Discovery Could Lead to Better Treatment for Rickets

Discovery Could Lead to Better Treatment for Rickets

Researchers are a step closer to finding more effective treatment for X-linked hypophosphatemia (XLH)—the most common form of heritable rickets. A rare condition most often diagnosed in toddlers, XLH is characterized by soft bones that deform, and the development of tooth abscesses that result from infection penetrating soft teeth that are not fully calcified.

Investigating factors that might contribute to this disease, a team of Canadian and Brazilian researchers has found that osteopontin, a bone and tooth substrate protein, plays a role in XLH. Evidence shows that loss of osteopontin—which inhibits mineralization in bones and teeth—allows these structures to harden normally. It has been determined that in XLH patients, who lack the enzyme of a particular gene, osteopontin and related peptides are allowed to accumulate in bone structures.

The findings build on earlier research that suggests mutations in the single gene PHEX cause XLH. In studying other factors that might contribute to XLH, the researchers used various methods to show that PHEX enzymatic activity leads to a complete breakdown of osteopontin.

“With the identification of osteopontin as a substrate protein for PHEX,” notes researcher Nilana M.T. Barros, PhD, of Brazil’s Federal University of San Paulo, “we can begin to develop an enzyme-replacement therapy to treat XLH patients who have nonfunctional PHEX—much as has been done using a different enzyme to treat another rare bone disease called hypophosphatasia.”

Because the standard treatment of this form of rickets focuses on improving phosphate levels, the researchers were interested in finding factors within the bone that blocked mineralization. Their investigation, jointly funded by the Canadian Institutes of Health Research and Fundação de Amparo à Pesquisa do Estado de São Paulo, is slated for publication in the March issue of the Journal of Bone and Mineral Research.