Prognosis and Treatment Commonly Used Terms Internet Links

EPIDEMIOLOGY

CHARACTERIZATION

INCIDENCE

Rare 1/20,000 births

DISEASE ASSOCIATIONS PAGET'S DISEASE

CHARACTERIZATION

Arch Intern Med 1983 Dec;143(12):2250-7 Abstract quote

Osteogenesis imperfecta Osteogenesis imperfecta (OI) and Paget's disease and Paget's disease of bone. Biochemical and of bone occurred in a patient whose brother has Paget's disease. Several other relatives have the morphologic studies. dominant variety of OI. Shapiro JR, Triche T,

Rowe DW, Munabi A, Cattell HS, Schlesinger S.

The familial occurrence of the two diseases is presumably due to chance and, to our knowledge, has not been previously reported. Examination of iliac crest bone biopsy specimens showed mild changes of both diseases in the proband. Electron microscopy of the bone collagen demonstrated type I collagen fibers, which are reduced in number, decreased in diameter, and stellate rather than smooth in outline. Three populations of collagen fibers were observed in the bone. The synthesis of type I collagen by dermal fibroblasts was diminished in the proband and affected relatives, but it was normal in the unaffected relatives. Since collagen fibers with a stellate outline have not been observed in OI bone, an intriguing question is the effect to the putative Paget agent (? viral) on collagen synthesis in OI.

PATHOGENESIS COLLAGEN SYNTHESIS DEFECT

CHARACTERIZATION

Eur J Clin Invest 1989 Apr;19(2):159-66 Abstract quote We analysed the composition of compact bone from 30 patients suffering from various forms of osteogenesis imperfecta (OI). Collagen and total protein content per cell of controls increased with the age of the donors, but were generally low in Osteogenesis imperfecta: OI. insufficient collagen In fibroblast cultures controls had a maximum of synthesis in early childhood as evidenced collagen synthesis between 2 and 9 years of age, by analysis of compact an observation which was not seen in OI cells. In bone collagen both OI type II patients showed bone and fibroblast overhydroxylation of lysyl residues as did some cultures. patients with OI type III (25%) and OI type IV Brenner RE, Vetter U, (33%). The collagen of OI type I patients was Nerlich A, Worsdorfer never found to be overmodified. In controls, O, Teller WM, Muller collagen III was found exclusively during fetal time while it was present in significant amounts PK. in bone tissue of all types of OI. The proportion Max Planck Institut fur of collagen V was somewhat higher in OI bones Biochemie, Martinsried, (about twice) than in controls. FRG. Our data suggest that the normal increase of collagen synthesis is defective in patients with OI. Perhaps some of these changes are due to specific molecular defects in collagen while others may be due to defective regulation of the maturation process.

Altered collagen metabolism in

Eur J Clin Invest 1990 Feb;20(1):8-14 Abstract quote The pattern of collagen metabolism was analysed

in fibroblast cultures from patients with diverse forms of osteogenesis imperfecta (OI). Generally, OI fibroblasts show an insufficient collagen synthesis which is most obvious in patients between 2 and 9 years of age during which period control fibroblasts have an elevated collagen synthesis. OI fibroblasts remain on a basal level except for fibroblasts from OI type IV patients which seem to approach normal levels. In addition, OI fibroblasts generally show a slightly increased degradation of newly synthesized collagen which again is most obvious between 2 osteogenesis imperfecta and 9 years. fibroblasts: a study on 33 These differences in collagen degradation, patients with diverse however, only contribute to a minor extent to the forms. lack of net collagen synthesis during early Brenner RE, Vetter U, childhood. No correlation could be found between the degree of overmodification of Nerlich A, Worsdorfer collagen and its degradation since fibroblasts of O, Teller WM, Muller both OI type I and OI type II have an elevated PK. degradation though only the latter ones produce Max Planck Institut fur overmodified collagen molecules. Pulse labelling Biochemie, Martinsried, of collagen with radioactivity labelled sugars was used to distinguish between normal collagen FRG. chains or CNBr-derived peptides and those which were overmodified. In all three cases studied (OI II, OI III, OI IV) the entire triple helical domain of alpha 1(I) and alpha 2(I) was overglycosylated. The amount of overmodification, however, was not uniform but rather unique for each patient studied. We assume that the molecular defects in the majority of OI cases may be located in the mechanisms operating on the control of both the age appropriate synthesis of collagen and its degree of post-translational modification. J Craniofac Genet Dev Biol 1997 JulSep;17(3):121-32 Abstract quote

Osteogenesis imperfecta: clinical, cephalometric, The aim of the study was to analyze craniofacial development in 54 patients with osteogenesis and biochemical investigations of OI types imperfecta (OI), who were classified into OI types I, III, and IV according to clinical criteria, I, III, and IV. and to relate the findings to the abnormalities in Jensen BL, Lund AM. collagen I production. Department of Pediatric Dentistry, Faculty of Health Sciences, School of Dentistry, Copenhagen N, Denmark.

In 33 patients, analysis of radioactively labelled procollagen was performed. Cephalometric radiographs, facial photographs, and CT-scans (a single case) were analyzed and mean facial diagrams for lateral and frontal films were produced based on registration of 221 reference points. Radiographs of 102 male and 51 female Danish students served as control material. In OI type I, size of the skull and jaws was generally slightly reduced, but morphology was within normal limits. In OI type IV and especially type

III more severe abnormalities were found; the cranial base was flattened, the maxilla posteriorly inclined, and nearly all size-measurements were reduced. In OI type III the sagittal jaw relations were reduced and a mandibular overjet recorded. Three OI type I patients, whose fibroblasts produced structurally abnormal collagen I, had the stature and several features in the craniofacial region, which corresponded to those recorded for the OI type IV group. Also, in three OI type IV patients whose fibroblasts produced a reduced amount of normal collagen I, craniofacial morphology showed several features resembling type I patients. We conclude that structural abnormalities of collagen I generally give rise to more severe alterations of the craniofacial features than a quantitative defect of collagen I. OI type I patients are only slightly affected in their craniofacial region, while patients with OI type IV and especially type III are moderately to severely affected. The combined cephalometric and biochemical findings suggest that future classification of patients with osteogenesis imperfecta should be based on biochemical/molecular and radiological analyses in combination with clinical criteria rather than on clinical features alone. SKIN Arch Dermatol 2002 Jul;138(7):909-11 Abstract quote

The mechanical BACKGROUND: Skin mechanics may be properties of skin in osteogenesis imperfecta. affected by several dermatological and systemic conditions. The skin can act as a marker of Hansen B, Jemec GB. generalized disease. Osteogenesis imperfecta Osteoporosis Research (OI) is a heritable disorder characterized by fragile bones caused by a generalized disorder of Clinic, Hvidovre collagen. The dermis has a relative increase of University Hospital, argyrophil and elastic fibers and a deficiency of University of adult collagen. The collagen defect is well Copenhagen, Kettegaard described, but functional changes in tissue Alle 30, DK-2650 mechanics have not been studied in the skin. The Hvidovre, Denmark. functional changes may reflect general changes and may give insight into the pathogenesis of clinical problems in these patients. OBJECTIVE: To examine skin mechanics (elasticity, distensibility, and hysteresis) in patients with OI. METHODS: Ten patients with OI (mean +/- SD age, 45.9 +/- 11.5 years) and 24 age-matched control subjects (mean +/- SD age, 43.3 +/- 13.8 years) were studied. The suction cup technique was used (Dermaflex; Cortex Technology, Hadsund, Denmark).

RESULTS: Significant differences between the patients and controls were found in all measurements (P