1. Clin Orthop Relat Res
DOI 10.1007/s11999-008-0556-1
SYMPOSIUM: ADVANCES IN LIMB LENGTHENING AND RECONSTRUCTION
Periosteal Grafting for Congenital Pseudarthrosis of the Tibia
A Preliminary Report
Ahmed M. Thabet MD, Dror Paley MD, Mehmet Kocaoglu MD,
Levent Eralp MD, John E. Herzenberg MD, Omer Naci Ergin MD
Ó The Association of Bone and Joint Surgeons 2008
Abstract The results of treatment of congenital pseudar- angular deformities. We used bisphosphonate as adjuvant
throsis of the tibia (CPT) are frequently unsatisfactory therapy in three patients with refracture without subsequent
because of the need for multiple operations for recalcitrant refracture. We performed no amputations in these 20
nonunion, residual deformities, and limb-length discrepan- patients. All patients were braced through skeletal maturity.
cies (LLD). Although the etiology of CPT is basically Combining periosteal and bone grafting, IM nailing, and
unknown, recent reports suggest the periosteum is the pri- Ilizarov fixation is an effective treatment. IM nailing
mary site for the pathologic processes in CPT. We decreases the severity of subsequent fracture.
hypothesized complete excision of the diseased periosteum Level of Evidence: Level IV, therapeutic study. See the
and the application of a combined approach including free Guidelines for Authors for a complete description of levels
periosteal grafting, bone grafting, and intramedullary (IM) of evidence.
nailing of both the tibia and fibula combined with Ilizarov
fixation would improve union rates and reduce refracture
rates. We retrospectively reviewed 20 patients at two cen- Introduction
ters. The minimum followup was 2 years (mean, 4.3 years;
range, 2–10.7 years). Union was achieved after the primary Congenital pseudarthrosis of the tibia (CPT) is challenging
operation in all patients. Ten refractures occurred in eight of because of the weak healing power of the dysplastic seg-
the 20 patients (two each in two patients, one each in six ment [4, 5, 7, 30, 31], the tendency to refracture until
patients). Seven patients underwent seven secondary sur- skeletal maturity [4, 5, 7, 30, 31], and the difficulty of
gical procedures to simultaneously treat refracture and stabilizing small osteoporotic bone fragments in small
children [4, 5, 7, 30, 31]. Various techniques for the man-
agement of CPT have been described. McFarland [30]
One author (DP) is a consultant for Smith & Nephew, Inc. described a bypass fibular graft. Boyd [4] and Boyd and
(Memphis, TN) and receives royalties from Pega Medical Sage [5] described a double onlay graft taken from the
(Laval, Quebec, Canada). opposite tibia combined with autologous iliac crest graft.
Each author certifies that his or her institution has approved the
human protocol for this investigation, that all investigations were Charnley [7] described intramedullary (IM) rods, and
conducted in conformity with ethical principles of research, and that Sofield [38] added fragmentation and reversal of fragments.
informed consent for participation in the study was obtained. Campanacci and Zanoli [6] described a ‘‘fibula pro tibia’’
technique with fibular fixation to the pseudarthrosis site.
A. M. Thabet, D. Paley (&), J. E. Herzenberg
Other methods include direct current or pulsed electro-
Rubin Institute for Advanced Orthopedics, Sinai Hospital
of Baltimore, 2401 West Belvedere Avenue, Baltimore, magnetic field [34, 35], ipsilateral transfer of the fibula [31]
MD 21215-5271, USA or contralateral free vascularized fibular transfer [12, 13,
e-mail: dpaley@lengthening.us 15, 16, 24, 36, 39, 41], circular external fixation [14, 16, 33,
39, 40], IM rodding [7, 10, 11, 21, 23, 26], and combined
M. Kocaoglu, L. Eralp, O. N. Ergin
Department of Orthopedic Surgery and Traumatology, Istanbul external fixation and IM rodding [14, 16, 33]. Recently,
School of Medicine, University of Istanbul, Istanbul, Turkey bone morphogenetic protein (BMP) [27, 37] and
123

2. Table 1. Review of the literature showing age at surgery, duration of followup, and limb-length discrepancy (LLD)
Author(s) Number of Classification Average age at index Average postoperative Average LLD (range)
patients (Cases) (number surgery in years (range) followup in years (range)
123
of patients) Preoperative Postoperative
Thabet et al.
Lee et al. [27] 5 Crawford [9] 6 (0.6–13) 1.2 (1–1.5) 3.3 cm (1–5 cm) NP
III (3)
IV (2)
El-Gammal et al. 3 Dysplastic (3) 9.7 (7–12) 2.2 (1.5–3) 7 cm (5–10 cm) 0.2 cm (0–0.5 cm)
[13]
Toh et al. [39] 7 Boyd [4] -Type II (7) 2.8 (1.1–5.3) 12.5 (7.3–16.7) NP 1.4 cm (0–6.5 cm)
Paley et al. [33] 15 (16) Andersen [1] 8 (2–17) 4 (2–7) 4 cm (1–8 cm) NP
Cystic (3)
Sclerotic (4)
Dysplastic (9)
Grill et al. [16] 108* Crawford [9] 7.36 (1.2–26) NP NP NP
Type I (6)
Type II (17)
Type III (19)
Type IV (18)
Gilbert and 29 NP 5.5 (0.7–13.6) 11.5 (6–16) 3.5 cm (0–9 cm) NP (0–11 cm)
Brockman [15]
Dobbs et al. [10] 21 Boyd [4] 5.1 (0.9–11) 14.2 (3–20) NP 5 cm (2–9 cm)
Type I (3)
Type II (9)
Type IV (6)
Type V (3)
Boero et al. [3] 21 Cystic (4) 8.8 (1.3–17) Minimum 2-year followup 6.3 cm (0–19 cm) 1.9 cm (0–12 cm)
Hourglass (11)
Normotrophic (1)
Sclerotic (5)
Weiland et al. [41] 19 Andersen [41] 5.1 (1.4–11.4) 6.3 years (2–11 years) NP 1.6 cm (0–4 cm)
Cystic (7)
Dysplastic (12)
Joseph and 14 (skeletally immature) NP Skeletally immature Skeletally immature NP Skeletally immature = NP
Mathew [23] 5 (skeletally mature) = 4.5 (0.5–11) = 3 (1–5.4) Skeletally mature =
Skeletally mature Skeletally mature 4.5 cm (0–10 cm)
= 18.6 (18–20) = 3.7 (2.3–6.3)
Johnston [21] 23 Crawford [9] 3.7 (0.9–9.4) 9 (4–14) NP NP
Type I (5)
Type II (7)
Type III (3)
Type IV (8)
Clinical Orthopaedics and Related Research

3. Periosteal Grafting for CPT
bisphosphonate therapy [18, 37] have been used. The
3.2 ± 3.3 cm (0–15 cm)
results of all the methods have been variable (Tables 1, 2).
More than 100 years ago, Codivilla [8] suggested the
1.5 cm (0–6 cm)
pathologic abnormality resided in the periosteum.
Postoperative
Although resection of hamartomatous fibrous tissue is part
of many treatment protocols, it does not prevent recur-
rence. El-Rosasy et al. [14] published on Paley’s technique
NP
of periosteal grafting of CPT in 2006 based on experience
Average LLD (range)
with this method since 1995. Weber [40] also reported
NP = not provided; *108 tibiae were treated with the Ilizarov device; data from all patients with clinically relevant LLD. Ten patients had LLD of 2 cm.
3.1 cm (0–9 cm)
experience with periosteal grafting of CPT.
Preoperative
We report our preliminary experience, results, and
complications with the Paley method of periosteal grafting
from two centers including the union rate, refracture rate,
NP
NP
the secondary procedures required to achieve union, repair
fractures, and/or correct angular deformities, and amount
of limb length discrepancy.
followup in years (range)
Average postoperative
6.7 ± 5.7 (3.8–21.1)
Materials and Methods
14.1 (5.4–32.9)
4.3 (2–10.7)
We retrospectively reviewed the charts and radiographs of
20 patients with CPT who were treated with periosteal
grafting and bone grafting combined with IM rodding of the
tibia and fibula and circular external fixation by the senior
surgery in years (range)
authors (DP, JEH, MK, LE) between 1997 and 2006 at two
Average age at index
centers (Table 3). The mean age at the index operation was
4.6 ± 3.5 (0.9–15)
4.2 years (range, 1–11.3 years). Eleven patients (55%) had
neurofibromatosis, in seven patients (35%) the condition
2.5 (0.5–8.8)
4.2 (1–11.3)
was idiopathic, and two patients (10%) had osteofibrous
dysplasia. Twelve patients (60%) had no previous surgery,
and eight patients (40%) had undergone at least one
unsuccessful operation (range, 1–14 unsuccessful proce-
dures). All patients had established pseudarthrosis. The
minimum followup from the index operation was 2 years
Dysplastic (45)
Dysplastic (15)
(mean, 4.3 years; range, 2–10.7 years). The mean preop-
Classification
Sclerotic (20)
Andersen [1]
Andersen [1]
Sclerotic (1)
Type IV (3)
of patients)
Type III (3)
Type II (6)
erative limb-length discrepancy (LLD) was 3.1 cm (range,
Cystic (8)
Cystic (4)
Boyd [4]
(number
0–9 cm). No patient treated by this method during the time
of the study was lost to followup (Table 3).
The patients were classified according to four of the
most commonly used classification systems [1, 4, 9, 14]
(Table 3). Because there is no universal agreement as to
which classification to use, we used all four classification
patients (Cases)
systems to make it possible to compare the results with
Number of
most previously published studies.
The patient was placed supine with a bump under the
11 (12)
ipsilateral buttock on a radiolucent table. The entire lower
73
20
extremity and hemipelvis were prepped and draped free. A
sterile tourniquet was placed on the thigh and inflated after
Table 1. continued
Ohnishi et al. [32]
[Current study]
elevation of the lower limb. For El-Rosasy-Paley types I
Weinstein [26]
and II (Fig. 1A–C), the pseudarthrosis site was approached
Paley et al.
Author(s)
through an anterior longitudinal incision. The thick peri-
Kim and
osteum was incised longitudinally. The periosteal incision
ended at the point at which the periosteum thins to a
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4. Thabet et al. Clinical Orthopaedics and Related Research
Table 2. Review of the literature showing union at final followup and number of refractures
Author(s) Number of Average postoperative Cases that achieved union Number of
patients (cases) followup in years (range) at final followup refractures
Lee et al. [27] 5 1.2 (1–1.5) 1 0
El-Gammal et al. [13] 3 2.2 (1.5–3) 3 1
Toh et al. [39] 7 12.5 (7.3–16.7) 7a 5
Paley et al. [33] 15 (16) 4 (2–7) 16 5 (One leg
refractured twice)
Grill et al. [16] 108b Not provided 82 47
Gilbert and Brockman [15] 29 11.5 (6–16) 28 4
Dobbs et al. [10] 21 14.2 (3–20) 19c 12
Boero et al. [3] 21 Minimum 2-year followup 14 4
Weiland et al. [41] 19 6.3 (2–11) 18 3d
Joseph and Mathew [23] 14 (skeletally immature) Skeletally immature Skeletally immature = 12 Skeletally immature = 0
5 (skeletally mature) = 3 (1–5.4) Skeletally mature = 3 Skeletally mature = 0
Skeletally mature
= 3.7 (2.3–6.3)
Johnston [21] 23 9 (4–14) 11 Not provided
Kim and Weinstein [26] 11 (12) 14.1 (5.4–32.9) 9 4 (One leg
refractured twice)
Ohnishi et al. [32] 73 6.7 ± 5.7 (3.8–21.1) Union = 54 10
Delayed union = 7
Ununited = 7
Amputation = 1
Lost to followup = 4
Paley et al. [Current study] 20 4.3 (2–10.7) 20 10
a
Tibial union achieved in all seven cases; union of the fibula was achieved in only one of the five cases in which both the tibia and fibula were
reconstructed.
b
108 tibiae were treated with the Ilizarov device.
c
Five patients underwent amputation (recalcitrant fracture, two patients; limb-length discrepancy, two patients; chronic lower-extremity
deformity, one patient).
d
Two patients had a fracture through what appeared to be normal bone distal to the vascularized fibular graft. One patient had a non-displaced
fracture of the tibia through a screw hole.
normal thickness. We dissected between the periosteum were shortened by 1 to 2 cm. In a previously unoperated
and the surrounding tissues circumferentially around the case, the only bone resection that was performed was the
tibia. Care must be taken laterally to avoid injury to the minimal required for opening the medullary canal. In a
anterior tibial artery and posteromedially to avoid injury to previously operated case, the tourniquet was released and
the posterior tibial neurovascular bundle. The hamartom- all nonviable bone resected.
atous periosteum was then excised in its entirety. The An IM rod was then inserted across the CPT site. The
proximal segment of the tibia was split in all cases by using implant used depended on age and the diameter of the CPT
multiple drill holes with a Kirschner wire (Fig. 2A–F). bone. One can use a Kirschner wire or Steinmann pin in
These drill holes were usually created in the frontal plane very small-diameter bone or a Rush rod or flexible titanium
then connected with an osteotome. The split was created in rod in larger-diameter bones. The rod was inserted either
such a way that it did not fracture across the tibia proxi- from distal to proximal via the medial malleolus or from
mally. The tibia then resembled an old-fashioned one-piece proximal to distal crossing the proximal physis. Most
wooden clothes pin. The fibular pseudarthrosis was ap- recently, we have used the Paley-modified Fassier-Duval
proached through the same tibial incision. Its periosteal telescopic IM nail system (Pega Medical, Inc., Laval,
hamartoma was also resected. The distal tibia was then Quebec, Canada) from proximal to distal (Figs. 2A–F,
drilled open and its end inserted into the split of the 3A–B, 4A–H). The Paley modification of this nail allows
proximal segment. The proximal fibula was invaginated locking into the distal tibial epiphysis using a Kirschner
into a similar split of the distal fibula. The tibia and fibula wire (Fig. 4A–H). The Paley-modified Fassier-Duval
123

5. Periosteal Grafting for CPT
Table 3. Patient data
Case Age at Diagnosis Classifications LLD (cm) Number of
number surgery previous
(years) El-Rosasy- Boyd [4] Andersen [1] Crawford [9] operations
Paley [14]
1* 7.3 OFD I III Cystic IV 9 11
2* 6.0 Idiopathic I V Dysplastic IV 2.4 0 (bracing
for 6 years)
3* 7.0 NF I II Dysplastic IV 3 0
4* 5.0 Idiopathic II II Dysplastic IV 6.3 3
5* 6.0 NF I II Dysplastic IV 6.5 0
6* 2.0 NF I II Dysplastic IV 0 0
7* 1.2 NF I II Dysplastic IV 2.4 0
8* 1.5 NF I II Dysplastic IV 2 0
9* 2.0 OFD I III Cystic IV 2.5 0
10* 3.0 NF I II Dysplastic IV 4.5 0
11* 1.0 NF I II Dysplastic IV 2.5 0
12* 2.8 NF II II Dysplastic IV 3 2
13 3.6 NF II II Dysplastic IV 0 1
14 3.4 Idiopathic I IV Sclerotic IV 3 1
15 4.3 Idiopathic II II Dysplastic IV 7 2
16 3.4 NF I II Dysplastic IV 1 0
17 6.9 Idiopathic II III Cystic IV 1 2
18 11.3 Idiopathic II II Dysplastic IV 0 14
19 5.6 NF II II Dysplastic IV 5 2
20 1.1 Idiopathic I III Cystic IV 1 0
* Patients who underwent treatment at the U.S. center; patients who underwent treatment at the Turkish center; LLD = limb-length
discrepancy; NF = neurofibromatosis; OFD = osteofibrous dysplasia.
telescopic IM nail system was used in three cases. It is Type l Type lI Type lII
preferable to avoid rodding across the ankle to
prevent stiffness of the joint and permanent poor push-off
strength [21].
An incision was then made along the crest of the ilium.
The apophysis was split and the medial periosteum with the
iliacus muscle reflected medially off the ilium. Cancellous
bone between the tables of the ilium was harvested. If more
bone was needed, the tables were separated under image
intensifier control and the bone in the supra-acetabular
region curetted out. This procedure was especially useful in
very small children. A B C
The medial periosteum of the undersurface of the iliacus
Fig. 1A–C Illustrations show the El-Rosasy-Paley classification of
muscle was then harvested. A knife was used to incise the
CPT: (A) Type I CPT (ie, atrophic [based on radiographic examin-
periosteum in as long and as wide a rectangular piece as ations], mobile, no previous surgery), (B) Type II CPT (ie, atrophic
possible. The periosteum was then separated from the [based on radiographic examinations], mobile, with previous surgery),
overlying muscle. The periosteum immediately shrinks in and (C) Type III CPT (ie, wide ends [based on radiographic
examinations], stiff, with or without previous surgery).
size after it is removed. To restore its size, it was placed
through the skin graft mesher (largest available ratio) and
expanded. The periosteum was then wrapped around the graft and any remaining periosteum were also placed
bone ends of the pseudarthrosis site. The cancellous bone around the fibular site. The wound was then closed over a
graft was placed circumferentially around the pseudar- drain. Recently we have added BMP-2 (Infuse bone graft,
throsis site with the cambium layer facing the bone. Bone Medtronic, Inc., Minneapolis, MN) to the CPT site. One
123

6. Thabet et al. Clinical Orthopaedics and Related Research
A B C D E
F
A B C D E
Fig. 2A–F Treatment for Type I CPT in the lateral and anteropos- Paley modification illustrated) into the fibula and tibia. (D) Periosteal
terior (AP) views is shown. (A) There is longitudinal splitting of the graft is wrapped around the pseudarthrosis and (E) iliac crest bone
proximal tibial and fibular fragments. (B) The bone ends are docked graft is applied to the tibial and fibular docking site. (F) External
and (C) IM rods are inserted (Fassier-Duval telescopic IM nail with fixator is applied.
medium-size package (graft volume, 5.6 cc) of Infuse was osteotomy or hemiepiphysiodesis, equalization of LLD,
used. Infuse bone graft is FDA-approved; however, when it treatment of refracture, pin site problem, rod exchange to a
is used in children or is used to treat CPT, it is considered longer rod, fibular surgery for nonunion after fibular oste-
off-label use. otomy, fibular transport for a short fibula, and distal
After closure, we applied an Ilizarov all-wire frame to tibiofibular synostosis to avoid ankle valgus deformity.
the limb. We used three wires in the proximal metaphysis Followup visits were conducted every month until heal-
(two counterposed olive wires and one smooth wire), three ing was achieved and then every year until skeletal maturity.
distal wires, and foot fixation. The wires should not be in Clinically, we (DP, JEH, MK, LE) assessed pain, ankle
contact with the IM rod. A walking ring was applied range of motion, push-off mechanism, and degree of limp-
postoperatively so the patient does not have to bear weight ing. We obtained erect lower limb radiographs for LLD and
on the foot. residual deformities and anteroposterior and lateral views of
Our approach was to treat associated residual problems the ankle to include the tibia. We (AMT, DP, MK, ONE)
simultaneously with refracture treatment so that the patient assessed radiographs for presence or absence of union, type
would not have to undergo extra surgical procedures. The of union or cross-sectional area, refracture, anterior distal
main indications for secondary surgery after the index tibial angle (ADTA), lateral distal tibial angle (LDTA), and
operation in our series were deformity correction with distal fibular proximal migration in millimeters.
123

7. Periosteal Grafting for CPT
A
Fig. 3A–B continued
123

8. Thabet et al. Clinical Orthopaedics and Related Research
B
Fig. 3A–B (A) Treatment for Type II CPT for cases in which the illustrated) and external fixation is removed (Panels VIII and IX).
bone defect is greater than 3 cm or when the bone ends are dead from (B) Shown is the treatment for Type II CPT for cases in which the
previous surgical treatment is pictured. Resection of dead bone ends bone defect is less than 3 cm. Resection of dead bone ends is
is combined with bone transport (Panels I–V). After the defect is combined with acute docking with shortening (Panels I and II). An IM
eliminated and lengthening is completed, periosteal and bone graft rod is inserted at the resection site and combined with proximal
is applied to the docking site (Panels VI and VII). Once the tibia is osteotomy for lengthening (Panels III–VII). Periosteal and bone graft
healed at both the docking and lengthening sites, an IM rod is inserted is applied to the docking site during the same surgical procedure
(Fassier-Duval telescopic IM nail with Paley modification is (Panels IV and V).
Results Refracture occurred in eight patients: six experienced
one refracture each, and two experienced two refractures
Initial union was achieved in all patients (Tables 4, 5). The each (Table 6). Six of the eight patients with refracture had
mean duration of treatment with external fixation fibular pseudarthrosis. We excised tissue from the recurrent
was 5.2 months (range, 3–12 months). No patients fracture sites and sent these samples to pathology. No
underwent amputation. neurofibromatosis was found. Fibrous hamartoma was
123

9. Periosteal Grafting for CPT
Fig. 4A–H (A) Anteroposterior
(AP) and (B) lateral view radio-
graphs of a 2-year-old boy with
neurofibromatosis and CPT
(Type I) that had not been pre-
viously treated are shown. (C)
AP view radiograph shows split
of the proximal segment with
invagination of the distal seg-
ment, rodding of tibia from
medial malleolus and of fibula
through lateral malleolus, and
application of Ilizarov external
fixator. (D) AP view radiograph
obtained immediately after exter-
nal fixator removed shows union
of the CPT. (E) AP view radio-
graph shows refracture of the
tibia 1 year later. (F) AP view
radiograph shows retreatment
with an Ilizarov device and
rerodding with Fassier-Duval
telescopic IM nail locked in both
proximal and distal epiphysis.
(G, H) Tibia remains healed
2 years later with good remode-
ling. The telescopic nail has
extended with growth.
noted in each case. The mean time between the index patients with refracture were treated with reapplication of
operation and refracture was 2.3 years (range, 1–5.8 years), the frame and bone grafting (because of atrophic ends).
and the mean time between the index operation and second Consequently, one patient underwent proximal osteotomy
refracture was 4.7 years (range, 3–6.4 years). The mean age for tibial lengthening and another underwent rod exchange,
at the index operation of patients who experienced refrac- both simultaneously with refracture treatment. Three re-
ture was 4 years (range, 1–7.3 years). fractures were treated with casting with or without
Five patients in the refracture group had associated bisphosphonate therapy (zoledronic acid). One of the three
deformities treated by osteotomy or hemiepiphysiodesis; refractures healed with casting alone. One was treated with
the other three had no associated deformities (Table 6). a trial of casting for 3 months without healing, and then
Four patients with refracture were treated with reapplica- healing began after zoledronic infusion was initiated. The
tion of the frame for distraction of the stiff wide ends at the third healed after treatment with casting and zoledronic
pseudarthrosis site without bone grafting. One of the four acid infusion started at the time of refracture diagnosis.
patients underwent rod exchange at the time of frame One patient had persistent fibular pseudarthrosis and fibular
application, and another had a Rush rod inserted through shortening at the time of refracture. These conditions ini-
the subtalar joint at the time of frame removal. Two tially were addressed with fibular transport by using the
123

10. Thabet et al. Clinical Orthopaedics and Related Research
Table 4. Results of treatment
Case Cross section Fibular Ankle Followup Number of EFT Lengthening
number area (union type) shortening (mm) ROM (years) refractures (months) amount (cm)
1* N 0 Stiff 6 1 6 6
2* N 13 Full 1.9 1 4 0
3* N 0 Full 2 1 3.5 0
4* N 8 Full 7.6 0 12 6
5* N 0 Full 6 1 4 6.5
6* N 7 Full 9.75 0 5 0
7* N 0 Full 9 2 4 0
8* N 10 Full 10.7 1 4 0, 5 as second stage
9* N 8 Full 4 0 3 0
10* N 3 Full 5 1 3 0
11* N 13 Full 8 2 5 0
12* N 0 Full 5.5 0 4 3
13 N 18 Full 2.4 0 3 7
14 N 3 Full 3 0 6 3
15 A 8 Full 3.9 0 11 1
16 A 10 Full 1.8 0 4 4
17 A 12 Full 2.4 0 5 5
18 A 11 Full 2.75 0 5 3
19 N 9 Full 2.1 0 6 3
20 A 3 Full 1.6 0 8 1
* Patients who underwent treatment at the U.S. center; patients who underwent treatment at the Turkish center; A = atrophic; EFT = duration
of treatment with external fixation; Fibular shortening = the distance in mm between the fibular growth plate and the ankle joint line;
N = normotrophic; ROM = range of motion.
monolateral frame for 3 weeks to maintain ankle valgus Discussion
correction. Ankle valgus correction was achieved with
eight-plate hemiepiphysiodesis before refracture treatment The goal of this study was to report the number of CPT
and then tibiofibular synostosis concurrently with refrac- cases that achieved union at final followup, number of
ture treatment. Bone grafting, BMP-2, and locking plate for refractures, the secondary procedures required to achieve
internal fixation were used for treatment of refracture. The union, repair fractures, and/or correct angular deformities,
patient received adjuvant zoledronic acid after surgery to and amount of limb length discrepancy. The natural history
maintain the bone graft. At the time of publication, the tibia of CPT is recalcitrant nonunion, progressive LLD and
had healed and a tibiofibular synostosis had formed deformity, and recurrent refracture even after initial union
(Table 6). When zoledronic acid was administered to a [4, 5, 20, 25, 28, 31]. The primary objective of treatment
patient, two infusions were given. No rod breakage for CPT is to obtain union. The secondary objective is to
occurred in the refracture group in our series. Nonunion of maintain union. In addition, many associated deformities of
fibular osteotomy occurred in one patient who had bone length and angulation should be addressed in the compre-
grafting at the time of frame removal; fibular transport was hensive management of CPT. Therefore, unless all patients
performed in two patients to correct ankle valgus defor- have reached skeletal maturity, the refracture rate reported
mity. There was no short-term or long-term bone-periosteal is always lower than actual [4, 5, 31].
graft donor site morbidity. None of our patients had We had no control group in this retrospective study and
reached skeletal maturity at the time of publication. it is therefore difficult to know exactly which factor of our
Limb lengthening was achieved in 12 of 20 patients. The combined approach was responsible for the healing of
average limb length discrepancy for 18 patients was 0 cm CPT. None of the patients in our series had reached skeletal
(range, -7 to 3 cm). The mean lengthening amount was maturity, and the average followup from the index opera-
2.5 cm (range, 0–7 cm); epiphysiodesis of the opposite tion was 4.3 years (range, 2–10.7 years). Additional
side was performed in one patient. refractures are expected until patients reach skeletal
123

11. Periosteal Grafting for CPT
Table 5. Results of treatment Weinstein [26] failed to achieve union in three of 12 cases
Case Union LDTA ADTA Pain Push-off Limping
with average age at treatment of 2.5 years (range, 0.5–
number (degrees) (degrees) strength 8.8 years). Ohnishi et al. [32] failed to achieve union in 15
of 73 using a variety of methods in a Japanese multicenter
1* + 88 76 No Weak Moderate
study in which the average age at treatment onset was
2* + 70 85 No Normal No 4.6 years (range, 0.9–15 years). Johnston [21] failed to
3* + 90 96 No Normal No obtain union in three of 23 and had tenuous or possible
4* + 95 86 No Normal No nonunion in nine of 23 using IM rodding for a group of
5* + 90 96 No Normal No patients whose average age at treatment onset was
6* + 90 102 No Normal No 3.7 years (range, 0.9–9.4 years). Dobbs et al. [10] had two
7* + 92 88 No Normal No of 21 cases that did not unite during a long-term followup
8* + 80 102 No Normal No study in which the average age at treatment was 5.1 years
9* + 87 86 No Normal No (range, 0.9–11 years).
10* + 90 85 No Normal No Refracture in our series occurred in eight of 20 patients
11* + 90 90 No Normal No (Table 2). All were retreated and all obtained union of the
12* + 90 90 No Normal No refracture site. One to five refractures occurred in 47 of 108
13 + 83 96 No Normal Minimum patients treated by the Ilizarov method in the multicenter
14 + 62 100 No Impaired Severe EPOS study [16]. Refracture occurred in 12 of 21 patients
15 + 78 89 No Normal Medium treated with IM rodding in the Dobbs et al. [10] study.
16 + 79 100.5 No Normal Minimum Most other studies [26, 33, 39] show similar or higher
17 + 86 84 No Normal Minimum refracture rates for all the various methods. El-Rosasy et al.
18 + 87 83 No Normal Minimum [14] showed the combination of intramedullary nailing
19 + 85 86 No Normal Minimum with external fixation reduced the refracture rate from 68%
20 + 83 78 No Impaired Moderate (with the Ilizarov device alone) to 29% (IM nailing and
external fixation).
* Patients who underwent treatment at the U.S. center; patients who
underwent treatment at the Turkish center; ADTA = anterior distal The use of the Ilizarov device allows simultaneous
tibial angle; LDTA = lateral distal tibial angle. correction of leg-length difference and ankle valgus
(Table 1). The average LLD at the time of review was
maturity. However, we believe the combination treatment 0 cm (range, –7 to 3 cm). Five of 20 patients had LDTA
(ie, periosteal grafting, bone grafting, internal rodding, and outside of the range of 85° to 95° (Table 5). Seven had
Ilizarov fixation) provides the best combination of biologic ADTA outside of the range of 75° to 90° (Table 5). Some
and mechanical properties for healing and is preferable to of these ankles might need additional surgery in the future.
any of these methods in isolation. The recent addition of Since all the patients use protective orthotic devices, the
pharmacologic management including bisphosphonates foot and ankle position has not been symptomatic.
and rhBMP is promising and is consistent with our shotgun As can be seen from the selected group of studies dis-
technique of management. cussed above, all previous methods resulted in recalcitrant
What is remarkable is that all patients in our study CPT in 13% to 50% of cases. All have used one or more
achieved primary union. In comparison, the initial union parts of the method applied in this series (eg, Ilizarov
rate in the EPOS multicenter study using the Ilizarov fixation, bone grafting, IM rodding, BMP, zoledronic acid,
method was 75.5% (82 of 108 patients) [16]. In another limb lengthening). None have combined all these methods
study, initial union was achieved in 17 of 21 patients [3]. or included the use of periosteal grafting.
Using IM rodding alone, unequivocal union was obtained Some authors suggest the results of treatment are better
in only 11 of 23 patients [21]. In two further recent studies when the patient is older [3, 16, 32]. The average age in
on the use of IM rodding, the initial union was achieved in this series is very young (Table 1). Therefore, observing
18 of 21 patients [10] and four of 12 patients [26]. The use such good results with patients who are so young is even
of BMP with IM rodding failed to achieve union in four of more remarkable.
five patients [27]. Of particular note is that all patients are The pathology of CPT is still unknown. During the
united at the time of followup and at the time of writing of past 100 years, a number of theories have been suggested
this manuscript (Tables 1, 2). There is no other series in the to explain the development of the disease. Pathologic
literature with such a high maintained union rate. Boero changes in the periosteum are one factor that could
et al. [3] reported seven of 21 patients with persistent explain the pathologic changes in congenital pseudar-
nonunion at the time of review with average age at throsis of the tibia [17]. Codivilla [8] was the first to
treatment of 8.8 years (range, 1.3–17 years). Kim and suggest the use of osteoperiosteal grafting from the sound
123

12. 123
Thabet et al.
Table 6. Patients with refractures after initial healing
Patient Site of refracture Diagnosis Treatment of fracture Time between index Classifications – Boyd [4], Age at refracture Fibular PA
number operation and El-Rosasy-Paley et al. [14] (years)
refracture (years)
1 Through different lesion OFD Frame without grafting 3.7 III, II 10.4 Yes
2 Original PA site Idiopathic Casting + zoledronic acid 1.3 V, I 8 Yes
therapy + fibular transport and then
regrafting + tibiofibular synostosis
with two screws + BMP-2 and
LCP; after two treatments of
intravenously administered
bisphosphonate, tibia healed
but fibula not completely consolidated
3 Original PA site NF Casting tried for 3 months (no healing 1.5 II, I 9.4 No
noticed); after zoledronic acid,
healing achieved
5 Original PA site NF Regrafting + external 1.0 II, I 7 Yes
fixation + proximal lengthening
7 Original PA site NF First fracture: FractureFrame + rod First refracture, 1.1 II, I First refracture, 2.3 Yes
exchange without regrafting from Second refracture, 6.4 Second refracture, 6.7
titanium nail to FDN
Second fracture: Frame reapplication,
regrafting, and rod exchange
8 Original PA site NF Frame reapplication without grafting 1.3 II, I 2.8 Yes
and then Rush rod subtalar joint
10 Original PA site OFD Casting + zoledronic acid, healing 5.8 III, I 7.9 No
achieved
11 Original PA site NF First fracture: Healed after 3 months First refracture, 2.8 II, I First refracture, 5 Yes
of casting Second refracture, 3.1 Second refracture, 5.3
Second fracture: Frame without grafting
and rod insertion at time of frame removal
BMP = bone morphogenetic protein; FDN = Fassier-Duval telescopic IM nail; LCP = locking compression plate; NF = neurofibromatosis; OFD = osteofibrous dysplasia;
PA = pseudarthrosis.
Clinical Orthopaedics and Related Research

13. Periosteal Grafting for CPT
tibia to provide all the tissues involved in the formation 2. Blauth M, Harms D, Schmidt D, Blauth W. Light- and electron-
and growth of bone, especially the periosteum. microscopic studies in congenital pseudarthrosis. Arch Orthop
Trauma Surg. 1984;103:269–277.
McElvenny [29] reported a markedly thickened, closely 3. Boero S, Catagni M, Donzelli O, Facchini R, Frediani PV.
attached periosteum that caused constriction of the bone Congenital pseudarthrosis of the tibia associated with neurofi-
with subsequent atrophy and pseudarthrosis. The findings bromatosis-1: treatment with Ilizarov’s device. J Pediatr Orthop.
presented by McElvenny were echoed by Boyd [4] and 1997;17:675–684.
4. Boyd HB. Pathology and natural history of congenital pseudar-
Boyd and Sage [5], who suggested that CPT was caused throsis of the tibia. Clin Orthop Relat Res. 1982;166:5–13.
by aggressive osteolytic fibromatosis and that those find- 5. Boyd HB, Sage FP. Congenital pseudarthrosis of the tibia. J Bone
ings had been confirmed by specimens of amputated legs. Joint Surg Am. 1958;40:1245–1270.
Blauth et al. [2] reported the findings of a pathology study 6. Campanacci M, Zanoli S. Double tibiofibular synostosis (fibula
pro tibia) for non-union and delayed union of the tibia: end-result
of 10 patients with CPT and postulated the thickened revıew of one hundred seventy-one cases. J Bone Joint Surg Am.
periosteum might be caused by myofibroblast overgrowth 1966;48:44–56.
[19]. A recent report [17] suggested the thickened peri- 7. Charnley J. Congenital pseudarthrosis of the tibia treated by
osteum was caused by neural-like cells that form a tight intramedullary nail. J Bone Joint Surg Am. 1956;38:283–290.
8. Codivilla A. On the cure of the congenital pseudoarthrosis of the
sheath around the small periosteal vessels, causing nar- tibia by means of periosteal transplantation. J Bone Joint Surg
rowing or obliteration of the vessels. This results in Am. 1906;s2–4:163–169.
disturbance of the blood circulation of the periosteum, 9. Crawford AH. Neurofibromatosis in childhood. Instr Course
which in turn results in impaired oxygen and nutrient Lect. 1981;30:56–74.
10. Dobbs MB, Rich MM, Gordon JE, Szymanski DA, Schoenecker
supply of the subperiosteal bone with subsequent fracture PL. Use of an intramedullary rod for treatment of congenital
and recalcitrant nonunion. pseudarthrosis of the tibia: a long-term followup study. J Bone
There is reason to believe combining BMP and bis- Joint Surg Am. 2004;86:1186–1197.
phosphonate treatment with zoledronic acid may be a 11. Dobbs MB, Rich MM, Gordon JE, Szymanski DA, Schoenecker
PL. Use of an intramedullary rod for the treatment of congenital
useful adjunct. In a review of CPT, Johnston and Birch [22] pseudarthrosis of the tibia: surgical technique. J Bone Joint Surg
advocated using BMP as an adjuvant treatment in all pri- Am. 2005;87(Suppl 1):33–40.
mary and recalcitrant cases. Despite optimism with the use 12. Dormans JP, Krajbich JI, Zuker R, Demuynk M. Congenital
of BMP, one must also consider theoretical risk of pseudarthrosis of the tibia: treatment with free vascularized fib-
ular grafts. J Pediatr Orthop. 1990;10:623–628.
tumorigenesis because BMP stimulates the RAS pathway, 13. El-Gammal TA, El-Sayed A, Kotb MM. Telescoping vascular-
which is also a tumor pathway. Patients with CPT have a ized fibular graft: a new method for treatment of congenital tibial
propensity for both benign and malignant tumors. Although pseudarthrosis with severe shortening. J Pediatr Orthop B.
there has never been a report of such a complication, it 2004;13:48–56.
14. El-Rosasy MA, Paley D, Herzenberg JE. Congenital pseudar-
should be discussed with patients since rhBMP is not FDA- throsis of the tibia. In: Rozbruch SR, Ilizarov S, eds. Limb
approved for children or for CPT. Lengthening and Reconstruction Surgery. New York: Informa
CPT is a biological problem as well as a mechanical Healthcare; 2007:485–493.
problem [31]. Many pathologic studies confirm periosteum 15. Gilbert A, Brockman R. Congenital pseudarthrosis of the tibia:
long-term followup of 29 cases treated by microvascular bone
plays a key role in the pathogenesis of CPT. Our protocol transfer. Clin Orthop Relat Res. 1995;314:37–44.
of combined procedures addresses both mechanical and 16. Grill F, Bollini G, Dungl P, Fixsen J, Hefti F, Ippolito E,
biologic aspects of the disease, including complete excision Romanus B, Tudisco C, Wientroub S. Treatment approaches for
of diseased periosteum and the use of combined bone congenital pseudarthrosis of tibia: results of the EPOS multi-
center study: European Paediatric Orthopaedic Society (EPOS).
grafting and periosteal grafting with Ilizarov external fix- J Pediatr Orthop B. 2000;9:75–89.
ation and IM rodding of both the tibia and fibula to achieve 17. Hermanns-Sachweh B, Senderek J, Alfer J, Klosterhalfen B,
and maintain union. ¨ ¨
Buttner R, Fuzesi L, Weber M. Vascular changes in the perios-
teum of congenital pseudarthrosis of the tibia. Pathol Res Pract.
Acknowledgments We thank Alvien Lee and Abigail K. Myers, 2005;201:305–312.
BS, for their assistance in preparing the figures for publication; Joy ¨
18. Hogler W, Yap F, Little D, Ambler G, McQuade M, Cowell CT.
Marlowe, MA, for her assistance with the illustrations; and Stacy Short-term safety assessment in the use of intravenous zoledronic
C. Specht, MPA, for her assistance with data analysis. The authors acid in children. J Pediatr. 2004;145:701–704.
also thank Amanda Chase, MA, and Dori Kelly, MA, for their 19. Ippolito E, Corsi A, Grill F, Wientroub S, Bianco P. Pathology of
editorial expertise. bone lesions associated with congenital pseudarthrosis of the leg.
J Pediatr Orthop B. 2000;9:3–10.
20. Jacobsen ST, Crawford AH, Millar EA, Steel HH. The Syme
amputation in patients with congenital pseudarthrosis of the tibia.
References J Bone Joint Surg Am. 1983;65:533–537.
21. Johnston CE II. Congenital pseudarthrosis of the tibia: results of
1. Andersen KS. Congenital pseudarthrosis of the leg. Late results. technical variations in the Charnley-Williams procedure. J Bone
J Bone Joint Surg Am. 1976;58:657–662. Joint Surg Am. 2002;84:1799–1810.
123

14. Thabet et al. Clinical Orthopaedics and Related Research
22. Johnston CE, Birch JG. A tale of two tibias: a review of treatment Treatment of congenital pseudarthrosis of the tibia: a multicenter
options for congenital pseudarthrosis of the tibia. J Child Orthop. study in Japan. J Pediatr Orthop. 2005;25:219–224.
2008;2:133–149. 33. Paley D, Catagni M, Argnani F, Prevot J, Bell D, Armstrong P.
23. Joseph B, Mathew G. Management of congenital pseudarthrosis Treatment of congenital pseudoarthrosis of the tibia using the
of the tibia by excision of the pseudarthrosis, onlay grafting, and Ilizarov technique. Clin Orthop Relat Res. 1992;280:81–93.
intramedullary nailing. J Pediatr Orthop B. 2000;9:16–23. 34. Paterson DC, Lewis GN, Cass CA. Treatment of congenital
24. Kanaya F, Tsai TM, Harkess J. Vascularized bone grafts for pseudarthrosis of the tibia with direct current stimulation. Clin
congenital pseudarthrosis of the tibia. Microsurgery. 1996;17: Orthop Relat Res. 1980;148:129–135.
459–469. 35. Paterson DC, Simonis RB. Electrical stimulation in the treatment
25. Keret D, Bollini G, Dungl P, Fixsen J, Grill F, Hefti F, Ippolito E, of congenital pseudarthrosis of the tibia. J Bone Joint Surg Br.
Romanus B, Tudisco C, Wientroub S. The fibula in congenital 1985;67:454–462.
pseudoarthrosis of the tibia: the EPOS multicenter study: Euro- 36. Romanus B, Bollini G, Dungl P, Fixsen J, Grill F, Hefti F,
pean Paediatric Orthopaedic Society (EPOS). J Pediatr Orthop B. Ippolito E, Tudisco C, Wientroub S. Free vascular fibular transfer
2000;9:69–74. in congenital pseudoarthrosis of the tibia: results of the EPOS
26. Kim HW, Weinstein SL. Intramedullary fixation and bone multicenter study: European Paediatric Orthopaedic Society
grafting for congenital pseudarthrosis of the tibia. Clin Orthop (EPOS). J Pediatr Orthop B. 2000;9:90–93.
Relat Res. 2002;405:250–257. 37. Schindeler A, Ramachandran M, Godfrey C, Morse A, McDonald
27. Lee FY, Sinicropi SM, Lee FS, Vitale MG, Roye DP Jr, Choi IH. M, Mikulec K, Little DG. Modeling bone morphogenetic protein
Treatment of congenital pseudarthrosis of the tibia with recom- and bisphosphonate combination therapy in wild-type and Nf1
binant human bone morphogenetic protein-7 (rhBMP-7): a report haploinsufficient mice. J Orthop Res. 2008;26:65–74.
of five cases. J Bone Joint Surg Am. 2006;88:627–633. 38. Sofield HA. Congenital pseudarthrosis of the tibia. Clin Orthop
28. Masserman RL, Peterson HA, Bianco AJ Jr. Congenital pseud- Relat Res. 1971;76:33–42.
arthrosis of the tibia: a review of the literature and 52 cases from 39. Toh S, Harata S, Tsubo K, Inoue S, Narita S. Combining free
the Mayo Clinic. Clin Orthop Relat Res. 1974;99:140–145. vascularized fibula graft and the Ilizarov external fixator: recent
29. McElvenny RT. Congenital pseudarthrosis of the tibia: the find- approaches to congenital pseudarthrosis of the tibia. J Reconstr
ings in one case and a suggestion as to possible etiology and Microsurg. 2001;17:497–508.
treatment. Q Bull Northwest Univ Med Sch. 1949;23:413–423. 40. Weber M. Congenital pseudarthrosis of the tibia redefined: con-
30. McFarland B. Pseudarthrosis of the tibia in childhood. J Bone genital crural segemental dysplasia. In: Rozbruch SR, Ilizarov S,
Joint Surg Br. 1951;33:36–46. eds. Limb Lengthening and Reconstruction Surgery. New York:
31. Morrissy RT. Congenital pseudarthrosis of the tibia: factors that Informa Healthcare; 2007:495–509.
affect results. Clin Orthop Relat Res. 1982;166:21–27. 41. Weiland AJ, Weiss AP, Moore JR, Tolo VT. Vascularized fibular
32. Ohnishi I, Sato W, Matsuyama J, Yajima H, Haga N, Kamegaya grafts in the treatment of congenital pseudarthrosis of the tibia.
M, Minami A, Sato M, Yoshino S, Oki T, Nakamura K. J Bone Joint Surg Am. 1990;72:654–662.
123