Osteopetrosis

Rare inherited bone disorder characterized by increased bone density

Osteopetrosis (Albers-Schönberg Disease)
Synonyms	N/A
Pronounce	N/A
Field	Orthopedics, genetics, endocrinology
Symptoms	Brittle bones, fractures, anemia, cranial nerve compression
Complications	Blindness, deafness, osteomyelitis, hypocalcemia
Onset	Infancy, childhood, or adulthood
Duration	N/A
Types	Autosomal dominant, autosomal recessive, X-linked
Causes	Genetic mutations affecting osteoclast function
Risks	Family history
Diagnosis	X-ray, MRI, genetic testing, bone marrow biopsy
Differential diagnosis	Osteosclerosis, osteoporosis, Paget’s disease
Prevention	None known
Treatment	Supportive care, bone marrow transplant (severe cases)
Medication	Calcitriol, gamma interferon, erythropoietin
Prognosis	Variable (severe forms can be life-threatening)
Frequency	1 in 100,000 to 500,000 births (severe forms)
Deaths	N/A

Osteopetrosis, also known as marble bone disease or Albers-Schönberg disease, is a rare genetic disorder characterized by abnormally dense bones due to defective osteoclast function. Unlike osteoporosis, where bones become weak and brittle, osteopetrosis leads to excess bone formation that is paradoxically fragile and prone to fractures.<ref>Stark, Zornitza,

 Osteopetrosis, 
 Orphanet Journal of Rare Diseases, 
 
 Vol. 4,
 pp. 5,
 DOI: 10.1186/1750-1172-4-5,</ref>

The disease can be autosomal dominant (mild), autosomal recessive (severe, infantile), or X-linked. Osteopetrosis was first described in 1903 by the German radiologist Heinrich Albers-Schönberg.

Classification

Osteopetrosis is classified based on genetic inheritance and severity:

• Autosomal Dominant Osteopetrosis (ADO) (Adult-onset, Albers-Schönberg Disease)
• Milder form
• Usually asymptomatic or diagnosed after fractures
• Affects 1 in 20,000 people

• Autosomal Recessive Osteopetrosis (ARO) (Malignant Infantile Osteopetrosis)
• Severe, early-onset form
• Fatal if untreated due to bone marrow failure
• Requires bone marrow transplant

• X-linked Osteopetrosis
• Extremely rare
• Associated with immune deficiencies and severe osteopetrosis

Symptoms

Despite increased bone density, affected individuals may suffer from brittle bones and fractures. Symptoms vary based on severity:

• Skeletal abnormalities:
• Stunted growth, scoliosis, bone deformities
• Frequent fractures despite dense bones
• Craniosynostosis (premature skull closure)

• Neurological complications:
• Blindness (optic nerve compression)
• Deafness (auditory nerve compression)
• Facial paralysis (cranial nerve compression)

• Bone marrow failure:
• Anemia
• Recurrent infections due to low white blood cells
• Hepatosplenomegaly (enlarged liver/spleen due to extramedullary hematopoiesis)

• Metabolic disturbances:
• Hypocalcemia (low calcium)
• Delayed tooth eruption
• Increased risk of osteomyelitis (bone infections)

Diagnosis

Diagnosis is based on radiographic imaging, genetic testing, and laboratory findings:

• X-rays – Classic "bone-in-bone" (endobone) pattern, Erlenmeyer flask deformity in long bones
• MRI/CT scans – To assess nerve compression
• Genetic testing – Identifies mutations in CLCN7, TCIRG1, RANKL, OSTM1, CA2 genes
• Bone marrow biopsy – Evaluates bone marrow failure in infantile osteopetrosis

Treatment

Treatment depends on severity:

1. Bone Marrow Transplantation (BMT)

• Curative for infantile osteopetrosis
• Replaces defective osteoclast precursors with healthy donor cells
• Most effective before irreversible complications develop

2. Medications

• Calcitriol (Vitamin D3) – Activates dormant osteoclasts to promote bone resorption
• Gamma interferon – Reduces bone density, improves immune function
• Erythropoietin – Treats anemia
• Corticosteroids – Stimulate bone resorption, reduce inflammation

3. Supportive Care

• Orthopedic management – Fracture treatment, surgical correction of deformities
• Hearing/vision aids – If cranial nerves are affected
• Dental care – Prevention of osteomyelitis (bone infections)

Prognosis

The prognosis depends on disease type:

• Infantile osteopetrosis (ARO) – Fatal if untreated, but curable with bone marrow transplantation
• Adult-onset osteopetrosis (ADO) – Normal life expectancy, but fracture risk remains high

Prevalence

• Severe (infantile) osteopetrosis – 1 in 100,000–500,000 births
• Mild (adult-onset) osteopetrosis – 1 in 20,000 individuals
• Higher prevalence in certain populations (e.g., Costa Rica, Denmark, Brazil)

Recent Research

New therapies are being explored:

• Gene therapy – Potential to correct defective osteoclast function
• RANKL administration – Improves osteoclast activity in RANKL-deficient patients<ref>Lo Iacono, Nadia,

 Osteopetrosis rescue upon RANKL administration, 
 Journal of Bone and Mineral Research, 
 
 
 
 DOI: 10.1002/jbmr.1712,</ref>

Notable Cases

• Laurel Burch – American artist with severe osteopetrosis<ref>

,

 Marin County artist Laurel Burch dead at 61 of rare bone disease Full text, 
 ,

</ref>

• Lil Bub – Internet-famous cat with osteopetrosis

See Also

• Paget’s disease of bone
• Osteoporosis
• Skeletal dysplasia

External Links

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