Pycnodysostosis (Pyknodysostosis)

  • Medical Reviewer: William C. Shiel Jr., MD, FACP, FACR
    William C. Shiel Jr., MD, FACP, FACR

    William C. Shiel Jr., MD, FACP, FACR

    Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.

What is the molecular story with pycnodysostosis?

In 1995, the gene for pycnodysostosis was first charted by Gelb and associates. It was found to travel preferentially with gene markers known to be in chromosome region 1q21. (This tendency for genes to travel together is termed linkage). Once the location of the pycnodysostosis gene was identified by linkage analysis, genes in that region that seemed logical candidates were seriously scrutinized. Among them was cathepsin K, which is active in bone. Cathepsin K qualified as a "candidate gene."

In 1996, patients with pycnodysostosis were shown by Gelb and coworkers consistently to have mutational changes in the gene for cathepsin K. The defective cathepsin K gene was thus demonstrated to be the gene responsible for pycnodysostosis. Pycnodysostosis is now clearly recognized as being due to cathepsin K deficiency.

What does cathepsin K normally do? Cathepsin K is an enzyme (a catalyst for a reaction of body metabolism) of the type called a cysteine protease. This protease is important in cells of normal bone (osteoclasts) that are responsible for bone reabsorption (or resorption). It is thought that osteoclasts in patients with pycnodysostosis are hampered by a lack of cathepsin K and cannot adequately reabsorb that component of bone called the organic matrix. (This process is essential for normal bone maintenance; a process referred to as remodeling). Because of this inadequate resorption, the bones in pycnodysostosis are abnormally dense and brittle.

Could there be a connection between pycnodysostosis and osteoporosis?

Both pycnodysostosis and osteoporosis cause brittle bones. However, pycnodysostosis is a disease with abnormally dense bones, whereas osteoporosis is exactly the opposite, a disease with washed-out porous bones. There would seem to be no conceivable connection between pycnodysostosis and osteoporosis.

The new findings about cathepsin K and pycnodysostosis have made it clear that cathepsin K is a major protease in bone resorption. Given this function, it may well have a role in osteoporosis. Cathepsin K may, in fact, provide a rational basis for a new approach to the treatment of osteoporosis. This is an excellent illustration of how research on a rare disease may bring benefits to those affected by a common disease.

Medically Reviewed by a Doctor on 10/26/2016

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