Genetic markers could predict loosening of THA, TKA implants

Searching for these markers could identify those at high risk of implant failure.

Aseptic loosening has emerged as the most frequent long-term problem and the most common cause for revision of hip arthroplasty, as well as the second most common cause for knee replacement revisions. To date, no specific attributes have been found that predict aseptic loosening of joint implants, but researchers in Brazil believe certain genetic markers may do just that.

“The osseous integration mechanism of prosthesis components is very similar to primary bone healing,” said Alexandre Godoy-Santos, MD, of Sao Paolo University Medical School in Brazil. This similarity means that an inflammatory process promotes hematoma and remodeling of the surrounding tissue. Eventually, new bone forms.

“Immediately after implantation, the implant becomes covered with a layer of organic and inorganic plasma components attached to inflammatory and mesenchymal cells. These cells can synthesize and release cytokines and lipid mediators, which control both the inflammatory and osteolytic processes,” Godoy-Santos said. Some researchers have hypothesized that bone reabsorption by those inflammatory processes plays a large role in aseptic loosening.

Fibroblast-type collagenase is a widely expressed matrix metalloprotease (MMP) and is important in collagen degradation and therefore bone reabsorption. Researchers believe that gene polymorphisms — or slight variations in genetic expression — of MMPs may be a predictor of aseptic loosening of joint arthroplasty.

Varied protein expression

“The study of genetic factors that alter expression of these biologic components and its association with failure of osseous integration becomes substantially important,” Godoy-Santos said. “Polymorphisms in inflammatory mediator genes, such as metalloproteases, can alter protein expression and have been associated with several pathologies.”

Previous research on dental prostheses found that patients bearing the 2G allele of the MMP-1 gene were three times more likely to lose the implant than those without that allele. According to Godoy-Santos, “[this] can indicate an influence of genetic polymorphism in osseous integration failure.”

With these results and hypotheses in mind, researchers at Sao Paolo University and Campinas University have begun a study examining the effects of MMP polymorphisms on aseptic loosening. The study will consist of two sets of patients. One group will be composed of patients who suffered aseptic loosening in their hip or knee implant, and the other group will have patients with at least five years of follow-up after hip or knee replacement and no signs of loosening.

The role of MMP

Researchers hope that comparing the genetic makeup of these sets of patients will give insight into the role of MMP on arthroplasty failure.

“We believe that finding several genetic markers related to arthroplasty could be of great clinical value to a precise and early identification of individuals at high risk for implant loss,” Godoy-Santos said. “It will lead to a more strict selection of patients and, in the future, individual therapies could be developed to increase the success rates of arthroplasty.”