Blame the genes. Researchers at Penn State College of Medicine have found that the non-healing of fractures in otherwise healthy people may be caused by their genes. J. Spence Reid, M.D., professor of orthopedics and rehabilitation, found associations between certain gene polymorphisms and delayed fracture healing in a sample of patients. “Our study was preliminary but it demonstrated the feasibility of a larger one, which we’re now working to set up, ” he said.
About 10% of the eight million bone fractures that take place in the U.S. every year fail to heal normally. Smoking, diabetes, low vitamin D levels and old age are risk factors, but in a significant number of cases, unknown factors also appear to be involved. “Some fractures are slow-healing for no obvious reason, and we wondered if there is a genetic basis for those cases, ” said Reid.
He and his colleagues selected 33 patients diagnosed with “atrophic nonunion”—the failure of a fracture to knit together on its own within six months—and paired them with 29 patients whose fractures had healed normally.
Using cheek swabs, the researchers obtained DNA from all of the patients. In each case they checked tiny sites of known DNA-sequence variations, called “single nucleotide polymorphisms, (SNP)” that mark common gene variants. They looked only at the SNPs within 30 genes suspected of involvement in fracture healing.
The analysis revealed three SNPs that appeared more often in the non-healing group than in the normal-healing group—suggesting that their gene variants may impair or fail to support fracture healing. Two of these SNPs were within a single gene, which codes for the enzyme nitric oxide synthase 2 (NOS2). Earlier studies on mice had shown that this enzyme is produced early in the fracture healing process and that deletion of the NOS2 gene delays healing in mice.
The other SNP of interest lies within the gene for interleukin 1-Beta which is a signaling molecule known as a promoter of inflammation. Interleukin 1-Beta is suspected to also be an early orchestrator of the new bone growth that knits together a fracture.
