Marble bone disease

Osteopetrosis (marble bone disease), characterized by increased bone density, is due to inability to resorb bone. One form occurs along with renal tubular acidosis and cerebral calcification. It is due to mutations in the gene (located on chromosome 8q22) encoding carbonic anhydrase II (CAII), one of four isozymes of carbonic anhydrase present in human tissues. The reaction catalyzed by carbonic anhydrase is shown below ... 

Slight or moderate elevations in serum TR-ACP activity often occur in Paget s disease, in hyperparathyroidism with skeletal involvement, and in the presence of malignant invasion of the bones by cancers, such as breast cancer in women. Increased concentrations of the osteoclast-derived AGP are also present in serum in osteoclastoma (giant-cell tumor), an osteoclastic neoplasm, and in osteopetrosis (marble bone disease) in which the osteoclasts fail to resorb bone. High concentrations... 

Osteopetrosis (marble bone disease) is marked by the formation of abnormally dense and condensed bone. It is a genetically, biochemically, and clinically heterogeneous disease. However, the underlying mechanism for the various types of osteopetrosis is a failure in bone resorption due to defects in osteoclasts. In some forms of osteopetrosis, providing normal osteoclastic precursors by bone marrow transplantation has yielded clinical improvement. Stimulation of osteoclast formation or activity with 1, 25-(0H)2D or recombinant interferon-y also has yielded modest clinical improvement. 

Osteopetrosis, also known as marble bone disease, describes a group of heritable disorders that are centered on a defect in osteoclast-mediated bone resorption. There are four autosomal recessive and one autosomal dominant forms of osteopetrosis (Table 35.4) (16). It generally is characterized by abnormally dense, brittle bone and increased skeletal mass. Unlike osteoporosis, this disorder results from decreased osteoclast activity, which has an effect on both the shape and structure of the bone. In very extreme cases, the medullary cavity, which houses bone marrow, fills with new bone, and production of hematopoietic cells is hampered. Like osteoporosis, this disease can be detected radiographically and appears as though there is a bone within a bone. There is limited evidence that bisphosphonates can induce osteopetrosis via their inhibition of osteoclast activity (17). 

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