Osteopetrosis — Know It All!


Osteopetrosis — Know It All!

All you need to know about Marble Bone Disease.


Know your ailment well, so you can manage it better!!

Here we come with Osteopetrosis today!

What is Osteopetrosis?

Osteopetrosis is also known as:

  • Albers-Schonberg disease
  • Marble Bone Disease
  • steosclerosis fragilis generalisata

Osteopetrosis is a rare condition that induces an irregular growth of the bones and becomes excessively thick. They are fragile when bones become too thick, and can easily crack. Furthermore, bones may be misshapen and big, causing other body problems. Changes in the bone size and skull density, for example , can cause pressure on the nerves leading to vision loss, hearing loss, and facial muscle paralysis.

If the size of the bone grows, the amount of room for the bone marrow (soft, sponge-like tissue in the centre of most bones containing blood cells) gets crowded up. Decreases in bone marrow space can lead to low levels of body cells that combat infection, bring oxygen to body cells, or prevent bleeding.

Osteopetrosis is a hereditary disorder inherited by an infant from its parents. The condition may be moderate to severe, and early in infancy or later in adulthood symptoms can progress. The treatment options depend on the type of person with osteopetrosis.

What happens in Osteopetrosis?

The lack of blood flow to the bone is causing osteopetrosis. The bone tissue dies without blood which causes the bone to break down and collapse.

The body is creating new bone in people with healthy bones to replace old or broken bones. This process takes place during normal growth and for keeping the bones intact after an injury. If you have osteopetrosis, the bone breaks down faster than enough fresh bone can produce.

The prognosis for osteoporosis sufferers varies from person to person. It depends on the part of the bone is damaged by osteopetrosis, how much of the bone is damaged and how well the bone itself is healed.

Most people with osteopetrosis need care to avoid more damage to the bone, protect the bones and joints and enhance the use of osteopetrosis joints.

Without medication, the condition worsens and the bone and joints break down, and within two years, most people with the disease will experience intense pain and reduced mobility.

Who gets the disease?

Every year in the United States about eight to 40 children are born with the malignant infantile form of osteopetrosis. With this type of osteopetrosis one in every 250,000 persons is born in the general population. Relevant areas of Costa Rica, the Middle East, Sweden and Russia have seen higher rates. In equal numbers, males and females get affected.

About 1,250 people in the United States are affected by the adult form of osteopetrosis. The occurrence is approximately one in every 20,000 people. In equal numbers, males and females get affected.

The X-linked type of osteopetrosis mainly affects males due to the mutation’s mode of inheritance. There are no population-wide trials, because of the prevalence of incidents.


What are the symptoms of Osteopetrosis?

Osteopetrosis is characterised by excessively thick bones all over the body. Symptoms include fractures, low blood cell output and loss of cranial nerve function resulting in paralysis of the blindness, deafness and/or facial nerve. Individuals affected can suffer recurrent teeth and bone infections in the jaw.

What are the types/forms of Osteopetrosis and the associated symptoms?

Autosomal recessive osteopetrosis; malignant infantile type.

The most serious form of osteopetrosis, a malignant form of baby, is evident from birth, and if left untreated, it can lead to death in the first decade. Symptoms differ according to the precise alteration in gene (mutation). Individuals affected can get an abnormally large head (macrocephaly). They may also have hydrocephalus, which is characterised by obstruction of regular cerebrospinal fluid flow (CSF) within and irregular widening (dilation) of brain cerebral spaces (ventricles), causing accumulation of CSF in the skull, and possibly increased pressure on brain tissue. Symptoms affecting the eyes can include dissipation (atrophy) of the retina, wide-spaced eyes (hypertelorism), eyes protruding from their orbits (exophthalmos), cross-eyed (strabism), repetitive rhythmic eye movements (nystagmus), and blinding.

Other symptoms associated with malignant infant form of osteopetrosis include hearing loss, abnormally small jaw (micrognathia), persistent mucous membrane inflammation in the nose (rhinitis), feeding problems and/or retarding development. Some individuals affected experience delays in acquiring skills that involve muscle coordination and voluntary movements (delayed psychomotor development). Some individuals affected may experience delayed development of the tooth, or serious dental caries. In addition , excessive liver and spleen enlargement (hepatosplenomegaly); excessive bone hardening (osteosclerosis); fractures, typically of the ribs and long bones; inflammation of the lumbar vertebrae (osteomyelitis); increased cranial bone density (cranial hyperostosis) leading to compression of the nerves; and/or increased pressure inside the skull can also occur. Even patients can experience seizures due to low calcium levels in the blood. Serious neurodegeneration symptoms can manifest in rare variants of malignant infant osteopetrosis.

Some affected individuals with the malignant infantile type of osteopetrosis may also suffer from reduced bone marrow space: marked deficiency of all forms of blood cells (pancytopenia), the formation and production of blood cells outside the bone marrow, such as spleen and liver (extramedullary hematopoiesis), and the presence of myeloid tissue in extramedullary sites (myeloid). This may result in repeated infections such as pneumonia and infections in the urinary tract. In red blood cells (anaemia), affected individuals may also experience low levels of iron due to both decreased bone marrow space and increased red blood cell loss due to an enlarged spleen. Note that haematological defects typically occur before neurological ones.

Osteopetrosis, Dominant Autosomal; Adult Type.

An adult case, a milder form of osteopetrosis, is typically diagnosed in late infancy or adulthood. Bone symptoms, including osteosclerosis, fractures following minor trauma (usually of the ribs and long bones), osteomyelitis (especially of the jaw), and cranial hyperostosis, predominate. In certain cases, sufferers can have pus-filled sacs in the tissue around their teeth (dental abscess). In certain cases , people do not show any (asymptomatic) symptoms.

Individuals affected can also develop rhinitis, hepatosplenomegaly, anaemia, and hematopoiesis extramedullary.

Osteopetrosis, Autosomal Recessive intermediate

The intermediate type is typically present in children and can be inherited as an autosomal dominant or recessive trait. The severity of the disorder is unpredictable. Symptoms can include irregular bone hardening; fractures; especially mandible osteomyelitis, abnormally close knees, and abnormally large separate ankles (genu valgum) and cranial hyperostosis

Symptoms of the intermediate form of osteopetrosis can also include progressive weakening of eye nerves (optic atrophy), vision loss , muscle weakness and rhinitis. Some affected individuals may experience irregular lower jaw protrusion (mandibular prognathism), dental defects, baby teeth not falling out (deciduous retention), malformation of the tooth crown, dental caries, and facial paralysis. Other signs include hepatosplenomegaly, anaemia, reduced blood platelet circulation (thrombocytopenia), pancytopenia, and extramedullary hematopoietic disorder.

Osteopetrose: Recessive X-linked:X-linked osteopetrosis is exceedingly rare but severe, with just a few recorded cases around the world. In addition to classic osteopetrosis-related symptoms, it is correlated with immunodeficiency, localised fluid retention and tissue swelling (lymphedema), as well as hair , skin, nails, and sweat gland defects (ectodermal dysplasia).

Classification/Types of Osteopetrosis?


What are the causes of Osteopetrosis?

Osteopetrosis can be inherited in either an autosomal dominant or recessive pattern, though very rarely in a recessive pattern that is related to X. An inadequate development or defective function of cells called osteoclasts is the essential defect in bone reabsorption. These cells are responsible for bone resorption and help in preserving healthy bone, which relies on a balance between bone resorption (by osteoclasts) and bone formation (by other advanced osteoblast cells). Every 10 years the human skeleton regenerates fully. Osteoclasts are important in this context for bone turnover (replacement of old bone by new bone), bone remodelling, as well as microfracture repair.

Human characteristics like the classic genetic disorders are the product of two alleles interacting for that disorder, one acquired from the father and one from the mother.

As an autosomal dominant genetic disorder, the adult form of osteopetrosis is inherited. Dominant genetic defects arise when only one mutated copy of a gene is enough to cause a specific disease. The mutated gene copy may either be inherited from either parent or can be the result of a mutational event that occurred directly in the person affected. The chance of transferring the defective copy of the gene from an infected parent to an offspring at each pregnancy is 50 percent. The danger to males and females is similar.

The malignant form of osteopetrosis in infants is inherited as an autosomal genetic recessive trait. Recessive genetic abnormalities arise when two defective copies of a gene are inherited by a child, one by parent. If an individual receives one normal and one abnormal copy of a disease gene, the person will be a carrier for the disease but will not normally be showing symptoms. The chance of both carrier parents transmitting the abnormal copy of the same gene and thus having an infected child at each pregnancy is 25 percent. At-birth, the chance of getting a child carrier, like the parents, is 50 percent. The probability for a child to inherit both parents’ usual copy of the gene is 25%. The danger to males and females is similar.

The osteopetrosis X-linked type is recessive, and exceptionally rare. X-linked recessive disorders on the X chromosome are caused by a defective gene and often occur in males. For this condition, females who have an irregular copy of a gene present on one of their X chromosomes are carriers: they typically do not show symptoms because females have two X chromosomes. Males have a single X chromosome inherited from their mother, and if a male inherits an X chromosome containing an abnormal gene, then the disorder will arise. Female carriers with an X-linked recessive condition have a 25 percent risk of having a carrier daughter as themselves for each birth, a 25 percent chance of having a non-carrier daughter, a 25 percent chance of having a disease-affected son and a 25 percent chance of having an unaffected son.

The intermediate form of osteopetrosis can be inherited as a genetic disorder which is autosomal recessive or autosomal dominant.


How is Osteopetrosis diagnosed?

A diagnosis of osteopetrosis is based on a comprehensive clinical examination, extensive history of the patient and a number of advanced tests such as improved x-ray imaging and bone mass density measurement (BMD). Skeletal X-ray results are very precise and are deemed appropriate for diagnosis to be made. Biochemical findings such as increased concentration of BB isoenzyme creatinine kinase and tartrate-resistant phosphatase acid (TRAP) can also help to make the diagnosis.

Work-up and clinical testing:

In over 90 per cent of cases, genetic testing can detect the mutation: this will classify types of osteopetrosis with specific clinical associations or complications and guide the treatment plan. Often a bone biopsy is performed to validate the diagnosis but not done regularly as it is an invasive procedure with non-negligible risks.

The following blood tests should be performed after the diagnosis is made: serum calcium, parathyroid hormone, phosphorus, creatinine, 25-hydroxyvitamin D, full blood count with differential, creatine kinase isoenzymes (specifically creatine kinase BB isozyme), and lactate dehydrogenase, respectively. These tests will assess the need for additional and referral to specialists. Baseline brain magnetic resonance imaging should be designed to determine involvement of cranial nerves, hydrocephalus and vascular anomalies. Affected individuals should be examined routinely by an optic nerve involvement ophthalmologist and benefit from a multidisciplinary approach including endocrinology, ophthalmology, genetics, and dentistry, with input from specialists in orthopaedics, otorhinolaryngology, neurology, neurosurgery, nephrology, infectious disease, and haematology as required.

Prenatal diagnosis of families in which the genetic mutation was found is potentially possible.


What is the treatment for Osteopetrosis? (Treatment Options)

Hematopoietic stem cell transplantation ( HSCT) for particular cases is currently the only known treatment for autosomal recessive, malignant infantile osteopetrosis. This helps Donor-derived osteoclasts to induce bone resorption. Genetic studies are critical in deciding whether HSCT is sufficient, as some particular mutations do not benefit from the transplant (those in the RANKL gene); however, some patients (all patients with mutations in the OSTM1 gene and some patients with two mutations in the CLCN7 gene) experience progressive neurodegeneration that is not reversed by HSCT. It is important to consider the risks and benefits in mild types of osteopetrosis as they do not merit the hazardous risks associated with HSCT such as rejection, serious infections and very high levels of calcium in the blood contributing to a substantial mortality rate in the first year. Corticosteroids can be recommended for patients in whom HSCT has been found unsafe but there is not enough evidence to justify their routine use.

Gamma-1b (Actimmune) earned U.S. approval. Food and Drug Administration to postpone the development of disease in people with serious malignant osteopetrosis in children. Horizon Pharma manufacturers Actimmtune. Inc. Inc ..

Good nutrition is very important for patients with osteopetrosis, including the use of supplements with calcium and vitamin D when calcium levels are low in the blood. Others are symptomatic and cooperative. Genetic therapy is prescribed for families suffering from this condition.

Coping with Osteopetrosis:

Any person living with osteopetrosis is different. Some people have little to no symptoms, while others have several symptoms that impair their everyday activity capacity. The following tips may be of use:

  • See your health care providers on a regular basis.
  • Talk to your doctor or physical therapist about which types of exercises are best for you based on the type of osteopetrosis you have.
  • Ask your doctor about nutrition.
  • Keep the lines of communication open. Ask family and friends for help when you need it.
  • Reach out to online and community support groups.








Gopala Krishna Varshith,

Content Developer & Editor,