Where art thou osteoclasts? A review of osteopetrosis.

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Osteopetrosis is a disease that results from defective osteoclast function. Failed bone resorption leads to dense bone that may cause fracture, bone marrow encroachment, or skull foramen narrowing.

Osteoclasts are multinucleated cells derived from monocytes; they produce an acidic environment to dissolve hydroxyapatite (inorganic bone) which exposes organic bone that is degraded by proteolytic enzymes (e.g. metalloproteinases).

Carbonic anhydrase and proton pumps play an important role in the production of the acidic environment. Two autosomal recessive forms of osteopetrosis involve dysfunctions in this process.

Malignant osteopetrosis involves a defect in osteoclast proton channels and is typically fatal in childhood. Intermediate osteopetrosis involves a dysfunction in carbonic anhydrase II, these patients may live into adulthood. The AD form involves a defect in Cl- channel.

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Radiologic evidence coupled with clinical findings are the mainstays for diagnosis. Imaging while show increased bone density and may show an "Erlenmeyer flask deformity" or "Rugger jersey spine". The clinical findings for three forms of the disease are as follows …

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Malignant osteopetrosis presents in the first few months of life. These patients may present with pathologic fractures, hepatosplenomegaly, deafness/blindness due to narrowing of skull foramen, and/or signs of bone marrow encroachment (infections, bleeding, bruising).

Intermediate osteopetrosis presents in the first decade of life. These patients may present with renal tubular acidosis due to the defect in CA-II. They may also present with similar symptoms to the malignant form, but symptoms are variable and not as severe.

Autosomal dominant osteopetrosis presents with fractures or early on-set OA (most commonly of the hip). This form of the disease is most commonly managed by orthopedic surgeons and these patients typically have normal life spans.

Due to variable presentations, management must be tailored to the individual. HSC transplant & INF-γ therapy are the only current treatment options. Ophthalmologic should be performed routinely, and fractures/arthritis should be managed by ortho.

There are many types of osteopetrosis that can range from mild to fatal. Treating patients with osteopetrosis requires a team of physicians and therefore communication is important for providing the best possible treatment for patients with this disease.

1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385565/
2: https://www.ncbi.nlm.nih.gov/books/NBK557529/

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