Osteogenesis Imperfecta Tarda Research Articles

Osteogenesis Imperfecta—A Human Temporal Bone Case Study

Osteogenesis imperfecta (OI) is defined as one of the inherited connective tissue disorders that can result in fragile bones, blue sclera, and deafness. This genetic disease affects collagen type 1 (COL1), which leads to different manifestations depending on the mutation. There are four subtypes of OI, based on different defects in the collagen synthesis, types I, II, III, and IV. OI type I, previously known as OI tarda, is the most common and least severe subtype, is autosomal dominant, and results in blue sclera, increased risk of bone fracture and progressive hearing loss in 50% of patients. OI type II, previously known as OI congenital, is the most severe form, it usually leads to perinatal death and is autosomal recessive. OI Type III is the most severe type among children who survive the neonatal period. The degree of bone fragility and the fracture rate vary widely. OI Type IV diagnosis often occurs later in life and usually represents the patients that do not fit into subtypes I–III (1,2). Deafness is one of the main features of osteogenesis imperfecta and conductive hearing loss is the most common form, but mixed or pure sensorineural hearing losses are not uncommon (3). In the University of Minnesota temporal bone collection, we found one case that fits in the OI diagnosis.

Mitral valve repair in a patient with mitral regurgitation and osteogenesis imperfecta tarda

We present the case of a 62-year-old female with a diagnosis of osteogenesis imperfecta and mitral valve regurgitation. The patient underwent a mitral valve repair without complications. We describe the case and our surgical technique.

Osteogenesis imperfecta: A Report Of Two Cases

Background: The diagnosis of two cases of osteogenesis imperfecta, which is a rare form of congenital skeletal anomaly in a space of one month in this young tertiary institution inspired this write up. Medical records confirmed that no such cases have been reported for at least two years prior to this. Case reports: Two Nigerian neonates diagnosed with osteogenesis imperfecta presented at the Lagos State University Teaching Hospital (LASUTH). At birth, they were found to be small for their gestational age. The heads were large while their limbs were deformed due to multiple fractures. They both had Osteogenesis imperfecta tarda (Type 11), which is the form that is associated with perinatal deaths1,2,3,4,5,6. Conclusion: Osteogenenesis imperfecta though rare, occurs in our environment. More attention has to be paid to antenatal diagnosis of this pathology and postpartum clinical and radiological investigations to mitigate the suffering of these patients. INTRODUCTION Osteogenesis imperfecta or Brittle bone disease,4,5,6,7,8, is defined as a rare hereditary disorder, characterized by increased bone fragility, resulting from abnormal collagen formation2,4,5,6,7,8,9,10,11. There are four clinical types, the hall mark of which is bone fragility5. Fractures, blue sclera and dentinogenesis imperfecta are associated findings6,7,8,9,10,11. It is usually due to qualitative and quantitative defects in the synthesis of collagen type 15,7,9,11It occurs in about 1:20,000-50,000 live births in developed countries4,9,10. Osteogenesis imperfecta could be either recessive (severe) or dominant (mild).

The brittle bone syndrome; an update

Abstract Many recent books still give old-fashioned accounts of osteogenesis imperfecta (OI). The current classification, which is based on Sillence 8 and is derived from clinical, genetic and more recently biochemical studies, identifies four main types (Table 1). It replaces previous divisions into OI congenita (fractures before birth) and OI tarda; it defines prognosis, and it aids appropriate treatment. The effects of the collagen gene mutations which cause the OI syndrome are modified by their nature, by their position within the collagen molecule, by mosaicism, by tissue expression and by treatment, so that considerable variability occurs in OI patients within families as well as between different families. In the great majority of OI subjects, including perinatal lethal (type II) OI, the collagen gene mutation behaves as an autosomal dominant. The most important differential diagnosis is from non-accidental injury. 9 Management of the OI patient should involve several disciplines and includes correct genetic advice. The most frequent surgery involves the insertion of rods into the long bones; current work emphasizes the possible therapeutic benefits of bisphosphonates; and specialized rehabilitation by those with an experience in OI is essential.

The brittle bone syndrome: an update

Many recent books still give old-fashioned accounts of osteogenesis imperfecta (OI). The current classification, which is based on Sillence 8 and is derived from clinical, genetic and more recently biochemical studies, identifies four main types (Table 1). It replaces previous divisions into OI congenita (fractures before birth) and OI tarda; it defines prognosis, and it aids appropriate treatment. The effects of the collagen gene mutations which cause the OI syndrome are modified by their nature, by their position within the collagen molecule, by mosaicism, by tissue expression and by treatment, so that considerable variability occurs in OI patients within families as well as between different families. In the great majority of OI subjects, including perinatal lethal (type II) OI, the collagen gene mutation behaves as an autosomal dominant. The most important differential diagnosis is from non-accidental injury. 9 Management of the OI patient should involve several disciplines and includes correct genetic advice. The most frequent surgery involves the insertion of rods into the long bones; current work emphasizes the possible therapeutic benefits of bisphosphonates; and specialized rehabilitation by those with an experience in OI is essential.

Autosomal dominanter Keratokonus als okuläres Leitsymptom bei Osteogenesis imperfecta tarda Lobstein

Osteogenesis imperfecta is an autosomal inherited generalized disease of the soft tissue which can be divided into a congenital form (Vrolik) and a late-onset form named Lobstein. As the typical ocular symptom we find blue sclera whereas corneal changes as keratoconus are rarely documented. We report a family of 6 patients, all 5 examined being affected by keratoconus. After a 14-year-period of wearing hard contact lenses due to a keratoconus a 26-year-old female patient developed a painful therapy-resistant keratitis (Acanthamoeba) which afforded a keratoplasty. A history of osteogenesis imperfecta tarda was known since childhood. Five further members in three generations of the family were certainly affected by osteogenesis imperfecta. We examined five patients with a computer-assisted corneal topography analysis system. Referring to localization and configuration of the keratoconus all of the five patients had a similar degree of affection. Only our patient revealed blue sclera. There was no correlation between the corneal curvature and the degree of affection of the bone. Both the keratoconus and the bone affections had shown no more progression after adolescence. With the use of computer-assisted corneal topography analysis we were able to show a keratoconus associated with osteogenesis imperfecta. The typical blue sclera was not found that often in this family. The shape of the keratoconus was similar in localization and configuration. Contrary to the normal progression of keratoconus in this family there was no more progression of refractive changes after adolescence. Association of keratoconus with osteogenesis imperfecta should be considered. Likewise in osteogenesis imperfecta the ophthalmologist should consider keratoconus beside blue sclera.

Bone Cell Defects in Osteogenesis Imperfecta

Iliac crest bone biopsies from nine children (6-15 years old) with osteogenesis imperfecta tarda (O.I.) have been studied by bone histomorphometry after double fluorescent labeling with tetracycline and compared to five unlabeled biopsies from normal children in the same age group. The results indicate that children with O.I. have a low trabecular bone volume associated with an increased bone turnover rate. Bone formation is increased at the tissue level despite a decrease in the activity of individual osteoblasts. The original defects in O.I. seem to be due to the altered rate of matrix synthesis by osteoblasts. It is, however, compensated by an increase in the number of these cells. These results suggest that these children were not losing bone at the time of the biopsy, which fits with the clinical stability of O.I. with age. Our study therefore suggests that the osteopenia observed in O.I. is most likely due to an inability to accumulate bone during growth, as normal children do, rather than to a progressive net loss of bone.

Basilar impression in osteogenesis imperfecta tarda

A case is presented of basilar impression secondary to osteogenesis imperfecta tarda, associated with hemifacial spasm and brain-stem compression syndrome. The symptoms improved with posterior fossa decompression and posterior fusion.

Osteogenesis imperfecta tarda: appearance of the temporal bones at CT.

The computed tomographic findings in the temporal bone of two patients with osteogenesis imperfecta tarda are described. One of the patients had bilateral facial nerve paresis, and both patients presented with hearing loss.

A clinical and audiological investigation of osteogenesis imperfecta.

Fifty-six patients with osteogenesis imperfecta underwent clinical and audiological assessment. They completed questionnaires regarding their physical and otological disabilities, and attended various centres for audiological testing. It was found that 31 patients had a hearing loss. Hearing loss began in the second and third decades as a conductive loss, and progressed to a mixed loss. Eight patients, found in all age groups, had a pure sensorineural loss in one or both ears. Patients with osteogenesis imperfecta congenita suffered more fractures, became more physically disabled and had more severe hearing loss than those with osteogenesis imperfecta tarda. Tympanometry was found to give unpredictable results and was unhelpful in assessing middle ear function in these patients.

Osteogenesis imperfecta associated with basilar impression and cerebral atrophy: a case report

Osteogenesis imperfecta is a disease of bone formation subdivided into two types, congenita and tarda. It is associated with bony fragility, blue sclerne and abnormality of tooth dentin. Rarely the tarda form is associated with basilar invagination or infolding of the foramen magnum and upper cervical segments into the posterior fossa. This results in hydrocephalus and a spectrum of neurologic dysfunction known as the foramen magnum compression syndrome. Many radiologic methods have been used to evaluate basilar invagination including plain film and CT. We describe a patient with osteogenesis imperfecta tarda examined with CT, with a unique finding of diffuse cerebral atrophy associated with basilar invagination.

Consequences of an osteogenesis imperfecta diagnosis for survival and ambulation.

In osteogenesis imperfecta, time of initial fracture and radiographic appearance of long bones and ribs at time of initial fracture provide good prognostic indicators concerning survival and ambulation. Osteogenesis imperfecta congenita (OIC) comprises those patients with intrauterine and/or birth fractures. Radiographs of newborns with OIC-A show short, broad, and crumpled femurs and ribs, whereas initial radiographs of patients with OIC-B demonstrate bones with normal contours in spite of fractures. Osteogenesis imperfecta tarda (OIT) comprises those patients who fracture initially after birth. Patients with OIT-A fracture initially before walking begins, and patients with OIT-B after walking has begun. In OIC-A, 15 of 16 (94%) died; one survived but was wheelchair bound. In OIC-B, only two of 27 (8%) died, with 59% in wheelchairs and 33% ambulatory. No patients with OIT died. In OIT-A, 33% were in wheelchairs and 67% were ambulatory. In OIT-B, 100% were ambulatory.

Increased bone turnover with decreased bone formation by osteoblasts in children with osteogenesis imperfecta tarda.

Iliac crest bone biopsies from nine children (6-15 yrs old) with osteogenesis imperfecta tarda (OI) have been studied by bone histomorphometry after double fluorescent labeling with tetracycline and compared to five unlabeled biopsies from normal children in the same age group. The results indicate that children with OI have a low trabecular bone volume associated with an increased bone turnover rate. Bone formation is increased at the tissue level despite a decrease in the activity of individual osteoblasts. The original defects in OI seems, therefore, to be in the rate of matrix synthesis by osteoblasts. It is, however, compensated by an increase in the number of these cells. These results suggest that these children were not losing bone at the time of the biopsy, which fits with the clinical stability of OI with age. Our study therefore suggests that the osteopenia observed in OI is most likely due to an inability to accumulate bone during growth, as normal children do, rather than to a progressive net loss of bone.

Ulnar artery aneurysm in ostegenesis imperfecta

A case of acute thrombosis of an ulnar artery aneurysm in a patient with osteogenesis imperfecta tarda is described. The pathophysiology of osteogenesis imperfecta is reviewed and the possible association of defective collagen maturation and aneurysm formation is postulated. Most ulnar artery aneurysms or thromboses should be surgically resected and the artery repaired by microsurgical technique with primary anastomosis if possible or a venous interpositional graft if direct repair is not possible without tension.

Basilar impression and platybasia in osteogenesis imperfecta tarda

Osteogenesis imperfecta, a rare, genetically transmitted disorder of bone, is known to be associated with the development of basilar impression and platybasia. These deformities of the base of the skull may cause neurosurgical abnormalities secondary to compression of the brainstem and hydrocephalus. The case is presented of a young boy with a family history of osteogenesis imperfecta tarda who suffered respiratory arrest during hospitalization. Cranial nerves and pyramidal tract signs were demonstrated. Roentgenograms showed severe basilar impression and hydrocephalus. Decompression of the brainstem and shunting were performed with improvement in the patient's neurological status. This case represents a rare by significant central nervous system complication of osteogenesis imperfecta. Early recognition and implementation of aggressive treatment are important if irreversible neurological deficits are to be avoided.

The Development of the Spinal Deformities in Osteogenesis Imperfecta

Evaluations were made of the spinal deformities in 22 of 30 patients (osteogenesis imperfecta congenita, eight; osteogenesis imperfecta tarda I, 13; osteogenesis imperfecta tarda II, one) treated at Hamagumi Gakuen Children's Hospital from 1959 to 1980. Seven of the congenital type patients were in the severe curve group (greater than 50 degrees), four of whom showed more than 100 degrees of curvature. The spinal deformities in the congenital type progressed rapidly after five years of age and reached a maximum around 12 years of age. The scoliosis in the tarda type patients developed slowly, but then progressed rapidly after the curve exceeded 50 degrees. The complications of the spinal deformities included disability on ambulation, inactivity in daily living, and possibly respiratory dysfunction. Progression of the spinal curvature should be prevented by functional bracing or surgical treatment before severe complications arise.

Upper Limb Surgery in Osteogenesis Imperfecta

Although 90% of the surgical procedures performed on patients with OI are on the lower limbs, intramedullary fixation of the humerus may at times be indicated also in the upper limb for the correction of deformity and improvement of function. Upper limb deformities are generally present only in patients with severe disease (osteogenesis imperfecta congenita or osteogenesis imperfecta tarda I). The recommendations expressed in this paper are based on experience with 36 intramedullary rod fixation procedures on the upper limb in 12 patients with osteogenesis imperfecta, including 24 on the humerus, five on the radius and seven on the ulna. A Rush pin provided satisfactory fixation for the humerus, when inserted from its proximal end. Intramedullary rods were extremely difficult to insert in the forearm bones, and the author considers the operation to be rarely indicated. Two interesting and unusual problems in the upper extremities have been encountered in patients with osteogenesis imperfecta: deformity of the clavicle severe enough to cause pain and limited motion, and unicameral bone cysts in the upper humerus.

Therapy of osteogenesis imperfecta with synthetic salmon calcitonin

We evaluated the long-term use of synthetic salmon calcitonin in the management of osteogenesis imperfecta tarda and congenita. Forty-eight children, ranging in age from 6 months to 15 years, and two young adults, received synthetic salmon calcitonin 2 MRC units/kg three days a week and a daily oral calcium supplement of 230 to 345 mg. The annual fracture rate was decreased during calcitonin therapy as compared to the period preceding therapy. There was an increase in the ability of the patient to stand and move and in the subjective feeling of strength in the lower extremities during calcitonin therapy. There was also a significant improvement in radiographic bone density, as determined by the method of photodensitometry, in patients under 5 years of age. Long-term administration of synthetic salmon calcitonin may be beneficial to young children with osteogenesis imperfecta.

Serum calcitonin and bone mineral content in patients with osteogenesis imperfecta.

Serum calcitonin and bone mineral content in the forearm, measured by photon absorptiometry, were investigated in 21 patients with osteogenesis imperfecta tarda. The bone mineral content was significantly reduced as compared with normal controls, whereas the bone mineral content corrected for bone width was normal in adult patients but subnormal in children and young adults. Serum calcitonin did not differ significantly from that in normal individuals and no relation was found between serum calcitonin and bone mineral content.

In vitro sulfate turnover in osteogenesis imperfecta congenita and tarda.

Sulfate (35SO4(-2)) uptake was studied in confluent skin fibroblasts from three patients with osteogenesis imperfecta "congenita," six patients with osteogenesis imperfecta "tarda," three clinically unaffected relatives of an osteogenesis imperfecta tarda patient, and four controls. Only two of the osteogenesis imperfecta congenita cell strains showed an increased uptake of sulfate, all other cell strains being comparable to the control group. The degradation rate of glycosaminolgycans in mutants as seen by the chase experimentas was comparable to that found in the normal control cell strains. Glucose oxidation was normal in the osteogenesis imperfecta cell strains having an abnormal sulfate uptake. This rules out the possibility of an hypermetabolic state of these cells. These findings do not warrant the use of 35SO4(-2) incorporation in cultured cells as a tool for prenatal diagnosis of osteogenesis imperfecta.