Rare metabolic bone disease characterized by a diffuse increase in skeletal density and obliteration of marrow spaces.


Albers-Schönberg disease or marble bone disease.


1 in 200 000 births in one series.


Congenital (juvenile, malignant or infantile)  - autosomal recessive.

Adult (tarda) – autosomal dominant.


May due to a defect in the thymus.

At least 9 forms of osteopetrosis exist.


There is a deficiency in osteoclast function – they are abnormal and lack a ruffled border.  The actual numbers of osteoclasts may be decreased, normal or increased.

The bones are usually smaller than normal but weigh 2-3 times as much.

The bone is very brittle and prone to fracture.

Fractures are typically transverse – chalk stick fractures.


The skeleton shows cores of calcified cartilage surrounded by areas of new bone.  The new bone formation is normal but there is a deficiency of bone remodeling and reabsorption.  The primary spongiosa persists.


In the juvenile form there is hepatosplenomegaly (due to extramedullary haematopoiesis) accompanied by anaemia, thrombocytopaenia and immune compromise.  There can be optic and other cranial nerve palsies.

Death often occurs at an early age from sepsis and anaemia.

Leukaemia and sarcoma are known sequelae.  There is a higher rate of osteomyelitis.

The adult form is characterized by a lifelong high risk of fractures.  The adult form is associated with a high rate of coxa vara; increased rates of osteomyelitis (particularly of the mandible) and increased rates of OA.


There is generalized sclerosis.

Failure of corticomedullary differentiation.

There can be a bone within a bone appearance (also known as endobones).

Failure of remodeling can result in the Erlenmeyer flask deformity (flared metaphyses) NB this disorder is also seen with Gaucher disease.

In the spine there are dense areas next to the endplates (giving the sandwich vertebra appearance).

In the iliac crests there are thick dense lines paralleling the crests.

In the tubular bones of the hands and feet there are alternating bands of dense and normal bone.

The ribs and clavicles are thick and undermodeled.


Fractures are frequent and they heal but more slowly than normal.


  1. Bone marrow transplant  - can result in a gradual restoration of patent bone marrow cavities.  It needs to be done early before the medullary canals are completely obliterated.  About 40% are able to find an appropriate HLA matched donor and the transplant is successful in 50%.
  2. High dose 1,25 dihydroxyvitamin D3 and a low calcium diet have been reported to be effective.  This may result in stimulation of a normal ruffled border in the osteoclasts or may induce the development of more osteoclasts.
  3. Interferon-alpha may stimulate increased activity in any osteoclasts that are present.
  4. Surgical treatment is very difficult with drill bits and reamers wearing out quickly; there is also an increased rate of bleeding and infection.



This is a form of short limbed dwarfism, one of the sclerosing bone dysplasias.  Toulouse-Lautrec may have suffered from it.


Autosomal Recessive inheritance


Can be craniofacial abnormalities such as a large calvarium, frontal bulging and a small face.  The mandible is hypoplastic, and the face may appear triangular.

The sclerae may be blue (may cause confusion with OI).

Causes of blue sclerae:

  • Osteogenesis imperfecta
  • Pyknodysostosis
  • Babies

Shortened terminal phalanges

Increased bone fragility with kyphosis, scoliosis and genu valgum


Generalized sclerosis with incomplete remodeling of tubular bones, often with multiple fractures of the metaphyseal region.  The medullary canal can be made out.

There is delay in the closure of the sutures and wormian bones are common.

There is hypoplasia of the distal end of the clavicle.

The ungual tufts are frequently absent.

Differential diagnosis

The main DDx is with osteopetrosis, and pyknodysostosis is distinguished by the shortened terminal phalanges, hypoplasia of the clavicle and normal haematology.


Normal life expectancy.

Paediatric fractures heal well but perhaps adult fractures do not.