Injury, Int. J.

Care Injured 46 S8 (2015) S48–S54

Contents lists available at ScienceDirect

Injury
journal homepage: www.elsevier.com/locate/injury

Long bone non-unions treated with the diamond concept: a case series of
64 patients
Peter V. Giannoudisa,b,*, Suri Gudipatia, Paul Harwooda, Nikolaos K. Kanakarisa
a
Academic Department of Trauma and Orthopaedics, Floor A, Clarendon Wing, LGI, University of Leeds, Leeds, UK
b
NIHR Leeds Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK

K E Y W O R D S A B S T R A C T

non-union The aim of this retrospective study with prospectively documented data was to report the clinical results
diamond concept of treatment of long bone non-unions using the “diamond concept”. Over a 4-year period, patients that
long bone presented with a long bone non-union and were managed with the diamond conceptual framework of
growth factors
bone repair were evaluated. Exclusion criteria were hypertrophic, pathological, and infected non-unions.
Fixation was revised as it was indicated whilst biological enhancement included the implantation of RIA
graft, BMP-7 and concentrated bone marrow aspirate. Data recorded included patient demographics,
initial fracture pattern and type of stabilisation, number of previous interventions, time to reoperation,
time to union and functional outcome. Painless full weight bearing defined clinical union. Radiological
union was defined as the presence of mature callous bridging to at least 3 bone cortices. The minimum
follow up was 12 months (range 12-32). In total 64 patients (34 males) with a mean age of 45 years
(17-83) were evaluated. Anatomical distribution of non-unions included the femur (54.68%), tibia
(34.38%), humerus (4.68%), radius (3.13%) and clavicle (3.13%). The median number of previous inter-
ventions was 1 (range 1-5). The majority of patients (82.62%) underwent revision of fixation whereas
only bone grafting was performed 9.38% of patients. Three patients developed superficial wound infec-
tion (one was MRSA), 1 had deep vein thrombosis and 1 developed heterotopic bone formation. Union
was successful in 63/64 (98.4%) non-unions at a mean time of 6 months (range 3-12). All patients were
mobilising pain free and returned to their daily living activities at the final follow up. The application
of the “diamond concept” in this cohort of patients was associated with a high union rate by provid-
ing an optimal mechanical and biological environment. Such an approach should be considered in the
­surgeon’s armamentarium particularly in such cases where difficulty of bone repair is foreseen.
© 2015 Elsevier Ltd. All rights reserved.

Introduction healing response with the implantation of cells, scaffolds and

Bone has the natural capacity to heal a fracture without scar
formation, a process resembling the embryo bone formation [1].
Any disruption in the physiological cascade of events governing
the bone repair pathway can lead to the development of delayed
healing or non-union. The incidence of non-union has been esti-
mated to be between 5-10% of all fractures, whereas aetiological
factors contributing to this phenomenon include the severity of
the initial injury, the profile of the patient, type of fracture, host
factors and a genetic predisposition amongst others [2-10].
Treatment of non-union is challenging for both the patient
and the treating physician with not infrequently an unpredict-
able result. Treatment modalities that have been described for
simple and complex cases include revision of fixation, bone graft-
ing, non-invasive means of bone stimulation and the ‘triangular
concept’ of biological stimulation (enhancement of the fracture
* Corresponding author at: Academic Department Trauma & Orthopaedic Surgery,
School of Medicine, University of Leeds, Leeds, UK.
Tel.: +44-113-3922750; fax.: +44-13-3923290.
E-mail address: pgiannoudi@aol.com (Peter V Giannoudis).
inductive signals (growth factors)) [11,12].
Lately, a specific management strategy has been described
for the treatment of recalcitrant and atrophic non-unions
under a generic term ‘diamond concept’ [13-15] advocating and
­highlighting that in addition to the ‘triangular concept’ of stimu-
lation, the mechanical environment should also be appropriately
addressed and restored, Fig. 1.
The aim of the herein study is to evaluate the results of
treatment in a cohort of patients that were managed with the
‘­diamond concept’ for long bone non-union at a regional tertiary
referral centre for limb reconstruction.
Patients and methods
Over a four-year period (January 2008 and December 2011)
consecutive patients that attended our institution or were
referred from other units and were treated with the diamond
concept for bone repair were eligible to participate in this study.
Exclusion criteria were pathological fractures, hypertrophic and
infected non-unions. This study was approved by the institu-
tional review board.
 Peter V. Giannoudis et al. / Injury, Int. J. Care Injured 46 S8 (2015) S48–S54
Vascularity
Mechanical stability Growth factors
DIAMOND
CONCEPT
Osteoconductive
Scaffolds Osteogenic cells
Vascularity
Fig. 1. The diamond Concept framework for bone repair.
Non-union was defined as a fractured bone that had failed to
unite within 9 months following injury and did not demonstrate
signs of repair on serial x-rays over a three-month period or 5
months after initial surgery in the event of implant failure [16,17].
Patient evaluation included clinical and radiological (x-rays,
CT scan) assessment with appropriate haematological and
biochemical investigations. Revision surgery was carried out
according to the principles of the ‘diamond concept’ [13-15]
(revision of the implant as appropriate together with the appli-
cation of an osteoinductive factor (BMP-7) or BMP-2 (3 cases),
osteoconductive scaffold (autologous bone graft harvested from
the contralateral femur using the Reamer-Irrigator-Aspirator
device) and concentrated Mesenchymal stem cells (MSC’s) har-
vested from the pelvic iliac crest. At the time of surgery, a tissue
biopsy from the non-union site was always sent to microbiology
for culture and for exclusion of low grade infection. All patients
received 3 doses of prophylactic antibiotics (cefuroxime) and
chemical thromboprophylaxis (tinzoparin 4,500 IU) for a period
of 4-6 weeks. Early physiotherapy was encouraged for resto-
ration of limb function and to reduce the risk of joint stiffness
and muscular wasting. Mobilisation included toe-touch weight
bearing using two crutches or a Zimmer frame for 4–6 weeks, fol-
lowed by progressive increase to full weight bearing by 8 weeks.
Outpatient follow-up with clinical and radiographic assessment
was performed at regular intervals at 2 weeks for wound assess-
ment and afterwards at 6 weeks, 3, 4, 5, 6, 8, 12 and 18 months or
until radiographic union.
Data was prospectively documented (theatre information
system and the hospital admission tracking system) and encom-
passed patient demographics, injury severity, type of fracture,
previous surgical interventions, and complications. Patient’s
characteristics involved presence of significant co-morbidities
(i.e. diabetes mellitus, steroid use, immunodeficiency, obesity,
peripheral vascular disease), malnutrition, smoking, drug use,
and alcohol intake. Injury characteristics included: mechanism
of injury, presence of associated fractures, open or closed injury
pattern. Surgery characteristic included: type of surgery and
time elapsed between injury and intervention, number of pre-
vious tries to enhance bone healing, type of graft material used,
time to bony repair, complications and mortality.
Bone healing was assessed both clinically (pain free full
weight bearing) and radiologically (evidence of callus formation
in 3 out of four cortices as assessed by both AP and Lateral plain
radiographs) [18,19].
S49
End points of the study were set as the establishment of
radiological union and whether the patient reported any limita-
tions whilst performing the day to day activities of living. The
minimum follow-up period was 12 months (range 12-32).
Results
Sixty-four patients (34 male) with a mean age of 45yrs
(17-83) met the inclusion criteria. 39 patients (60.9%) had at least
one associated medical com-morbidity (myocardial infarction,
hypertension, chronic obstructive pulmonary disease, depres-
sion, psoriasis, migraine, arthritis, etc.). Smoking habits were
recorded in 21.8% of the patients. Distribution of non-unions per
anatomical site included the femur in 35 patients (54.68%), tibia
22 (34.38%); with distal third tibia being involved in 14 patients
(21.87%) followed by middle third in 6 patients (9.37%) and the
proximal tibia only in 2 patients; humerus 3 (4.68%), radius 2
(3.13%) and clavicle 2 (3.13%), Fig. 2. In the majority of the patients
(65.63%), the initial injury was the result of high energy trauma
(road traffic accident and fall from a horse or a height), Fig. 3. The
remaining of the patients (34.37%) sustained injuries as a result
of low energy trauma. 16 patients (25%) had previously sustained
an open fracture and 11 of them had associated injuries to the
other body organs (chest, pelvis, tibia and /or femur).
After the initial injury, all patients were operated except
5 patients who were managed non-operatively. At least one
previous unsuccessful attempt to treat the non-union was
attempted in 43.75% of the patients, Fig. 4. Revision of fixation
was necessary in 82.62% of the patients, Fig. 5-14. All patients but
one progressed uneventfully to fracture non-union at the mean
time of 6 months (3-12months). One patient who achieved union
in 2 cortices after a period of nine months required additional
grafting at the site of non-union in the form of injection of cells
and BMP-7. He successfully healed after a period of 3 months.
However, as he had to undergo an addition grafting procedure he
is considered as a failure of treatment. One patient with femoral
non-union required further revision surgery after he was admit-
ted acutely with an implant failure following a fall from steps.
He subsequently had a successful healing after 8 months of the
re-intervention procedure.
Superficial wound infection developed in three patients (one
was MRSA). They were managed successfully with a course of
antibiotics. One patient was diagnosed with deep vein throm-
bosis and was managed with warfarin therapy for 6 months.
Another patient developed heterotopic bone formation from the
donor site of the contralateral femur, which necessitated surgical
excision. One patient developed avascular necrosis (AVN) of the
femoral head 2 years after successful management of her proxi­
mal femoral non-union. She subsequently underwent total hip
arthroplasty for the management of her hip pain. One elderly
patient died recently for unknown reasons after fracture healing.
Fig. 2. Distribution of non-unions according to injured bone.
S50 Peter V. Giannoudis et al. / Injury, Int. J. Care Injured 46 S8 (2015) S48–S54
Fig. 3. Patient Distribution according to the energy levels of injury.
Fig. 4. Number of previous attempts to promote fracture healing.
Fig. 5. 55 yr old female sustained proximal femoral fracture. Past Medical History:
Smoker and diabetic. a) Fracture was stabilized initially with Gamma nail as shown.
After 5 months patient was provided with bone stimulator. b) 3D images - by 8
months no progress of healing.
At the final follow up all patients were satisfied with the func-
tional status of their affected extremity and reported no lim-
itations in their capacity to perform the day to day activities of
living.
Discussion
The development of fracture non-union remains one of the
most common post-fixation bone complications. Its pathogen-
esis remains obscure although is considered multifactorial.
Fortunately, most of the fractures progress to union thus leaving
Fig. 6. Patient referred to our institution. Biochemical profile was normal (WBC, CRP,
ESR). Clinically, no rotational deformity but 1.5 cm shorter. In pain since operation,
unable to weight bear. Non-union score (NUSS) = (bone component = 16, soft
tissue component = 2, patient component = 8). Total points 26X 2 = 52. a) Images
of harvesting RIA graft from the contralateral femur. b) Harvesting of bone marrow
aspirate for concentration of osteoprogenitor cells.
Fig. 7. a) Removal of previous Gamma nail. b) Exposure of non-union site. Fracture
edges note (arrows completely apart).
a small number of patients suffering with either delayed union or
non-union that usually necessitates further surgical intervention.
The management of fracture non-union remains a challenge for
the clinician and exploration of innovative techniques is ongoing
[11,20-22].
Careful assessment of both the clinical and biomechanical
characteristics as well as the comorbidities surrounding the
patient is of utmost importance for a successful treatment strat-
egy and outcome.
Clinical evaluation should involve assessment of angular
deformity, shortening, the state of soft tissues, the presence of
movement on stressing of the non-union site, and the range of
motion of the joints above and below. Radiological assessment
should include in addition to the plain radiographs, CT scan and
when there is suspicion of infection bone scan. MRI can be help-
ful but usually the presence of the underlying metal work and
the generation of artefact preclude this as the choice of inves-
tigation to exclude infection. Careful documentation of factors
that have been implicated to contribute to an impaired fracture
healing response should also take place. Clear analysis of all of
 Peter V. Giannoudis et al. / Injury, Int. J. Care Injured 46 S8 (2015) S48–S54 S51

Fig. 8. a) Using osteotome fragments being apart are mobilized for reduction. b) Insertion of guide wire. c),d),e),f) Insertion of
Affixus proximal femoral nail for stabilization of non-union.

Fig. 9. Composite bone graft (polytherapy) preparation prior to implantation.
the above parameters would assist the treating surgeon to make
the right decisions in terms of the timing of intervention and the
method of treatment to be applied.
Fracture healing can be affected by several factors and m­ edical
conditions, including diabetes and peripheral vascular [23-25].
In this study, only 9 patients (14.1%) had diabetes of whom only
2 patients were insulin dependent. Two of the patients had been
diagnosed with hypothyroidism and 1 patient had o ­ steogenesis
imperfecta with a history of multiple fractures. Most of the
remaining patients either had hypertension, asthma, migraine,
depression or previous skeletal injuries alone or in combination.
Whilst a number of patients were suffering from asthma, none
was on long term steroid therapy.
Fig. 10. a),b),c) Using the nail as a template fragments were mobilized and reduced
to reconstitute the femoral bone (tube);BMP-2 sponge is used around the mobilized
fragments for protection and induction prior to circulage wiring application for
maintenance of reduction.
Smoking impairs bone healing which has been proven both by
basic science and clinical studies [26-29]. Only 21.9% of patients
were smokers and were advised to stop smoking during their
course of treatment. Most of the patients had sustained lower
limb injuries (89% femur and tibia) and 11 of them had sustained
previously open fractures. This is in agreement with the higher
incidence of non –union following open fractures previously
reported by Gustillo et al. [30].
Evaluation of the biological state and the mechanical environ-
ment of the non-union are crucial. Analysis of the original frac-
ture pattern, the type of implant used, the number of previous
S52 Peter V. Giannoudis et al. / Injury, Int. J. Care Injured 46 S8 (2015) S48–S54
Fig. 11. a),b) Application of composite graft over non-union site.
Fig. 12. 3 months’ radiographic examination.
surgeries, and the overall state of the vascularity potential of the
non-union area can assist the clinician to decide the type and the
extent of biological enhancement being necessary. Similarly, the
state of the mechanical stability (presence of osteolysis around
the screws, loosening of plate/nail, breakage of the implant) will
dictate the necessity for revision of the fixation. The ‘diamond
concept’ was proposed to make aware the clinician of the impor-
tance of both the biological and the mechanical environments. It
assists the clinician in the understanding of the requirements in
fracture healing and provides a simplified process for decision
making in the successful management of non-union [13-15].
In our cohort of patients all the issues raised in the diamond
conceptual framework for fracture healing were addressed.
Optimisation of the mechanical environment was achieved by
revision of the fixation in the vast majority of the patients and
given the complexity of these cases and the compromised bio-
logical healing potential, the osteogenic potential was enhanced
by the implantation of composite grafting consisting of the com-
bination of osteoinductive protein (BMP-7), osteoconductive
scaffold (RIA graft) and osteoprogenitor cells (MSC’s from the
iliac crest). This strategy was noted to be associated with a high
percentage of success rate (almost 100%).
Such biological enhancement of implanting a growth factor
(signal), cells and a matrix (scaffold) for cell homing, prolifera-
tion and differentiation can be considered as a potent osteogenic
Fig. 13. 6 months’ radiographic examination.
Fig. 14. 8 months’ radiographic examination.
stimulus. It is not a surprise therefore that we noted such a high
union rate. Previously, BMP’s were considered as the most potent
inductive stimuli for bone repair. Despite this, their implantation
was not associated always with a successful outcome. This can
be attributed to the following parameters: a) poor containment,
b) not adequate local availability of progenitor cells to accept
the message of induction, c) inappropriate timing of implanta-
tion, d) not optimum dose selection, and e) suboptimal carrier
properties.
It is of note that implantation of the autologous bone graft
in isolation has achieved a good rate of union ranging from
60%-100% [31-35] although in another study a failure rate of
50% using ABG was reported [33]. Other biological enhancement
options have been used with limited success [35-40]. We had the
same experience over the years using autologous bone graft or
BMP alone in patients with aseptic long bone non-unions.
It is our belief that delivering locally all of the essential con-
stituents of bone repair creates an optimum molecular milieu
in a previous deprived biological environment. While such an
approach could also contribute to an accelerated healing pro-
cess, and in spite of observing such a phenomenon in a number
of cases, we are not in a position to accurately report on this
matter due to the small number of patients studied in each
different anatomical site. Future studies should address this
important issue.
 Peter V. Giannoudis et al. / Injury, Int. J. Care Injured 46 S8 (2015) S48–S54 S53

Table 1
Literature search showing options for treatment of aseptic non-union and associated complications.

Author/journal No patient management outcome complications

Single stage

Amorosa LF et al, 87/104 (62 aseptic nonunion) Single stage revision, culture 58/62 healed 4/62-persistent non-union
JOT Oct 2013 [43] Average age-49.6yrs samples and ORIF or Exchange
nailing

Augementation technique

Atesch Ateschrang et al 28/104 Dynamization of nail 27/28 healed 1 persistent non-union- need
Mar 2013 [44] Avg age-47yrs + plate augmentation grafting later

Nadkarni et al 11 Locking compression plate 11 head none

J of Trauma Aug 2008 [45] Avg age-47y + Iliac crest graft

Birjandinejad A et al. 38 Locking compression plate 36/38 healed 2 tibial non-union persisted
Orthopedics Jun 2009 [46] Avg age-31.4 + Iliac crest graft

Exchange Nailing

Court-brown CM 33patients Exchange nail 29 healed 4 nonunion

JBJS May 1995 [47] Avg Age-36.3 1 infection

Paul A. Banaszkiewicz 18patients Femoral exchange nail 17 healed ( some after 2 nonunion, 2infection and
Injury (34) 2003 [48] Avg age 36y repeat surgery) 2 implant failure

[4] Heim D, Herkert F, Hess P, Regazzoni P. Surgical treatment of humeral shaft

Other studies reporting on the management of aseptic
non-union have described results with a success rate ranging
between 70%-100% [41,42]. Amorosa et al. have recently reported
successful healing in 58 of the 62 patients in their cohort using
a single stage revision either with exchange nailing or revision
of internal fixation with 4 patients still having persistent non-
union [43]. Other relevant studies reporting on outcomes after
re-­intervention are shown in Table 1 [44-48]. External fixation
using Ilizarov frame has been used as well with a success up to
93% [49]. Non-surgical methods have also been used such as
electric shock wave therapy, low intensity pulsed ultra sound and
electric stimulation with success rates of 70%-86% [50-56]. One
however, needs to appreciate that there is a great heterogeneity
between patients and the local non-union environment and as
such it is difficult to analyse and compare accurately the results
of treatment [57-61].
Limitations of the study include the sample size and the
absence of a comparative group as well as the fact that we did not
use a validated health related outcome instrument. However, the
main end point of this study was to assess the success rate (union)
of the described technique. Strengths of the study include the
prospective follow up and documentation of patient treatment
details and reporting on the experience of a single tertiary refer-
ral center managing a large volume of patients with non-unions.
In conclusion, the ‘diamond concept’ for bone repair provides
a frame work to assist the treating surgeon to evaluate and to
treat both the mechanical and the biological environment of the
chronic recalcitrant non-unions. This strategy should become
another weapon in to the surgeon’s armamentarium in order
to enhance the outcomes of treatment as seen in this series of
patients.
Conflict of interest
All the authors report no conflict of interest.
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