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Osteopetrosis

Updated : September 3, 2022





Background

The Greek language is where the word osteopetrosis originated. Osteo and petrosis both refer to bone and stone, respectively. As a result, the illness is frequently referred to as “marble bone sickness.” Dr. Albers-Schonberg, a radiologist from Germany, first described the condition in 1904. The most important radiographic observation is unusually high bone density.

The damaged bones become excessively brittle as a result of the increased density, which is a result of osteoclast dysfunction. The term “osteopetrosis” refers to a set of genetic metabolic bone illnesses that all adversely affect bone growth and remodeling, resulting in generalized osteosclerosis, the possibility of pancytopenia, pathologic fracturing, or even cerebral neuropathies and hepatosplenomegaly in extreme cases. The known illness forms are four.

The malignancy autosomal recessive variant (ARO), which is extremely severe and frequently results in early childhood mortality, is not labeled malignant because it has anything to do with oncology but rather because of how terrible the disorder is. Typically, for the first ten years of life, the intermediary ARO starts to have clinical significance. Even though these affected patients develop increasing cranial nerve compressive neuropathies and pathologic injuries, they typically survive until maturity.

Autosomal dominant osteopetrosis (ADO) has two subtypes, and people with these conditions frequently remain asymptomatic until adulthood. The cranial vault has isolated osteosclerotic thickness in type I, which normally does not carry an increased risk of fracture risk. Pathologic fractures, anemia, or initial arthritis are common adult manifestations in type II patients.

Epidemiology

Fortunately, the disease’s ARO is much less common than its ADO. About 1 in every 250,000 births had the ARO. Notably, the occurrence has been discovered to be much greater in Costa Rica, where it is estimated to occur in about 3.4 out of each 100,000 births. The frequency of the disease’s ADO is roughly 1:20,000.

Anatomy

Pathophysiology

In order for osteoclast-mediated absorption and deposition to coexist in a healthy manner, bone must be in a dynamic equilibrium. Osteopetrosis is characterized by abnormal osteoclast growth and function, which disturbs the normal homeostasis of the bone.

Chloride channels, Proton pumps, as well as CAII protein deficiencies, prevent osteoclasts from successfully resorbing bone. As a result, the fracture-prone, disorganized, and excessively dense bone develops unregulated.

Etiology

The osteoclastic malfunction has been linked to a minimum of Eight gene alterations, according to a genetic study. An autosomal recessive, malignant variant of the illness is linked to six among these eight traits. An osteoclast-rich form of ARO is caused by the deletion of function mutations in AND SNX10, OSTM1, TCIRG1, CLCN7, and PLEKHM1.

This version has a lot of osteoclasts. The poor ruffled boundary development, however, prevents the osteoclasts from the adequately resorbing bone. Osteoclast formation is disturbed and osteoclast poor osteopetrosis results from function loss mutations in TNFRSF11A and TNFSF11.

The Carbonic anhydrase II (CAII) gene, which codes for the CAII protein, has a loss-of-function mutation that causes intermediate ARO. Because of a dominant-negative mutation in chloride channel 7 (CLCN7), CLCN7 becomes dysfunctional, leading to ADO.

Genetics

Prognostic Factors

Without a successful bone marrow transplant, the malignant, ARO frequently results in death during the first few years of life. Bone marrow transplantation may be attempted on many patients with varying degrees of success.

With the ADO, the other disease forms often allow patients to live into adulthood with relatively little impact on life expectancy and general health.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

 

romosozumab

210

mg

Solution

Subcutaneous (SC)

once a month

1

year



ipriflavone 

Take a dose of 200 mg orally three times daily



 

romosozumab

Safety and efficacy are not seen in pediatrics



 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK557529/

Osteopetrosis

Updated : September 3, 2022




The Greek language is where the word osteopetrosis originated. Osteo and petrosis both refer to bone and stone, respectively. As a result, the illness is frequently referred to as “marble bone sickness.” Dr. Albers-Schonberg, a radiologist from Germany, first described the condition in 1904. The most important radiographic observation is unusually high bone density.

The damaged bones become excessively brittle as a result of the increased density, which is a result of osteoclast dysfunction. The term “osteopetrosis” refers to a set of genetic metabolic bone illnesses that all adversely affect bone growth and remodeling, resulting in generalized osteosclerosis, the possibility of pancytopenia, pathologic fracturing, or even cerebral neuropathies and hepatosplenomegaly in extreme cases. The known illness forms are four.

The malignancy autosomal recessive variant (ARO), which is extremely severe and frequently results in early childhood mortality, is not labeled malignant because it has anything to do with oncology but rather because of how terrible the disorder is. Typically, for the first ten years of life, the intermediary ARO starts to have clinical significance. Even though these affected patients develop increasing cranial nerve compressive neuropathies and pathologic injuries, they typically survive until maturity.

Autosomal dominant osteopetrosis (ADO) has two subtypes, and people with these conditions frequently remain asymptomatic until adulthood. The cranial vault has isolated osteosclerotic thickness in type I, which normally does not carry an increased risk of fracture risk. Pathologic fractures, anemia, or initial arthritis are common adult manifestations in type II patients.

Fortunately, the disease’s ARO is much less common than its ADO. About 1 in every 250,000 births had the ARO. Notably, the occurrence has been discovered to be much greater in Costa Rica, where it is estimated to occur in about 3.4 out of each 100,000 births. The frequency of the disease’s ADO is roughly 1:20,000.

In order for osteoclast-mediated absorption and deposition to coexist in a healthy manner, bone must be in a dynamic equilibrium. Osteopetrosis is characterized by abnormal osteoclast growth and function, which disturbs the normal homeostasis of the bone.

Chloride channels, Proton pumps, as well as CAII protein deficiencies, prevent osteoclasts from successfully resorbing bone. As a result, the fracture-prone, disorganized, and excessively dense bone develops unregulated.

The osteoclastic malfunction has been linked to a minimum of Eight gene alterations, according to a genetic study. An autosomal recessive, malignant variant of the illness is linked to six among these eight traits. An osteoclast-rich form of ARO is caused by the deletion of function mutations in AND SNX10, OSTM1, TCIRG1, CLCN7, and PLEKHM1.

This version has a lot of osteoclasts. The poor ruffled boundary development, however, prevents the osteoclasts from the adequately resorbing bone. Osteoclast formation is disturbed and osteoclast poor osteopetrosis results from function loss mutations in TNFRSF11A and TNFSF11.

The Carbonic anhydrase II (CAII) gene, which codes for the CAII protein, has a loss-of-function mutation that causes intermediate ARO. Because of a dominant-negative mutation in chloride channel 7 (CLCN7), CLCN7 becomes dysfunctional, leading to ADO.

Without a successful bone marrow transplant, the malignant, ARO frequently results in death during the first few years of life. Bone marrow transplantation may be attempted on many patients with varying degrees of success.

With the ADO, the other disease forms often allow patients to live into adulthood with relatively little impact on life expectancy and general health.

romosozumab

210

mg

Solution

Subcutaneous (SC)

once a month

1

year



ipriflavone 

Take a dose of 200 mg orally three times daily



romosozumab

Safety and efficacy are not seen in pediatrics



https://www.ncbi.nlm.nih.gov/books/NBK557529/