7/27/2019 BMP haste

http://slidepdf.com/reader/full/bmp-haste 1/4

806 THE JOURNAL OF BONE AND JOINT SURGERY

! CASE REPORT

Intramedullary application of bone

morphogenetic protein in the management of a major bone defect after an Ilizarovprocedure

K. J. Burkhart,P. M. Rommens

From University

Hospital Mainz,Mainz, Germany

! K. J. Burkhart, MD, Resident

Trauma Surgery

! P. M. Rommens, MD, PhD,

DirectorDepartment of Trauma Surgery,

University Hospital Mainz,

Langenbeckstrasse 1, 55131

Mainz, Germany.

Correspondence should be sent

to Dr K. J. Burkhart; e-mail:

burkhart@unfall.klinik.uni-

mainz.de

©2008 British Editorial Society

of Bone and Joint Surgery

doi:10.1302/0301-620X.90B6.

20147 $2.00

J Bone Joint Surg [Br] 

2008;90-B:806-9.

Received 24 August 2007; 

Accepted after revision 23 January 2008 

We describe a patient with insufficient bone regeneration of the tibia after bone transport

over an intramedullary nail, in whom union was ultimately achieved after exchange nailing

and intramedullary application of rh-bone morphogenetic protein-7 at the site of distraction.

The Ilizarov technique is widely used in the

treatment of patients with leg-length discrep-

ancy, deformity of an extremity and for bone

defects after resection of tumours or surgical

debridement for infection. In most patients,

bone regenerates uneventfully during distrac-

tion or transport through an osseous defect,

and then consolidates successfully. For the

occasional failure, different solutions such as

shortening of the bone or cancellous grafting

have been used. We present such a patient in

whom union was eventually achieved after

exchange nailing and the use of a morphoge-netic protein at the site of distraction.

Case report

A 12-year-old girl developed a pleomorphic

rhabdomyosarcoma of the proximal right tibia.

A wide local excision, radiation therapy includ-

ing the whole lower leg and chemotherapy were

undertaken at another hospital. Activity of the

proximal tibial growth plate ceased after the

radiation and the proximal tibia became

necrotic over at least 5 cm. She suffered a

fatigue fracture of the proximal tibia two yearsafter the initial treatment. This was treated with

an above-knee plaster cast. The tibia healed

with a significant varus deformity. Six months

later, the deformity was corrected with a valgus

osteotomy and stabilised with a broad medial

buttress plate, which was retained for 2.5 years.

A second fatigue fracture occurred, four months

after removal of this plate. This was also treated

in a cast, but failed to heal leading to a stiff atro-

phic pseudarthrosis (Fig. 1). On several occa-

sions, bone biopsies were taken. Histological

examination showed large areas of bone necro-sis, but no local recurrence of the tumour.

She presented to us for the first time at the

age of 19. At that time, she had 3.5 cm of 

shortening of the right lower leg, severe muscle

wasting and a varus deformity of 10º at the

level of the atrophic pseudarthrosis. She

limped significantly, and was unable to partic-

ipate in sports or dancing.

We recommended staged surgical pro-

cedures to solve the problems of atrophic

pseudarthrosis, varus deformity and shorten-

ing, beginning with complete resection of the

Fig. 1

Anteroposterior and lateral radiographsshowing atrophic pseudarthrosis of a recur-rent fatigue fracture of the right proximaltibia (arrows). There is varus malalignmentof 10º and disturbance of the bone structure

following osteosynthesis, radiation andchemotherapy.

7/27/2019 BMP haste

http://slidepdf.com/reader/full/bmp-haste 2/4

APPLICATION OF BMP IN THE MANAGEMENT OF A MAJOR BONE DEFECT AFTER AN ILIZAROV PROCEDURE 807

VOL. 90-B, No. 6, JUNE 2008

necrotic bone, correction of the varus deformity and stabi-

lisation with an intramedullary nail. We also planned to fill

the defect by a bone transport at a later stage and to con-

tinue tibial lengthening.

During the first operation, nearly 7 cm of the proximal

tibia was resected and consisted mostly of necrotic bone.

The remaining part of the proximal tibia contained only the

medial and lateral condyles and the tuberosity, and was

4 cm long. In order to enable correction of the deformity, a

fibular osteotomy was carried out 8 cm below the proximal

end of the fibula, with resection of 1 cm of bone. A custom-

made intramedullary nail was implanted to hold the frag-ments in their correct positions (Fig. 2). Interlocking screws

were introduced into the proximal 5 cm of the nail and

were directed in three different planes at 45º oblique

towards the medial condyle, 45º oblique towards the lateral

condyle and in the sagittal plane from the tibial tuberosity

towards the popliteal fossa. The posterior cortices were not

perforated. The screws fitted tightly into the nail to create

high stability in all planes.1,2 The distal end of the nail also

had three interlocking screws. Wound healing was unevent-

ful. Six weeks later, a midshaft corticotomy was performed

and an external fixator placed with two Schanz screws in

both the intermediate and the distal fragments. No bridging

external fixation was placed across the ankle joint. A week

later, transport of the segment was begun at 1 mm per day

from distal to proximal. When the transported segment

reached the proximal tibial docking site, a cancellous bone

graft was added to promote healing. Since the leg was still

3.5 cm short, distraction of the regenerated segment was

continued with the same external fixator. This required

removal of the three distal interlocking screws. Because of 

the rigidity of the crural musculature, lengthening of only

2.5 cm was obtained (Fig. 3). A rigid pes equinovarusdeformity developed which was corrected by lengthening of 

the tendo Achillis and the tendon of tibialis posterior,

together with release of the capsule of the ankle. Complete

correction could not be achieved and the amount gained

was maintained with a plaster cast for six weeks. After

lengthening, the nail was locked again with three distal

screws, three months after the beginning of the lengthening

procedure.

She was allowed to mobilise with half of her body weight

on the right leg. Bone remodelling progressed very slowly in

the distraction zone. There was still incomplete filling of the

area with new cortical bone, although she was asymptomatic

1.5 years later. Since further bone formation had ceased, an

exchange nailing was carried out. Five consecutive reamings

Fig. 2

Radiographs following resectionof 7 cm of necrotic bone and sta-bilisation of the proximal and dis-tal fragments with an unreamedintramedullary nail prior to callusdistraction.

Fig. 3

Following lengthening, the dis-tal interlocking screws havebeen removed. The tip of theintramedullary nail is now situ-ated 2.5 cm above the ankle

 joint (arrows). Cancellous bonegrafting has been performed atthe docking site to encouragebony healing. Callus can beseen on the dorsolateral site of 

the diaphyseal defect.

7/27/2019 BMP haste

http://slidepdf.com/reader/full/bmp-haste 3/4

808 K. J. BURKHART, P. M. ROMMENS

THE JOURNAL OF BONE AND JOINT SURGERY

were carried out using heads increasing from 9 mm to 11 mm

in steps of 0.5 mm. All the reaming debris were carefully col-

lected, the volume being about 10 cm3. It was then mixed

with one dose of rh-bone morphogenetic protein (BMP)-7

(Osigraft, OP-1 Stryker Biotech, Hopkinton, Massachusetts).

A tube and an impactor were used to place the mixture care-

fully in the intramedullary canal in the most proximal part of 

the bone defect. Its position was checked with image intensi-

fication. The nail was then smoothly introduced with small

rotary movements. Although some distal migration of the

mixture was seen, most remained at the level of the bone

defect. The nail was locked with three screws both proxi-mally and distally (Fig. 4). Regeneration of cortical bone then

resumed and healing appeared complete six months later.

There was a slight but acceptable collapse of the medial pla-

teau after removing of a loose medial oblique locking screw.

At 2.5 years from the final intervention, the patient has no

complaints. She is able to walk without crutches, has normal

knee function but limited movement in the ankle. The tibia

remains 1 cm short, is fully united and has radiological evi-

dence of remodelling (Fig. 5). Due to the rigidity of the foot in

slight equinovarus, sport and dancing are still limited.

Discussion

This patient presented with a complex surgical problem.

Resection of the tumour at the level of the proximal tibia

followed by irradiation and chemotherapy was curative,

but at the cost of destruction of the growth plate and necro-

sis of the metaphysis and the proximal part of the shaft.

The first osteotomy using fixation with a broad plate prob-

ably increased the local bone necrosis. As with post-

traumatic or chronic osteomyelitis, resection of necrotic

bone was required in order to restore viable bone with poten-

tial for healing. An Ilizarov procedure with distal corticot-

omy and retrograde transport of the intermediate fragment

seemed to be the best solution to fill the large defect.3-6 A

custom-made intramedullary nail and three interlocking

screws in the proximal and distal fragments provided enoughstability for the Ilizarov procedure.7 We carried out the

transport corticomy in the shaft instead of the biologically

more favourable distal metaphysis in order to avoid prob-

lems with fixation of a short distal segment. Retrograde bone

transport occurred without problems. Subsequent leg length-

ening was limited by the development of a rigid pes equino-

varus, which persisted in spite of tendon lengthening.

Recombinant bone morphogenetic protein-7 promotes

and accelerates healing in persistent nonunion in long

bones.8-12 The BMPs have a great osteoinductive capability

as they promote the differentiation of pluripotential mesen-

chymal cells into osteochondrogenic lineage cells.13,14 They

can be placed together with blood and cancellous bone

grafts in the fracture gap.15,16 In our patient, the size of the

Fig. 4

Radiographs immediately afterexchange nailing. The collectedspongiosa reamings have beenmixed with rh-bone morphoge-netic protein-7 and placed in theintramedullary canal at the level of the defect.

Fig. 5

Anteroposterior, lateral and oblique radio-graphs two and a half years after exchangenailing and application of rh-bone morphoge-netic protein-7 showing consolidation withabundant callus.

7/27/2019 BMP haste

http://slidepdf.com/reader/full/bmp-haste 4/4

APPLICATION OF BMP IN THE MANAGEMENT OF A MAJOR BONE DEFECT AFTER AN ILIZAROV PROCEDURE 809

VOL. 90-B, No. 6, JUNE 2008

defect was such that the volume of the mixture of BMP,

blood and cancellous bone grafts would have been too small

to completely fill the existing defect. Intramedullary applica-

tion of rh-BMP-7 offered a promising solution in that it

allowed placement of the bone reamings at the level of thedefect,17 giving an intramedullary rather than an external

bone graft.18,19 Some benefit has also been shown in a rabbit

model.16 Exchange nailing is an accepted procedure to pro-

mote healing in long bone pseudarthrosis but is not always

successful.20-22 However, the use of rh-BMP-7 in combina-

tion with exchange intramedullary nailing was associated

with rapid bone regeneration. We do not know whether the

combination of reaming, enhanced mechanical stability and

rh-BMP-7 application, or one of these factors alone was

responsible for the healing in the presented case, but each

can make a contribution to bone healing.8,10-12,17,22

No benefits in any form have been received or will be received from a commer-cial party related directly or indirectly to the subject of this article.

References1. Hansen M, Mehler D, Rommens P. Das biomechanische Verhalten winkelstabiler 

Implantatsysteme an der proximalen Tibia . Bern: Verlag Hans Huber, 2004;110 (in German).

2. Laflamme GY, Heimlich D, Stephen D, Kreder HJ, Whyne CM. Proximal tibial

fracture stability with intramedullary nail fixation using oblique interlocking screws. J 

Orthop Trauma 2003;17:496-502.

3. Ilizarov GA. Clinical application of the tension-stress effect for limb lengthening.

Clin Orthop 1990;250:8-26.

4. Raschke MJ, Mann JW, Oedekoven G, Claudi BF. Segmental transport after

unreamed intramedullary nailing: preliminary report of a “Monorail” system. Clin 

Orthop 1992;282:233-40.

5. Robert Rozbruch S, Weitzmann AM, Tracy Watson J, et al. Simultaneous treat-

ment of bone and soft-tissue defects with the Ilizarov method. J Orthop Trauma 

2006;20:197-205.

6. Kocaoglu M, Eralp L, Rashid HU, Sen C, Bilsel K. Reconstruction of segmental

defects due to chronic osteomyelitis with use of an external fixator and an intramed-

ullary nail. J Bone Joint Surg [Am] 2006;88-A:2137-45.

7. Kuhn S, Hansen M, Rommens PM. Extending the indication of intramedullary nail-

ing of tibial fractures. Eur J Trauma Emerg Surg 2007;33:159-69.

8. Dimitriou R, Dahabreh Z, Katsoulis E, et al.Application of recombinant BMP-7 on

persistant upper and lower limb non-unions. Injury 2005;36(2Suppl):51-9.

9. Ronga M, Baldo F, Zappala G, Cherubino P. Recombinant human bone morphoge-

netic protein-7 for treatment of long bone non-union: an observational, retrospective,non-randomized study of 105 patients. Injury 2006;37(Suppl):51-6.

10. Friedlaender GE, Perry CR, Cole JD, et al. Osteogenic protein-1 (bone morpho-

gentic protein-7) in the treatment of tibial nonunions: a prospective, randomized clin-

ical trial comparing rhOP-1 with fresh bone autograft. J Bone Joint Surg [Am] 

2001;83-A(Suppl 1):151-8.

11. Fabeck L. Ghafil D, Gerroudj M, Baillon R, Delincé Ph.Bone morphogenetic pro-

tein 7 in the treatment of congenital pseudarthrosis of the tibia. J Bone Joint Surg [Br] 

2006;88-B:116-18.

12. Pluhar GE, Turner AS, Pierce AR, Toth CA, Wheeler DL. A comparison of two

carriers for osteogenic protein-1 (BMP-7) in an ovine critical defect model. J Bone 

Joint Surg [Br] 2006;88-B:960-6.

13. Obert L, Deschaseaux F, Garbuio P. Critical analysis and efficacy of BMPs in long

bones non-union. Injury 2005;36(Suppl):38-42.

14. Urist MR. Bone: formation by autoinduction. Science 1965;698:893-9.

15. Johnson EE, Urist MR. One stage lengthening of femoral non-union augmented

with human bone morphogenetic protein. Clin Orthop 1998;347:105-16.

16. Watanabe K, Tsuchiya H, Sakurakichi K, Tomita K. Bone transport using hydrox-

apatite loaded with bone morphogenetic protein in rabbits. J Bone Joint Surg [Br] 

2007;89-B:1122-9.

17. Hammer TO, Wieling R, Green JM, et al. Effect of reimplanted particles from

intramedullary reaming on mechanical properties and callus formation: a laboratory

study. J Bone Joint Surg [Br] 2007;89-B:1534-8.

18. Frolke JP, Bakker FC, Patka P, Haarmann HJ. Reaming debris in osteotomized

sheep tibiae. J Trauma 2001;50:65-70.

19. Wenisch S, Trinkaus K, Hild A, et al. Human reaming debris: a source of multipo-

tent stem cells. Bone 2005;36:74-83.

20. Weresh MJ, Hakanson R, Stover MD, et al. Failure of exchange reamed intramed-

ullary nails for ununited femoral shaft fractures. J Orthop Trauma 2000;14:335-8.

21. Banaszkiewicz PA, Sabboubeh A, McLeod I, Maffulli N.Femoral exchange nail-ing for aseptic non-union: not the end to all problems. Injury 2003;34:349-56.

22. Court-Brown CM, Keating JF, Christie J, McQueen MM. Exchange intramedul-

lary nailing: its use in aseptic tibial non-union. J Bone Joint Surg [Br] 1995;77-B:407-

11.