osteogenesis imperfecta

OSTEOGENESIS IMPERFECTA AND OSTEOPOROSIS

OSTEOGENESIS IMPERFECTA Comprises a heterogeneous group of heritable

disorders characterized by impairment of collagen maturation.

It arises due to mutations in one of two genes that guide the formation of type 1 collagen : COL 1 A1 gene on chromosome 17 and COL 1 A2 gene on chromosome 7.

Collagen forms a major portion of bone, dentin,sclerae,ligaments and skin; osteogenesis imperfecta demonstrate a variety of changes that involve these sites.

CLINICAL FEATURES

Extreme fragility and porosity of the bones, with proneness to fracture.

Some affected individuals also have blue sclera , altered teeth , hypoacusis , long bone and spine deformities , and joint hyperextensibility.

Many patients also have a tendency towards capillary bleeding.

Opalescent dentin in patient with osteogenesis imperfecta

CLASSIFICATION

Based on Sillence et al classification, 4 types of osteogenesis imperfecta exist –

1. TYPE 1 Osteogenesis imperfecta2. TYPE 2 Osteogenesis imperfecta3. TYPE 3 Osteogenesis imperfecta4. TYPE 4 Osteogenesis imperfecta

TYPE 1 OSTEOGENESIS IMPERFECTA

Most common and mildest form. Symptoms include blue sclera , in utero

fractures in 10 % of patients , mild to moderate bone fragility with frequency of fractures decreasing after puberty , hearing loss , easy bruising and short stature.

It is an autosomal dominant trait.


Most severe form. Exhibits extreme bone fragility and frequent

fractures. In utero fractures are present in 100% of cases. Blue sclera may be present , hearing loss is not

common. Small nose, micrognathia and short trunk may

be present. Both autosomal recessive and dominant

patterns may occur.


Most severe form noted in individuals beyond the prenatal period.

Sclera of variable hue , limb shortening and progressive deformities and pulmonary hypertension.

In utero fractures occur in 50% of cases. No hearing loss reported in this type. Both autosomal recessive and dominant

patterns may occur.


Associated with mild to moderately severe bone fragility.

Symptoms include normal sclera, normal hearing, fractures that begin in infancy and mild angulation and shortening of long bones.

The frequency of fractures decreases with puberty.

This variant is an autosomal dominant trait.

RADIOGRAPHIC FEATURES The radiographic hallmarks of

osteogenesis imperfecta include osteopenia, bowing, angulation or deformity of the long bones, multiple fractures and wormian bones ( sutural bones ) in the skull.

Radiograph typically reveal premature pulpal obliteration , although shell teeth rarely may be seen.

HISTOLOGIC FINDINGS

The bone cortex is thin and porous. The bone trabeculae are thin delicate and widely separated.

Osteoblastic activity appears retarded and imperfect and for this reason the thickness of long bone is deficient.

Failure of woven bone to become transformed to lamellar bone.

Defective microvascular system and decreased collagen fibril diameter have been observed.

Microscopic changes of OI

TREATMENT AND PROGNOSIS

There is no cure for OI, thus symptomatic improvement is the primary goal of currently available treatment options.

The mainstays of treatment are PHYSIOTHERAPY, REHABILITATION and ORTHOPEDIC SURGERY.

The prognosis varies from relatively good to very poor.

OSTEOPOROSIS

Also known as – MARBLE BONE DISEASE , ALBERS-SCHONBERG DISEASE , OSTEOSCLEROSIS FRAGILIS GENERALISATA.

It is a rare hereditary bone disease of heterogeneous pathophysiology in which failure of osteoclastic bone resorption leads to increased bone mass.

A German radiologist, Albers- schonberg, first described osteoporosis in 1904.

ETIOLOGY

The primary underlying defect is failure of the osteoclasts to resorb bone.

Defective osteoclastic bone resorption , combined with continued bone formation and endochondral ossification , results in thickening of cortical bone and sclerosis of the cancellous bone.

Heterogeneous molecular or genetic defects can result in impaired osteoclastic function.

CLINICAL FEATURES

Three distinct forms of the disease are based on age and clinical features – ADULT ONSET, INFANTILE , and INTERMEDIATE.

The infantile and intermediate types have an autosomal recessive mode of transmission, while adult onset type shows autosomal dominant inheritance.

If untreated, infantile type results in death by first decade of life.

Adult onset type are asymptomatic and have good long term survival rates.

INFANTILE OSTEOPOROSIS

Also called MALIGNANT OSTEOPOROSIS. Diagnosed early in life. Failure to survive and growth retardation are

symptoms. Bony defects occur Nasal stuffiness due to mastoid and paranasal

sinus malformation is often the presenting feature.

Cranial nerve entrapment neuropathies occur. Manifestations include deafness, proptosis and

hydrocephalus.

Dentition might be delayed. Bones are fragile and can fracture easily,

osteomyelitis of mandible is common due to deficient blood supply.

Patients might have anemia, easy bruising, bleeding, recurrent infections, hepatospleenomegaly, hypersplenism, hemolysis, sleep apnea and blindness.

ADULT OSTEOPOROSIS

Also called BENIGN OSTEOPOROSIS. Diagnosed in late adolescence or

adulthood. Approximately one half of the patients are

asymptomatic and diagnosis is made incidentally or is based on family history.

Other patients might present with osteomyelitis or fractures.

Many patients have bone pain. Bones are fragile and might fracture easily.

Bony defects are common and include cranial nerve entrapment neuropathies and osteoarthritis.

40% of patients have recurrent fractures while osteomyelitis of mandible occur in 10% of patients.

Other manifestations include visual entrapment, hepatospleenomegaly, short stature, large head and nystagmus.

RADIOGRAPHIC FEATURES Patients usually have generalized osteosclerosis. The bones might appear club like or show an

appearance of a bone within bone. Vertebrae are extremely radiodense. They may

show alternating bands, known as the Rugger – jersy sign.

The entire skull is thickened and dense , especially at the base.

The roots of the teeth often are difficult to visualize because of the density of the surrounding bone.

HISTOPATHOLOGIC FEATURTES

Several patterns of abnormal endosteal bone formation have been described.These include the following –

Tortuous lamellar trabeculae replacing the cancellous portion of bone.

Globular amorphous bone deposition in the marrow spaces.

Osteophytic bone formation. Numerous osteoclasts may be seen, but

there is no evidence that they function.

TREATMENT AND PROGNOSIS

Calcitriol appears to help by stimulating dormant osteoclasts and thus stimulating bone resorption.

Erythropoietin can be used to correct anemia. Corticosteroids have been used with the hope

of stimulating bone resorption and treating the anemia.

Treatment with gamma interferon has been shown to produce long term benefits.

No specific medical treatment exists for the adult type.

osteogenesis imperfecta

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