Bone grafting procedures are frequently performed in orthopedic surgery, with more than 500,000 bone grafting procedures performed each year in the United States alone . Historically, autogenous bone graft has been considered the “gold standard”, and typically has been discussed as graft taken from the iliac crest. This has been described in spine surgery [23,24] and also specifically evaluated in foot and ankle surgery [25-27]. However, because of complications associated with the harvest of the autogenous graft, alternatives to the iliac crest have proliferated [28-30]. This has led to development of over 200 different commercially available bone graft substitutes, some of which can be very expensive and most with little or no high level evidence to support their use . Research continues to find the ideal autogenous bone graft alternative. Ideally, this will be something that is effective, safe, readily available, non-morbid and relatively inexpensive.
An article by Roh et al., in 2013 was published comparing recombinant human BMP (rhBMP-2, Infuse, Medtronic Inc., Fridley, MN, USA) to AMP (OsteoAMP) in lumbar interbody fusion procedures . This was a multicenter study comparing the fusion rate of the two products, as well as the cost associated with them. A total of 321 consecutive patients were evaluated over 5 years, 95 in the BMP group and 226 in the AMP group. The study reported universally favorable findings of AMP versus BMP, including time to fusion, percentage fusion, and complications. In addition, the AMP group also reported approximately 80% lower costs as well (about $650 for AMP vs $2500 for BMP). Several concerns are raised about the article. Statistical analysis of the findings between the groups was not consistently reported, and there was a potential commercial bias . Even with these limitations, the results were impressive and lead to the current investigation.
The AMP used in this investigation not only has favorable clinical studies [18-20], but internal data and analysis also compares favorably to competing products. It shows high levels of BMP-2, BMP-7, and TGF-β1, and others in the sponge product . In addition to the clinical and laboratory data, the product is also practical and versatile in the surgical setting and has excellent handling abilities. It is available in a compressible sponge, and has higher concentrations of BMP-2 than another commercially available compressible sponge product (Bacterin Osteosponge; Bacterin International Holdings, Inc., Belgrade, MT, USA) . The authors in the present study utilized the putty or the granule forms and mixed with BMA in 50% of the cases. Bone marrow aspirate can quickly, easily, and safely be harvested from lower extremity sites, and although there are fewer colony-forming units in lower extremity sites compared to the iliac crest, only a minimal concentration of cells may be needed to achieve clinical fusion [33-35].
High risk foot and ankle fusions are often augmented with some biologic adjunct. Two options that have been recommended are recombinant human BMP and MSC. After extensive study in long bone fractures, segmental defects, and nonunions, recombinant human BMP was explicitly studied in the foot and ankle. A study published in 2009 by Schuberth et al., performed a multicenter evaluation of recombinant human BMP in foot and ankle surgery. Overall, out of 38 procedures in 35 patients, the incidence of successful healing was 84.2% (32 procedures), and multiple statistical analyses teased out predictors of success . Another study in 2009 evaluated 69 patients, but broke the results down to 112 fusion sites augmented with recombinant human BMP. The authors reported a 96% fusion rate (108 sites), and this was confirmed with CT scan. The patient population consisted of 64% smokers, 19% diabetic patients, 68% high energy trauma, and 22% Avascular Necrosis (AVN) of the talus. In addition to the excellent fusion rate, low complication rates were reported as well . DeVries et al., in contrast reported a 69.6% (16 of 23 patients) rate of arthrodesis for revision nonunion cases treated with intramedullary tibiotalocalcaneal nail. No clear benefit was demonstrated with the addition of recombinant human BMP, although again no specific adverse effects of the BMP were seen .
Similarly, evaluation of MSCs has been undertaken in the foot and ankle. Rush et al., published several studies looking into the use of MSCs, including a retrospective review of 23 patients in 2009. Here the authors found an overall union rate of 91.3% (21 patients), and observed new bone formation in all patients at the level of implantation. No graft specific complications were found . Scott and Hyer also evaluated this graft in 20 patients in 2013. All patients were undergoing primary arthrodesis, but were classified as “high-risk” based on smoking status, high Body Mass Index (BMI), or presences of diabetes. The authors presented a 90% (18 patients) union rate, with 2 patients resulting in nonunion that required additional surgery. Again, no graft specific complications were noted .
The current study demonstrates that AMP compares very well to both BMP and MSC. There was successful arthrodesis in 90% (9 out of 10) patients, and this included 95.7% (22 out of 23) total arthrodesis sites. The graft also demonstrated new bone formation in these patients (Figure 4). This included “high-risk” patients including revision surgery, diabetics, advanced age, and smokers. AMP has some notable advantages over these other adjuncts. Recombinant human BMP (Infuse) is indicated for spinal fusion and open tibia fractures, and is not specifically intended for use in the foot and ankle, and has been reported to have some adverse events in the spine and an increase in cancer incidence of 1.8-3% . It also has poor handling characteristics and does not provide any space-filling properties. The viable cells in MSC are a benefit, but also have drawbacks. The product must be stored in a freezer at -70?C to -80?C and has a shelf life of 3 months. Careful thawing of the product has to be undertaken to ensure cell viability, and must be used within 2 hours of thawing . The AMP product provides high levels of BMP-2 as well as a variety of other growth factors. It provides a scaffold and space-filling properties, and when mixed with autogenous BMA can provide all three properties of bone healing. It is freeze dried and can be stored at room temperature for 5 years. Finally, the AMP used in this study (OsteoAMP) is substantially less expensive than other products at the authors institution. A package of 5 cc granules is priced at $1755.00, compared to medium Infuse® priced at $4893.00 and 5 cc of Trinity Evolution (Orthofix, Verona, Italy) priced at $2259.00. Although a cost comparative analysis is beyond the scope of this paper, cost advantages were cited in spine literature .Figure 4:
New bone growth is demonstrated in patient 7. AP image two weeks post-operative (A) shows open joints at the 1st tarsometatarsal and medial naviculocuneiform. AP image at 48 days post-operative (B) shows solid arthrodesis at those joints. AP image at 139 days post-operative (C) demonstrates new bone growth at the 1st interspace between the 1st and 2nd metatarsal base.