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Age Appears to Be a Risk Factor for Nonunion Following Foot or Ankle Arthrodesis Surgery

Key findings

  • This study specifically analyzed the outcomes of various population subsets from a prospective, randomized trial in which 397 adults had hindfoot or ankle arthrodesis supplemented with either an autologous bone graft or rhPDGF-BB/β-TCP
  • In the autograft group, younger adults (age 18-59) had significantly higher odds of fusion compared to adults 60-64 years (OR, 2.24) or 65-69 years (OR, 2.74). Similar trends were noted for adults over 70 years, although these did not reach significance
  • In contradistinction, when standardized recombinant growth factor technology (rhPDGF-BB/β-TCP) was used as an alternative to autograft, the odds of fusion were found to be similar across all groups, for both older and younger subjects
  • The odds of a fusion were significantly higher for rhPDGF-BB/β-TCP groups than autograft groups in patients ≥60 years (OR, 1.87) and patients ≥65 (OR, 2.03). Similar differences (although nonsignificant) were noted for patients aged 70+
  • This data suggests that, as patients age, the bioactivity of their own host bone may diminish, and thus not be as productive in facilitating healing when compared with alternative adjuvant recombinant technologies that maintain more bioactivity

In a recent international survey of 100 foot and ankle surgeons published in the Journal of Orthopaedic Surgery, patient age, when greater than 60 years, was perceived as a less important risk factor for nonunion after foot or ankle arthrodesis compared with comorbidities such as smoking, poor vascularity and diabetes.

However, following subset data analysis from an international, randomized, controlled, prospective, multi-center trial, Christopher W. DiGiovanni, MD, professor, vice chair and chief of Foot & Ankle Surgery in the Foot and Ankle Center at Massachusetts General Hospital, and research colleagues have determined that patients older than 60 years may be more than twice as likely as younger adults to develop nonunion following foot or ankle fusion surgery when augmented by autologous graft supplementation. They published their findings in JBJS Open Access.

The Previous Trial

The prospective, randomized controlled trial, published in The Journal of Bone & Joint Surgery, was conducted at 37 centers in the U.S. and Canada, including Mass General. 397 adults (597 joints) underwent hindfoot or ankle open arthrodesis because of arthritis.

Patients were randomly assigned 2:1 to have the surgery supplemented with either an autologous bone graft or recombinant human platelet-derived growth factor–BB homodimer carried in β-tricalcium phosphate (rhPDGF-BB/β-TCP). All other surgical techniques were identical. Gender and average age were similar in the two treatment groups.

For the current analysis, the primary outcome was the odds of fusion, defined as CT evidence of ≥50% osseous bridging, at 24 weeks postoperatively. CT scans were judged by an independent reviewer.

Comparison by Age


  • Age threshold 60—Fusion occurred in 72% of the younger group vs. 53% of the older group (OR, 2.24; P=0.003)
  • Age threshold 65—72% vs. 48% (OR, 2.74; P<0.001)
  • Age threshold 70—65% vs. 53% (OR, 1.64; P=NS)
  • Age threshold 75—63% vs. 57% (OR, 1.28; P=NS)


  • No significant differences between age groups in the odds of fusion

Comparison by Material Used

  • Age ≥60—Fusion occurred in 68% of the rhPDGF-BB/β-TCP group vs. 59% of the autograft group (OR, 1.87; P=0.007)
  • Age ≥65—65% vs. 48% (OR, 2.03; P<0.008)
  • Age ≥70—68% vs. 53% (OR, 1.87; P=NS)
  • Age ≥75—73% vs. 57% (OR, 2.06; P=NS)

The Need for More Individualized Management

Whenever bone is injured or triggers a healing event, one key component of the healing cascade is the attraction of mesenchymal stem cells (MSCs) to the injury site. These cells then multiply and differentiate into osteoblasts or scavenger cells to help shepherd the healing process. Recent laboratory research, however, seems to suggest that not all MSCs maintain equal healing potential, and that those collected from older patients may exhibit decreased osteogenic potential and migration capacity by virtue of "age."

This study suggests that for older (≥60 years) in need of foot or ankle arthrodesis, consideration should be given to using alternative recombinant bone healing supplementation adjuncts to the surgical site in lieu of historical host bone graft harvest to promote osteoinduction. The addition of novel recombinant orthobiological technologies such as rhPDGF-BB/β-TCP, now FDA approved for such indications, seem to dampen the negative impact of aging on bone healing.

greater odds of fusion after foot or ankle arthrodesis supplemented with an autograft in patients <60 years than in those ≥60 years
greater odds of fusion after foot or ankle arthrodesis supplemented with an autograft in patients <65 than in those ≥65 years
greater odds of fusion in patients ≥60 years who had foot or ankle arthrodesis supplemented with rhPDGF-BB/β-TCP than in those who received an autograft

greater odds of fusion in patients ≥65 years who had foot or ankle arthrodesis supplemented with rhPDGF-BB/β-TCP than in those who received an autograft

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