Chapter 13 Bone Grafts in Hip Surgery

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Chapter 13 

Bone Grafts in Hip Surgery


Paul Tee Hui Lee, Sandor Gyomorey,
Oleg A. Safir, David J. Backstein,
and Allan E. Gross

KEY POINTS performed in 1668 by a Dutch surgeon named Job Van


Meekeren, who successfully inserted a fragment of a
• Autologous bone graft is osteogenic, osteoinduc- dog bone into the skull of an injured soldier.5 The first
tive, and osteoconductive, with complete histocom- documented successful autograft transplant was per-
patibility and no risk of infectious disease formed in Germany in 1821 by Philips von Walter in
transmission. It is considered the gold standard for experimentally created animal bone defects.7 The first
bone graft and is the most favored graft material in documented allograft transplant was performed in 1879
musculoskeletal reconstruction. by Sir William MacEwen in Scotland, who replaced the
• Advantages of bone allograft use include availability infected proximal two thirds of a humerus in a 4-year-
of materials and avoidance of donor site morbidity old boy with the tibia from another child with rickets.6
associated with autograft harvesting. Disadvan- In 1915, F. H. Albee published his work on autologous
tages of bone allograft use include lack of osteo- bone graft in the United States, which promoted the use
genic cells, decreased osteoinductive factors, host of bone transplantation.8 In 1942, Inclan reported his
immune response, and risk of infection. experience in a large number of operations using auto-
• Impaction bone grafting is generally excellent for graft and allograft.9 Similar to other surgeons, Inclan
treating patients with small to moderate-sized con- considered the difficulties of finding suitable grafts for
tained cavitary defects but poor with regard to operations. When met with supply difficulties for autol-
implant fixation stability for patients with large ogous bone transplant, he used homologous bone graft
uncontained segmental defects. between living patients of the same blood group. He did
• For such large uncontained segmental bone defects, this because immune-related problems were known
structural bulk allograft can provide adequate then, and graft from cadaver was prohibited on religious
support for primary implant fixation stability with and sentimental grounds. Modern-day bone banks
relatively reasonable long-term outcomes, despite emerged in the 1960s and 1970s with improvements in
mixed concerns over long-term resorption. cooling techniques combined with allograft processing;
• The success of graft incorporation depends on this led to the relative immunogenic impunity of
several factors, principally graft revascularization, allografts after transplantation. Several reports have
new bone formation (around and within the graft), helped to define safety and techniques in bone banking,
and healing at the graft-host interface. These in thereby facilitating increased use of bone allografts.10-12
turn depend on a combination of the biological In recent times, despite its limitations, allogeneic bone
activity of the graft, the vascularity of the host bed, graft is the most commonly used graft tissue.13 Several
and the mechanical stability of the graft-host important clinical applications include restoration of
interface. bone stock in tumor surgery and in revision hip
arthroplasty.
In hip surgery, the use of bone graft includes auto-
grafts, allografts, and bone substitutes. We will focus
our discussion on the use of autologous and allogeneic
bone grafts and will include various grafting techniques,
INTRODUCTION their clinical applications and results, the basic scien-
Historical Perspective tific basis of these materials, current controversies, and
future directions.
Bone grafting is an ancient art. Anthropologist A. Jag-
harian at Erivan Medical Centre in Armenia examined a
prehistoric Khuritic skull from the ancient Centre of Bone Autograft
Ishtkun and found a piece of animal bone filling a 7-mm
defect with bony regrowth around the grafted bone.4 It Clinical indications for the use of bone autograft include
has been suggested that the ancient Egyptians and primary total hip replacement for hip dysplasia and
Greeks attempted bone transplantation. In the modern protrusio to treat bone defects and achieve primary
age, the first documented bone graft was successfully implant fixation stability and restore the center of
182
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Chapter 13  Bone Grafts in Hip Surgery 183

rotation for the joint.1-3 Femoral head osteonecrosis can Results


also be treated by vascularized and nonvascularized
autologous bone grafts. Morselized autografts generally Acetabular Side
are used for treating smaller contained defects, and The results of acetabular reconstructions using this
structural autografts are used for larger defects that technique for contained cavitary defects have generally
may be uncontained. The resected host femoral head is been good, with survivorship approaching 85% to 90%
the most frequently used form of autograft bone. It is at 20 years.28,29 Buma and colleagues31 took core biop-
readily available, adequate in size, cheap, biomechani- sies from 8 patients after 1 to 72 months from surgery
cally compatible, and easy to contour to fit defects, and to show the different stages of graft incorporation. At 4
it does not need processing. Total hip replacements months after surgery, histologic analysis showed revas-
performed in dysplastic hips using femoral head auto- cularization of the graft. Osteoclasts had removed parts
graft have shown graft incorporation in most cases, of the graft, and woven bone had formed on the rem-
with generally good clinical outcomes over the short nants of the graft and in the stroma that was invading
term to midterm.1,17-27 Longer-term results have been the graft (Fig. 13-1). Between 8 and 28 months after
mixed. Harris and associates reported a 10% revision surgery, the mixture of graft and new bone showed
rate (n = 47) at a mean of 7.1 years,1 a 20% revision rate remodeling with time into normal trabecular bone
(n = 46) at a mean of 11.8 years,19 and a 29% revision structure with viable bone marrow that contained few
rate (n = 55) at a mean of 16.5 years.20 The authors or no remnants of the original graft (Fig. 13-2). Although
expressed concern regarding low stem offset and pos- some specimens showed the presence of graft-cement
terior cup uncoverage in this cohort. Gross and col- interface and local apposition of vital bone with the
leagues21 reported a revision rate of 13% (n = 15) at a cement layer, a soft tissue interface predominated (see
mean of 8.4 years’ follow-up and later, Nousiainen and Fig. 13-2B and D).
co-workers27 reported a revision rate of 32% (n = 31) at For uncontained segmental defects, concerns with
a mean of 14 (8 to 18) years’ follow-up. Inao and associ- impaction bone grafting include early mechanical
ates22 reported 0% revision rate (n = 20) at a mean of 8.4 failure, mesh rupture, frequent significant cup migra-
years; however, Iida and colleagues25 reported a 4% revi- tion, and poor survivorship.32,33 Reports suggest that
sion rate (n = 133) at a mean of 12.3 (8 to 24) years, and this technique is excellent for patients with small to
Akiyama and associates26 reported a 4% revision rate (n moderate-sized contained cavitary defects, but poor for
= 147) at a mean of 11.8 (6.3 to 15.4) years. Note that those with large uncontained segmental defects.
mean patient weight was 51 (29 to 78) kg in Iida’s cohort
and 51.6 ± 7.9 kg in Akiyama’s. With regard to resorption Femoral Side
of the autologous graft, results from various series were Published reports have shown good clinical success in
similarly mixed.17,19,21,27 Nevertheless, there is consensus patients with significant cavitary femoral bone loss
among most authors that the bulk autograft incorpo- treated with impaction grafting34-37 and radiographic
rated well, restored pelvic bone stock, and facilitated and histologic evidence of revascularization of impacted
revision surgery. allograft.38
In a retrieval study of a well-fixed stem with good
Allograft radiographic graft incorporation (Fig. 13-3), Ling and
co-workers39 showed at 3.5 years’ follow-up that the
Allografts, morselized or structural, have been used grafted bone had become organized into three zones
mainly to address significant bone loss in revision hip (Fig. 13-4): a newly regenerated cortical surface, an
arthroplasty and post tumor resection. interface zone, and a deep zone. In the regenerated
cortical surface, the bone was fully mineralized and
Impaction Bone Grafting revascularized. The fatty bone marrow was normal
looking with no fibrosis. The bone was generally viable,
Impaction bone grafting is used because it is considered as shown by more than 90% of filled osteocyte lacunae
a biological technique for restoring host bone stock. (Fig. 13-5), but occasional islands of dead bone were
Metal wire meshes are used to enclose segmental bone evident. The interface zone was irregular with direct
defects, which then are filled with morselized bone contact between bone cement and osteoid. Foreign
allograft that is densely impacted before cementing of body giant cells were visible, and in some areas, there
the acetabular or femoral component. Studies have indi- was a thin soft tissue lining (Fig. 13-6). No direct contact
cated that the success of the construct depends upon occurred between viable mineralized bone and cement.
graft incorporation, which relies on the quality of the The deep layer included trabeculae of dead bone,
host bone bed. entombed in cement at the time of its insertion. These
The choice of bone graft is controversial. A system- trabeculae had empty lacunae but were linked to sur-
atic review performed by the Cochrane Database dem- rounding viable bone by bridges of soft tissue, osteoid,
onstrated insufficient evidence to suggest differences and bone (see Fig. 13-6).
between processed (freeze dried or irradiated) and In cases with substantial and fully circumferential
unprocessed (fresh-frozen) bone for impaction graft- bone loss of the proximal femur, concerns with impac-
ing.119 However, it is recommended that the graft be tion grafting techniques remain because of the risk of
used in the form of cancellous cubes that are 7 to 10 mm prosthetic migration and periprosthetic fracture.40,41
in width. Some would consider this a contraindication

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184 Section I  Basic Science

A
A C

WB

WB

D E

Figure 13-1. A through C, One month post acetabular reconstruction. A, Graft-cement interface in fuchsin-stained thick
section. Note penetration of cement into the graft. B and C, No incorporation of graft in hematoxylin and eosin (H&E)-
stained section. Note acellular medullary tissue in C (A and B, ×20; C, ×90). D and E, Case 2.4 months postoperatively.
New woven bone (We) is formed on the remnants of the graft (G) by active osteoblasts (arrows). (D, H&E-stained section;
E, Goldner-stained adjacent section.) Note red-stained osteoid indicating active bone formation (×225). (From Buma P,
Lamerigts N, Schreurs BW, et al: Impacted graft incorporation after cemented acetabular revision: histological evaluation in 8
patients. Acta Orthop Scand 67:536–540, 1996, Fig. 2.)

for impaction bone grafting. Few studies have shown Disadvantages include lack of universal availability,
reasonable results in this situation. Buttaro and associ- technical difficulties, and concerns over long-term graft
ates42 reported the use of this technique for 15 cases of resorption and collapse.
severe proximal femoral bone defects averaging 12 cm
in length that were followed for an average of 43.2 Acetabular Side
months (range, 20 to 72 months). The Merle d’Aubigné A minor column or shelf allograft is a structural graft
and Postel score improved from a mean of 4.8 to 14.4 that provides 50% or less support to the new acetabular
points, and implant survivorship was 100% at 1 year and component. The bulk graft is shaped intraoperatively,
87% at 72 months. However, a high incidence of severe is snug-fitted into the defect, and is held with compres-
complications was reported, including 2 (13%) frac- sion screws with washers (Fig. 13-7). Midterm results
tures, 3 (20%) dislocations, and 3 (20%) deep for treatment of uncontained segmental defects involv-
infections. ing <50% of the acetabulum have been around 80% for
cup survivorship at 10 years, with aseptic loosening as
Structural Allografts the endpoint.43,44 Similar results have been reported
with the use of bulk femoral head and acetabular and
Structural allograft can provide adequate support distal femur allografts.43,44
for primary implant fixation stability in revision sur­ Despite concerns about long-term graft resorption,
gery with large uncontained segmental bone loss. collapse, and failure, mid- to long-term studies have

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Chapter 13  Bone Grafts in Hip Surgery 185

short-term to midterm survivorships of 45% to 60%.45,46


Treatment of the same defects with cemented cups sup-
ported by reconstruction cages securely fixed to the
ilium and ischium in conjunction has led to more
encouraging midterm results, with survivorships of 77%
to 87%.47,48 The cage protects the structural graft by
NB
providing pelvic stability in spanning across the ilium
and ischium and by offloading the graft until bony inter-
digitation occurs.
Hooten and colleagues49 examined two acetabuli that
C were revised with femoral head structural allografts and
cementless cups at 25 and 48 months’ follow-up. Both
grafts were functioning well at revision and were radio-
graphically stable without evidence of graft collapse,
cup loosening, or failure of union at the graft-host inter-
face. Histologic examination showed that vascularity
was increased at the host-graft interface, but evidence
of bone union between the graft and the host was
limited, in contrast to the radiographic appearance
(Figs. 13-9 and 13-10). In areas where union had occurred,
A B revascularization extended to 2 mm beyond the graft-
host interface. Within the body of the graft, revascular-
ization and remodeling were limited; the trabecular
matrix appeared acellular, but the structural integrity
C
was maintained at 48 months after surgery. In areas
where the allograft was adjacent to an implant, fibrous
tissue was oriented parallel to the implant surface. Bony
ingrowth was limited to areas of porous coating that
were in contact with viable host bone but did not occur
between the ingrowth coating and the graft (Fig. 13-11).
F
Femoral Side
Uncontained fully circumferential proximal femur seg-
C D mental defects may be addressed with the use of a
proximal femoral structural allograft in conjunction
Figure 13-2. A through C, Eight months postacetabular with a long-stem prosthesis. The stem is cemented into
reconstruction. The graft is incorporated into a new tra- the proximal femur allograft to form an allograft-
becular structure. If inspected with polarized light, the prosthesis composite. Fixation of the prosthesis to the
structure mainly consists of woven bone, with many active
host distal femur is maintained by a stem extension,
bone remodeling sites indicated by red osteoid staining
(Goldner staining, ×30). C, Magnification of part of Figure which is implanted into the medullary canal and aug-
13-2A. Note active osteoblasts (arrows) (×55). B and D, 28 mented with a step or oblique cut at the graft-host junc-
months postoperatively. At the graft-cement (C) interface, tion, multiple cerclage wires at the graft-host junction,
new bone (NB) is locally present, graft remnants are absent, and the optional addition of cortical (fibular or ulnar)
and locally a soft tissue interface (I) and/or fibrocartilage strut grafts.
(F) is present (hematoxylin and eosin [H&E] and Goldner This method of treatment has shown good long-term
staining, ×140). (From Buma P, Lamerigts N, Schreurs BW, survivorship and functional outcomes.50-53 Safir and
et al: Impacted graft incorporation after cemented acetabular associates54 reported 82% survivorship (n = 93) at a
revision: histological evaluation in 8 patients. Acta Orthop mean follow-up of 16 years (range, 15 to 22 years) with
Scand 67:536–540, 1996, Fig. 3.)
stem revision as the endpoint. Two (4%) infections, 6
(11%) aseptic loosenings, 3 (6%) nonunions, and 4 (7%)
dislocations were reported. Complication rates were
shown that during rerevision surgery, most of the bulk considered acceptable in view of the complexity of the
allograft remained intact with host-graft boundaries clinical condition.
obscured, enabling cup-only exchanges.43,44 The main advantages of treatment with proximal
A major column allograft is a structural graft that femoral allografts over distally fixed proximal femoral
provides more than 50% support to the new acetabular replacements (cementless) include lower dislocation
component (Fig. 13-8). These allografts are used in revi- rates,55,56 better abductor function, less frequent Tren-
sion cases with uncontained segmental defects involv- delenburg limp,57 and better survivorship with a lower
ing more than 50% of the acetabulum and both columns, rate of loosening of the distal stem.57,58
with or without pelvic discontinuity. The use of major Hamadouche and colleagues,59 in a case report,
column allografts without support by an anti–protrusio showed the histologic appearance of a proximal femoral
ilioischial cage has met with poor results, with allograft via biopsies taken during stem revision for

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186 Section I  Basic Science

A B C
Figure 13-3. A, The fractured femoral stem with an adjacent cortical defect. B, The femur 1 year after removal of the
prosthesis and cement. Two cortical defects are present: the distal one was created surgically to remove the distal cement.
C, Two years after revision arthroplasty with impaction cancellous grafting. Cerclage wires, which secure the wire mesh,
mark the levels of cortical defects; these appear to be filled by bone. (From Ling RS, Timperley AJ, Linder L: Histology of
cancellous impaction grafting in the femur: a case report. J Bone Joint Surg Br 75:693–696, 1993, Fig. 1.)

Figure 13-4. Low-power view of a histologic section taken


at the level of the upper cortical window. Cement has been
dissolved out, and staining indicates mineralized bone. At
one point (*), cement has protruded between the cortex
and the graft. The three zones of interest are shown: (1)
cortical bone; (2) interface between living tissue and
cement; and (3) bone trabeculae buried in the cement Figure 13-5. High-power view of regenerated bone showing
(Goldner stain, ×4). (From Ling RS, Timperley AJ, Linder L: filled osteocyte lacunae in a mineralized stroma with all the
Histology of cancellous impaction grafting in the femur: a histologic characteristics of normal cortical bone (Goldner
case report. J Bone Joint Surg Br 75:693–696, 1993, Fig. 5.) stain, ×600). (From Ling RS, Timperley AJ, Linder L: Histology
of cancellous impaction grafting in the femur: a case report.
J Bone Joint Surg Br 75:693–696, 1993, Fig. 6.)

loosening after 10 years following surgery. Three layers


were seen within the allograft: inner, intermediate, and
superficial layers. The inner layer of the bone graft con- host bone, was composed of areas of remodeling bone
sisted of the zone of contact between the graft and bone and osteoclasts, osteoblasts, and fatty bone marrow
cement and was composed of trabeculae of dead bone (see Fig. 13-8). Evidence of creeping substitution was
and cellular debris without evidence of remodeling (Fig. noted with new bone and osteoid formation. Revascu-
13-12). The superficial or interfacial layer, correspond- larization occurred through the formation of woven
ing to the region of contact between the graft and the bone to a depth of 5 mm. Between inner and superficial

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Chapter 13  Bone Grafts in Hip Surgery 187

Figure 13-6. The interface between viable tissue and bone


cement that has been dissolved out. Viable bone has been
capped with osteoid, which is in direct contact with the Figure 13-8. Low-power magnification photomicrograph of
(absent) cement surface. Some dead bone trabeculae (*) the allograft-host junction. Newly formed bone (white
are probably remnants of the graft. Bridges of soft tissue arrow) was present on the allograft surface and bridging to
and osteoid connect these trabeculae to living bone. Mul- host. The microfractures (black arrows) are parallel or per-
tinucleated giant cells are also seen in contact with pendicular to the newly formed osteons (van Gieson picro-
the cement surface (Goldner stain, ×120). (From Ling RS, fuchsin, ×40). (From Hamadouche M, Blanchat C, Meunier
Timperley AJ, Linder L: Histology of cancellous impaction A, et al: Histological findings in a proximal femoral structural
grafting in the femur: a case report. J Bone Joint Surg Br allograft ten years following revision total hip arthroplasty:
75:693–696, 1993, Fig. 7.) a case report. J Bone Joint Surg Am 84:269–273, 2002,
Fig. 4.)

Flying
buttress
graft

Cancellous
screws

A B
Figure 13-7. A, An uncontained defect involving less than 50% of the acetabulum. B, A minor column (shelf) graft sup-
porting less than 50% of the cup is held with two cancellous screws. The flying buttress graft is cancellous autograft bone.
(Redrawn from Gross AE, Duncan CP, Garbuz D, Mohamed MZ: Revision arthroplasty of the acetabulum in association with
loss of bone stock. J Bone Joint Surg Am 80:440–451, 1998.)

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188 Section I  Basic Science

Case 2
preop Case 2
A B postop

Case 2
C 1 year

D
Figure 13-9. A, Preoperative radiograph showing superolateral acetabular deficiency with associated femoral head defi-
ciency. B, Radiograph after femoral head allografting and cementless total hip arthroplasty. C, One year after surgery with
trabecular bridging superolaterally (black arrows) and obscured interface medially, consistent with partial incorporation.
D, Specimen radiograph showing persistence of the sclerotic border circumferentially around the femoral head allograft
with partial graft healing in two areas (white arrows). (From Hooten JP Jr, Engh CA, Heekin RD, Vinh TN: Structural bulk
allografts in acetabular reconstruction: analysis of two grafts retrieved at post-mortem. J Bone Joint Surg Br 78:270–275, 1996,
Fig. 2A-D.)
Bone graft Host bone

Host
bone

Fibrous
interface

Fibrous Graft union


Graft union Bone graft
A interface B
Figure 13-10. A, Appearance of the superolateral graft-host junction (area depicted by white arrows in Fig. 13-12D).
B, Appearance of the superomedial graft-host junction (area depicted by black arrow in Fig. 13-12D) (hematoxylin
and eosin, ×1.5). (From Hooten JP Jr, Engh CA, Heekin RD, Vinh TN: Structural bulk allografts in acetabular reconstruction:
analysis of two grafts retrieved at post-mortem. J Bone Joint Surg Br 78:270–275, 1996, Fig. 4A and B.)

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Chapter 13  Bone Grafts in Hip Surgery 189

Allograft

Graft
union

Fibrous gap

Bone
ingrowth

Figure 13-12. Photomicrograph of an unremodeled area of


the allograft, showing empty lacunae (black arrows) and
microfractures (white arrows). Cellular debris is present in
the middle of the image (Stevenel blue and van Gieson
picrofuchsin, ×100). (From Hamadouche M, Blanchat C,
Meunier A, et al: Histological findings in a proximal femoral
Figure 13-11. Graft-host junction (25-µm methylmethacry- structural allograft ten years following revision total hip
late section, hematoxylin and eosin). (From Hooten JP Jr, arthroplasty: a case report. J Bone Joint Surg Am 84:269–273,
Engh CA, Heekin RD, Vinh TN: Structural bulk allografts in 2002, Fig. 3.)
acetabular reconstruction: analysis of two grafts retrieved
at post-mortem. J Bone Joint Surg Br 78:270–275, 1996,
Fig. 5.)

precursor cells and osteoblastic cells that are involved


in new bone synthesis. It is osteoinductive, as it con-
layers within the substance of the graft lay the interme- tains noncollagenous bone matrix proteins, including
diate layer, which consisted of a sparsely cellular area growth factors that modulate the recruitment of mesen-
with resorption and no remodeling. Of note, numerous chymal stem cells and differentiation into chondro-
microfractures were seen in the unremodeled area of blasts and osteoblasts. It is osteoconductive, as it is a
the allograft, especially under high magnification, but three-dimensionally ordered scaffold of bone mineral
not in the remodeled area. These microfractures were and collagen that facilitates ingrowth of capillaries, peri-
parallel or perpendicular to the bone lamellae and vascular tissue, and mesenchymal stem cells; this
bypassed newly formed osteons at the level of the allows the formation of new bone in an organized
cement line. fashion. In addition, complete histocompatibility occurs
No fibrous membrane was seen between the allograft without the potential for immune-related problems, and
and the host femur. Radiologically, the graft appeared there is no risk for infectious disease transmission. As
united (Fig. 13-13). Macroscopically, the allograft a result, autograft is considered the gold standard for
appeared as viable bleeding bone surrounded by host bone graft and is the most favored graft material in
bone. It had united to the host bone but remained dis- musculoskeletal reconstruction. However, several
tinguishable from the recipient bone as it appeared potential disadvantages to autograft use have been
denser. This was confirmed by microradiographic analy- identified. These include an insufficient amount of graft
sis, which showed that the allograft was more densely material, donor site morbidity, increased surgical time,
mineralized with smaller pore size than the host bone and increased blood loss. Potentially significant post-
(Fig. 13-14). surgical donor site morbidity includes infection, pain,
hemorrhage, muscle weakness, and nerve injury.14
Donor site morbidity is relatively common, and compli-
cation rates from harvesting range from 10% to 25%.15,16
BASIC SCIENCE
Autograft Bone Cancellous Autograft
Cancellous autograft is highly osteogenic and promotes
General Biology rapid revascularization and incorporation into host
Autologous bone graft is bone that is taken from an bone, because it has a large surface area lined with
individual and transplanted into another site of the numerous osteoblasts. However, its poor initial mechan-
same individual. Several advantages have been noted ical strength often necessitates the use of early mechan-
with the use of autologous bone graft. It is osteogenic, ical protection to allow graft-induced formation of new
as it contains marrow-derived preosteoblastic bone to provide early anchorage to the recipient bed.

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190 Section I  Basic Science

Figure 13-13. Serial anteroposterior radio-


graphs of the patient in Figure 13-12.
A, Preoperative radiograph showing major
structural bone loss on the femoral side with
deficient proximal part of the femur. B, One
year after arthroplasty, the graft has healed
to the host (arrows). C, At 10 years, resorp-
tion of the proximal portion of the allograft is
seen (arrow). No migration of the femoral
stem is seen. (From Hamadouche M, Blanchat
C, Meunier A, et al: Histological findings in a
proximal femoral structural allograft ten years
following revision total hip arthroplasty: a case
report. J Bone Joint Surg Am 84:269–273, 2002,
Fig. 1.)

A B C

Host bone plasma cells, osteoclasts, mononuclear cells, and poly-


nuclear cells. Some early fibrous tissue forms. In the
second week, fibrous granulation tissue is predominant
and osteoclastic activity increases. Macrophages arrive
to remove necrotic debris within the haversian canals
1
of the graft. Mediators released by the macrophages,
combined with low oxygen tension and low pH, have a
2 chemotactic effect on undifferentiated mesenchymal
stem cells, which migrate from the host to the graft,
subsequently repopulating the marrow. These primitive
3 cells differentiate into osteogenic cells under the influ-
ence of osteoinductive agents such as cytokines, growth
factors, and prostaglandins. By the fourth week, osteo-
blastic bone formation and osteoclastic resorption
Allograft bone occur in a coordinated fashion.
In the secondary phase of graft incorporation, the
osteoblasts cover the edges of the dead trabeculae and
Figure 13-14. Microradiograph of a transverse section at
the graft-host junction. Differences in pore size and density
lay down osteoid around central cores of dead bone.77
are evident between the host bone (1) and the allograft (3). This is followed by osteoclastic resorption, formation
No demarcation line is present, indicating that the graft has of hematopoietic marrow cells within the new marrow
healed to the host. However, remodeling has not proceeded of the graft, and remodeling at the graft-host junction.
more than a few millimeters into the graft (2). (From Hama- Radiographically, an initial increase in radiodensity
douche M, Blanchat C, Meunier A, et al: Histological findings is due to osteoblastic activity. This gradually decreases
in a proximal femoral structural allograft ten years following as necrotic bone undergoes osteoclastic resorption.
revision total hip arthroplasty: a case report. J Bone Joint Evidence of graft interdigitation can be seen radiograph-
Surg Am 84:269–273, 2002, Fig. 2.) ically by the blurring of margins between graft and
host bone. This is due to bone remodeling at the graft-
host junction, which may take several months to
In the primary phase of graft incorporation, immedi- complete.91
ately after bone grafting, inflammation117 and hematoma Biomechanically, cancellous autografts have increased
formation lead to coagulation. Infiltration of vascular initial strength as the result of new bone formation on
buds into the recipient bed begins and neovasculariza- a necrotic bed. Subsequently, resorption of the necrotic
tion promptly occurs over the next few days. In the first bed causes a decrease in mechanical strength. With
week, the graft is bathed by a soup of lymphocytes, remodeling of the graft-host junction, the strength of the

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Chapter 13  Bone Grafts in Hip Surgery 191

interface between graft and host bone eventually cells, decreased osteoinductive factors, host immune
improves. response, and infection risks.74,75,79 Morselized and
structural cancellous allografts are commonly used in
Cortical Autograft revision hip arthroplasty for acetabular and femoral
Incorporation of nonvascularized cortical grafts involves bone defects. Structural allografts are used primarily to
slower revascularization and a lesser degree of osteoin- support mechanical loads and resist failure at sites
duction than cancellous grafts118 (see Fig. 13-14). where structural support is desired.
However, the process is similar during early stages of
hematoma formation and inflammation. The cortical Bone Banks
graft has a dense architecture that impairs revas­ The development of modern tissue banks has resulted
cularization and has fewer endosteal cells to promote in a supply of high-quality allogeneic tissue for recon-
neovascularization.91 Unlike cancellous autograft, structive orthopedic surgery. More than 50 tissue banks
incorporation is initiated by osteoclasts instead of in the United States are accredited by the American
osteoblasts. Association of Tissue Banks (AATB). The success of
At about 2 weeks after grafting, extensive resorption allografting in recent years may be directly related to
begins and increases until about 6 months, before it stringent measures to ensure the safety of transplanted
gradually decreases to normal levels over the following tissue and to improvements in processing technology.61
6-month period. Initial revascularization and resorption Combined efforts of the U.S. Food and Drug Administra-
follow along peripheral haversian canals and interstitial tion (FDA) and the AATB have helped ensure that tissue
lamellae. Resorption of inner cortical material occurs at donors are adequately screened, and that allograft
a much slower rate. When the central osteonal canal material is properly processed, labeled, and distrib-
reaches a certain size, osteoblastic new bone formation uted. Screening of cadaveric donors begins with a
replaces osteoclastic bone resorption, which is further detailed medical, social, and sexual history question-
impaired by appositional bone growth. Eventually, naire completed by the life partner or next of kin. Any
creeping substitution occurs when the entire graft is of the following automatically disqualifies the individual
resorbed and replaced by new living bone. Creeping as a donor: positive history of exposure to specific com-
substitution is most evident at the graft-host junction municable disease, unprotected sexual contact, drug
and progresses in a parallel manner along the longitu- use, neurologic disease, autoimmune disease, collagen
dinal axis of the graft toward its middle.60 disorder, or metabolic disease.
Radiographically, increasing radiolucencies are seen
at irregular peripheral bony margins between 6 months Infection Risks and
and 1 year.120 With continuing osteogenesis, a gradual Sterilization Methods
increase in radiodensity occurs, initially at the graft- The risk of viral disease transmission with allograft use
host junction, and progresses into the middle of the is very small. Primary concerns include hepatitis C,
graft. The cortical autograft remains as a composite of hepatitis B, and human immunodeficiency virus (HIV).73
necrotic and new bone for prolonged periods. Two reported cases of HIV transmission in the 1980s
Biomechanically, the remodeling process initiated by were due to bone allograft74 but none since that time,
osteoclastic activity leads to initial bone loss and a because of implementation of strict donor screening
decrease in mechanical strength of up to 75%.83 In vas- programs by the AATB and mandatory screening
cularized cortical autografts, the graft heals much more of blood tests for all donors. Blood tests required by
rapidly at the graft-host junction, as the remodeling the FDA for all tissue transplants include HIV-1 and
process is similar to normal bone and virtually no resid- HIV-2 antibody, hepatitis B surface antigen, hepatitis B
ual weakness is noted.83 core antibody, hepatitis C antibody, syphilis, human
T-lymphotropic virus I antibody, and HIV p24 antigen.75,76
Allograft Bone harvested for use as allograft is subjected to
rigorous processing to remove all antigenic compo-
General Biology nents to decrease the host immune response and ensure
Because of limitations in the use of bone autograft, such sterility while desirable biological and biomechanical
as lack of availability and donor site morbidity, bone properties are retained. Processing methods include
allograft has been used as an alternative. Bone allograft- low-dose (<20 kGy) irradiation, physical débridement,
ing is the process by which bone is transferred from one ultrasonic or pulsatile water washes, ethanol treatment,
individual to another individual within the same species. and antibiotic soaking (4° C for >1 hour).77
Most commonly, bone is procured from patients who Terminal sterilization by gamma irradiation, electron
underwent primary hip arthroplasty or postmortem beam irradiation, or ethylene oxide treatment may be
from organ donors. It is available as fresh or preserved performed when contamination is anticipated. These
specimens. Preserved specimens are frozen or freeze have an adverse dose-dependent effect on the mechani-
dried. Fresh specimens elicit a higher level of immuno- cal strength of the graft.78
logic response62 and are reserved for tumor reconstruc- A fatal clostridial infection associated with implanta-
tion or joint resurfacing.63 Advantages of bone allograft tion of a femoral condyle allograft79 was reported in
use include availability and avoidance of donor site 2002. An investigation by the Centers for Disease Control
morbidity associated with autograft harvesting. Disad- and Prevention determined that the likely source of con-
vantages of bone allograft use include lack of osteogenic tamination was hematogenous seeding from bowel flora

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192 Section I  Basic Science

before harvesting. Twenty-six patients with allograft- Although immunologic reaction to bone allografts has
associated infections were identified (13 with clostridial been recognized in patients and in animal models,65-70 it
infections); 14 infections were associated with a single has been reduced by deep-freezing and, to a larger
tissue-processing unit. The time interval between extent, by freeze-drying (lyophilizing).71,72
death of the donor and tissue retrieval, delays in refrig- Fresh allografts incorporate unsatisfactorily, and
eration, and the mechanism of death (i.e., trauma) processing of allografts is favored for clinical use.
were likely factors that contributed to contamination Processing involves removal of antigenic cells and pro-
from the bowel. Of note, cultures obtained before and teins by removal of the periosteal sleeve and other
after processing in antibiotic/antifungal solution by the immunogenic soft tissues such as donor marrow.82 Pres-
tissue processor were negative. This showed that bac- ervation techniques include deep-freezing at −70° C and
teriostasis was unsatisfactory and sterilization must freeze-drying. Deep frozen grafts retain their mechani-
include methods that can kill bacterial spores such cal properties and may be implanted after thawing.
as gamma irradiation. When a sporicidal method is Freeze-drying diminishes immunogenicity to a greater
unavailable, tissue should be cultured before soaking extent but causes deterioration in the biomechanical
in antimicrobial solutions, and if bowel flora is properties of the graft.81 Rehydration (reconstitution) of
isolated, all tissue from that particular donor should the allograft before implantation improves the biome-
be discarded.79 chanical properties, but the allografts remain weak
and are vulnerable to mechanical failure in torsion and
Immune Response and Graft Processing bending.
It is unclear what relationship exists between cells and
cytokines of the immune system and cells of the bone Cancellous Bone Allograft
remodeling and repair system. A variety of antigens Allogeneic cancellous bone is a poor promoter of bone
present in allograft bone elicit a host immune response. healing compared with autologous cancellous bone.
This is primarily a cell-mediated response to major With fresh allografts, an aggressive host immune
histocompatibility complex class I and II antigens response occurs121 in the first 2 weeks of grafting with
on specialized antigen-presenting cells. Horowitz and high lymphocyte and macrophage activity. This impairs
Friedlander67 reported that allogeneic bone cells acti- the efficiency of osteoinductive growth factors to
vate host T cells of the suppressor phenotype and promote union at the graft-host interface. A delay in
induce their proliferation. neovascularization occurs in the presence of adjacent
In a prospective multicenter study on large fresh- inflammatory cells, which cause vessel occlusion
frozen structural allograft used in revision hip arthro- and graft necrosis. By about 2 months, the necrotic
plasty, Ward and colleagues64 showed that donor and allograft is surrounded by fibrous tissue. This prompts
recipient human leukocyte antigen (HLA) mismatches the use of fresh-frozen or freeze-dried allografts in
and recipient antibody responses to donor HLA anti- an attempt to reduce immunogenicity and improve
gens did not affect union rates at the graft-host junction. incorporation.80
Donor-specific HLA sensitization occurred in 57% of Allograft cancellous chips are incorporated more
patients but had no demonstrable effect on graft incor- completely and more rapidly than cortical bone
poration or union. The type of host-allograft junction allografts because they are more easily revascular-
did have a major effect on graft incorporation. Cortical- ized.122 Cancellous grafts act as a scaffold to allow the
cortical allograft-host junctions healed more slowly host to lay down new bone. However, they usually do
(mean, 542 days) than corticocancellous allograft-host not undergo complete osteoclastic resorption by the
junctions (mean, 243 days), although most healed host, and necrotic graft remnants are usually trapped
allografts survived for the minimum 3-year follow-up within host bone.77
period, and no correlation was noted between HLA
status and the prevalence of other complications, revi- Cortical Bone Allograft
sions, or articular deterioration. It is our view that During attempts at revascularization, the host inflam-
longer-term follow-up is required to determine if there matory response against graft-derived cellular antigens
is an association between HLA sensitization and long- leads to occlusion of invading host vessels, graft necro-
term graft survival. sis, and invasion by granulation tissue. Cortical allograft
Measures to further minimize or modulate HLA sen- incorporates by sporadic appositional bone formation.
sitization or response are not indicated at present to Poor vascularization is seen in larger cortical allografts
improve the union of reconstructions using structural as the result of increased density of cortical bone, lack
bone allografts. However, other benefits could be of construct stability, and immune response to the
derived from minimizing the rate of HLA sensitization. grafts.
One drawback for sensitized patients is the greater dif-
ficulty in finding suitably matched organs should they Factors Affecting Graft Incorporation
ever need a living tissue organ transplantation such as
a kidney or heart transplant.68 At the present moment, The success of graft incorporation depends on several
allograft bone procedures are performed without HLA factors, principally, graft revascularization, new bone
matching because tissue matching of bone between formation (around and within the graft), and healing at
donors and recipients currently is considered unneces- the graft-host interface. These in turn depend on a com-
sary by the Musculoskeletal Transplant Foundation. bination of biological activity of the graft, vascularity of

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Chapter 13  Bone Grafts in Hip Surgery 193

the host bed, and mechanical stability of the graft-host Host-Graft Union
interface (Table 13-1). The principal determinants of host-graft union include
stability of the construct and contact between host
Revascularization of the Substance of bone and graft.69,70 In animal studies, healing has
the Graft occurred when host-graft interfaces are intimately
The principal determinant of the rate, pattern, and apposed and stably fixed, regardless of whether the
amount of revascularization is the availability of a vas- grafts were autogenous or allogeneic, or fresh or
cular pedicle. Animal studies with dogs showed that frozen.86 When intimate contact between host bed and
vascularized autografts exhibited minimal disruption of graft was absent, healing was very severely impaired
osteonal remodeling patterns, osteocyte death, and despite stable graft fixation. Local and systemic inter­
peripheral resorption or centripetal vessel ingrowth.83 ference with the biological activity of the graft and
The nonvascularized bone graft is totally dependent on surrounding tissue secondary to irradiation or chemo-
the condition of the host bed for its revascularization, therapy (e.g., cisplatin) severely impairs graft healing.69
which occurs at a much slower rate via centripetal A mismatch in immunohistocompatibility and deep-
vessel ingrowth. freezing of the graft during preparation or storage have
Factors that have been associated with impaired been shown to impair graft healing to a certain extent.69
revascularization of cortical grafts include freezing,84,85 Freezing muted the effects of mismatch in immunohis-
histocompatibility discrepancy,84-86 and treatments that tocompatibility but simultaneously reduced the biologi-
interfere with biological properties of the graft and sur- cal activity of the graft by killing viable cells.88
rounding tissue, such as irradiation.87 Clinically, the frozen or processed mismatched
allograft is the most commonly implanted graft, and
New Bone Formation it has a less predictable process of incorporation.
The rate and amount of new bone formation in and However, the effects of freezing and mismatch in immu-
around grafts are mainly dependent on the availability nohistocompatibility on impairment of graft healing
of viable osteoblasts. The pattern of new bone forma- have not been shown to be sufficiently clinically
tion is determined by the availability of a vascular significant to warrant routine tissue-antigen matching
pedicle. Fresh vascularized autografts, whether cortical and the use of fresh-matched cortical bone grafts—a
or cancellous, show rapid bone formation. In nonvascu- practice that would be challenging from a feasibility
larized bone grafts, the living cells that are needed to standpoint.
form new bone must be derived from host tissues, and
so new bone formation is delayed. In cancellous auto- Impairment of Bone Graft Healing
grafts, new bone forms on the surface of trabeculae,
but in cortical autografts, new bone forms on the Several factors may impair bone graft incorporation.
periosteum.83,86,87 Smoking inhibits cellular proliferation and causes vaso-
constriction. Systemic steroid use inhibits differentia-
tion of progenitor cells into osteoblasts. Nonsteroidal
anti-inflammatory drugs inhibit prostaglandin forma-
tion and lead to diminished local blood flow and delay
Table 13-1. Local and Systemic Factors in graft resorption. They are contraindicated during the
Influencing Graft Incorporation acute healing phase because they reduce inflammatory
responses and inhibit osteoblasts at endosteal surfaces.
Factor Positive Negative Malnutrition, especially deficiency of calcium and phos-
Local Good vascular supply Radiation phorus, has been associated with delayed mineraliza-
at the graft site tion of new bone.89
Large surface area Tumor
Mechanical stability Mechanical instability
Mechanical loading Local bone disease CURRENT CONTROVERSIES AND
Growth factors Denervation FUTURE DIRECTIONS
Electrical stimulation Infection
The use of bone graft material in hip surgery still pres-
Systemic Growth hormone Corticosteroids ents major challenges. The most commonly used mate-
Thyroid hormone Nonsteroidal anti- rials are autograft, allograft, and synthetic materials.
inflammatory drugs*
The gold standard, however, is still considered to be
Somatomedins Chemotherapy autogenous bone graft, as it provides all three elements
Vitamins A and D Smoking necessary to generate and maintain bone: a scaffold for
Insulin Sepsis osteoconduction, growth factors for osteoinduction,
Parathyroid hormone Diabetes and progenitor cells for osteogenesis. However, auto-
Malnutrition graft is in limited supply, and its harvesting can result
Metabolic bone disease in significant donor site morbidity.
Processed allograft and synthetic bone graft substi-
*The effect of new selective cyclo-oxygenase (COX)-2 inhibitors is unknown.
From Khan SN, Cammisa FP Jr, Sandhu HS, et al: The biology of bone graft- tutes are more readily available and do not pose an
ing. J Am Acad Orthop Surg 13:77–86, 2005, Table 2. additional insult to the patient. However, they lack living

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194 Section I  Basic Science

cells and thus only function as an osteoconductive scaf- morselized allograft for reconstitution of an area of
fold for bone ingrowth.90,91 Therefore, in the recent past, absent femoral cortex. In each case, the authors con-
an explosion has occurred in the development of bone cluded that new bone formed earlier and graft incorpo-
substitutes and growth factors that have made their ration was more rapid than they would have expected
way to the medical market and into operating rooms.92,93 in the absence of BMPs. However, clinical trials are still
The biology of allograft incorporation is poorly under- lacking, and reports remain anecdotal.
stood; most studies lack histologic support and are Mesenchymal stem cells have been shown experi-
based on radiographic data alone, which may not reflect mentally to be involved in bone graft healing through
true incorporation. Analysis of retrieved allografts dem- activation of osteogenesis and angiogenesis.110-112 Mul­
onstrates that incorporation is very slow, irregular, and tipotent mesenchymal stem cells found in periosteum
incomplete. Cortical-cortical union is observed from can differentiate into bone as well as cartilage, but
internal cancellous-cancellous interfaces but is con- the molecular mechanisms involved are poorly
fined to only 20% of the superficial surface and the ends understood.
of the graft at 5 years post implantation.94,95 This leads Genetically engineered human mesenchymal stem
to graft fracture and implant failure in the short to cells have been used as a platform for the delivery of
medium term in up to 35% of cases.48,96,97 Moreover, osteogenic factors (BMPs) and have proved effective in
massive allografts are estimated to have a 10-year sur- vitro in enhancing proliferation and osteogenic differen-
vival rate of between 40% and 60% because of accumula- tiation. They have also demonstrated the ability to
tion of unremodeled microfractures, which decrease engraft and form bone and cartilage in ectopic sites and
their torsional properties, leading to catastrophic to regenerate bone defects when transplanted into
failure.99-101 Nonetheless, mechanical strength provided mice.113,114
by large structural allografts is probably the main Studies have also been performed to look at the use
reason why they are used in difficult reconstructions in of freeze-dried recombinant adeno-associated viruses
an attempt to avoid early mechanical failures. Thus the (rAAVs) carrying angiogenic, osteogenic, and remodel-
race is ongoing between incorporation of the graft and ing signals to stimulate graft incorporation through
failure of the implant. mediation of in vivo gene transfer. Addition of the freeze-
Biological advantages of particulate grafts over struc- dried virus to the cortical surface of allografts led to
tural grafts are well documented and include better marked revascularization and new bone formation in
revascularization, incorporation, and remodeling as a mice.115,116
consequence of the increased surface area between Although the therapies discussed here have not as
implant and host bone.29,101 Because particulate grafts yet been expanded to the clinical setting, good evidence
lack the mechanical support required for many applica- suggests that allograft incorporation, bone formation,
tions, several adjuvants have been proposed to enhance and remodeling may be enhanced by using several of
the biological response and incorporation of structural these emerging adjuvant therapies, as our understand-
allografts. One strategy is to add factors to the host bed ing of the mechanism of osteoinduction and osteogen-
to stimulate angiogenesis and bone formation around esis expands.
massive allografts; these factors include bone morpho-
genic proteins, mesenchymal stem cells, and the use of
gene therapy. REFERENCES
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196 Section I  Basic Science

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Chapter 13  Bone Grafts in Hip Surgery 197

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