An important advance in the understanding of X-linked hypophosphatemia (XLH)—the most common heritable form of rickets—has led NIAMS-supported scientists to a potential treatment for a disorder in which low levels of phosphate lead to bone and tooth abnormalities.
In a pilot study published in the New England Journal of Medicine, scientists at the Yale University School of Medicine found that a single injection of calcitonin decreased levels of a hormone called fibroblast growth factor 23 (FGF-23), and subsequently increased serum phosphate levels in seven people with XLH. Because calcitonin controls the elevated levels of FGF-23 found in XLH, it may be effective in reversing the disorder—something that has not been possible with current therapies.
In earlier studies, scientists found FGF-23 to be key to the development of XLH, a disease characterized by impaired bone growth, dental abscesses leading to tooth loss, bone pain and calcification of the tendons and ligaments. Unlike most growth factors, which affect only the local tissue where they are made, FGF-23 circulates through the body and can act at distant sites. Made in bone cells called osteocytes, FGF-23 works in the kidney, providing a way for bone to communicate with the kidneys to regulate phosphate, which is crucial to skeletal development. In people with XLH, the researchers found, FGF-23 is over produced, leading to excessive urinary losses of phosphate.
Available treatments for XLH have focused on supplementing phosphate and vitamin D. But this treatment doesn’t cure the disease, and, for many people, complications of the supplements make them hard to take or are unacceptable, says Thomas O. Carpenter, M.D., of the NIAMS-supported study team. Furthermore, the team’s research has shown that the current treatment actually further increases levels of FGF-23.
Based on these findings, the researchers sought a treatment that would improve the bone disease without the complications of current therapy. Their search led them to calcitonin, a medication derived from salmon that, when given intramuscularly or administered nasally, helps regulate calcium and bone loss.
With evidence that a single dose of injected calcitonin can, in fact, reduce circulating FGF-23 levels and increase serum phosphate, the next step will be to determine if nasally administered calcitonin given for a longer period of time can sustain and further enhance these effects. The researchers at Yale are planning clinical trials to determine that now. Because calcitonin is a readily available medication, the trials’ success could mean a promising new treatment for people who have XLH.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.
Calcitonin administration in X-linked hypophosphatemia. Liu ES, Carpenter TO, Gundberg CM, Simpson CA, Insogna KL. N Engl J Med. 2011 Apr 28;364(17):1678-80. PMID: 21524226.