August 2017

Early warnings: Data support aggressive intervention #611076268

By Jordana Bieze Foster

Osteoarthritis (OA) is commonly thought of as a disease that takes decades to manifest. But two new studies suggest some critical aspects of the ankle OA disease process actually develop quite quickly, emphasizing the importance of early intervention.

Both studies were presented in July at the annual meeting of the American Orthopaedic Foot & Ankle Society (AOFAS), held in Seattle. Both studies were also finalists for the society’s Leonard J. Goldner Award for the best basic science paper.

Open reduction and internal fixation of intra-articular ankle fractures is typically performed within 10 to 14 days of injury. But in a study of 54 patients with an intra-articular ankle fracture, investigators from the Duke University School of Medicine in Durham, NC, found synovial biomarkers for cartilage breakdown are evident as early as three days after injury.

Synovial fluid samples were analyzed at three time points corresponding to stages in the clinical process after an ankle fracture: zero to two (typical time frame for emergency department [ED] presentation), three to nine days (clinic presentation), and 10+ days (definitive fixation).

Mediators and products of cartilage catabolism—including matrix metalloproteinases (MMPs) 1, 2, 3, and 10, and C-telopeptide fragments of type II collagen—were evident between three and nine days and persisted thereafter. In a 2015 study, the same group found significantly higher concentrations of the same MMPs in patients 17 days after ankle fracture, compared with controls.

“It turns out that time from fracture does matter,” said Samuel B. Adams, MD, an assistant professor of orthopedic surgery at Duke, who presented the findings. “There is definite evidence of cartilage destruction by day ten, and it’s probably starting to happen much earlier. Ten days is probably too long to wait for surgery to intervene.”

Intervention to slow or prevent cartilage breakdown—and the eventual development of ankle OA—could involve administration of MMP blockers, possibly when the patient presents to the ED, Adams said.

A second study presented at the AOFAS meeting served as a reminder that synovial markers of pathology remain a concern even after total ankle arthroplasty, and that, again, early intervention may be warranted.

Investigators from the University of Chicago analyzed 57 patients who had developed
osteolysis a mean of six years after undergoing total ankle arthroplasty with a fixed bearing polyethylene implant, and found histological evidence of implant wear particles in nearly all.

Macrophages, which are associated with very small (less than 1 µm in diameter) implant wear particles and have been reported to be the primary driver of osteolysis in the hip and knee arthroplasty literature, were present in 96.5% of samples analyzed. Giant cells, which are associ­ated with larger implant wear particles (3-5 µm), were found in 49% of specimens.

The findings suggest implant wear should be considered seriously as a cause of osteolysis after total ankle arthroplasty, said Oliver N. Schipper, MD, now a member of the Anderson Orthopedic Clinic in Northern Virginia, who presented the findings at the AOFAS meeting.

Of particular concern, Schip­­per said, is that 12% of patients in the current study required a revision arthroplasty or bone grafting due to osteolysis within just two years of their initial arthroplasty procedure.

“Osteolysis is real, it happens early, and until we address it, it’s going to be hard for total ankle arthroplasty to reach the levels of effectiveness we’ve seen in the hip and knee,” he said.

Ensuring that the ankle is well balanced during the initial arthroplasty procedure may help reduce implant wear, Schipper said, and researchers are currently investigating whether the newer cross-linked polyethylene implants are associated with lower rates of osteolysis than
devices made of conventional polyethylene.


Adams S, Reilly R, Huebner J, et al. Synovial fluid composition of inflammatory cytokines, matrix metalloproteinases, and cartilage breakdown products are dependent on time after intra-articular ankle fracture. Presented at the American Orthopaedic Foot & Ankle Society Annual Meeting, Seattle, WA, July 2017.

Adams SB, Setton LA, Bell RD, et al. Inflammatory cytokines and matrix metalloproteinases in the synovial fluid after intra-articular ankle fracture. Foot Ankle Int 2015;36(11):1264-1271.

Schipper O, Haddad S. Histological analysis of early osteolysis in total ankle arthroplasty. Presented at the American Orthopaedic Foot & Ankle Society Annual Meeting, Seattle, WA, July 2017.

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