Editor’s note: The following content was published in the AAOS Now Special Edition and distributed in June 2020. The content was originally scheduled for the AAOS Now Daily Edition, which publishes each year onsite at the AAOS Annual Meeting but this year’s meeting in March was canceled due to COVID-19. Despite the cancellation, members can access virtual content from the Annual Meeting by visiting the Academy’s Annual Meeting Virtual Experience webpage.

A study presented as part of the Annual Meeting Virtual Experience indicates that age is an identifiable and concerning risk factor for hindfoot or ankle arthrodesis nonunion, a finding the authors say is “in contrast to wider perception of the surgeon community.” Specifically, the study found that patients older than 60 years have statistically lower odds of fusion success with the use of autograft. The data reveal that use of recombinant human protein-derived growth factor (rhPDGF-BB/β-TCP) as an alternative bone-healing adjunct may help mitigate the risk of nonunion when these procedures are performed in the older population.

The study, presented by Gregory C. Berlet, MD, FRCS(C), of the Orthopedic Foot and Ankle Center in Worthington, Ohio, analyzed data from the largest level 1 clinical trial ever conducted in hindfoot and ankle arthrodesis.

That study compared fusion success in 397 hindfoot or ankle arthrodesis patients (597 joints) supplemented with either autograft or osteoinductive rhPDGF-BB/β-TCP bone graft. The odds of fusion success were compared in patients older or younger than age thresholds of 55, 60, 65, 70, and 75 years. Odds of fusion success were also compared for autograft and rhPDGF-BB/β-TCP for patients older than each threshold.

“Hindfoot and ankle arthrodesis nonunion rates have remained stubbornly high despite advances in surgical techniques and internal fixation,” Dr. Berlet told AAOS Now. “This persistent healing challenge suggests that patient factors play a substantial role in outcomes. Several factors, like smoking and diabetes, have been examined closely in previously published literature, but few have looked at the impact of age and graft material on fusion success.”

Dr. Berlet and colleagues suspected that age and graft material may have a significant impact on nonunion rates because bone healing is highly dependent on mesenchymal stem cells and their ability to differentiate into osteoblasts. Several studies, Dr. Berlet noted, have shown that these cells, when taken from older patients, exhibit decreased osteogenic potential and migration capacity. “This suggests that the quality and effectiveness of autologous bone, one of the most common grafting materials, would be highly dependent on the age of the donor patient.”

The primary endpoint for this analysis was the odds of arthrodesis success based on CT analysis at 24 weeks after operation. Arthrodesis success was defined as evidence of at least 50 percent osseous bridging.

As previously noted, the analysis found that autograft may have negative age-related variability when used to supplement hindfoot and ankle fusions. Specifically, patients younger than 60 years had twice the odds of successful fusion as those older than 60 years when treated with autograft (Figs. 1 and 2).

“We then wanted to get a sense if the difference was caused by the decreased potential of the body to heal as we age or if it was the quality of the donor bone,” Dr. Berlet explained. “We looked at arthrodesis patients who received an alternative to autograft, rhPDGF-BB/β-TCP.” They found that the odds of fusion success were not statistically different for patients receiving the alternative to autograft whether they were younger or older than 60 years.

The investigators then compared patients older than 60 years receiving either autograft or the recombinant human platelet-derived growth factor. “These older patients who received the recombinant human platelet-derived growth factor had nearly twice the odds of successful fusion as those receiving autograft,” Dr. Berlet said. “This suggests that there is a negative age-related variability of autologous bone quality and that an alternative to autograft, recombinant human platelet-derived growth factor used in this study, may help to mitigate this variability.”

He said the lack of difference in the odds of fusion success with the use of recombinant human platelet-derived growth factor was a surprising factor. “We did not know the strong negative influence of age prior to this study,” he said.

In terms of future research, Dr. Berlet noted that manifestations of aging are expressed throughout the body, including the biologic activity of the osteoprogenitor cells found in bone graft. “Risk mitigation of the age effect using stimulative proteins—in this case, PDGF—appears to be an innovative way to help patients heal with their index surgery,” he said. “Further studies may explore other geographic areas of healing and whether this age effect is also expressed.”

Addressing limitations of the analysis, Dr. Berlet noted that despite being a large, multicenter, randomized, controlled trial, the study that was analyzed was not designed for the ad-hoc analysis. Therefore, there were lower numbers of joints available for analysis at the oldest age thresholds (70 and 75 years).

Many studies use radiographs as their measure of bone healing. “X-rays are inaccurate, and CT studies are much higher quality with more reliable information,” Dr. Berlet said. “Thus, comparing these data, using modern CT techniques, to historical research, often incorporating plain radiograph assessment, may lead to inaccuracies in comparative analysis.”

The original clinical trial providing data for this analysis was funded by Biomimetics Therapeutics Inc., which is now owned by Wright Medical Group, N.V.

Dr. Berlet’s coauthors of Paper 179, “Impact of Patient Age and Graft Type on Fusion Following Ankle and Hindfoot Arthrodesis,” are Judith F. Baumhauer, MD, MPH; Mark Glazebrook, MSc, PhD, MD, FRCSC; Alastair Younger, MD, FRCSC; W. Hodges Davis, MD; Jovelyn D. Quiton, MSc; David A. Fitch, PhD; Timothy R. Daniels, MD, FRCSC; and Christopher W. DiGiovanni, MD.

Terry Stanton is the senior medical writer for AAOS Now. He can be reached at tstanton@aaos.org.