Osteopetrosis, literally "stone bone", also known as marble bone disease and Albers-Schönberg disease, is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, in which the bones become less dense and more brittle, or osteomalacia, in which the bones soften. Osteopetrosis can cause bones to dissolve and break.
It can cause osteosclerosis and the cause of the disease is understood to be malfunctioning osteoclasts. Radiological findings will show a bone-in-bone appearance.
Despite this excess bone formation, people with osteopetrosis tend to have bones that are more brittle than normal. Mild osteopetrosis may cause no symptoms, and present no problems.
However, serious forms can result in
- Stunted growth, deformity, and increased likelihood of fractures
- Patients suffer anemia, recurrent infections, and hepatosplenomegaly due to bone expansion leading to bone marrow narrowing and extramedullary hematopoiesis
- It can also result in blindness, facial paralysis, and deafness, due to the increased pressure put on the nerves by the extra bone
- Abnormal cortical bone morphology
- Abnormal form of the vertebral bodies
- Abnormality of temperature regulation
- Abnormality of the ribs
- Abnormality of vertebral epiphysis morphology
- Bone pain
- Cranial nerve paralysis
- Hearing impairment
The various types of osteopetrosis are caused by genetic changes (mutations) in one of at least ten genes. There is nothing a parent can do before, during or after a pregnancy to cause osteopetrosis in a child.
The genes associated with osteopetrosis are involved in the development and/or function of osteoclasts, cells that break down bone tissue when old bone is being replaced by new bone (bone remodeling). This process is necessary to keep bones strong and healthy. Mutations in these genes can lead to abnormal osteoclasts, or having too few osteoclasts. If this happens, old bone cannot be broken down as new bone is formed, so bones become too dense and prone to breaking.
- Mutations in the CLCN7 gene cause most cases of autosomal dominant osteopetrosis, 10-15% of cases of autosomal recessive osteopetrosis (the most severe form), and all known cases of intermediate autosomal osteopetrosis.
- Mutations in the TCIRG1 gene cause about 50% of cases of autosomal recessive osteopetrosis.
- Mutations in the IKBKG gene cause X-linked osteopetrosis.
- Mutations in other genes are less common causes of osteopetrosis.
- In about 30% percent of affected people, the cause is unknown.
People with questions about the specific cause of osteopetrosis in themselves or a family member are encouraged to speak with a genetics professional.
Normally, bone growth is a balance between osteoblasts (cells that create bone tissue) and osteoclasts (cells that destroy bone tissue). Sufferers of osteopetrosis have a deficiency of osteoclasts, meaning too little bone is being resorbed, resulting in too much bone being created.
The differential diagnosis includes other disorders which can cause diffuse osteosclerosis, such as hypervitaminosis D, and hypoparathyroidism, Paget's disease, diffuse bone metastasis of breast or prostate cancer intoxication with fluoride, lead or beryllium, and hematological disorders such as myelofibrosis, sickle cell disease and leukemia.
The long-term-outlook (prognosis) for people with osteopetrosis depends on the subtype and the severity of the condition in each person.
The severe infantile forms of osteopetrosis are associated with shortened life expectancy, with most untreated children not surviving past their first decade. Bone marrow transplantation seems to have cured some infants with early-onset disease. However, the long-term prognosis after transplantation is unknown. For those with onset in childhood or adolescence, the effect of the condition depends on the specific symptoms (including how fragile the bones are and how much pain is present). Life expectancy in the adult-onset forms is normal.
There is no cure, although curative therapy with bone marrow transplantion is being investigated in clinical trials. It is believed the healthy marrow will provide the sufferer with cells from which osteoclasts will develop.
If complications occur in children, patients can be treated with vitamin D. Gamma interferon has also been shown to be effective, and it can be associated to vitamin D. Erythropoetin has been used to treat any associated anemia. Corticosteroids may alleviate both the anemia and stimulate bone resorption. Fractures and osteomyelitis can be treated as usual.
Treatment for osteopetrosis depends on the specific symptoms present and the severity in each person. Therefore, treatment options must be evaluated on an individual basis.
Nutritional support is important to improve growth and it also enhances responsiveness to other treatment options. A calcium-deficient diet has been beneficial for some affected people.
Treatment is necessary for the infantile form:
- Vitamin D (calcitriol) appears to stimulate dormant osteoclasts, which stimulates bone resorption. Large doses of calcitriol witalcium intake soh restricted cmetimes improves osteopetrosis dramatically, but the improvement seen with calcitrol is not sustained when therapy is stopped.
- Gamma interferon can have long-term benefits. It improves white blood cell function (leading to fewer infections), decreases bone volume, and increases bone marrow volume.
- Erythropoietin can be used for anemia, and corticosteroids can be used for anemia and to stimulate bone resorption.
Bone marrow transplantation (BMT) markedly improves some cases of severe, infantile osteopetrosis associated with bone marrow failure, and offers the best chance of longer-term survival for individuals with this type.
In pediatric (childhood) osteopetrosis, surgery is sometimes needed because of fractures.
Adult osteopetrosis typically does not require treatment, but complications of the condition may require intervention. Surgery may be needed for aesthetic or functional reasons (such as multiple fractures, deformity, and loss of function), or for severe degenerative joint disease.