Osteopetrosis
Osteopetrosis, also known as marble bone disease or Albers-Schönberg disease, is a rare hereditary bone disorder characterized by the abnormal hardening and thickening of bones. This condition arises from malfunctions in osteoclasts, the cells responsible for breaking down bone tissue. As a result, bone density increases, but the bones become fragile and prone to fractures, leading to various complications. There are three forms of osteopetrosis: osteopetrosis tarda, which manifests in adulthood; osteopetrosis congenital, which appears in infancy and is typically severe; and marble bone disease, a milder variant of the congenital form.
Symptoms vary by type but may include brittle bones, growth deformities, liver and spleen enlargement, and neurological issues such as blindness and deafness. Infants with osteopetrosis congenital often face life-threatening complications, while those with osteopetrosis tarda might experience minimal symptoms. Currently, there are limited treatment options, including high doses of vitamin D and Interferon Gamma-1b to help manage the condition, along with supportive therapies and nutritional guidance. Genetic counseling is recommended for families with a history of the disorder who are considering having children.
Subject Terms
Osteopetrosis
Osteopetrosis, also referred to as marble bone disease and Albers-Schönberg disease, is a rare hereditary bone disorder that causes the bones to harden and thicken. The disease causes a malfunctioning of cells called osteoclasts. These cells are responsible for breaking down and reabsorbing bone tissue. Malfunctions in the osteoclasts results in the thickening and excess formation of bones, which affects a person's growth.
Osteopetrosis can manifest in one of three forms: osteopetrosis tarda (autosomal dominant), osteopetrosis congenital (autosomal recessive), or marble bone disease (mild autosomal recessive). Osteopetrosis tarda, also known as Albers-Schönberg disease, occurs in adulthood, while the other two types form in infancy and childhood. Problems associated with osteopetrosis include growth deformities, brittle bones, liver and spleen enlargement, blindness, and deafness.
Causes and Symptoms
Two types of cells work together to make and break down bone tissue: osteoblasts and osteoclasts. Osteoblasts build bone tissue while osteoclasts dissolve bone tissue. These cells allow the bones to take different shapes as a person ages and grows over the lifespan. The formation and reabsorption of bones and bone tissue is a continuous process throughout a person's development.
Osteoclasts absorb bone tissue during growth and healing and play an important role in the normal development of bones. Osteoclasts make enzymes that dissolve bone tissue. The osteoclast cells then absorb this dissolved bone tissue, breaking it down into its component parts of amino acids, calcium, and phosphate, which are released and used in different parts of the body. This allows osteoblasts to make new bone tissue that reshapes the bone. When osteoclasts malfunction, which may occur due to a genetic defect, bone tissue is not dissolved properly and builds up on the bone, making it difficult for the bone to reform. If developed at an early age, osteopetrosis can stunt a person's growth and cause physical deformities and bone marrow failure. Infants born with osteopetrosis usually die within two years.
The major symptoms of osteopetrosis include bone marrow failure and brittle bones. Bone marrow failure is caused when defective bone tissue replaces bone marrow in the cavities of the bone. Bone marrow is needed to produce red blood cells and other immune system cells. If bone marrow fails to develop properly, a blood cell deficiency results, which can negatively affect the immune system. A compromised immune system leads an individual to be more susceptible to disease, especially certain blood diseases such as anemia. Blood cell deficiency can also impair the clotting process, causing excessive bleeding in affected individuals.
Despite the thickening of the bones, osteopetrosis makes the bones fragile and easily fractured. The disorder also caused bone deformities, which include an increase in bone density and abnormal curvature of the spine. Some patients with osteopetrosis suffer from breathing difficulties due to cranial malformations. Other bone displacements may occur in the skull that can cause nerve damage and lead to blindness, deafness, and fluid accumulation in the brain. Brain fluid accumulation often results in brain damage.
Three Types
The three types of osteopetrosis develop during different stages of the lifespan. Osteopetrosis tarda, the benign form, presents itself in adulthood and shows no symptoms in fifty percent of patients. This form is often discovered accidentally during routine X-ray examinations. The most common symptom for this type of osteopetrosis is brittle bones. The affected individual’s bones are more sensitive to fractures and breakage. Bone healing is normal for patients with osteopetrosis tarda, however. Some patients experience degenerative joint disease as well. Bone marrow failure can occur but is rare. Other adult symptoms include chronic pain, arthritis, and a bone infection known as osteomyelitis.
Osteopetrosis congenital is a malignant (deadly) form of osteopetrosis. This type manifests in infancy and causes severe bone marrow failure, growth failure and deformity, and accumulation of brain fluid. Blindness and deafness are common. Bone marrow failure normally leads to pancytopenia, a medical condition that results in a low number of red cells, white cells, and platelets. Low blood cell counts lead to a weak immune system, leaving the child vulnerable to disease. Most infants with this type of osteopetrosis do not live past the age of two and die as a result of severe bleeding or infection.
The other infantile form of osteopetrosis is referred to as marble bone disease. This type does not involve bone marrow failure and survival rates are higher. Other symptoms caused by the disease can shorten a patient's lifespan, however. Marble bone disease can lead to chronic kidney problems, which can have fatal consequences. Patients are normally short in stature and display calcium buildup in their skull. Hearing loss and a slowing of physical and emotional reactions are also common.
Prevention and Treatment
Osteopetrosis is a hereditary disorder and cannot be prevented. Few medical treatments are available for the disease. Infants are often given high doses of vitamin D to help activate inactive osteoclasts. Some patients with severe osteopetrosis are also administered a drug known as Interferon Gamma-1b (Actimmune) to delay the disease's progression. Doctors also recommend that patients with osteopetrosis engage in physical therapy and maintain a well-balanced diet.
Couples with a family history of bone disorders who are considering pregnancy should consider a visit to a genetic counselor for assistance.
Cait Caffrey
Bibliography
Blank, Robert. "Osteopetrosis." Medscape. WebMD LLC. Web. 7 Jan. 2015. http://emedicine.medscape.com/article/123968-overview
Carolino, Jerome, Juan A. Perez, and Anca Popa "Osteopetrosis." American Academy of Family Physicians. American Academy of Family Physicians. Web. 7 Jan. 2016. http://www.aafp.org/afp/1998/0315/p1293.html
"Osteopetrosis." Genetics Home Reference. U.S. National Library of Medicine, U.S. National Institutes of Health. Web. 7 Jan. 2015. http://ghr.nlm.nih.gov/condition/osteopetrosis
"Osteopetrosis." National Organization for Rare Disorders. National Organization for Rare Disorders, U.S. National Institutes of Health. http://rarediseases.org/rare-diseases/osteopetrosis/
"Osteopetrosis: Types and Genetics." The OsteoPETrosis Society. The OsteoPETrosis Society. Web. 7 Jan. 2015. http://www.osteopetrosis.org/types-and-genetics1.html