Xenograf Versus Allograft
Xenograf Versus Allograft
Xenograf Versus Allograft
a, b
Naohiro Shibuya, DPM, MS *, Daniel C. Jupiter, PhD
KEYWORDS
Bone Autogenous graft Foot Ankle Incorporation Union
KEY POINTS
Structural integrity and fast incorporation are essential to foot and ankle surgery because
of the importance of early weight-bearing and rehabilitation.
Both allografts and xenografts eliminate donor site complications, but osteogenicity and
osteoinductivity can be sacrificed.
Even though allogenic bone grafts theoretically possess lower healing potential than
autogenous grafts, clinical outcomes may not differ.
A bovine-based xenograft may not be ideal in foot and ankle surgeries.
Retrospective reviews of surgical cases using bone grafts can be subject to selection bias;
well-controlled prospective studies are necessary to understand the effectiveness and
safety of each graft type.
INTRODUCTION
Fast incorporation of bone grafts to achieve structural rigidity is essential in most foot
and ankle surgeries, because early range of motion, exercise, and weight-bearing are
the keys to a successful rehabilitation process. Structural and nonstructural bone
grafts have been utilized in reconstructive foot and ankle surgeries for many years.1–4
They can add length, height, and volume to the skeletal structure of the foot or ankle to
alter alignment, function, and appearance (Fig. 1).
There are several different types of bone grafts utilized in foot and ankle surgeries
where structural rigidity is necessary. These include corticocancellous autografts, al-
lografts, xenografts, and synthetic bone grafts. An autogenic bone graft is ideal in
many situations because it is harvested from the patient himself or herself. It is thus
less likely to be rejected and more likely to be incorporated than allografts or
Disclosures: None.
a
Section of Podiatry, Department of Surgery, Texas A&M University Health Science Center, Col-
lege of Medicine, Central Texas Health Care System, Baylor Scott and White Health Care Sys-
tem, Temple, TX, USA; b Preventive Medicine and Community Health, University of Texas
Medical Branch, Galveston, TX, USA
* Corresponding author. 5112 Wildflower Lane, Temple, TX 76502.
E-mail address: shibuya@medicine.tamhsc.edu
Fig. 1. (A) To correct pes planovalgus deformity in this pediatric patient, lateral column
lengthening and medial column plantarflexory opening wedge osteotomies were utilized.
A structural freeze-dried allogenic calcaneal graft was used to maintain the correction.
(B) To restore the hindfoot height in this patient with neglected calcaneal fracture, a
fresh-frozen femoral head allograft was utilized. (C) Autograft harvested from the resected
tibial plafond was packed into the subchondral cysts before implantation.
xenografts. It also has both osteogenic and inductive properties that can assist bone
healing. However, harvesting an autograft adds an extra procedure to the reconstruc-
tive surgery, and donor site complication is common.5–9 In addition, in patients who
have multiple comorbidities, harvesting the compromised bone does not lend any
Bone Graft Substitute 23
bone healing potential to the operative osteotomy and fusion sites. Further, an auto-
graft needs to have intact cortices to ensure structural rigidity.
Other forms of bone grafts, such as allografts, xenografts, and synthetic grafts, elimi-
nate the need for secondary procedures and obviate donor site complications. However,
rejection and slower incorporation can be disadvantages of the use of these grafts. In
well-vascularized bone, such as the calcaneus, it has been documented that there is
no difference in the complication rate at the osteotomy site between autograft and allo-
grafts.10,11 However, in less vascularized areas, incorporation can be difficult.12,13
OVERVIEW
Allogenic Bone Graft
Allografts are procured from humans and undergo vigorous sterilization processes
before they are ready for surgeons to use.14 They can be prepared using a combina-
tion of different processing procedures. Because of this diversity in processing proce-
dures, the properties of the allografts can vary widely. In general, allogenic bone grafts
can be classified into fresh, fresh-frozen, freeze dried, and demineralized types,
depending on the preparation process. Although a more vigorous sterilization process
can eliminate the chances of disease transmission and infection, it can also reduce
osteogenic and osteoinductive properties (Fig. 2). In general, fresher grafts are
more expensive and less readily available than other grafts that have a longer shelf life.
Although there are no general rules, fresh grafts are mostly used for osteochondral
repair, namely in the talus (Fig. 3) in foot and ankle applications. Because fresh grafts
possess more viable chondrocytes and greater subchondral structural support, they
are more suitable when both osseous and chondral structures need to be replaced
at the same time.15 Fresh-frozen allografts are often used in places where structural
rigidity is necessary (Fig. 4). Although they may not be as rigid as fresh grafts, they
are more easily obtainable by surgeons. The most abundant allografts, freeze-dried
grafts, are generally used in well-vascularized areas where the host can provide
enough native osteoinductive factors (Fig. 5). Although these grafts can be substituted
with fresher grafts, cost effectiveness is greater if freeze-dried grafts provide similar
outcomes. Demineralized allogenic grafts are commonly used to fill a void or a dead
space (Fig. 6). Many believe that demineralized allografts can also be used to enhance
bone healing in areas where bone healing is difficult, believing that these grafts provide
extra osteoinductive properties, but the evidence of this is scarce.16
Fig. 2. Fresh allograft possesses the best strength and osteogenicity; however, shelf life, cost
effectiveness, and availability are compromised.
24 Shibuya & Jupiter
Fig. 3. A fresh talar allograft is often used for osteochondral defect repair.
Xenograft
A xenograft comes from a nonhuman species. Therefore, antigenicity is significantly
greater than that of allografts. Naturally, it requires more sterile processing, which
can result in reduced osteoinductive properties. However, owing to the abundance
of donors, these grafts may be less expensive and more readily available. Also
because of the extensive sterilization processes, the shelf life is generally long. The
most common xenogenous bone graft used in orthopedic surgery is bovine based.
Clinical Studies
Allograft
Although autogenous bone graft is considered the gold standard, the efficacy of allo-
genic graft in foot and ankle surgeries has been shown to be adequate in many
Fig. 4. This patient underwent a revisional subtalar fusion for correction of decreased talar
declination. To maintain the correction under a tremendous amount of compression from
weight bearing and contracted soft tissues, a more rigid fresh-frozen allograft was used
instead of a freeze-dried allograft.
Bone Graft Substitute 25
Fig. 5. For this first metatarsal lengthening procedure in a healthy young female, a freeze-
dried allograft was used for the most cost-effective result. Because of the “Z” lengthening
technique utilized, there was still a good apposition of native bones, and the construct did
not have to rely greatly on graft incorporation for its short-term stability.
settings. Therefore, this may obviate the need for harvesting autogenic bone grafts in
many situations in foot and ankle surgery.
There are multiple case series utilizing allogenic bone graft in foot and ankle surgery
with no clinically significant complication rates, especially in a well-vascularized area of
Fig. 6. Demineralized allograft was injected via a syringe in this arthroscopic subtalar joint
arthrodesis to fill the void and space, mainly for good osteoconduction.
26 Shibuya & Jupiter
the foot. Further, many of the successes with allografts come in primary arthrodesis and
osteotomies. For example, John and colleagues17 found in their study of allografts used
in 53 anterior calcaneal osteotomies that allografts incorporated in a mean of 9.1 weeks
in adolescents and 9.8 weeks in adults. The incorporation rate was 100% in adoles-
cents and 90% in adults. Graft incorporation and bone union were defined as the radio-
graphic appearance of trabeculation across the host–graft interface.
Nowicki and colleagues18 found that, of 31 autografts used, the incorporation rate
was 90% with a mean incorporation time of 9.2 months. Thirteen grafts were used
for lateral column lengthening and 18 grafts were used for extra-articular subtalar
arthrodesis. It was noted that all 18 patients were pediatric patients who had an under-
lying neuromuscular disorder. Their definition of graft incorporation was no pain in the
affected foot, and trabecular bone from normal bone bridging the allograft bone on
both sides of the graft with no further trabecular bridging or changes on subsequent
follow-up radiographs. Philbin and colleagues19 in their retrospective review found
that graft incorporation of allograft, when used in lateral column lengthening proce-
dures, was at an average of 10.06 weeks with only 1 nonunion out of 28 feet. They
did not, however, define “graft incorporation.”
Although there are a vast number of case series with utilization of allograft in
different locations of the foot, most of the studies are noncomparative case studies.
Therefore, interpretation is difficult. There are few well-designed, comparative studies,
and the case series may be subject to publication bias. In particular, unfavorable out-
comes resulting from allograft application may be underrepresented. However, it may
be fair to note that good success with allograft use has been observed in area of good
healing potential, such as a calcaneus.
Table 1
Comparative studies evaluating efficacy of structural allograft versus autograft in foot
procedures mainly for lateral column lengthening procedures
demonstrated by cortical or trabecular bridging across both sides of the graft in the
absence of graft collapse, and clinical evidence of healing.
Grier and Walling23 compared allograft with platelet-rich plasma (PRP) versus auto-
graft. Again, no difference was detected between the groups in terms of union rate.
Similar results are found in other physiologic locations, specifically in hindfoot ar-
throdeses and osteotomies.24 Müller and colleagues24 discovered that equivalent
incorporation was seen in comparing allogenic and autogenous bone grafts as used
in hindfoot procedures. In their systematic review and meta-analysis, they evaluated
structural and nonstructural grafts separately. For the analysis of structural grafts
used in the hindfoot, they also included many of studies already mentioned, which
evaluated the effectiveness in lateral column lengthening procedures.
28 Shibuya & Jupiter
Xenograft
Bovine-based xenografts are suggested to provide structural integrity and ease of use
in reconstructive foot surgeries. However, to date, there are a limited number of
studies that evaluate the efficacy of the bovine-based bone xenograft.30–34 Schwarz
and colleagues35 showed poor incorporation of bovine-based xenograft in dog
jaws. Their histologic study compared bovine-based bone blocks with equine-
based bone blocks. Bovine-derived cancellous grafts showed no sign of biodegrada-
tion and were embedded in fibrous tissue in this animal model. New bone ingrowth
was also consistently lower in the bovine group than the equine group.
There are limited data on the characteristics of bovine-based bone graft incorpora-
tion in humans (Table 2). Bansal and colleagues31 evaluated incorporation of nonstruc-
tural bovine-based xenogenous bone granules in management of tibial plateau
fracture. The bovine-based xenograft they used was processed via osmotic treatment,
oxidative treatment, solvent dehydration, low-dose gamma irradiation, and delipidiza-
tion with acetone bathing and ultrasonic agitation. Their cohort consisted of 19 geriatric
patients greater than 60 years of age (mean, 74). The time to union ranged from 16 to
24 weeks with average bony collapse of 4 mm. All patients had good clinical and radio-
graphic outcomes. Bony union and incorporation were not defined.
Shibuya and colleagues33 evaluated the incorporation rate of another bovine-
based xenogenous bone graft product, processed via a different method (Bio-
Cleanse). Patients who had reconstructive foot surgery using this bovine-based
xenograft were identified, and the rate of radiographic incorporation of the grafts
was evaluated. A survival analysis was utilized to show the trend of incorporation
Table 2
Studies evaluating results of xenograft application in foot and ankle surgeries
of the xenografts over time. Of the 21 grafts observed for at least 12 weeks, none
showed radiographic graft incorporation by 12 weeks. The analogous numbers for
24, 36, and 48 weeks were 3 of 15 (20%), 4 of 13 (31%), and 3 of 11 (27%). A total
of 19 of the 31 studied grafts were never observed to have incorporated radio-
graphically over the entire length of the study (Fig. 7). A Kaplan–Meier estimate
of graft time revealed that median time to graft incorporation was 56 weeks.
Ledford and colleagues36 cautioned against use of bovine-based xenografts in foot
surgery. They reviewed 13 pediatric reconstructive cases with use of bovine-based
xenograft for correction of deformities. Of those 13 feet, they found 7 complications
associated with the xenogeneous bone graft. In their series, the mean follow-up
was 22 months and the patient mean age was 14 years.
Fig. 7. This 22-year-old man with no significant past medical history underwent Cotton
medial cuneiform plantarflexory osteotomy as a part of flatfoot reconstruction. The patient
continued to have deep, achy pain over 6 months after the surgery in the area of osteotomy.
It was determined to be caused by a nonunion of the xenogenous bone graft clinically and
radiographically. During the revision case, it was discovered that the graft was not incorpo-
rated at all.
Bone Graft Substitute 31
1.0 Auto/Allo
Xeno
0.6
0.4
0.2
0.0
0 50 100 150
Weeks
Fig. 8. Survival analysis, with “bone incorporation” as event of interest. The Kaplan–Meier
curve shows overall “time to event” trend, with starting time the day of surgery. Incomplete
and censored data included those with nonunion at data collection, those lost to follow-up
before bone incorporation, and those who underwent a revision procedure before union.
Vertical lines represent examination points at 12, 24, 36, and 48 weeks (n 5 61).
partial incorporation. Of the 11 patients who had xenogenous cancellous block, only 2
had integration. Osteointegration was determined by both plain radiographs and
computed tomography in this study. The particular bovine xenograft they used was
processed in the same way as the graft used in Bansal and colleagues’ study31 on
the tibial plateau fracture.
DISCUSSION
Even though bovine-based xenografts may possess some of the key features neces-
sary for foot and ankle surgeries, studies show that the graft incorporation may not be
adequate for the purpose of foot and ankle reconstructive surgery. Comparatively,
with the available literature, it seems that allograft outperforms xenograft in both union
rate and incorporation time. On the other hand, in comparing allograft and autograft,
there are multiple studies unable to show any difference in bone healing complications
or time to incorporation between these two treatments. This result was observed in
both pediatric and adult patients. When choosing structural bone graft materials in
foot and ankle surgery, these results should be considered to guide the choice of
the most cost-effective material to perform operative procedures.
However, these studies should be interpreted with caution. Many of the procedures
included in these studies are primary procedures. The effectiveness of a particular
bone graft in foot and ankle surgery may be significantly different in revision cases. Be-
side what is discussed herein and what has been studied in literature, intuitively there
are a few other considerations in choosing the best or most appropriate bone graft
material.
Is the patient high risk? There are many comorbid factors that are yet to be stud-
ied in a clinical setting that may impact the incorporation of a bone graft. Does
your patient need extra osteogenicity and inductivity?
32 Shibuya & Jupiter
Is this a revision surgery? If it is, which neurovascular structures are more likely to
be already compromised (Fig. 9)?
Has any other type of graft already been tried? If 1 type of graft has already failed,
it is likely to fail again.
How much defect/distance does the bone have to heal? The larger the defect or
longer the distance, the more time it takes for the graft to be incorporated. Can
the graft of your choice withstand the pressure and force for that time period?
There is limited evidence-based surgical practice with regard to the selection of
bone grafts. Because there are myriad factors that can influence bone healing, we
cannot account for every situation in the context of clinical studies. Therefore, intuitive
but educated clinical judgment is still needed to select the best bone graft in some sit-
uations. Also, it should be noted that many of the clinical studies may have large se-
lection bias, because most of the studies are not randomized. For example, when
discussing autografts versus allografts, surgeons may prefer to use autografts in
higher risk patients for fear of nonunion. Because many studies are retrospective, sur-
geon selection of autografts in higher risk patients can favor and bias toward allo-
grafts. Dolan’s study,11 however, had a randomized selection of an autograft or
allograft for use in adult lateral column lengthening surgery. In their study, the differ-
ence remained nonsignificant: All the osteotomies heeled by week 12, regardless of
the bone graft used. In Shibuya and colleagues’ study, they determined from the
Cox regression that gender, age, and surgery site did not affect the overall result.
Further, the reason for xenograft use over allograft was not related to patient charac-
teristics. Therefore, these studies are less likely to have selection bias.
Another caveat when evaluating these studies is oversimplification of classification
of the grafts, which may result in overgeneralization. Within the allograft group, the ma-
terial properties can significantly differ owing to different processing methods and
sterilization techniques. Antigenicity, ostetoinductivity and structural integrity can
differ greatly owing to those different processing techniques. Similarly, in bovine-
based xenografts, the results can be significantly different between those processed
with BioCleanse, versus those processed with a combination of osmotic treatment,
Fig. 9. Even though only a 7-mm deficit had to be filled, a calcaneal autograft was used for
this 50-year-old man because this was a revision case and most likely the biology of the first
metatarsophalangeal joint was violated from the previous surgery.
Bone Graft Substitute 33
REFERENCES
1. Bingold AC. Ankle and subtalar fusion by a transarticular graft. J Bone Joint Surg
Br 1956;38B:862–70.
2. Chuinard EG, Peterson RE. Distraction-compression bone-graft arthrodesis of the
ankle. A method especially applicable in children. J Bone Joint Surg Am 1963;
45A:481–90.
3. Enneking WF, Morris JL. Human autologous cortical bone transplants. Clin Or-
thop Relat Res 1972;87:28–35.
4. McCall RE, Lillich JS, Harris JR, et al. The Grice extraarticular subtalar arthrod-
esis: a clinical review. J Pediatr Orthop 1985;5:442–5.
5. Stevens KJ, Banuls M. Sciatic nerve palsy caused by haematoma from iliac bone
graft donor site. Eur Spine J 1994;3:291–3.
6. Banwart JC, Asher MA, Hassanein RS. Iliac crest bone graft harvest donor site
morbidity. A statistical evaluation. Spine (Phila Pa 1976) 1995;20:1055–60.
7. Schulhofer SD, Oloff LM. Iliac crest donor site morbidity in foot and ankle surgery.
J Foot Ankle Surg 1997;36:155–8 [discussion: 161].
8. Cricchio G, Lundgren S. Donor site morbidity in two different approaches to ante-
rior iliac crest bone harvesting. Clin Implant Dent Relat Res 2003;5:161–9.
9. Chou LB, Mann RA, Coughlin MJ, et al. Stress fracture as a complication of autog-
enous bone graft harvest from the distal tibia. Foot Ankle Int 2007;28:199–201.
10. Mahan KT, Hillstrom HJ. Bone grafting in foot and ankle surgery. A review of 300
cases. J Am Podiatr Med Assoc 1998;88:109–18.
11. Dolan CM, Henning JA, Anderson JG, et al. Randomized prospective study
comparing tri-cortical iliac crest autograft to allograft in the lateral column length-
ening component for operative correction of adult acquired flatfoot deformity.
Foot Ankle Int 2007;28:8–12.
12. McCormack AP, Niki H, Kiser P, et al. Two reconstructive techniques for flatfoot
deformity comparing contact characteristics of the hindfoot joints. Foot Ankle
Int 1998;19:452–61.
13. Danko AM, Allen B Jr, Pugh L, et al. Early graft failure in lateral column length-
ening. J Pediatr Orthop 2004;24:716–20.
14. Cook EA, Cook JJ. Bone graft substitutes and allografts for reconstruction of the
foot and ankle. Clin Podiatr Med Surg 2009;26:589–605.
15. Tomford WW, Springfield DS, Mankin HJ. Fresh and frozen articular cartilage al-
lografts. Orthopedics 1992;15:1183–8.
16. Aghdasi B, Montgomery SR, Daubs MD, et al. A review of demineralized bone
matrices for spinal fusion: the evidence for efficacy. Surgeon 2013;11:39–48.
17. John S, Child BJ, Hix J, et al. A retrospective analysis of anterior calcaneal osteot-
omy with allogenic bone graft. J Foot Ankle Surg 2010;49:375–9.
18. Nowicki PD, Tylkowski CM, Iwinski HJ, et al. Structural bone allograft in pediatric
foot surgery. Am J Orthop (Belle Mead NJ) 2010;39:238–40.
19. Philbin TM, Pokabla C, Berlet GC. Lateral column lengthening using allograft
interposition and cervical plate fixation. Foot Ankle Spec 2008;1:288–96.
34 Shibuya & Jupiter
20. Mosca VS. Calcaneal lengthening for valgus deformity of the hindfoot. Results in
children who had severe, symptomatic flatfoot and skewfoot. J Bone Joint Surg
Am 1995;77:500–12.
21. Templin D, Jones K, Weiner DS. The incorporation of allogeneic and autogenous
bone graft in healing of lateral column lengthening of the calcaneus. J Foot Ankle
Surg 2008;47:283–7.
22. Vining NC, Warme WJ, Mosca VS, et al. Comparison of structural bone autografts
and allografts in pediatric foot surgery. J Pediatr Orthop 2012;32(7):719–23.
23. Grier KM, Walling AK. The use of tricortical autograft versus allograft in lateral col-
umn lengthening for adult acquired flatfoot deformity: an analysis of union rates
and complications. Foot Ankle Int 2010;31:760–9.
24. Muller MA, Frank A, Briel M, et al. Substitutes of structural and non-structural
autologous bone grafts in hindfoot arthrodeses and osteotomies: a systematic re-
view. BMC Musculoskelet Disord 2013;14:59.
25. Pallante-Kichura AL, Chen AC, Temple-Wong MM, et al. In vivo efficacy of fresh
versus frozen osteochondral allografts in the goat at 6 months is associated with
PRG4 secretion. J Orthop Res 2013;31:880–6.
26. An HS, Lynch K, Toth J, et al. Prospective comparison of autograft vs allograft for
adult posterolateral lumbar spine fusion: differences among freeze-dried, frozen,
and mixed grafts. J Spinal Disord 1995;8(2):131–5.
27. Thalgott JS, Fogarty ME, Giuffre JM, et al. A prospective, randomized, blinded,
single-site study to evaluate the clinical and radiographic differences between
frozen and freeze-dried allograft when used as part of a circumferential anterior
lumbar interbody fusion procedure. Spine (Phila Pa 1976) 2009;34(12):1251–6.
28. Dallari D, Fini M, Stagni C, et al. In vivo study on the healing of bone defects
treated with bone marrow stromal cells, platelet-rich plasma, and freeze-dried
bone allografts, alone and in combination. J Orthop Res 2006;24:877–88.
29. Wei LC, Lei GH, Sheng PY, et al. Efficacy of platelet-rich plasma combined with
allograft bone in the management of displaced intra-articular calcaneal fractures:
a prospective cohort study. J Orthop Res 2012;30(10):1570–6.
30. Taheri ZE, Gueramy M. Experience with calf bone in cervical interbody spinal
fusion. J Neurosurg 1972;36:67–71.
31. Bansal MR, Bhagat SB, Shukla DD. Bovine cancellous xenograft in the treatment
of tibial plateau fractures in elderly patients. Int Orthop 2009;33:779–84.
32. Taheri M, Molla R, Radvar M, et al. An evaluation of bovine derived xenograft with
and without a bioabsorbable collagen membrane in the treatment of mandibular
Class II furcation defects. Aust Dent J 2009;54:220–7.
33. Shibuya N, Holloway BK, Jupiter DC. A comparative study of incorporation rates
between non-xenograft and bovine-based structural bone graft in foot and ankle
surgery. J Foot Ankle Surg 2014;53:164–7.
34. Shibuya N, Jupiter DC, Clawson LD, et al. Incorporation of bovine-based struc-
tural bone grafts used in reconstructive foot surgery. J Foot Ankle Surg 2012;
51:30–3.
35. Schwarz F, Ferrari D, Balic E, et al. Lateral ridge augmentation using equine- and
bovine-derived cancellous bone blocks: a feasibility study in dogs. Clin Oral Im-
plants Res 2010;21:904–12.
36. Ledford CK, Nunley JA 2nd, Viens NA, et al. Bovine xenograft failures in pediatric
foot reconstructive surgery. J Pediatr Orthop 2013;33:458–63.
37. Schultheiss M, Sarkar M, Arand M, et al. Solvent-preserved, bovine cancellous
bone blocks used for reconstruction of thoracolumbar fractures in minimally inva-
sive spinal surgery-first clinical results. Eur Spine J 2005;14:192–6.