This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF) Free
Right arrow Letters to the Editor: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Letters to the Editor are posted
Right arrow Alert me if a correction is posted
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowReprints and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by GROSS, A. E.
Right arrow Articles by MOHAMED, E. M. Z.
Right arrow Search for Related Content
PubMed
Right arrow Articles by GROSS, A. E.
Right arrow Articles by MOHAMED, E. M. Z.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Technorati  
What's this?
The Journal of Bone and Joint Surgery (American) 80:440-51 (1998)
© 1998 The Journal of Bone and Joint Surgery, Inc.

Instructional Course Lecture

Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Revision Arthroplasty of the Acetabulum in Association with Loss of Bone Stock*{dagger}

ALLAN E. GROSS, M.D., F.R.C.S.(C){ddagger}, TORONTO, CLIVE P. DUNCAN, M.B., M.SC., F.R.C.S.(C)§, DONALD GARBUZ, M.D., F.R.C.S.(C)# and ELSAYED MORSI Z. MOHAMED, M.B.B.C.H., M.S.(ORTH)**, VANCOUVER, BRITISH COLUMBIA, CANADA

An Instructional Course Lecture, The American Academy of Orthopaedic Surgeons


   Introduction
Top
 Introduction
Principles of Bone-Grafting
 Classification of Bone Defects
 Operative Technique
 Results
 Discussion
 References
 
The goals of revision arthroplasty of the hip are to relieve pain and to improve function. These goals can be accomplished by insertion of a new implant with stable fixation of the interface and restoration (or at least near restoration) of the anatomy.

Stable fixation may be achieved with use of components inserted either with cement12,55 or without cement11,32. However, marked osteolysis caused by wear debris, abrasion, or inflammation may make this task extremely difficult14,19-21,29,33,38,44,46.

If there is no loss of bone stock, the anatomy may be restored by simply inserting a new implant. If there is loss of bone stock on either the acetabular or the femoral side, however, the deficit should be categorized as either contained or uncontained and should be dealt with accordingly.

Contained, or cavitary, defects are more easily dealt with because the skeleton, while weakened, is basically intact. A contained defect of the acetabulum is one in which the anterior and posterior columns and the peripheral supporting bone for the acetabular component are intact. A pelvis with a contained defect can support an implant with a little help. This help may be biological (in the form of a bone graft) or it may involve modification of the implant. Impaction grafting with use of morseled bone is a biological alternative53. Large cups and asymmetrical cups that are designed to make contact with host bone, with no or minimum use of morseled bone, are examples of modified implants that may be used to treat a cavitary defect56.

Uncontained, or segmental, defects are more of a challenge. Small and even moderate defects can be dealt with by placing the implant against host bone without structural grafting but perhaps with some compromise of the normal anatomical relationships. Placement of a cup in a high hip-center position without cement allows the cup to make contact with host bone, thereby facilitating biological fixation by bone ingrowth36,47,49.

If the patient has a large segmental defect and there is no possibility of placing the implant against host bone or of restoring nearly normal anatomy, then the use of a structural bone graft may be indicated. This technique, if successful, restores bone stock and anatomical relationships and, if failure occurs, the revision operation may be less challenging3,25.

Revision of the acetabular side of a total hip arthroplasty requires that considerable resources, including a variety of implants and banked bone, be available to the treating orthopaedic surgeon; that the surgeon be well versed in the use of comprehensive operative exposures that allow access to the anterior and posterior aspects of the pelvis and femur; and that he or she be aware of and be able to treat the various complications that can occur in association with revision operations1. Some defects are not amenable to any kind of reconstruction and are best treated with arthrodesis35 or excision arthroplasty22,27.

Revision arthroplasty of the hip on the acetabular side is one of the most controversial procedures in orthopaedic surgery, partly because a wide variety of implants and techniques is available and partly because certain issues regarding bone-grafting, particularly the use of structural allografts, remain unresolved. In certain situations, however, the restoration of bone stock is necessary. The purpose of the current paper is to describe the principles, operative techniques, and results of the use of allograft bone, in morseled and structural form, for the restoration of bone stock in revision arthroplasty of the hip on the acetabular side.


   Principles of Bone-Grafting
Top
 Introduction
 Principles of Bone-Grafting
Classification of Bone Defects
 Operative Technique
 Results
 Discussion
 References
 
The spectrum of opinion regarding the treatment of bone defects on the acetabular side of an arthroplasty has ranged from recommendations to avoid the use of bone graft if possible31,47 to suggestions that morseled bone only53 or complex structural grafts41 be used. In some situations, bone stock must be restored because the loss of bone is too extensive for alternatives such as the use of a high hip center or the insertion of either a so-called jumbo cup or an asymmetrical cup. Posterior column defects and pelvic discontinuity with associated loss of bone stock are examples of such situations. Also, patients who are likely to need additional revision operations should have restoration of bone stock in order to facilitate another arthroplasty, should one be necessary41.

There is broad agreement that the use of structural grafts on the acetabular side may be associated with a guarded long-term prognosis and should be avoided if possible1,24,25,31,36,41. Rates of failure as high as 47 per cent (fourteen of thirty hips) have been reported at ten years36. However, there are situations in which bulk allograft must be used. If used properly, bulk allograft can provide a successful clinical result without the need for a revision for at least five years and can supply bone stock for additional procedures24.

Bone grafts can be classified as heterogenous grafts (bone from another species), allografts (bone from the same species), and autogenous grafts (bone from another part of the anatomy of the same individual). Because of the quantity and quality of bone that often is needed for revision operations, an allograft is usually more practical than an autogenous graft. There are, however, certain advantages and disadvantages associated with each type of graft.

Autogenous grafts have the advantages of being non-immunogenic and, even more importantly, of being best able to induce new-bone formation by the host. Their main disadvantages are that the supply of available bone is limited and that the strength, shape, and form of the graft usually cannot duplicate those of the bone that originally was present at the site of the deficit.

Allografts, in contrast, are available in large quantity, can have very good initial strength, and can be shaped to fit almost any deficit. However, they are expensive, immunogenic7,8,37, and not as effective as autogenous grafts for inducing new-bone formation7,8,18. Allograft bone can be further classified as morseled or structural, depending on how it is used.

Morseled bone (fragments of cancellous bone ranging from five to ten millimeters in diameter) is used as a filler scaffold in contained defects. It can undergo revascularization and remodeling, and it strengthens with time. If morseled bone is used with a cup that is designed to be inserted without cement, at least 50 per cent of the cup should make contact with host bone and screws probably will be necessary for fixation56. If it is not possible for at least 50 per cent of the cup to make contact with host bone, then a roof-reinforcement ring and a cup that is designed to be inserted with cement25, or, alternatively, the technique of cementing into impacted bone53, should be used.

The term simulated structural graft is used when bone from another anatomical region is shaped to fit the deficit. For example, the distal aspect of a femur can be sculpted to duplicate an acetabulum. The condyles can be reamed to accept an acetabular cup, and the metaphysis can provide bone for internal fixation to the ilium. Alternatively, a femoral head from either a male donor or a premenopausal female donor can be sculpted to the desired shape.

The term anatomical structural graft is used when the bone is from the same anatomical part as that being duplicated. For example, an acetabular allograft can be used, in whole or in part, to replace an acetabular defect. We have found anatomical grafts easier to shape than simulated grafts. Theoretically, an anatomical graft is better able to withstand the biomechanical forces subsequently placed on it. We prefer to use an anatomical graft, but, if one is not available, then a simulated graft is acceptable.

The advantages of structural grafts include the potential to restore the anatomy and to provide structural support for the implant. The disadvantage of these grafts is that revascularization and remodeling can lead to resorption or collapse, or both; in other words, the grafts weaken with time.

A structural graft is indicated for the treatment of an uncontained defect when it is necessary to restore the anatomy and the limb length and to provide bone support for the implant. However, if the anatomy and the limb length are acceptable and adequate bone stock is available, we prefer to use an alternative method, such as placement of the cup at a high hip center47. If a high hip center is used, lateralization of the implant should be avoided and there should be enough bone stock to allow the component to be seated, with or without cement, against healthy host bone36,47. The limb-length discrepancy must be compensated for with use of a long-neck femoral component, and impingement of the femoral neck against the ischium must be avoided47.

A structural allograft may fail because of resorption or fragmentation24. It is therefore important to use an implant that extends from host bone to host bone, thereby bridging and protecting the graft. It also is important to use strong bone. Allograft bone that is obtained from the femoral head of a postmenopausal woman should be used in morseled form only. For structural grafting of the acetabulum, it has been our custom to use acetabular allografts because they are strong and can be readily sculpted to fit segmental defects in this area. These grafts are fixed with cancellous-bone screws, and, if they support more than 50 per cent of the cup, they are protected with a reconstruction ring. Alternatives to the use of a whole acetabular allograft include excision arthroplasty27 and the insertion of a custom implant.

When a structural allograft is employed, it is important to use morseled autogenous graft, which usually is available in the operative field, for bone-grafting of the host bone-allograft junctions because allograft bone has poor bone-induction properties18.

If an infection is suspected, it must be ruled out before allograft reconstruction and revision arthroplasty is performed. Technetium, gallium, or indium scanning as well as aspiration of the hip may be helpful for this purpose2,23,34. If, at the time of the operation, the findings on gross examination, gram-staining, or frozen-section analysis lead to a suspicion of infection, the reconstruction should be carried out in two stages in order to avoid bone-grafting into an infected site.


   Classification of Bone Defects
Top
 Introduction
 Principles of Bone-Grafting
 Classification of Bone Defects
Operative Technique
 Results
 Discussion
 References
 
It is important to have a functional, relatively simple system for the classification of bone defects associated with loose hip implants. Although more complicated systems have been described in the literature9,43, we have classified acetabular defects as follows. Type-I, or cavitary, defects are contained; that is, the acetabular walls and columns are intact (Figs. 1-A, 1-B, 1-C, 1-D through 1-E). A central defect, even if it involves more than 50 per cent of the acetabulum, may be considered contained as long as the acetabular rim and columns are intact and there is enough bone for the fixation of a cup or ring. Type-II, or segmental, defects are uncontained; that is, they involve structural bone loss. Type-II defects can be classified further as type-IIA defects (those involving less than 50 per cent of the acetabulum) and type-IIB defects (those involving at least 50 per cent of the acetabulum). Type-IIA defects involve loss of part of the rim and the corresponding structural wall (Figs. 2-A, 2-B, 2-C, 2-D, 2-E, 2-F through 2-G), and type-IIB defects involve loss of one column or both with an associated defect of the corresponding wall or walls, with or without pelvic discontinuity (Figs. 3-A, 3-B, 3-C through 3-D).



View larger version (19K):
[in this window]
[in a new window]
  		Figs. 1-A through 1-E: Type-I defects. Fig. 1-A: Schematic drawing showing a contained cavitary defect of the acetabulum.

 


View larger version (71K):
[in this window]
[in a new window]
  		Fig. 1-B: Radiograph of the hip of a thirty-year-old man, made five years after a hemiarthroplasty was performed because of avascular necrosis of the femoral head, showing a contained cavitary defect with superomedial protrusion.

 


View larger version (89K):
[in this window]
[in a new window]
  		Fig. 1-C: Radiograph made eleven years after a revision arthroplasty was performed with use of morseled allograft bone and a porous-coated cup inserted without cement.

 


View larger version (91K):
[in this window]
[in a new window]
  		Fig. 1-D: Radiograph of the hip of a sixty-five-year-old woman, made ten years after a hemiarthroplasty was performed because of a fracture, showing a contained defect with protrusion.

 


View larger version (87K):
[in this window]
[in a new window]
  		Fig. 1-E: Radiograph made four years after a revision arthroplasty was performed with use of morseled allograft bone, a roof-reinforcement ring, and a cup inserted with cement.

 


View larger version (20K):
[in this window]
[in a new window]
  		Figs. 2-A through 2-G: Type-IIA segmental defects (those involving less than 50 per cent of the acetabulum). Fig. 2-A: Schematic drawing showing a type-IIA defect.

 


View larger version (18K):
[in this window]
[in a new window]
  		Fig. 2-B: Schematic drawing showing a high hip center. The socket is placed high so that the cup can be placed primarily against host bone for the treatment of a minor column defect.

 


 Fig. 2-C: Schematic drawing showing the use of a structural minor column allograft fixed with two cancellous-bone screws. A so-called flying-buttress graft consisting of autogenous morseled cancellous bone is placed between the structural allograft and the ilium. (Reproduced, with modification, from: Gross, A. E., and Solomon, M.: The flying buttress acetabular bone-graft. J. Arthroplasty, 12: 707, 1997. Reprinted with permission.)

 


View larger version (74K):
[in this window]
[in a new window]
  		Fig. 2-D: Radiograph of the hip of a fifty-year-old woman, made ten years after a total hip arthroplasty performed with cement.

 


View larger version (77K):
[in this window]
[in a new window]
  		Fig. 2-E: Radiograph made nine years after a revision arthroplasty was performed with use of a minor column allograft and a cup inserted without cement. The graft was fixed with two obliquely directed cancellous-bone screws. There has been minor resorption of the lateral non-weight-bearing part of the graft.

 


View larger version (80K):
[in this window]
[in a new window]
  		Fig. 2-F: Radiograph of the hip of a seventy-year-old woman, made eight years after a bipolar arthroplasty.

 


View larger version (109K):
[in this window]
[in a new window]
  		Fig. 2-G: Radiograph made seven years after a revision was performed with use of a high hip center. The use of a high hip center allowed the cup to be placed against host bone rather than cement or bone graft. The bone stock was adequate, and the limb length was not a problem.

 


 Figs. 3-A through 3-D: Type-IIB segmental defects (those involving at least 50 per cent of the acetabulum). Fig. 3-A: Schematic drawing showing a type-IIB defect with pelvic discontinuity. (Reprinted, with permission, from: Garbuz, D.; Morsi, E.; Mohamed, N.; and Gross, A. E.: Classification and reconstruction in revision acetabular arthroplasty with bone stock deficiency. Clin. Orthop., 324: 102, 1996.)

 


 Fig. 3-B: Schematic drawing showing reconstruction with use of a major column allograft involving more than 50 per cent of the acetabulum. The graft is held with two cancellous-bone screws and is protected with a reconstruction ring extending from the host bone of the ilium to the host bone of the ischium. (Reprinted, with permission, from: Garbuz, D.; Morsi, E.; Mohamed, N.; and Gross, A. E.: Classification and reconstruction in revision acetabular arthroplasty with bone stock deficiency. Clin. Orthop., 324: 102, 1996.)

 


 Fig. 3-C: Radiograph of the hip of a sixty-two-year-old woman, made ten years after a total hip replacement performed with cement, showing a type-IIB segmental defect with pelvic discontinuity. (Reprinted, with permission, from: Garbuz, D.; Morsi, E.; Mohamed, N.; and Gross, A. E.: Classification and reconstruction in revision acetabular arthroplasty with bone stock deficiency. Clin. Orthop., 324: 102, 1996.)

 


 Fig. 3-D: Radiograph made four years after a revision arthroplasty was performed with a major column graft. The graft was fixed with two cancellous-bone screws and was protected with a reconstruction ring. The ring was fixed to the host bone of the ilium and the host bone of the ischium, bridging the graft. (Reprinted, with permission, from: Garbuz, D.; Morsi, E.; Mohamed, N.; and Gross, A. E.: Classification and reconstruction in revision acetabular arthroplasty with bone stock deficiency. Clin. Orthop., 324: 102, 1996.)

 
These defects usually can be classified on the basis of plain radiographs. However, the final decision regarding treatment depends on the intraoperative findings after the cement and membrane have been excised. Therefore, an inventory of morseled and structural bone should be available at the time of the operation.


   Operative Technique
Top
 Introduction
 Principles of Bone-Grafting
 Classification of Bone Defects
 Operative Technique
Results
 Discussion
 References
 

Approach
A contained defect of the acetabulum can be reconstructed through any conventional approach, often without the need for a trochanteric osteotomy. For a structural defect, we prefer to have access to the anterior and posterior columns; therefore, we use a transtrochanteric approach (a so-called trochanteric slide)17. This type of osteotomy preserves more stability than does a transverse trochanteric osteotomy because the trochanter remains in continuity with the abductor and vastus lateralis muscles and tendons, making trochanteric migration unlikely. If more exposure is needed, the trochanteric slide can be converted to a transverse osteotomy by releasing the vastus lateralis. In our experience, the prevalence of non-union and trochanteric migration associated with the classic transverse osteotomy was unacceptably high (25 per cent; thirty-two of 130 hips)26.

A Steinmann pin is inserted into the iliac crest, and the distance between the pin and a fixed point on the resected trochanteric bed is measured as a reference for limb length. The sciatic nerve should be identified, particularly if limb-lengthening of more than three centimeters is anticipated.

The acetabulum is prepared after the hip has been dislocated. After the acetabular component and the cement have been removed, the interface membrane is gently excised. The defect then is defined by means of visualization, palpation, and the insertion of a trial cup. After the defect has been classified as cavitary or segmental, the decision is made as to which types of reconstruction and bone graft are to be used. Much of this decision-making can be done preoperatively on the basis of the radiographic findings, but the final decision is based on the intraoperative findings.

Preparation of the Graft
The allograft bone, which has been deep-frozen and irradiated at a dose of 2.5 megarad (25,000 gray), is not unwrapped until infection in the host joint has been ruled out and the bone defect has been classified. After the graft has been unwrapped and specimens have been obtained for culture, the graft is thawed in a warm, 50 per cent Betadine (povidone-iodine) solution. After the bone has thawed, it is prepared on a separate table. If morseled bone is needed, morselization may be carried out manually with use of rongeurs or with use of a bone mill that does not make the bone too mushy. Alternatively, previously prepared morseled bone can be obtained from some bone banks in freeze-dried or deep-frozen form. The pieces should be approximately three to five millimeters in diameter.

A structural allograft can be prepared from an acetabulum, a femoral head (from either a male donor or a premenopausal female donor), or the distal part of a femur.

The allograft bone is rinsed with a mixture of one-third 3 per cent hydrogen peroxide and two-thirds normal saline solution and then is rinsed with bacitracin (30,000 units in 1000 milliliters of normal saline solution) before it is placed into the acetabular bed. This is our preferred mixture of cleansing solutions, although we have no data to support this combination. As the allograft bone is dead and irradiated, these solutions have no negative effect of which we are aware.

Type-I Defects (Figs. 1-A, 1-B, 1-C, 1-D through 1-E)
Morseled bone is compacted into the cavitary defect with use of reamers in the reverse mode. A porous-coated acetabular implant that is designed to be inserted without cement can be used if it is possible for at least 50 per cent of the cup to make contact with host bone. Screws usually are needed for fixation.

If it is not possible for at least 50 per cent of the cup to make contact with bleeding host bone, we use a roof-reinforcement ring of the Müller design (Sulzer, Bern, Switzerland), which is impacted superomedially and is held with two or three cancellous-bone screws that are directed into the dome. The cup then is cemented into the ring. It is important that the rim of the ring be in contact with host bone superolaterally and inferiorly or it will not be stable and will loosen, possibly leading to breakage of the screws. If the ring is sitting completely on morseled bone inferiorly, then a reconstruction ring that provides support from the ilium superiorly to the ischium inferiorly should be used.

Type-IIA Defects (Figs. 2-A, 2-B, 2-C, 2-D, 2-E, 2-F through 2-G)
A structural acetabular allograft is used for the treatment of type-IIA segmental defects, which involve less than 50 per cent of the acetabulum. The size and shape of the graft are determined with a trial cup in place. A minor column allograft, also termed a shelf graft, which supports less than 50 per cent of the cup, is fixed with two 4.5-millimeter cancellous-bone screws. Because at least 50 per cent of the cup will be in contact with host bone, the cup can be inserted either with or without cement. If the cup is inserted without cement, screws probably will be required. A so-called flying-buttress graft consisting of autogenous morseled cancellous bone is placed between the proximal surface of the structural allograft and the ilium (Fig. 2-C). If possible, the cut surface of the allograft should not be placed in contact with host soft tissue in order to minimize resorption.

Type-IIB Defects (Figs. 3-A, 3-B, 3-C through 3-D)
Type-IIB segmental defects, which involve at least 50 per cent of the acetabulum, may be associated with pelvic discontinuity. Most commonly, these defects are posterior and superior. An acetabular allograft involving at least 50 per cent of the acetabulum is fashioned to fit the defect and is fixed with two 6.5-millimeter cancellous-bone screws that are directed into residual host bone, usually superoposteriorly. Any associated cavitary defects are filled with morseled bone. A Burch-Schneider reconstruction ring (Sulzer) that extends from the ilium to the ischium is used to protect the graft; two or three cancellous-bone screws are inserted for fixation at both sites. If fixation of the screws to the ischium is not adequate, then that part of the ring can simply be buttressed against or slotted into the ischium. Because less than 50 per cent of the cup will be in contact with host bone, the cup must be inserted with cement.

The surgeon should try to make contact between at least 50 per cent of the cup and host bone so that a minor column or shelf graft (rather than a major column graft) can be used, for reasons that will be discussed in the Results section of this paper.

Morseled bone and a roof-reinforcement ring are used for cavitary defects only. A reconstruction ring that spans the defect from the ilium to the ischium is used for segmental defects that involve at least 50 per cent of the acetabulum. In the latter situation, we prefer to use a well fixed structural graft rather than morseled bone because a structural graft will be load-sharing. If morseled bone is used, it will not be load-sharing until it remodels. During the remodeling period, therefore, the ring will bear the entire load; theoretically, this situation could cause the ring to fatigue and break.

Overview
In summary, cavitary defects are treated with impacted, morseled allograft bone. If at least 50 per cent of the cup will be in contact with host bone, the cup can be inserted without cement, usually with screw fixation. Otherwise, a roof-reinforcement ring should be used and the cup should be inserted with cement. If a segmental defect cannot be treated by placement of the cup at a high hip center, a structural allograft is used. We attempt to make contact between at least 50 per cent of the cup and host bone so that a minor column or shelf graft can be used. If it is not possible for at least 50 per cent of the cup to make contact with host bone, a major column graft is used. Under these circumstances, the graft should be protected with a reconstruction ring and the cup should be inserted with cement.


   Results
Top
 Introduction
 Principles of Bone-Grafting
 Classification of Bone Defects
 Operative Technique
 Results
Discussion
 References
 
Between January 1, 1982, and January 1, 1997, 502 hips were revised with use of allograft bone at Mount Sinai Hospital, University of Toronto. Four hundred and eighteen of the hips had a revision involving the acetabulum. Of these, 244 hips were revised with use of morseled allograft bone; sixty-seven, with use of a minor column allograft; and 107, with use of a major column allograft.

Eleven (4.5 per cent) of the 244 hips that were revised with use of morseled allograft bone had a repeat revision by January 1, 1997. Seven hips had a repeat revision because of recurrent dislocations and four, because of loosening of the cup. Fifty-one of the 244 hips were studied after a minimum duration of follow-up of five years (average, 6.8 years); the rate of success in that study was 90 per cent16. Success was defined as an increase of at least 20 points in the modified Harris hip score, a stable cup (no migration of the cup or fractures of the cement), and no need for an additional operation on the acetabular side. Four hips needed an additional operation on the acetabular side.

Six (9 per cent) of the sixty-seven hips that were revised with use of a minor column allograft had a repeat revision by January 1, 1997. Twenty-nine of the sixty-seven hips were studied after a minimum duration of follow-up of five years (average, 7.1 years); the rate of success, as already defined, was 86 per cent39. Four patients needed an additional operation on the acetabular side. Three patients had marked resorption of the graft, and two of them needed an additional operation because of loosening of the cup. One patient had an excision arthroplasty because of loosening of the cup. Another patient had exploration of the joint because of pain, but the graft was intact and the cup was solidly fixed.

Thirty (28 per cent) of the 107 hips that were revised with use of a major column allograft had a repeat revision by January 1, 1997. Ten of these thirty hips had an excision arthroplasty, and the other twenty were revised successfully. The reasons for the excision arthroplasties included loosening of the cup (three hips), infection (three hips), dislocation (two hips), fracture (one hip), and non-union (one hip). The reasons for the other twenty revisions included loosening of the cup (fourteen hips), dislocation (five hips), and sciatic-nerve injury (one hip). Thirty-three of the 107 hips were studied after a minimum duration of follow-up of five years (average, 7.1 years); eighteen (55 per cent) had a successful result15. In that study, success was defined as an increase of at least 20 points in the hip score; a stable cup and a united, structurally intact allograft; and no need for an additional operation related to the acetabulum. Six hips had an additional operation because of loosening of the cup, but the graft was intact and united. One hip had an additional operation for exploration of a sciatic-nerve injury. These seven hips were considered to have had a partially successful result because no additional bone-grafting was necessary. Eight other hips needed an additional operation because of failure of the graft. The overall success rate was therefore 76 per cent (twenty-five of thirty-three hips).

In the entire group of 502 hips that had a femoral or acetabular revision with restoration of bone stock, the complications included two deaths related to the operation, four vascular and nine nerve injuries, forty-one dislocations (prevalence, 8.2 per cent), and twelve infections (prevalence, 2.4 per cent).


   Discussion
Top
 Introduction
 Principles of Bone-Grafting
 Classification of Bone Defects
 Operative Technique
 Results
 Discussion
References
 
Revision arthroplasty of the hip on the acetabular side is a controversial topic among orthopaedic surgeons. A variety of solutions has been proposed. Although there is agreement that a stable interface must be achieved, the indications for restoration of bone stock, particularly with use of structural allografts, continue to be debated.

The use of morseled allograft bone for the treatment of cavitary defects is well accepted, and the results have been universally good28,42,51,52,54,58. Morseled allograft bone can be used in conjunction with cups inserted with or without cement as well as cups inserted with cement and a ring. Heekin et al., in a retrieval study of three cups that had been inserted without cement in conjunction with morseled allograft bone, reported excellent remodeling and incorporation after an average duration of follow-up of fifty-one months28. Silverton et al. also investigated the use of morseled allograft bone in conjunction with cups that were inserted without cement; those authors reported excellent clinical and radiographic results and a rate of revision of 11 per cent (thirteen of 115 hips) after an average duration of follow-up of 100 months51,52. Slooff et al., in a study on the use of impacted allograft bone in conjunction with cups that were inserted with cement, reported excellent clinical and radiographic results for seventy-eight (89 per cent) of eighty-eight hips after an average duration of follow-up of seventy months54. At our center, the use of impacted allograft bone and a roof-reinforcement ring in conjunction with a cup inserted with cement yielded a successful result for fifteen of sixteen hips after an average duration of follow-up of seven years16.

The use of a structural graft is more of a challenge, and mixed results have been reported in the literature3,15,36,43. Shinar and Harris reported a rate of failure of more than 60 per cent in a study of seventy structural grafts that had been followed for an average of 16.5 years50. Such results have led to the need for alternative solutions. A high hip center allows for contact between the host bone and the acetabular component, making it possible for bone to grow into a cup that has been inserted without cement. This technique produced acceptable intermediate-term results at forty months in the study by Schutzer and Harris49, and it certainly is preferable to the use of a structural graft under some conditions. In order for the technique to be successful, the cup should not be lateralized, contact must be made with healthy bleeding bone, and limb length must be correctable with use of a long-neck or calcar-replacement femoral component.

Under certain circumstances, however, the use of a structural graft is indicated. In younger patients, for example, bone stock should be restored because of the potential for additional revision operations; therefore, if such a patient has a defect that is not contained, a structural graft should be used. Ideally, the graft should support less than 50 per cent of the cup because the results are much worse when a structural graft supports more than 50 per cent of the cup16. There are occasions, however, when the graft must support more than 50 per cent of the cup; in such situations, the prognosis is more guarded15.

A structural graft also is indicated when alternatives such as the use of a high hip center or a so-called jumbo cup are not technically possible. This is more likely to be the case when the patient has a posterior column defect or a defect that is associated with pelvic discontinuity.

Our experience with the use of allograft bone for revision arthroplasty of the hip has taught us that, in order to optimize the result, a number of principles should be adhered to. Cavitary defects should be treated with morseled bone. If at least 50 per cent of the cup will be in contact with host bone, then the cup can be inserted without cement; otherwise, it should be inserted with cement and a roof-reinforcement ring should be used. If a structural graft is necessary, at least 50 per cent of the cup should make contact with host bone. If less than 50 per cent of the cup will make contact with host bone, the cup should be cemented to the allograft and the allograft should be protected with an internal fixation device that extends from the ilium to the ischium.

The adherence to good operative principles and the use of good-quality bone from accredited banks have improved the results of restoration of bone stock with allograft bone on the acetabular side. The results associated with the use of morseled bone16 and minor column structural grafts39 have been encouraging and reproducible. These types of grafts are used widely. The use of major column grafts, which support more than 50 per cent of the acetabular component, is more controversial, and the prognosis is more guarded15. In some situations, however, the only alternative to the use of such a graft is an excision arthroplasty. In tertiary-care centers that specialize in revision or tumor procedures, the results have been encouraging, although the use of these grafts is still associated with a high rate of repeat revision15. Improvements in implants designed to be used as fixation devices for allografts should yield even better results15. The quality of the allograft tissue is also important. Optimally, female donors should be less than fifty-five years old and male donors, less than sixty years old, especially when a structural graft is needed. Allograft bone that is obtained from the femoral head of a postmenopausal woman should be used in morseled form only.

Transmission of disease is a potential hazard associated with the use of allograft bone. There are documented instances of transmission of hepatitis C, hepatitis B, and the human immunodeficiency virus through the use of bone allografts6,57. Deep-freezing alone does not notably decrease the risk. Radiation, administered at a dose of 2.5 megarad (25,000 gray), eliminates all bacteria as well as hepatitis B and C and markedly decreases the bioburden of the human immunodeficiency virus5,6,13. A dose of at least 3.0 megarad (30,000 gray) is needed to completely eliminate the DNA of the virus5,13; however, such a dose would substantially weaken the bone10. It is therefore imperative that strict screening procedures be adhered to and that the bone bank be accredited30,40. Properly screened blood carries a one in 493,000 risk of transmission of the human immunodeficiency virus48, whereas properly screened deep-frozen bone that has not been irradiated carries a one in 1,667,600 risk of transmission of the human immunodeficiency virus4. Radiation administered at a dose of 2.5 megarad (25,000 gray) decreases the risk further but does not eliminate it completely. Antigen tests that narrow the window period for viral detection, and the use of secondary sterilization, have notably decreased the risk of transmission of disease.

Most large tissue banks offer the surgeon a choice of deep-frozen, deep-frozen and irradiated, and freeze-dried bone. Bone that is used in structural grafts is most commonly deep-frozen or deep-frozen and irradiated. A combination of processing and freeze-drying reduces or eliminates viable organisms but decreases the torsional and bending strength of bone45; therefore, we do not use freeze-dried bone for structural grafts.

Allograft bone has limited bone-induction properties18. These bone-induction properties are decreased further by irradiation10.

In conclusion, restoration of bone stock in revision arthroplasty of the acetabulum remains a challenging problem. The use of morseled bone for the treatment of cavitary defects and the use of structural grafts that support less than 50 per cent of the cup have provided reproducible, encouraging results. Structural grafts that support more than 50 per cent of the cup are associated with a more guarded prognosis, but in some situations there is no alternative to their use. It is therefore imperative that surgeons who perform arthroplasty develop techniques to improve the performance of these large grafts rather than abandon their use. Better-quality bone and improved internal fixation devices have yielded encouraging results at some tertiary-care centers, but more research in these areas is required. Transmission of disease is a cause for concern throughout the entire field of transplantation, but it is of particular concern in the field of orthopaedic surgery, where the problems usually are not life-threatening but, rather, quality-of-life threatening.


   Footnotes
 
*Printed with permission of The American Academy of Orthopaedic Surgeons. This article will appear in Instructional Course Lectures, Volume 48, The American Academy of Orthopaedic Surgeons, Rosemont, Illinois, March 1999.

{dagger}No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

{ddagger}Division of Orthopaedic Surgery, Mount Sinai Hospital, Suite 476(A), 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. E-mail address: allan.gross@utoronto.ca.

§Department of Orthopaedics, The University of British Columbia, Third Floor, 910 West 10th Avenue, Vancouver, British Columbia V5Z 4E3, Canada.

#910-943 West Broadway, Vancouver, British Columbia V5Z 4E1, Canada.

**25 El-Mohteseb Street, Mohdram Bak, Alexandria, Egypt.


   References
Top
 Introduction
 Principles of Bone-Grafting
 Classification of Bone Defects
 Operative Technique
 Results
 Discussion
 References
 

  1. Allan, D. G.; Lavoie, G.; and Gross, A. E.: Complications of small fragment allograft reconstruction in revision total hip arthroplasty. In Complications of Limb Salvage. Prevention, Management and Outcome, pp. 285-287. Edited by K. L. B. Brown. Montreal, International Symposium on Limb Salvage, 1991.
  2. Barrack, R. L., and Harris, W. H.: The value of aspiration of the hip joint before revision total hip arthroplasty. J. Bone and Joint Surg., 75-A: 66-76, Jan. 1993.[Abstract/Free Full Text]
  3. Brick, G. W.; Tsahakis, P. J.; and Sledge, C. G.: Solid allograft reconstruction of acetabular deficiencies. In Total Hip Revision Surgery. Bristol-Myers Squibb/Zimmer Orthopaedic Symposium, pp. 325-333. Edited by J. O. Galante, A. G. Rosenberg, and J. J. Callaghan. New York, Raven Press, 1995.
  4. Buck, B. E.; Malinin, T. I.; and Brown, M. D.: Bone transplantation and human immunodeficiency virus. An estimate of risk of acquired immunodeficiency syndrome (AIDS).. Clin. Orthop., 240: 129-136, 1989.
  5. Campbell, D. G.; Li, P.; Stephenson, A. J.; and Oakeshott, R. D.: Sterilization of HIV by gamma irradiation. A bone allograft model. Internat. Orthop., 18: 172-176, 1994.[Medline]
  6. Conrad, E. U.; Gretch, D. R.; Obermeyer, K. R.; Moogk, M. S.; Sayers, M.; Wilson, J. J.; and Strong, D. M.: Transmission of the hepatitis-C virus by tissue transplantation. J. Bone and Joint Surg., 77-A: 214-224, Feb. 1995.[Abstract/Free Full Text]
  7. Czitrom, A. A.: Immunology of bone and cartilage allografts. In Allografts in Orthopaedic Practice, pp. 15-25. Edited by A. A. Czitrom and A. E. Gross. Baltimore, Williams and Wilkins, 1992.
  8. Czitrom, A. A.; Gross, A. E.; Langer, F.; and Sim, F. H.: Bone banks and allografts in community practice. In Instructional Course Lectures, The American Academy of Orthopaedic Surgeons. Vol. 37, pp. 13-24. Park Ridge, Illinois, The American Academy of Orthopaedic Surgeons, 1988.
  9. D'Antonio, J. A.; Capello, W. N.; Borden, L. S.; Burgar, W. L.; Bierbaum, B. F.; Boettcher, W. G.; Steinberg, M. E.; Stulberg, S. D.; and Wedge, J. H.: Classification and management of acetabular abnormalities in total hip arthroplasty. Clin. Orthop., 243: 126-137, 1989.
  10. Eastlund, D. T.: Infectious hazards of bone allograft transplantation: reducing the risk. In Orthopaedic Allograft Surgery, pp. 11-28. Edited by A. Czitrom and H. Winkler. New York, Springer, 1996.
  11. Engh, C. A., Sr., and Macalino, G. E.: Clinical results of cementless revision surgery. Are we doing better using extensively porous-coated stems? In Total Hip Revision Surgery. Bristol-Myers Squibb/Zimmer Orthopaedic Symposium, pp. 295-303. Edited by J. O. Galante, A. G. Rosenberg, and J. J. Callaghan. New York, Raven Press, 1995.
  12. Estok, D. M., II, and Harris, W. H.: Long-term results of cemented femoral revision surgery using second-generation techniques. An average 11.7-year follow-up evaluation. Clin. Orthop., 299: 190-202, 1994.
  13. Fideler, B. M.; Vangsness, C. T., Jr.; Moore, T.; Li, Z.; and Rasheed, S.: Effects of gamma irradiation on the human immunodeficiency virus. A study in frozen human bone-patellar ligament-bone grafts obtained from infected cadavera. J. Bone and Joint Surg., 76-A: 1032-1035, July 1994.[Abstract/Free Full Text]
  14. Freeman, M. A. R.; Bradley, G. W.; and Revell, P. A.: Observations upon the interface between bone and polymethylmethacrylate cement. J. Bone and Joint Surg., 64-B(4): 489-493, 1982.[Abstract/Free Full Text]
  15. Garbuz, D.; Morsi, E.; and Gross, A. E.: Revision of the acetabular component of a total hip arthroplasty with a massive structural allograft. Study with a minimum five-year follow-up. J. Bone and Joint Surg., 78-A: 693-697, May 1996.[Abstract/Free Full Text]
  16. Garbuz, D.; Morsi, E.; Mohamed, N.; and Gross, A. E.: Classification and reconstruction in revision acetabular arthroplasty with bone stock deficiency. Clin. Orthop., 324: 98-107, 1996.
  17. Glassman, A. H.; Engh, C. A.; and Bobyn, J. D.: A technique of extensile exposure for total hip arthroplasty. J. Arthroplasty, 2:211-21,21987.
  18. Goldberg, V. M., and Stevenson, S.: Biology of bone and cartilage allografts. In Allografts in Orthopaedic Practice, pp. 1-13. Edited by A.2A. Czitrom and A. E. Gross. Baltimore, Williams and Wilkins, 1992.
  19. Goldring, S. R.; Jasty, M.; Roelke, M. S.; Rourke, C. M.; Bringhurst, F. R.; and Harris, W. H.: Formation of a synovial-like membrane at the bone-cement interface. Its role in bone resorption and implant loosening after total hip replacement. Arthrit. and Rheumat., 29: 836-842, 1986.
  20. Goldring, S. R.; Schiller, A. L.; Roelke, M.; Rourke, C. M.; O'Neill, D. A.; and Harris, W. H.: The synovial-like membrane at the bone-cement interface in loose total hip replacements and its proposed role in bone lysis. J. Bone and Joint Surg., 65-A: 575-584, June 1983.[Abstract/Free Full Text]
  21. Goodman, S. B.; Schatzker, J.; Sumner-Smith, G.; Fornasier, V. L.; Gotfen, N.; and Hunt, C.: The effect of polymethylmethacrylate on bone: an experimental study. Arch. Orthop. and Traumatic Surg., 104: 150-154, 1985.
  22. Grauer, J. D.; Amstutz, H. C.; O'Carroll, P. F.; and Dorey, F. J.: Resection arthroplasty of the hip. J. Bone and Joint Surg., 71-A: 669-678, June 1989.[Abstract/Free Full Text]
  23. Gristina, A. G., and Kolkin, J.: Current concepts review. Total joint replacement and sepsis. J. Bone and Joint Surg., 65-A: 128-134, Jan. 1983.[Free Full Text]
  24. Gross, A. E.: Revision arthroplasty of the hip using allograft bone. In Allografts in Orthopaedic Practice, pp. 147-174. Edited by A. A. Czitrom and A. E. Gross. Baltimore, Williams and Wilkins, 1992.
  25. Gross, A. E.: Reconstruction of the acetabulum. In Total Hip Revision Surgery. Bristol-Myers Squibb/Zimmer Orthopaedic Symposium, pp. 335-345. Edited by J. O. Galante, A. G. Rosenberg, and J. J. Callaghan. New York, Raven Press, 1995.
  26. Gross, A. E.; Hutchison, C. R.; Alexeeff, M.; Mahomed, N.; Leitch, K.; and Morsi, E.: Proximal femoral allografts for reconstruction of bone stock in revision arthroplasty of the hip. Clin. Orthop., 319: 151-158, 1995.
  27. Harris, W. H., and White, R. E., Jr.: Resection arthroplasty for nonseptic failure of total hip arthroplasty. Clin. Orthop., 171: 62-67, 1982.
  28. Heekin, R. D.; Engh, C. A.; and Vinh, T.: Morselized allograft in acetabular reconstruction. A postmortem retrieval analysis. Clin. Orthop., 319: 184-190, 1995.
  29. Howie, D.; Oakeshott, R.; Manthy, B.; and Vernon-Roberts, B.: Bone resorption in the presence of polyethylene wear particles. In Proceedings of the Australian Orthopaedic Association. J. Bone and Joint Surg., 69-B(1): 165, 1987.
  30. Jacobs, N. J.: Establishing a surgical bone bank. In Tissue Banking, pp. 67-96. Edited by K. Fawcett and A. Barr. Arlington, Virginia, American Association of Blood Banks, 1987.
  31. Jasty, M., and Harris, W. H.: Salvage total hip reconstruction in patients with major acetabular bone deficiency using structural femoral head allografts. J. Bone and Joint Surg., 72-B(1): 63-67, 1990.
  32. Jasty, M., and Harris, W. H.: Cementless acetabular revisions. In Total Hip Revision Surgery. Bristol-Myers Squibb/Zimmer Orthopaedic Symposium, pp. 317-323. Edited by J. O. Galante, A. G. Rosenberg, and J. J. Callaghan. New York, Raven Press, 1995.
  33. Jasty, M. J.; Floyd, W. E.; Schiller, A. L.; Goldring, S. R.; and Harris, W. H.: Localized osteolysis in stable, non-septic total hip replacement. J. Bone and Joint Surg., 68-A: 912-919, July 1986.[Abstract/Free Full Text]
  34. Johnson, J. A.; Christie, M. J.; Sandler, M. P.; Parks, P. F., Jr.; Hamra, L.; and Kaye, J. J.: Detection of occult infection following total joint arthroplasty using sequential technetium-99m HDP bone scintigraphy and indium-111 WBC imaging. J. Nucl. Med., 29: 1347-1353, 1988.[Abstract/Free Full Text]
  35. Kostuik, J., and Alexander, D.: Arthrodesis for failed arthroplasty of the hip. Clin. Orthop., 188: 173-182, 1984.
  36. Kwong, L. M.; Jasty, M.; and Harris, W. H.: High failure rate of bulk femoral head allografts in total hip acetabular reconstructions at 10 years. J. Arthroplasty, 8: 341-346, 1993.[Medline]
  37. Langer, F.; Czitrom, A.; Pritzker, K. P.; and Gross, A. E.: The immunogenicity of fresh and frozen allogeneic bone. J. Bone and Joint Surg., 57-A: 216-220, March 1975.[Abstract/Free Full Text]
  38. Linder, L.; Lindberg, L.; and Carlsson, Å.: Aseptic loosening of hip prostheses. A histologic and enzyme histochemical study. Clin. Orthop., 175: 93-104, 1983.
  39. Morsi, E.; Garbuz, D.; and Gross, A. E.: Revision total hip arthroplasty with shelf bulk allografts. A long-term follow-up study. J. Arthroplasty, 11: 86-90, 1996.[Medline]
  40. Mowe, J. C. [editor]: Standards for Tissue Banking. Arlington, Virginia, American Association of Tissue Banks, 1984.
  41. Oakeshott, R. D.; Morgan, D. A. F.; Zukor, D. J.; Rudan, J. F; Brooks, P. J.; and Gross, A. E.: Revision total hip arthroplasty with osseous allograft reconstruction. A clinical and roentgenographic analysis. Clin. Orthop., 225: 37-61, 1987.
  42. Padgett, D. E.; Kull, L.; Rosenberg, A.; Sumner, D. R.; and Galante, J. O.: Revision of the acetabular component without cement after total hip arthroplasty. Three to six-year follow-up. J. Bone and Joint Surg., 75-A: 663-673, May 1993.[Abstract/Free Full Text]
  43. Paprosky, W. G.; Perona, P. G.; and Lawrence, J. M.: Acetabular defect classification and surgical reconstruction in revision arthroplasty. A 6-year follow-up evaluation. J. Arthroplasty, 9: 33-44, 1994.[Medline]
  44. Pazzaglia, U. E.; Ceciliani, L.; Wilkinson, M. J.; and Dell'Orbo, C.: Involvement of metal particles in loosening of metal-plastic total hip prostheses. Arch. Orthop. and Traumatic Surg., 104: 164-174, 1985.
  45. Pelker, R. R.; Friedlaender, G. E.; and Markham, T. C.: Biomechanical properties of bone allografts. Clin. Orthop., 174: 54-57, 1983.
  46. Revell, P. A.; Weightman, B.; Freeman, M. A.; and Roberts, B. V.: The production and biology of polyethylene wear debris. Arch. Orthop. and Traumatic Surg., 91: 167-181, 1978.
  47. Russotti, G. M., and Harris, W. H.: Proximal placement of the acetabular component in total hip arthroplasty. A long-term follow-up study. J. Bone and Joint Surg., 73-A: 587-592, April 1991.[Abstract/Free Full Text]
  48. Schreiber, G. B.; Busch, M. P.; Kleinman, S. H.; and Korelitz, J. J.: The risk of transfusion-transmitted viral infections. New England J. Med., 334: 1685-1690, 1996.[Abstract/Free Full Text]
  49. Schutzer, S. F., and Harris, W. H.: High placement of porous-coated acetabular components in complex total hip arthroplasty. J. Arthroplasty, 9: 359-367, 1994.[Medline]
  50. Shinar, A. A., and Harris, W. H.: Bulk structural autogenous grafts and allografts for reconstruction of the acetabulum in total hip arthroplasty. Sixteen-year-average follow-up. J. Bone and Joint Surg., 79-A: 159-168, Feb. 1997.[Abstract/Free Full Text]
  51. Silverton, C. D.; Rosenberg, A. G.; Sheinkop, M. B.; Kull, L. R.; and Galante, J. O.: Revision total hip arthroplasty using a cementless acetabular component. Technique and results. Clin. Orthop., 319: 201-208, 1995.
  52. Silverton, C. D.; Rosenberg, A. G.; Sheinkop, M. B.; Kull, L. R.; and Galante, J. O.: Revision of the acetabular component without cement after total hip arthroplasty. A follow-up note regarding results at seven to eleven years. J. Bone and Joint Surg., 78-A: 1366-1370, Sept. 1996.[Abstract/Free Full Text]
  53. Slooff, T. J.; Schimmel, J. W.; and Buma, P.: Cemented fixation with bone grafts. Orthop. Clin. North America, 24: 667-677, 1993.[Medline]
  54. Slooff, T. J. J. H.; Buma, P.; Schreurs, B. W.; Schimmel, J. W.; Huiskes, R.; and Gardeniers, J.: Acetabular and femoral reconstruction with impacted graft and cement. Clin. Orthop., 324: 108-115, 1996.
  55. Stromberg, C. W.; Herberts, P. G.; and Hultmark, P. N.: Cemented acetabular revisions. In Total Hip Revision Surgery. Bristol-Myers Squibb/Zimmer Orthopaedic Symposium, pp. 311-316. Edited by J. O. Galante, A. G. Rosenberg, and J. J. Callaghan. New York, Raven Press, 1995.
  56. Tanzer, M.; Drucker, D.; Jasty, M.; McDonald, M.; and Harris, W. H.: Revision of the acetabular component with an uncemented Harris-Galante porous-coated prosthesis. J. Bone and Joint Surg., 74-A: 987-994, Aug. 1992.[Abstract/Free Full Text]
  57. Tomford, W. W.: Current concepts review. Transmission of disease through transplantation of musculoskeletal allografts. J. Bone and Joint Surg., 77-A: 1742-1754, Nov. 1995.[Free Full Text]
  58. Woolson, S. T., and Adamson, G. J.: Acetabular revision using a bone-ingrowth total hip component in patients who have acetabular bone stock deficiency. J. Arthroplasty, 11: 661-667, 1996.[Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 JBJSHome page
E. Winter, M. Piert, R. Volkmann, F. Maurer, C. Eingartner, K. Weise, and S. Weller
Allogeneic Cancellous Bone Graft and a Burch-Schneider Ring for Acetabular Reconstruction in Revision Hip Arthroplasty
J. Bone Joint Surg. Am., June 1, 2001; 83(6): 862 - 867.
[Abstract] [Full Text]

This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF) Free
Right arrow Letters to the Editor: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Letters to the Editor are posted
Right arrow Alert me if a correction is posted
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowReprints and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by GROSS, A. E.
Right arrow Articles by MOHAMED, E. M. Z.
Right arrow Search for Related Content
PubMed
Right arrow Articles by GROSS, A. E.
Right arrow Articles by MOHAMED, E. M. Z.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Technorati  
What's this?