Introduction

Osteogenesis imperfecta (OI) (also known as brittle bone disease) is an inborn bone disorder. Children born with OI have soft bones that break (fracture) easily, which could result in recurrent fracture, bone deformity or even loss of ambulation. They might also have other extra-skeletal issues including dental and hearing problems. However, the exact signs and symptoms and the severity of the disease vary with the exact OI subtypes.

Causes

OI is a genetic condition. Most babies with OI is caused by a genetic defect in the COL1A1/2 gene, which is responsible for forming collagen. Collagen is a major component of connective tissue, including the bones. With the genetic defect, there would be abnormal or inadequate collagen, resulting in fragile bone and other symptoms in children with OI.

Rarely, some children with OI is caused by a genetic defect in other genes that results in abnormal collagen formation or bone development. As of now, there are at least 18 genes implicated in the pathogenesis of OI.

Mode of Inheritance

OI can be inherited as a dominant (one copy of gene affected), recessive (two copies of gene affected), or X-linked disorder (one copy of gene on X-chromosome affected). Most often, it is a dominant disease caused by a genetic defect in the COL1A1/2 gene.

The mutated gene may be inherited from one or both parents, sometimes, the gene might undergo mutation spontaneously (de novo mutation).

Prevalence

OI is a rare condition with a prevalence of 1:15,000 to 1:20,000 births.

Signs and Symptoms

The symptoms vary widely in different types, which include:

Fragile bones and recurrent broken bones, starting from early childhood or even before birth (in-utero)

Bone deformities, e.g. leg bowing, deformed chest wall, curved spine

Bluish of grayish discoloration of the white of the eye (sclera)

A triangle-shaped face

Soft, discolored teeth or delayed teeth eruption

Lax joints

Easily bruising

Hearing impairment in early adulthood

Diagnosis

The diagnosis could be made based on the child’s medical history, family and pregnancy history. The doctor will also examine your child for signs and symptoms of OI.

Generic tests

Initial investigations include:

X-ray: to look for abnormal bone changes e.g. weak or deformed bones

Blood work: basic biochemistry including blood calcium and vitamin D levels

Further investigations would be arranged to confirm the diagnosis, these include

Lab tests: Blood or saliva may be checked. The tests would include genetic testing.

Dual Energy X-ray Absorptiometry scan (DXA or DEXA scan): A scan of the bones to measure the bone mineral density and to assess the extent of 'softening'.

Bone biopsy: A sample of the hip bone is taken for analysis. With the advancement of genetic testing, this test is now rarely indicated.

Special tests / investigations available in HKCH

In HKCH, your child will be assessed by a multidisciplinary team (MDT) with paediatric endocrinologists, orthopaedic surgeons, clinical geneticists, dental surgeons, paediatric radiologists, physiotherapists and occupational therapists for joint assessment. This MDT service model is the worldwide trend as the standard care for children with rare bone disorders. This one-stop service allows joint discussions between teams and save your travelling time for repeated hospital visits.

Management

General

The main goals of OI management are to prevent fracture and bone deformities. A multi-disciplinary approach to care is recommended to address not only the fractures, reduced mobility, growth and bone pain but also other extra-skeletal issues.

Bisphosphonates treatment: These are drugs that help to strengthen bones and prevent fractures. In children, it is usually given by IV (intravenous line) once every few months.

Fractures management: The lightest possible materials would be used to fixate (cast) the fractured bones to facilitate healing. Analgesics would be given for pain. Depending on the severity of the fracture, orthopaedic surgery might be indicated occasionally.

Orthopaedic management: In addition to fracture care, it might also include bracing, splinting and in some situations, surgery to correct leg deformity (e.g. rodding surgery, in which metallic rods are inserted to stabilize and prevent bowing of long bones).

Dental procedures: Treatments including teeth capping, braces, and surgery might be needed.

Physiotherapy and occupational therapy: Both are important to train up the muscles and their daily functioning.

Assistive devices: For children with limited mobility, wheelchairs and other custom-made equipment may be needed.

Special treatment options available in HKCH

In HKCH, children with OI would be followed by a multidisciplinary team (MDT) consisting of paediatric endocrinologists, orthopaedic surgeons, clinical geneticists, dental surgeons, paediatric radiologists, physiotherapists and occupational therapists.

Children would be seen in the MDT clinic to facilitate one-stop service and communications between various expert teams.

Physiotherapy sessions, including hydrotherapy, would be provided by physiotherapists who are experienced in taking care of children with OI.

Children with OI would also be assigned to a case manager (a paediatric endocrine nurse):

To enhance communication with the MDT

To support daily care and integration into community

Daily Care

If your baby has medium to severe OI, he or she needs to be held, diapered, and dressed very carefully. Please refer to our leaflet on Handling Babies with Brittle Bone Disease ( PDF Version | Text Version ). It is known that physical activity is an important part of managing children and adults with OI.

Bone growth requires muscle pull and weight bearing through standing, walking and lifting. Immobilization could cause loss of muscle and bone mass.

Your child should be encouraged to have regular and appropriate exercise as tolerated.

There is an increased risk of fractures in children with OI during contact sport. Please talk to your medical team if you are unsure whether a sport will be suitable for your child.

Dental hygiene and regular dental checkups.

References and Useful Resources

Little People of Hong Kong Taiwan Osteogenesis Imperfecta Foundation U.S. Osteogenesis Imperfecta Foundation U.K. Brittle Bone Society

Acknowledgement

Principal author: Dr Joanna Tung Yuet-ling on behalf of Endocrine Team, HKCH
Initial posting: Mar 2024

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