Osteogenesis Imperfecta for medical grauduates

Osteogenesis imperfacta

1. Dr Adkine Shubham JR 1 Dept . of Orthopedics DUPMC & H Dr Pramod Sarkelwad Ass. Prof & HOU Dept of Ortho DUPMC & H Dr Deepak Agrawal Prof & Head Dept of Ortho DUPMC & H

2. Osteogenesis Imperfecta

3. Introdution Synonyms and other uncommon terms used Osteomalacia Congenita Osteoporosis Fetalis Brittle Bone Disease Fragilitas Ossium Lobstein’s Disease Vrolik Disease Van der Hoeve Disease

4. Osteogenesis imperfecta etymology means imperfect development of bones. Osteogenesis imperfecta is series of syndromes representing classes of Molecular defects, each with reasonably well-defined clinical pattern. It is most common genetic cause of osteoporosis due to generalised disorder of connective tissue. It is a hereditary condition resulting from abnormality in type I collagen that is manifested by an increased fragility of bones and low bone mass ( osteopenia ). The spectrum of disorder is so broad that it ranges from perinatally lethal forms to barely recognizable disease in adulthood.

5. Classification

6. Pathophysiology of OI In normal bones, the collagen is almost entirely type I, although, in fetal tissues and in very young infants, some of the collagen is in the form of type III or V. The collagen types III and V decrease with age and in older children, only type I collagen can be recognized. In lethal OI, a considerable increase in the concentration of types III and V and a marked variation in cross-linking are found. Cartilage-associated protein (CRTAP) is a protein required for prolyl 3-hydroxylation, and with the protein products of the LEPRE1 and PPIB genes, forms a heterotrimeric protein that is crucial for proper posttranslational modification of collagen I.

7. Osteogenesis imperfecta caused by mutations in CRTAP have been designated type VII disease, OI caused by mutations in LEPRE1 and PPIB are designated type VIII and type IX disease. The autosomal recessive forms of the disease account for less than 10% of the OI.

8. Cliniacal Features: Non leathal forms of OI are dominated by bone fragility and fractures. General Features include The characteristic fragility of bone, with diffusely osteopenic bones with thin cortices and attenuated trabecular pattern Short stature, Laxity of ligaments, Defective or deciduous or permanent teeth or both, Premature middle ear deafness, Blue Tympanic Membranes

9. Repeated microfractures in OI bone combined with healing and remodeling is responsible for the “soft” bones Which in turn produces following defects protrusio acetabuli in the pelvis. Basilar invagination at the craniovertebral junction. Symptoms of basilar invagination in OI typically occur in the third and fourth decades but may be present during the teenage years . These symptoms include brainstem dysfunction such as apnea , altered consciousness, lower cranial nerve deficits, myelopathy , and ataxia.

10. Pelvis in OI often develops a trefoil shape presumably because of repeated fractures. The forearm may be in minimal pronation , and its rotation is often severely limited. Angulation is generally greater in the upper part of both bones of the forearm . Coxa vara deformity of proximal femur. The long bones have narrow diaphyses and bowing ( saber shin), and fractures are common. Bowing results from multiple transverse fractures of the long bones and muscle contraction across the weakened diaphysis .

11. The fracture-healing process is undisturbed in terms of sequence of events, but the new bone has the same deficient biomechanical characteristics. Fractures may occur at any age. Fracture callus is wispy but may be occasionally hypertrophic. The frequency of fractures declines sharply after adolescence.

12. Osteogenesis imperfecta in a grown-up female with typical vertebral changes (picture frame vertebra and bone within bone appearance of ilium )

13. Diagnosis Skin biopsies and fibroblast cultures may be helpful, but are only positive in 80% of patients with type IV OI ( the most commonly confused with nonaccidental trauma ) Prenatal DNA mutation analysis can be performed in pregnancies with risk of OI to analyze uncultured chorionic villus cells.

14. Differential Diagnosis Juvenile osteoporosis. Nonaccidental injury (multiple fractures at different stages of healing, posterior rib fractures, and metaphyseal corner fractures are highly specific for nonaccidental injury ). Fractures from child abuse occur most frequently in children younger than 3 years of age. A patient with Menkes kinky hair syndrome can present with metaphyseal corner fractures . A malignancy such as leukemia . Blue sclera may also occur in other disorders, such as progeria , cleidocranial dysplasia, Menkes syndrome, cutis laxa , Hajdu -Cheney syndrome, and pyknodysostosis .

15. Nonsurgical Treatment Treatment depends on the type of OI. Cyclic administration of bisphosphonates has been used to treat patients with types III and IV OI quite extensively. Bisphosphonates decrease the resorption of bone by suppressing the activity of osteoclasts . Pamidronate ( injectable bisphosphonate given in doses of 4.5–9 mg/ kg/y depending on protocol used), increases cortical bone thickness and, in severe forms of OI, improves overall bone mass. It decreases the incidence of fractures, relieves chronic bone pain, increases activity levels, decreases the reliance on mobility aids, and increases the height of the collapsed vertebral bodies.

16. There has been no decrease in the incidence of scoliosis . Radiographically , pamidronate therapy creates growth lines in the bone. Radiographically , pamidronate therapy creates growth lines in the bone. These radiodense areas of bone probably represent the inhibition of osteoclastic resorption , whereas the clear areas between the lines represent the interval growth between treatment cycles . Bone marrow transplantation, which introduces normal marrow stem cells that could potentially differentiate into normal osteoblasts , has been used with some success for severely affected patients with OI. Problems of graft rejection and graft versus host reactions limit this approach.

17. Hematogenous infusion of mesenchymal stem cells (MSCs) has been tried with success in these patients . The MSCs are infused from bone marrow that home the bone to produce normalized collagen Orthotic devices are indicated to stabilize lax joints, prevent progression of deformity and fractures, and allow early weight bearing following surgical intervention. Sex hormones, sodium fluoride, calcitonin , calcium, growth hormone, magnesium oxide, vitamin D and C have shown no consistent results. Recombinant human growth hormone has been used in the past because of its anabolic effects on bone; however, clinical studies showed no increase in bone mass or change in natural history

18. The fracture in femur was managed with elastic intramedullary nails SURGICAL TREATMENT

19. Principal is to decrease the risk of fracture, allow for early weight bearing and to achieve union. The mainstay of orthopedic surgical treatment of patients with OI is realignment osteotomy . This is performed to improve the mechanical axis of appendicular bones, which in turn, also helps in balancing and reducing morbidity by reducing stress on other parts of bone and other bones . Other surgical interventions include management of basilar invagination and correction of scoliosis.

20. The realignment osteotomies should be performed through small incisions to preserve the blood supply, some prefer closed osteoclasis . Sofield -Millar procedure entails multiple diaphyseal osteotomies (fragmentation) with intramedullary fixation for long bone deformities that preclude orthotic fitting, good function and are susceptible to repeated fractures. Intramedullary devices are preferred for stabilization including the telescopic (Sheffield rod, Fassier -Duval rod) and nontelescopic forms (Rush rods, Williams rods ). Telescopic rods appear to decrease the incidence of re- rodding to accommodate for growth (51% for simple rods versus 27% for telescopic rods) and therefore are preferred for use when possible.

21. For spinal deformities, when the curves approach 45° in the mild forms of OI and 30°–35° in the severe forms, a posterior spinal fusion with segmental instrumentation to prevent progression of the curve should be considered . Surgery for basilar invagination is indicated for patients with radiographic progression or with neurologic deficits resulting from brainstem and high cervical cord compression. The recommended treatment of basilar invagination in OI consists of extensive removal of bony compression by a transoral approach followed by a posterior fusion and posterior rigid fixation that transfers the weight of the head to the thoracic spine.

22. Complications of Osteogenesis Imperfectaa Hyperplastic callus formation Basilar invagination Osteogenic sarcoma Formation of aneurysmal bone cyst (ABC) and unicameral bone cysts (UBC)

23. References Essential orthopedics principles & practice – Manish Kumar Varshney

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