New research is helping to identify early biomarkers of prosthetic performance as well as genetic polymorphisms that predict risk of osteolysis, according to new research presented at a joint session of the Orthopedic Research Society and the American Academy of Orthopaedic Surgeons (AAOS) during the annual meeting in Chicago, Illinois.1

Serum and urine levels of metal ions, biomarkers of bone metabolism, and collagen degradation can have diagnostic utility for predicting future implant failure, says Joshua J. Jacobs, MD, an orthopaedic surgeon at Rush University Medical Center in Chicago, Illinois. Moreover, genomic studies looking at gene expression profiling may serve as a genetic fingerprint of loose or infected implants, he says.

Specifically, decreases in type-I C-terminal peptide (PICP) and increases in cross-linked amino-terminal telopeptide of type I collagen (NTx) may be markers of loose implants. Moreover, more than 8 parts per billion (ppb) of serum titanium can indicate that the implant is loose, that there are multiple implants, or that there is polyethylene wear-through and metal is rubbing on metal, among other possibilities. Markers of serum and urine collagen degradation may also serve as early markers of osteolysis and loosening well before symptoms appear, explains Dr. Jacobs.

"We need large-scale, long-term, controlled and prospective studies to validate the clinical utility of these biomarkers," says Dr. Jacobs. If validated, they may be "powerful surrogate endpoints for clinical trials and have a significant clinical impact on the management of patients who are at risk for implant loosening or failure." However, he says, "I don't think all of us should be doing this yet, but there is a great potential to use this sort of information."


Genetics of osteolysis

In a related talk, Mark J. Wilkinson, MB, ChB, PhD, of the Bone Metabolism Group in the division of clinical sciences at the University of Sheffield in Sheffeld, UK, said that progress is being made in identifying genetic polymorphisms that increase or decrease risk of osteolysis.2 For example, polymorphisms in interleukin-1 and FRZB genes may decrease risk of osteolysis, he says.

"The genetic polymorphisms associated with risks of osteolysis tell us something important about the genetics of the disease process and provide a target for gene and drug therapies," Dr. Wilkinson explains. Another aspect of this research is the potential development and use of gene panels to assess risks of osteolysis even before a patient undergoes arthroplasty. The new findings are a "good first start in understanding the genetics of osteolysis," he says. Now, we "need to elucidate the mechanism of actions of the associations that we [identified]."

References

  1. Jacobs, JJ. Biomarkers of prosthetic performance. Presented at: 52nd Annual Meeting of the Orthopaedic Research Society. March 18–22, 2006; Chicago, Ill.
  2. Wilkinson, JM. The genetics of osteolysis and loosening. Presented at: 52nd Annual Meeting of the Orthopaedic Research Society. March 18–22, 2006; Chicago, Ill.