eMedicine Specialties > Endocrinology > Metabolic Bone Disease
Osteopetrosis: Differential Diagnoses & Workup
Updated: Oct 13, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Hypoparathyroidism
Myeloproliferative Disease
Paget Disease
Pseudohypoparathyroidism
Toxicity, Lead
Other Problems to Be Considered
Osteoblastic metastases
Pyknodysostosis
Fluoride poisoning
Beryllium poisoning
Leukemia
Sickle cell diseases
Workup
Laboratory Studies
- Findings in infantile osteopetrosis
- 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 is increased due to increased release from defective osteoclasts.
- Levels of creatinine kinase isoform BB (CK-BB) is increased due to increased release from defective osteoclasts.
- Findings in adult osteopetrosis
- 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.
- Other findings
- In addition to the results of routine laboratory investigations listed above, mutation screening of appropriate candidate genes should be undertaken in patients whose presentations correspond 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.
Imaging Studies
- Radiologic features are usually diagnostic. Because the disease is a heterogeneous group of disorders, the findings vary depending on the subtype.12
- Patients usually have generalized osteosclerosis. Bones may be uniformly sclerotic, but alternating sclerotic and lucent bands may be noted in iliac wings and near ends of long bones. The bones might be clublike or appear like a bone within bone (endobone).
- 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 in History).
- Radiographs may show evidence of fractures or osteomyelitis.
- Two types of adult osteopetrosis are identified on the basis of radiographs. Typing the patient's disease might be important to predict a fracture pattern because type II disease appears to increase the risk of fracture (see Table 3 in History).
- 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.
- MRI can be used to assess bones over time after bone marrow transplantation (BMT).
Procedures
- Bone biopsy is not essential for diagnosis because radiographs usually are diagnostic.
- Histomorphometric studies of bone might 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.
More on Osteopetrosis |
| Overview: Osteopetrosis |
 Differential Diagnoses & Workup: Osteopetrosis |
| Treatment & Medication: Osteopetrosis |
| Follow-up: Osteopetrosis |
| References |
| Further Reading |
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References
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Further Reading
Clinical guidelines:
Evaluating infants and young children with multiple fractures. American Academy of Pediatrics - Medical Specialty Society. 2006 Sep. 5 pages. NGC:005253
Clinical trials:
Allogeneic Transplantation For Severe Osteopetrosis
rhPTH Therapy for Low Turnover Bone Fragility
Keywords
osteopetrosis, osteoclast, osteoblast osteoclast, osteosclerosis, osteosclerotic, Albers-Schönberg disease, marble bone disease, osteoclastic bone resorption, infantile osteopetrosis, infantile malignant osteopetrosis, adult osteopetrosis, benign osteopetrosis
