n Case Report
Treatment of Humeral Shaft Aseptic
Nonunions in Elderly Patients With
Opposite Structural Allograft, BMP-7,
and Mesenchymal Stem Cells
Luigi Murena, MD; Gianluca Canton, MD; Ettore Vulcano, MD; Michele Francesco Surace, MD;
Paolo Cherubino, MD
abstract
Full article available online at Healio.com/Orthopedics. Search: 20140124-26
Humeral shaft aseptic nonunions occur in 2% to 10% of patients managed conservatively and 10% to 15% of patients treated surgically. The complex muscular and
neurovascular anatomy of the upper limb makes the surgical approach to the fracture
site demanding and risky, especially when previous surgeries have been attempted.
The clinical consequence of atrophic humeral shaft nonunions is a severe functional
limitation that may significantly affect activities of daily living, especially in the elderly.
The surgical treatment of humeral shaft nonunions is challenging for orthopedic surgeons. Patients with atrophic nonunions require both a stable fixation and enhancement of the biologic response because of the weak biologic reaction observed at the
fracture site. The gold standard of treatment in elderly patients has not been described.
Nonetheless, older age and comorbidities are associated with potentially malignant
nonunions. This study reports the authors’ experience using opposite cortical allograft
combined with bone morphogenetic protein 7 and mesenchymal stem cells to treat
humeral shaft atrophic nonunions in 2 elderly patients. The nonunion site healed at 4
months (patient 1) and 8 months (patient 2) postoperatively, with full return to activities of daily living and no pain. Neither patient reported complications of the radial
nerve, which is at high risk of injury during this type of surgery. The only reported
complication (patient 2) was an intraoperative longitudinal partial distal humeral fracture, probably caused by compression screw overtightening. The use of a locking plate
and opposite cortical allograft, combined with BMP-7 and mesenchymal stem cells,
represents a safe and effective treatment for malignant nonunions in older patients.
Figure: Preoperative anteroposterior radiograph of
a right humerus midshaft nonunion.
The authors are from the Department of Orthopaedic and Trauma Surgery, Universià dell’Insubria,
Varese, Italy.
The authors have no relevant financial relationships to disclose.
Correspondence should be addressed to: Ettore Vulcano, Department of Orthopaedic and Trauma
Surgery, Universià dell’Insubria, Viale Borri 57, Varese 21100, Italy ([email protected]).
Received: May 24, 2013; Accepted: September 26, 2013; Posted: February 7, 2014.
doi: 10.3928/01477447-20140124-26
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H
umeral shaft aseptic nonunions
occur in 2% to 10% of patients
managed conservatively and
10% to 15% of patients treated surgically. Risk factors for nonunion include the
type of fracture (ie, transverse and short
oblique fractures), smoking, osteoporosis,
alcoholism, obesity, previous surgeries,
and inadequate treatment.1-3
The surgical treatment of humeral
shaft fractures is challenging. The loss of
mechanical stability may lead to severe
nonuse osteopenia and stiffness of the adjacent joints. Furthermore, the complex
muscular and neurovascular anatomy of
the upper limb makes the surgical approach to the fracture site demanding and
risky, especially when previous surgeries
have been attempted.4
The clinical consequence of humeral
shaft nonunions is a severe functional
limitation that may significantly affect
activities of daily living. Therefore, surgical treatment should always be an option,
even in older patients.2,3
Patients affected by hypertrophic
nonunion may heal if a stable fixation is
achieved. However, patients with atrophic
nonunions require both a stable fixation
and enhancement of the biologic response
because of the weak biologic reaction observed at the fracture site.3,4
The literature reports several techniques address humeral shaft nonunions,
A
both in terms of fixation (ie, plates, nails,
external fixators) and biological enhancement (ie, autologous or homologous bone
graft, demineralized bone matrix, mesenchymal stem cells, bone morphogenetic
proteins, platelet-rich plasma).2,5-10 Overall the results are good, especially for
open reduction and internal fixation and
autologous bone grafting (success rate,
70%-92%).1
Few studies assess treatment of humeral shaft nonunion in the elderly. The
gold standard of treatment in this patient
population has yet to be described. Nonetheless, older age and comorbidities are
associated with potentially malignant
nonunions.2,3,11
The current authors report their experience using opposite cortical allograft
combined with bone morphogenetic protein 7 (BMP-7) and mesenchymal stem
cells to treat humeral shaft atrophic nonunions in 2 elderly patients.
Case Reports
Patient 1
A 77-year-old man presented 19
months after having a humeral shaft spiroid fracture of the right arm. His medical
history included hypertension, dysrhythmia, ischemic cardiopathy, type 2 diabetes
mellitus, obesity, and severe hip and knee
osteoarthritis that forced him to walk using
crutches.
B
The patient reported right-sided functional impotence and preternatural mobility. The humeral shaft fracture had been
previously treated elsewhere with 4 months
of functional bracing. On clinical examination, both deformity of the arm and preternatural mobility were evident. Range of
motion of the elbow was unremarkable,
as opposed to the stiff shoulder joint. Radiographic examination revealed atrophic
nonunion of the proximal/middle third of
the humeral shaft associated with severe
nonuse osteopenia (Figures 1A-1B).
The patient was admitted for surgery.
The approach to the humeral shaft was
performed through a deltopectoral incision extended to the mid-arm. The nonunion site was exposed and debrided.
Then, 1.5 cm of necrotic stump was resected and intramedullary canal reaming
performed. At the same time, another surgeon aspirated 60 cc of bone marrow from
the iliac crest of the patient. The aspirate
was processed and concentrated using the
SmartPReP 2 bone marrow aspirate concentrate (BMAC) (Harvest Technologies,
Plymouth, Massachusetts) to obtain 10 cc
of BMAC. A sample (0.5-1 cc) of BMAC
was sent to the microbiology laboratory to
assess cellularity. Pre- and postconcentration nucleated cells were 16.7×103/µL and
75.1×103/µL, respectively; pre- and postconcentration platelets were 142×103/µL
and 502×103/µL, respectively. The non-
C
Figure 1: Preoperative radiographs in complementary views showing humeral shaft aseptic nonunion (A, B). Intraoperative photograph of the final result prior
to wound closure (C).
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A
B
C
Figure 2: Postoperative radiographs in complementary views (A). Radiographs showing bone healing at the nonunion site 8 months postoperatively, with cortical
allograft not completely integrated as clearly shown on the left view (B). Radiographs in complementary views showing cortical allograft integration 11 months
postoperatively (C).
union site was stabilized (Figure 1C) with
an opposite cortical strut (homologous
tibial diaphysis), fixed with 2 tricortical
compression screws at both sides of the
nonunion, and filled with fresh-frozen cadaver cancellous bone, BMP-7 (Osigraft
OP-1; Stryker, Mahwah, New Jersey), and
BMAC. The nonunion site was stabilized
with a locking compression plate (LCP)
(Synthes, West Chester, Pennsylvania).
The wound was closed as usual, and no
drain was inserted.
The arm was protected in a sling for
pain control during the first few days
postoperatively. The postoperative protocol consisted of early active range of
motion of the shoulder and elbow. Radiographic evaluation revealed full healing
of the nonunion site 8 months postoperatively. The cortical graft appeared to
be fully integrated 11 months postoperatively (Figure 2). At final follow-up 1
year postoperatively, the patient had full
functional recovery of the shoulder and
return to all activities of daily living. No
pain or other complications were associated with BMAC harvesting.
Patient 2
An 81-year-old woman presented 23
months after having a transverse fracture
of the mid-distal third of the right humeral
shaft. Her medical history was significant
for hypertension, severe stenosis of the
supra-aortic trunks, chronic renal insufficiency, and pulmonary emphysema.
FEBRUARY 2014 | Volume 37 • Number 2
B
A
C
Two years prior to the humeral shaft
fracture, the patient had been treated elsewhere for a right-sided proximal humeral
fracture that healed with a locking plate.
The latter was removed before fixing the
midshaft fracture with Ender nails and
Figure 3: Preoperative radiographic (A) and clinical assessment (B) of the nonunion. Intraoperative
photograph showing the metal cerclages stabilizing the partial longitudinal distal fracture of the
humerus (C).
cerclages. The humeral shaft nonunion
was observed on serial radiographs, ultimately resulting in the rupture of the nails
15 months postoperatively (Figure 3A).
On physical examination, right arm impotence, preternatural mobility, and elbow
stiffness (40° of passive range of motion)
were observed (Figure 3B). Radiographic
examination was also remarkable for severe nonuse osteoporosis.
The patient underwent surgery to
treat the humeral shaft nonunion. The
nonunion site was exposed through an
extensile posterior approach to the humeral shaft. The Ender nails and cerclages were removed. As for patient 1,
the nonunion site was debrided, 2 cm
of necrotic stump was resected, and the
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A
B
C
Figure 4: Postoperative radiographs in complementary views (A). Complementary radiographic views showing bone healing at the nonunion site 4 months
postoperatively (B). Complementary radiographic views showing cortical allograft integration 10 months postoperatively (C).
intramedullary canal was reamed. The
nonunion site was filled with fresh-frozen
cadaver bone, BMP-7, and BMAC and
stabilized with a Synthes LCP plate and
opposite tibal cortical allograft. A sample
(0.5-1 cc) of BMAC was sent to the microbiology laboratory to assess cellularity. Pre- and postconcentration nucleated
cells were 14.3×103/µL and 68.6×103/µL,
respectively; pre- and postconcentration
platelets were 159×103/µL and 492×103/
µL, respectively. Intraoperatively, a longitudinal incomplete fracture of the
distal humerus, most probably caused
by compression screw overtightening,
was observed. This fracture was treated
with metal cerclages (Figure 3C) and 2
months of splint immobilization. Eight
weeks postoperatively, the patient started
physical therapy to recover both shoulder
and elbow range of motion. At about 4
months postoperatively, the nonunion site
had healed fully. The cortical strut was
fully integrated 10 months postoperatively (Figure 4). At 1-year follow-up, the
patient reported no pain and full return
to activities of daily living despite mild
shoulder and elbow stiffness. No pain or
other complications were associated with
BMAC harvesting.
Discussion
The complex anatomy, the nonuse osteopenia, and the joint stiffness resulting
e204
from prolonged immobilization all contribute to making treatment of humeral
shaft nonunions challenging.2,4 Comorbidities and pretrauma osteoporosis make
treatment even more complex in the elderly.2,4 King et al1 suggested that older
patients be managed nonsurgically, despite
inadequate functional results. Conversely,
Ring et al2 reported severe functional impairment, compromising activities of daily
living, if atrophic nonunions of the humeral shaft were left untreated. Despite a clear
indication for surgical intervention, the
ideal surgical technique to treat humeral
shaft nonunions remains controversial.1
A review of the literature yields only
a few studies with small patient cohorts
and different classifications, treatments,
and data analyses. A search narrowed to
include only those assessing the treatment
of atrophic nonunions of the humeral shaft
in the elderly yields even fewer studies.
Despite the good results observed with
different surgical techniques, advanced
age seems to be a clear risk factor for failure.2,6,11,12 Volgas et al3 assessed the impact of several risk factors on the outcome
and nonunion rate of humeral fractures.
Advanced age, comorbidities, and previous surgeries all contributed to malignant
nonunion. Indeed, the 2 cases reported
here match these findings.
Regardless of the type of surgery, investigators seem to agree on the following
principles to achieve bone union in atrophic humeral shaft fractures: achieving
mechanical stability through rigid fixation
and enhancing the suboptimal biologic response.
Mechanical stability can be achieved
with several fixation devices, such as
plates, intramedullary nails, and external
fixators. The literature reports satisfactory results with all of these devices.2,5,6,10-15
In patients with osteoporotic bone, clinical and biomechanical studies have observed significantly improved stability
with the use of a locking plate.2,16 In light
of these findings, the current 2 patients
were treated with a Synthes LCP plate,
which allows use of either a locking or a
compression screw in any hole. The use
of long plates (76% of the total length of
the bone or at least 11-hole plates) can
enhance the mechanical stability, along
with the use of 6.5-mm cancellous (preferably locking) screws, as opposed to
4.5-mm cortical screws in cases of poor
grip.2 Moreover, a cadaver cortical bone
graft as an opposite cortical strut, fixed
with tricortical screws, may improve the
mechanical stability and act as an osteoconductive and osteoinductive scaffold.7,17 The potential risks of this procedure are infection and a more aggressive
soft tissue stripping required to insert the
strut. Marinelli et al7 reported a cohort of
57 cases of humeral shaft nonunion, 40
ORTHOPEDICS | Healio.com/Orthopedics
n Case Report
of which were atrophic nonunions. They
observed a 93% union rate, whereas the
complication rate was comparable to that
with other surgical techniques. To limit
the soft tissue stripping and to prevent
the excessive rigidity of the construct,
these authors also recommended using
grafts that were shorter than the plate,
fixed with 2 proximal and distal screws
(with respect to the nonunion site). This
allows for early active mobilization. Patient 1 was successfully treated with this
technique.
Hypertrophic nonunions are usually
secondary to an insufficient biomechanical stability, as opposed to atrophic nonunions, which result from suboptimal biologic responses.4 Therefore, bone healing
stimulation in patients affected by atrophic nonunion seems to be crucial. The
autologous iliac crest bone graft (ICBG)
is the gold standard for providing osteogenic, osteoinductive, and osteoconductive stimuli for bone healing.18 However,
in older patients with age-related comorbidities, ICBG may be associated with
potentially severe complications, such as
donor site morbidity and blood loss.5,9
Furthermore, the quality of ICBG may be
too poor in elderly patients to guarantee
good mechanical stability and osteogenic
potential.5 Therefore, the authors did not
use autologous ICBG for patient 1 or 2.
Available options included demineralized
bone matrix, cadaver cancellous bone
graft, mesenchymal stem cells, and bone
morphogenetic proteins.5-9,17 The latter
have been successfully used in other bones
and districts, including nonunions of the
humeral shaft.8,19 Despite the satisfactory
results reported with these techniques, the
most effective bone graft material has yet
to be determined through prospective randomized trials.1
The 2 cases described here were treated with BMP-7 (osteoinductive stimulus),
cadaver bone grafts (osteoconductive
stimulus), and mesenchymal stem cells
(osteogenic stimulus). Despite previous
FEBRUARY 2014 | Volume 37 • Number 2
reports19-21 regarding the low cellularity
in bone marrow concentrate in the elderly,
the BMAC cell count reported demonstrated numerous mesenchymal stem cells
in the bone marrow concentrate in these 2
elderly patients.
Both cases reported here showed satisfactory results. The nonunion site healed
at 4 months (patient 1) and 8 months (patient 2) postoperatively, with full return
to activities of daily living and no pain.
Neither patient reported complications of
the radial nerve, which is at high risk of
injury during this type of surgery.1,3,4 The
only reported complication (patient 2)
was an intraoperative longitudinal partial
distal humeral fracture, probably caused
by compression screw overtightening.
The fracture was successfully treated with
metal cerclages and cast immobilization
for 2 months. This complication, previously reported by Ring et al,2 highlights
the technical difficulty of the procedures
used to treat these complex cases. It also
supports the current authors’ recommendation to use locking screws whenever possible. After 2 months of immobilization, the patient healed successfully
without further stiffness in joint motion
compared with the preoperative range
of motion. King et al1 suggested making
bone healing (as opposed to allowing early motion) the priority for elderly patients
with humeral atrophic nonunions that do
not have sufficient mechanical stabilization to allow for early range of motion.
Conclusion
The surgical treatment of humeral
shaft atrophic nonunions in the elderly
represents a challenging scenario for orthopedic surgeons. Successful treatment
relies on both mechanical stability and optimal biologic response. The use of a locking plate and opposite cortical allograft,
combined with BMP-7 and mesenchymal
stem cells, represents a safe and effective treatment for malignant nonunions in
older patients.
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