Although human osteopetrosis is a heterogeneous disorder encompassing different molecular lesions and a range of clinical features, all forms share a single pathogenic nexus in the osteoclast.

Diagnosis is principally based on clinical and radiographic evaluation, confirmed by gene analysis where applicable.

[5] As a result of medullary canal obliteration and bony expansion, grave pancytopenia, cranial nerve compression, and pathologic fractures may ensue.

The classic radiographic features include endobone or "bone-within-bone" appearance in the spine, pelvis and proximal femora, upper limbs, and short tubular bones of the hand.

[5] The precise and early diagnosis of infantile osteopetrosis is important for management of complications, genetic counselling, and timely institution of appropriate treatment, namely hematopoietic stem cell transplantation (HSCT), which offers a satisfactory treatment modality for a considerable percentage of infantile osteopetrosis.

[6] Amelioration of radiographic bone lesions after HSCT in infantile osteopetrosis has been proposed as an important indicator of success of the therapy.

A few publications with limited study participants have demonstrated the resolution of skeletal radiographic pathology following HSCT.

However, those who do show symptoms will typically have a curvature of the spine (scoliosis) and multiple bone fractures.

The defects are very common and include neuropathies due to cranial nerve entrapment, osteoarthritis, and carpal tunnel syndrome.

[12] Osteopetrosis can be caused by underlying mutations that interfere with the acidification of the osteoclast resorption pit, for example due to a deficiency of the carbonic anhydrase enzyme encoded by the CA2 gene.

[citation needed] There is no cure, although curative therapy with bone marrow transplantion is being investigated in clinical trials.

The severe infantile forms of osteopetrosis are associated with shortened life expectancy, with most untreated children not surviving past their first decade.

For those with onset in childhood or adolescence, the effect of the condition depends on the specific symptoms (including how fragile the bones are and how much pain is present).

[17] Approximately eight to 40 children are born in the United States each year with the malignant infantile type of osteopetrosis.

[20][21] Recent research demonstrated that the systematic administration of RANKL for one month to Rankl(-/-) mice, which closely resemble the human disease, significantly improved the bone phenotype and has beneficial effects on bone marrow, spleen and thymus; major adverse effects arise only when mice are clearly overtreated.

Overall, it provided evidence that the pharmacological administration of RANKL represents the appropriate treatment option for RANKL-deficient ARO patients, to be validated in a pilot clinical trial.

[22] Interferon gamma-1b is FDA-approved to delay the time to disease progression in patients with severe, malignant osteopetrosis.