Introduction:
Osteopetrosis, the word, is literally translated as “stone bone.” This is a condition characterized by the increased bone density that occurs due to a defect in the functioning of the osteoclasts (bone-resorption cells). Increased bone density leads to brittle bones with defective architecture, accumulation of bones, and bones becoming highly prone to fractures due to their brittle nature. The condition may be asymptomatic in its milder form. There are multiple types of osteopetrosis depending upon their inheritance method.
What Is Osteopetrosis?
Osteopetrosis is a rare, inherited condition in which the density of the bones increases remarkably. This occurs due to dysfunction of the cells responsible for bone resorption, the osteoclasts. There is an imbalance between the formation of the bone by osteoblasts (bone-forming cells) and bone resorption by osteoclasts. In the case of osteopetrosis, the osteoclasts fail to resorb old bone; therefore, an accumulation of bone occurs. The high-density bone formed is generally very brittle and prone to fractures due to trivial injuries. In addition, the bones may be extraordinarily large and misshapen, which may cause other problems in the body, like loss of vision due to increased density of the skull bone, etc. As the bone increases in size, the bone marrow (tissue present in the center of the bone responsible for the production of blood cells) becomes congested within the bone. This leads to a decrease in the formation of red blood cells (RBC), white blood cells (WBC), and platelets).
What Are the Other Names of Osteopetrosis?
Other names of osteopetrosis are:
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Marble bone disease.
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Albers-Schonberg disease.
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Osteosclerosis fragilis generalisata.
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Congenital osteopetrosis.
Is Osteopetrosis Common?
Osteopetrosis is becoming a fairly common condition that affects men and women equally. About eight to 40 children are speculated to be born with a malignant infantile type of osteopetrosis in the United States every year. In the general population, about one in every 2,50,000 individuals are born with this type of osteopetrosis. In adults, the incidence of the disease is one in every 20,000 individuals.
Is Osteopetrosis Inherited?
Osteopetrosis is a hereditary disorder which means it is a condition that is passed down from parents to their offspring. It is inherited in several different ways:
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Autosomal Dominant Pattern: In this mode of inheritance, one copy of the altered gene is sufficient to cause the disorder. This condition is inherited from an affected parent.
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Autosomal Recessive Pattern: In this method of inheritance, both copies of the mutated gene cause the disorder. This condition is inherited from both parents, who carry a copy of the altered gene. Individuals affected by autosomal recessive patterns are typically asymptomatic for a long time.
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X-Linked Recessive Pattern: A rare form of inheritance in which the altered gene is present on the X chromosome. Men have only one X chromosome, and women have XX chromosomes. Therefore, in males, only one copy of the altered gene is sufficient to cause the disorder, and in women, mutation should occur in both copies of the gene for the condition to occur. Males are more commonly affected by this condition because the presence of one altered gene is more prevalent than the presence of two copies of the altered gene.
What Are the Types of Osteopetrosis?
Osteopetrosis is further subdivided into the following types:
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Osteopetrosis autosomal dominant (adult type) is also known as ADO.
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Osteopetrosis autosomal recessive (malignant infantile type), also known as OAR.
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Osteopetrosis (intermediate autosomal) is also known as OIA.
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Osteopetrosis X-linked recessive, also known as XLO.
What Causes Osteopetrosis?
The basic cause of osteopetrosis is a defect in bone resorption cells due to the osteoclasts' insufficient production or impaired functioning. These cells are responsible for maintaining bone turnover (replacing old bone with new bones) by balancing cell resorption and cell formation. Mutation in as many as nine genes causes the various types of osteopetrosis. Mutation in the chloride voltage-gated channel (CLCN7) gene is responsible for causing 75 % of the total autosomal dominant osteopetrosis. And about ten to 15 % of the cases of autosomal recessive osteopetrosis. Mutations in the T cell immune regulator 1 (TCIRG1) are responsible for causing about 50 % of autosomal recessive osteopetrosis. The less common form of osteopetrosis is the X-linked type of osteopetrosis caused by a mutation in the inhibitor of the nuclear factor-kappa B kinase subunit gamma (IKBKG) gene. In addition, about 30 % of cases of osteopetrosis occur sporadically, and their exact etiology is still unknown.
What Are the Symptoms of Osteopetrosis?
The symptoms of osteopetrosis include:
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Presence of overly dense bones that are brittle and prone to fracture.
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Stunted growth and deformities.
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Anemia (lack of enough healthy red blood cells).
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Recurrent infections.
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Simultaneous enlargement of both the liver and the spleen (hepatosplenomegaly) as the bone expansion leads to bone marrow narrowing.
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Blindness, facial paralysis, or deafness.
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Abnormal bone structure and morphology of the cortical bone.
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The abnormal form of vertebral bodies.
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Temperature regulation is not normal.
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Abnormality in the structure of the ribs.
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Pain in the bone.
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Low calcium levels in the blood may cause seizures (fits).
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Small jaw in case of infantile osteopetrosis.
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Chronic inflammation of the mucous lining of the nose (also known as rhinitis).
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Delayed psychomotor development ( coordination between muscles and voluntary movements).
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Abnormal hardening of the bones (osteosclerosis).
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Abnormally large head in case of malignant infantile type osteopetrosis.
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Wasting away or atrophy of the retina (area of the eye that is sensitive to light and sends images of what is seen to the brain).
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Abnormally spaced eyes.
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Cross eyes (a condition in which both eyes cannot look in the same direction at the same time).
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Abnormally protruding eyes.
How Is Osteopetrosis Diagnosed?
The diagnosis of osteopetrosis is based on the medical and family history of the patients, clinical examination of the symptoms, and laboratory testing, including image tests. The tests done to confirm the diagnosis include:
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Imaging Tests: X-rays, CT scans (computed tomography and MRI (magnetic resonance imaging) are done to evaluate the abnormal density, altered structure, and misshape of the bone.
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Blood Examinations: Blood samples are collected, and serum levels are checked for; calcium, parathyroid hormone, creatinine, phosphorus, vitamin D, BB isoenzyme of creatine kinase, and lactate dehydrogenase. A complete and differential blood count should also be done.
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Genetic Testing: Genetic testing is done to narrow down the mutation in about 90 % of the cases. This test easily evaluates the form, association, and complications of the condition.
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Bone Biopsy: In rare cases, a bone biopsy may be done to confirm the diagnosis.
How Is Osteopetrosis Treated?
The standard treatment modalities of osteopetrosis include:
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The treatment possible for the autosomal recessive malignant infantile type of osteopetrosis is hematopoietic stem cell transplantation (also known as bone marrow transplant, and it involves transplantation of healthy hematopoietic stem cells derived from bone marrow, peripheral blood cells, umbilical cord, etc.) This helps in allowing a normal bone resorption pattern.
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Interferon-gamma 1b is used to delay the progression of osteopetrosis.
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Corticosteroids may help in improving blood cell levels.
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Physical and occupational therapies may be given to children to develop motor skills.
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Bone care may be advised, which is done with the help of casts, splints, or surgery. This is done to correct the structural abnormalities and altered shapes of the bones.
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A bone marrow transplant may be recommended for infants with severe kinds of osteopetrosis.
What Is the Difference Between Osteopetrosis and Osteoporosis?
Osteopetrosis is often confused with osteoporosis; the difference between the two conditions is as follows:
Conclusion:
As mentioned earlier, osteopetrosis is a condition characterized by an extremely high density of the bones leading to accumulation of bones, formation of structurally and morphologically altered bones, and weakening of the bone due to brittleness that makes it susceptible to fractures. The condition is rare and hereditary, and it occurs when the bone-resorbing cells fail to function efficiently, and bone turnover is imbalanced. There are different types of osteopetrosis depending upon their mode of inheritance. The diagnosis of the condition involves blood examinations, imaging tests, along with gene testing. The treatment of osteopetrosis is helpful if the condition is diagnosed early. Life expectancy in the severe infantile form is low, whereas the life expectancy of osteopetrosis of adult-onset forms is normal.
