The Impact of Patient Age on Foot and Ankle Arthrodesis Supplemented with Autograft or an Autograft Alternative (rhPDGF-BB/ß-TCP).

A recent survey of orthopaedic surgeons asking about risk factors for nonunion following foot and ankle arthrodesis revealed that patient age is considered to be a relatively low risk factor, despite the potential for autologous graft quality to deteriorate with increasing age. The purpose of the current study was to evaluate the impact of patient age and graft type on fusion rates following hindfoot and ankle arthrodesis. METHODS: In this study, we analyzed data from a previously published clinical trial, comparing fusion success in 397 subjects who underwent hindfoot or ankle arthrodesis (597 joints) supplemented with either autograft or an osteoinductive autograft alternative, recombinant human platelet-derived growth factor-BB homodimer carried in beta-tricalcium phosphate (rhPDGF-BB/ß-TCP). The odds of fusion success were compared among subjects older or younger than age thresholds of 55, 60, 65, 70, and 75 years. The odds of fusion success were also compared between autograft and rhPDGF-BB/ß-TCP among subjects older than each age threshold. RESULTS: In the autograft group, the joints of subjects who were younger than the age thresholds of 60 and 65 years had >2 times the odds of successful fusion compared with those of older subjects. There was no significant difference in the odds of fusion success between the older and younger subjects at the age threshold of 55 years. In the rhPDGF-BB/ß-TCP group, there was no significant difference in the odds of successful fusion between older and younger subjects at any age threshold. When the odds of fusion success were compared between the 2 graft materials in subjects who were older than each age threshold, rhPDGF-BB/ß-TCP had approximately 2 times the odds of fusion success compared with autograft for all thresholds, except 55 years. CONCLUSIONS: The presented evidence suggests that age is an identifiable and concerning risk factor for hindfoot and ankle arthrodesis nonunion, a finding in contrast to the wider perception in the surgeon community. Notably, patients ≥60 years of age had significantly lower odds of fusion success with the use of autograft. The data reveal that use of rhPDGF-BB/ß-TCP as an alternative bone-healing adjunct may help mitigate the risk of nonunion when these procedures are performed in the elderly population. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Long-term Autograft Harvest Site Pain After Ankle and Hindfoot Arthrodesis.

BACKGROUND: Pain following autograft harvest has been studied; however, published literature has typically focused on the iliac crest with follow-up limited to only a few years. It remains unknown if pain continues or improves over time. The purpose of this study was to evaluate long-term pain associated with autograft harvest to supplement hindfoot or ankle arthrodesis. METHODS: Subjects in the control arm of a previously conducted trial comparing autograft with a synthetic bone graft for hindfoot or ankle arthrodesis were invited back for a single visit at a minimum of 5 years following their initial surgery. Harvest site, fusion site, and weight-bearing pain were evaluated using a 100-point visual analog scale (VAS). Of the 130 invited subjects, 60 (46.1%) returned for assessment, 58 of whom completed pain assessments. RESULTS: At a mean follow-up of 9.0 years (range, 7.8-10.5), more than a third (36.6%) of subjects had some level of harvest site pain. Using VAS greater than 20 mm as a threshold of clinical significance, pain remained clinically significant in 5.2% of subjects. There was a significant correlation between harvest site pain and both weight-bearing and fusion site pain. There was not a significant correlation between harvest site pain and volume of graft harvested. CONCLUSION: Autograft harvest can result in chronic, clinically significant pain that can last up to 10 years. In the era of shared decision making, this information will help surgeons and patients quantify the risks of chronic pain after arthrodesis procedures that include a secondary operative incision for graft harvest. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Recombinant Human Platelet-Derived Growth Factor BB in Combination With a Beta-Tricalcium Phosphate (rhPDGF-BB/ß-TCP)-Collagen Matrix as an Alternative to Autograft.

BACKGROUND: Joint arthrodesis often employs autograft to promote union; graft harvesting can lead to perioperative morbidity. A Canadian randomized controlled trial (RCT) demonstrated that recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) combined with beta-tricalcium phosphate (ß-TCP)-collagen was a safe, effective alternative to autograft. This multicenter North American RCT compared the safety and efficacy of rhPDGF-BB/ß-TCP-collagen with autograft for ankle and hindfoot fusion. Subclassification using propensity scores (PS) incorporated patients from previous trials for enhanced statistical power for noninferiority testing and broader review of treatments. METHODS: Patients requiring ankle or hindfoot arthrodesis and supplemental bone graft were treated with rhPDGF-BB/ß-TCP-collagen (n = 69) or autograft (n = 35). Outcomes included joint fusion on computed tomography (24 weeks), clinical healing status, visual analog scale (VAS) pain, Short-Form 12 (SF-12), American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Foot Function Index (FFI) scores over 52 weeks. PS methodology addressed potential selection bias arising from pooling data among these patients and 2 previous RCTs with similar inclusion criteria, surgical techniques, graft harvest techniques, and outcomes. All 132 rhPDGF-BB/ß-TCP-collagen-treated patients and 167 of 189 candidate autograft-treated controls were selected for comparison by an independent statistician blinded to outcomes. RESULTS: In the PS subclassification, 68.1% treatment patients and 68.4% controls achieved >50% osseous bridging at fusion sites. Clinical healing status was achieved in 84.8% of treated patients and 90.7% of controls at 52 weeks. Clinical, functional, and quality of life results demonstrated noninferiority of rhPDGF-BB/ß-TCP-collagen to autograft. Safety-related outcomes were equivalent. CONCLUSION: PS subclassification analysis of 3 RCTs demonstrated that rhPDGF-BB/ß-TCP-collagen was as effective as autograft for ankle and hindfoot fusions, with less pain and morbidity than treatment with autograft. LEVEL OF EVIDENCE: Level I, prospective randomized study.

Prospective Randomized Controlled Trial of Hindfoot and Ankle Fusions Treated With rhPDGF-BB in Combination With a ß-TCP-Collagen Matrix.

BACKGROUND: Ankle and hindfoot arthrodesis is often supplemented with autograft to promote bony union. Autograft harvest can lead to increased perioperative morbidity. Purified recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) has stimulated bone formation in mandibular defects and hindfoot fusion. This randomized controlled trial evaluated the efficacy and safety of rhPDGF-BB combined with an injectable, osteoconductive beta-tricalcium phosphate (ß-TCP)-collagen matrix versus autograft in ankle and hindfoot fusions. METHODS: Seventy-five patients requiring ankle or hindfoot fusion were randomized 5:1 for rhPDGF-BB/ß-TCP-collagen (treatment, n = 63) or autograft (control, n = 12). Prospective analysis included 142 autograft control subjects from another clinical trial with identical study protocols. Standardized operative and postoperative protocols were used. Patients underwent standard internal fixation augmented with autograft or 0.3 mg/mL rhPDGF-BB/ß-TCP-collagen. Radiologic, clinical, and quality-of-life outcomes were assessed over 52 weeks. Primary outcome was joint fusion (50% or more osseous bridging on computed tomography) at 24 weeks. Secondary outcomes included radiographs, clinical healing status, visual analog scale pain score, American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale score, Foot Function Index score, and Short Form-12 score. Noninferiority P values were calculated. RESULTS: Complete fusion of all involved joints at 24 weeks as indicated by computed tomography was achieved in 53 of 63 (84%) rhPDGF-BB/ß-TCP-collagen-treated patients and 100 of 154 (65%) autograft-treated patients (P < .001). Mean time to fusion was 14.3 ± 8.9 weeks for rhPDGF-BB/ß-TCP-collagen patients versus 19.7 ± 11.5 weeks for autograft patients (P < .01). Clinical success at 52 weeks was achieved in 57 of 63 (91%) rhPDGF-BB/ß-TCP-collagen patients and 120 of 154 (78%) autograft patients (P < .001). Safety-related outcomes were equivalent. Autograft controls had 2 bone graft harvest infections. CONCLUSIONS: Application of rhPDGF-BB/ß-TCP-collagen was a safe, effective alternative to autograft for ankle and hindfoot fusions, eliminating the pain and morbidity associated with autograft harvesting. LEVEL OF EVIDENCE: Level I, prospective randomized study.