Osteopetrosis Workup

Updated: Sep 11, 2017
  • Author: Robert Blank, MD, PhD; Chief Editor: George T Griffing, MD  more...
  • Print

Approach Considerations

Laboratory findings in infantile osteopetrosis include the following:

  • Serum calcium - Generally reflects oral intake; hypocalcemia can occur and cause rickets if it is severe enough

  • Parathyroid hormone (PTH) - Often is elevated (secondary hyperparathyroidism)

  • Acid phosphatase - Increased due to increased release from defective osteoclasts

  • Creatinine kinase isoform BB (CK-BB) - levels are increased due to increased release from defective osteoclasts

Laboratory findings in adult osteopetrosis include the following:

  • Acid phosphatase and CK-BB - Concentrations are often increased in type II disease

  • Serum bone-specific alkaline phosphatase - Values may also be increased in various types of the disease

Genetic screening

In addition to the routine laboratory investigations listed above, mutation screening of appropriate candidate genes should be undertaken in patients whose presentation corresponds to any of the known genetic lesions. Knowledge of the molecular basis of the osteopetrosis allows clinicians to provide informed genetic counseling and, in some cases, to choose appropriate therapy.


Bone biopsy is not essential for diagnosis, because radiographs usually are diagnostic. Histomorphometric studies of bone may be useful to predict the likelihood that BMT will succeed. Patients with crowded bone marrow are less likely than others to respond to a transplant.

Histologic findings

Failure of osteoclasts to resorb skeletal tissue is the pathognomonic feature of true osteopetrosis. Remnants of mineralized primary spongiosa are seen as islands of calcified cartilage within mature bone. Woven bone is commonly seen. Osteoclasts can be increased, normal, or decreased in number.

Histologic analysis has revealed that type I adult-onset osteopetrosis is not a genuine form of osteopetrosis, because it lacks the characteristic findings.



Radiologic features of osteopetrosis are usually diagnostic. Because osteopetrosis encompasses a heterogeneous group of disorders, findings differ according on the variant. [17]

Patients usually have generalized osteosclerosis. Bones may be uniformly sclerotic, but alternating sclerotic and lucent bands may be noted in iliac wings and near the ends of long bones. The bones may be clublike or may have the appearance of a bone within bone (endobone). Radiographs may also show evidence of fractures or osteomyelitis.

The entire skull is thickened and dense, especially at the base. Sinuses are small and underpneumatized. Vertebrae are extremely radiodense. They may show alternating bands, known as the rugger-jersey sign (see Table 3).

Differentiating type 1 from type 2 adult osteopetrosis

Two types of adult osteopetrosis are identified on the basis of radiographs. Typing the patient's disease may be important in predicting a fracture pattern, because type II disease appears to increase the risk of fracture (see Table 3). Radiographic characteristics of type I and type II disease are as follows:

  • Type I disease - Sclerosis of the skull mainly affects the vault with marked thickening; the spine does not show much sclerosis.

  • Type II disease - Sclerosis is found mainly in the base of the skull; the spine always has the rugger-jersey appearance, and the pelvis always shows subcristal sclerosis; transverse banding of metaphysis is common in patients with type II disease but not in patients with type I disease (this finding confirms type II disease, but its absence does not necessarily indicate type I disease)