Osteopetrosis (Stone Bones, Marble Bone Disease)


Osteopetrosis is a group of disorders where bone resorption is impaired and the bones become denser than normal but are prone to fractures. It is also known as stone bone, marble bone disease and Albers-Schonberg disease. It should not be confused with osteoporosis, a more common condition where there is loss of bone mass and subsequent weakening of the bones. On the contrary, in osteoporosis there is an increase in bone mass yet the bones are more prone to fracture.

The effects of osteopetrosis extend beyond bone strength. There may also be disruption in bone marrow function, entrapment of nerves, delayed tooth eruption and abnormalities in growth. The condition can be present from infancy or develop later in life, and is sometime only incidentally discovered in adulthood. Overall, osteopetrosis is a rare condition. The more common and usually milder form that tends to develop in adolescence or early adulthood affects only about 1 in 20,000 people.


Bone is constantly undergoing remodeling. Osteoblasts lay down new bone and osteoclasts resorb bone. This remodeling is key to maintaining the strength and optimal structure of bone. Despite being such a hard structure, acidification in osteoclast pits can dissolve the strong calcium hydroxyapatite of bone, thereby allowing for the bone to be resorbed by the osteoclast. An enzyme that allows for this acidification is known as carbonic anhydrase II (CA2) which is encoded for by specific genes. The osteoclasts also have to be abundant for sufficient bone to be resorbed as it is estimated that as much as 20% of the bone is undergoing remodeling an any specific time.

Osteoclast ‘Rich’ and ‘Poor’ Osteopetrosis

In osteopetrosis, there is a problem with acidification in the osteoclast pit due to a defect in the gene that codes for the carbonic anhydrase II enzyme.In these cases there is sufficient osteoclasts present yet it is unable to function properly. It is also referred to as osteoclast-rich osteopetrosis. Another variation is where a genetic defect affects the maturity of precursor cells into osteoclasts. This simply means that the development of osteoclasts are impaired and therefore there is a deficiency of osteoclasts within the bone matrix. This type is also referred to as osteoclast-poor osteopetrosis.

Sometimes there is a third variation where there is no dysfunction with osteoclast bone resorption nor is there a deficiency in osteoclast numbers. Bone mass increases due to a genetic defect but does not involve the osteoclasts as such. This is not true osteopetrosis although the clinical features may be similar.

Abnormal Osteoclast Activity

In true osteopetrosis, osteoclasts are therefore unable to resorb bone as it normally would. Ultimately this affects the balance between osteoblast and osteoclast function which is necessary for bone remodeling. Bone mass increases since osteoblasts are laying down bone as normal while bone is not resorbed by osteoclasts as would be expected. However, this increased bone mass does not translate to stronger bones. In fact, the bones are actually more prone to fractures in osteopetrosis.


The symptoms of osteopetrosis can vary depending on the age of the patient, clinical form and type. A higher bone mass and bones that fracture easily are common features. The common term ‘stone bones’ or ‘marble bone disease’ is fairly accurate in that the bones are heavier and thicker but not necessarily stronger.


Also referred to as infantile malignant osteopetrosis, there is failure to thrive, hydrocephalus, anemia and impaired growth. Death may occur soon after birth in severe cases. The other symptoms that may be seen depends on bony areas that are most affected. For example cranial nerve compression may result in neurological symptoms while obstructions in the respiratory passages can affect breathing. Some of the symptoms that may be noted includes :

  • Delayed dentition.
  • Easy bruising and bleeding.
  • Deafness and/or blindness.
  • Facial paralysis.
  • Sleep apnea.
  • Enlarged liver and spleen (hepatosplenomegaly).
  • Repeated infections.


Also called benign osteopetrosis, the condition may not have as pronounced symptoms as in infants. In fact, about half of all patients with adult osteopetrosis have no symptoms (asymptomatic). Patients may be diagnosed with conditions like carpal tunnel syndrome, osteoarthritis, bone infections (osteomyelitis) and various neuropathies before the underlying condition of osteopetrosis is identified. Apart from the associated symptoms of these other conditions, patients may experience bone pain and have a short stature with a history of fractures.


Osteopetrosis is a genetic condition. It may be autosomal recessive or autosomal dominant. This means that osteopetrosis only arises when there are two abnormal genes passed down by the parents (recessive) or just one gene is passed down from a parent (dominant). With autosomal recessive inheritance, the parents do not usually show signs of the disease while with autosomal dominant inheritance one parent usually has the condition. There are defects in about many different genes that can lead to osteopetrosis but the main genes involved includes :

  • CLCN7
  • TNFSF11
  • TCIRG1

Autosomal dominant osteopetrosis is more common than autosomal recessive inheritance. These genetic defects can affect the ability of osteoclasts to resorb bone or lead to diminished numbers of osteoclasts within the bone. Ultimately there is greater bone deposition than resorption leading to a increased bone mass but susceptibility of the bones to fracture easily.


There are three different forms of osteopetrosis depending on the age of onset and clinical features. These three forms include infantile, intermediate and adult onset.


  • Diagnosed before the age of 1 years.
  • Prognosis is poor.
  • Bone marrow failure is severe.
  • Autosomal recessive inheritance.


  • Diagnosed in childhood.
  • Prognosis is poor.
  • No bone marrow failure occurs.
  • Autosomal recessive inheritance.

Adult Onset

  • Diagnosed in adolescence or early adulthood.
  • Prognosis is good.
  • No bone marrow failure occurs.
  • Autosomal dominant inheritance.
  • Two types – type I and type II.


Osteopetrosis is diagnosed based on the findings of certain investigations. Conditions such as rickets, hypoparathyroidism and Paget disease of the bone may be suspected and therefore need to be excluded. Osteopetrosis can be definitively diagnosed with X-rays. CT scans may sometimes be utilized and MRIs can help identify the involvement of the bone marrow. Generalized osteosclerosis may be noted meaning that the bone density is higher than normal on X-ray causing the bones to appear more opaque than would be expected (refer to the video below). As a consequence of bone thickening, certain cavities like the paranasal sinuses may be smaller than normal. There are various other changes that will be noted by a radiologist.


Therapeutic measures for osteopetrosis are primarily directed at stimulating osteoclast function. While infantile osteopetrosis requires treatment, adult osteopetrosis is usually mild and no specific treatment is required unless complications arise.


Although medication may reduce the severity of the condition and minimize complications, the benefits are only derived while the drug is being used.  There are no drugs that can cure osteopetrosis. Medication used for treating osteopetrosis itself by stimulating osteoclast activity includes :

  • Calcitriol (vitamin D analog)
  • Corticosteroids

Various medication may be used for treating complications such as anemia :

  • Corticosteroids
  • Erythropoietin

Since patients are at the risk of developing recurrent infections, gamma interferon may be used to increase the white blood cell count.


Surgery in both infants and adults may be necessary for bone fractures. In addition, surgery in adults may be done for degenerative bone diseases like osteoarthritis that arises with osteopetrosis or for aesthetic benefits.

Bone marrow transplantation may be an option when there is bone marrow failure in infants. It may help with anemia and restoring white blood cell levels. Sometimes a bone marrow transplant be curative in that it may assist with restoring the numbers of osteoclasts when these cells are lacking.

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