Mitchell S. Fourman M.Phil Eugene Borst BS Eric Bogner, MD S. Robert Rozbruch MD Austin T. Fragomen, MD

Transcription

1 Post-Operative CT Measurements Accurately Predict the Need for Clinical Intervention Retrospective Findings to Support Prospective Clinical Trial Protocol Mitchell S. Fourman M.Phil Eugene Borst BS Eric Bogner, MD S. Robert Rozbruch MD Austin T. Fragomen, MD Institute for Limb Lengthening and Complex Reconstruction Hospital for Special Surgery, New York NY

2 Introduction rhbmp-2 (Infuse, Medtronic) continues to be a hot topic in bone healing Only FDA indications for rhbmp-2 are spinal fusions and tibial fractures Off-label use frequent in a myriad of fields Lack of quantitative findings and RCT results prevents expansion of FDA approval

3 BMP-2 Mechanism Vascular Endothelial Growth Factor Migration BMP-2 Osteoblast Differentiation Fibroblast Growth Factor-2

4 BMP-2 Clinical Benefits Increased Healing Rate Increased Bone Quality Tibial Fx Fewer Hardware Failures Ankle Fusions Increased Fusions in Complex Patients Garrison, K.R., et al., Bone morphogenetic protein (BMP) for fracture healing in adults. Cochrane Database Syst Rev, 2010(6): p. CD

5 Prior Work Retrospective analysis of 82 ankle fusions performed by a single surgeon from with INFUSE as graft material or adjunct 40 without INFUSE treatment Patient groups separated into acute vs. gradual ankle fusions, and those who required simultaneous lengthening Statistical analysis performed between groups and pertinent comorbidities Primary Outcome: Fusion Success (%) Secondary Outcome: Total time in frame (days)

6 Successful Initial Unions BMP-2 = 92.9% Non BMP-2 = 52.5% Successful End Unions BMP-2 = 95.2% Non BMP-2 = 82.5%

7 Limitations to our Findings Retrospective study Clinical decision making vs. increased surgeon experience Removal of frame does not signify union but rather a projection of healed outcome based on prior patients with similar findings Prospective trial necessary to justify retrospective findings

8 Specific Aims AIM 1 Attempt to quantify rhbmp-2 effectiveness with quantitative CT-readings AIM 2 Establish quantitative CT cut-offs suggestive of ankle fusion success AIM 3 Compose a clinical trial criteria composed of qualitative and quantitative factors to illustrate the effects of rhbmp-2 on ankle fusion outcomes

9 Methodology CT Readings performed 3 months post-fusion using criteria previously defined by Jones et al [1] 1 mm incremental sagittal cuts throughout tibiotalar joint Quantitative area of bone as percentage of total joint space Patient groups stratified based on co-morbidity, time in frame, and fusion success 1. Jones, C.P., M.J. Coughlin, and P.S. Shurnas, Prospective CT scan evaluation of hindfoot nonunions treated with revision surgery and low-intensity ultrasound stimulation. Foot Ankle Int, (4): p

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11 Joint Space Bone Bridging Percentage Fusion = Total Joint Bridging Total Joint Space

12 35.9 mm Joint Space Measurement = 35.9 mm

13 0.7 mm 0.8 mm 0.3 mm 2.1 mm 1.5 mm 1.2 mm 3.8 mm 2.7 mm Total Bone Bridging = 13.1 mm

14 36.5 % Fusion

15 52.7 % Fusion

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17 42.4 mm Joint Space Measurement = 42.4 mm

18 1.1 mm 1.8 mm 5.6 mm 18.3 mm 9 mm Total Bone Bridging = 35.8 mm

19 84.4 % Fusion

20 Results BMP-2 Fusion (%) Non BMP-2 Fusion (%) P-value ± 4.18 (n = 26) ± 5.9 (n = 10) <.05 - Diabetics, Smokers, and Obese patients excluded - Average ossification of TT joint in TTC vs. only TT fusions equivalent (p >.05) - Patients who had frame removal + good fusion within 100 days of surgery averaged ± 6.88% fusion at 3 months - 1 of 3 patients with < 30% fusion required stimulation drilling - The only patient with < 10% healing required regrafting

21 Clinical Trial CT Criteria Healing > 50% = Remove frame within 1 month Healing 20-50% = Remove frame in 2-3 months Healing 10-20% = Bone stimulation drilling, consider percutaneous bone grafting Healing < 10% = Open bone grafting and re-assess CT in 3 months

22 Prospective Trial Elements Pilot trial to include 60 patients Physician-blinded via pre-operative randomization Collagen sponges placed into all patients, treated with rhbmp-2 vs. Ringer s Lactate Frame removal dictated by CT criteria based on 3 month studies Outcomes Primary Outcome: Initial + Final Fusion Success Secondary Outcome 1: Time in Frame Secondary Outcome 2: Functional Outcome Surveys Secondary Outcome 3: Cost vs. Benefit Analysis