G Model

JINJ-6312; No. of Pages 9

Injury, Int. J. Care Injured xxx (2015) xxxxxx

Contents lists available at ScienceDirect

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

Review

The investigation and management of suspected malignant

pathological fractures: A review for the general orthopaedic surgeon
D.J. Bryson a, L. Wicks b, R.U. Ashford c,d,*
a

Department of Orthopaedics, Nottingham University Hospitals NHS Trust, Queens Medical Centre, Derby Road, Nottingham, Nottinghamshire, NG7 2UH, UK
Leicester Orthopaedics, University Hospitals of Leicester NHS Trust, Inrmary Square, Leicester, LE1 5WW, UK
c
East Midlands Sarcoma Service, University Hospitals of Leicester NHS Trust, Inrmary Square, Leicester, LE1 5WW, UK
d
Academic Orthopaedics, Trauma & Sports Medicine, University of Nottingham, Queens Medical Centre, Derby Road, Nottingham, Nottinghamshire, NG7
2UH, UK
b

A R T I C L E I N F O

A B S T R A C T

Article history:
Accepted 19 July 2015

The management of malignant pathological fractures necessitates careful diagnostic work-up, preoperative investigation, planning and multidisciplinary input from specialists in the elds of radiology,
pathology, oncology, trauma and orthopaedics. Malignant and non-malignant conditions including
metabolic disorders, benign tumours and pharmacological therapies can be implicated. The majority of
patients who present with suspected pathological fractures will be managed by general orthopaedic and
trauma surgeons rather than specialists in orthopaedic oncology. Skeletal metastases can result in
considerable morbidity and predispose to pathological fractures. With advances in the medical
management of malignancy, life expectancy in cancer patients is increasing, leading to an increasing risk
of skeletal metastasis and the potential for pathological fractures. Conventional modes of trauma
xation for pathological fractures may not be appropriate. The aim of this review is to outline diagnostic
and management strategies for patients who present with a long bone fracture that is potentially
pathological in nature.
2015 Elsevier Ltd. All rights reserved.

Keywords:
Pathological fracture
Skeletal Metastases
Radiological Investigation
Blood Investigations
Surgical management

Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
The pathological fracture. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Primary bone malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Approaching the patient with a possible primary bone malignancy .
Metastatic disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Multiple myeloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
When to be suspicious . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aims of investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Radiographs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Management: generic principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Surgical management of metastatic pathological fractures . . . . . . . .
Bone cement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pathological fractures of the femoral neck . . . . . . . . . . . . . . . . . . . . .
Peritrochanteric fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Subtrochanteric and diaphyseal femoral fractures . . . . . . . . . . . . . . .

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

000
000
000
000
000
000
000
000
000
000
000
000
000
000
000
000
000

* Corresponding author at: Leicester Orthopaedics, University Hospitals of Leicester NHS Trust, Leicester Royal Inrmary, Inrmary Square, Leicester, LE1 5WW, UK.
Tel.: +44 7830727856.
E-mail addresses: davidjbryson@hotmail.com (D.J. Bryson), laurence.wicks@uhl-tr.nhs.uk (L. Wicks), robert.ashford@uhl-nhs.uk (R.U. Ashford).
http://dx.doi.org/10.1016/j.injury.2015.07.028
00201383/ 2015 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Bryson DJ, et al. The investigation and management of suspected malignant pathological fractures: A
review for the general orthopaedic surgeon. Injury (2015), http://dx.doi.org/10.1016/j.injury.2015.07.028

G Model

JINJ-6312; No. of Pages 9

D.J. Bryson et al. / Injury, Int. J. Care Injured xxx (2015) xxxxxx

The distal femur. . . . . . . . . . . . . . . . . . . . .

The humerus . . . . . . . . . . . . . . . . . . . . . . .
The tibia, foot and ankle . . . . . . . . . . . . . .
Amputation . . . . . . . . . . . . . . . . . . . . . . . .
Non-surgical managementradiotherapy.
Medical therapy . . . . . . . . . . . . . . . . . . . . .
Summary . . . . . . . . . . . . . . . . . . . . . . . . . .
Conict of interest . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . .

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

Introduction
Patients with skeletal malignancy, whether primary or secondary, whose rst presentation of the disease is with a pathological
fracture, will usually be initially managed by a trauma service. As a
result, management of these pathological fractures can vary
between hospitals and individual surgeons.
Not all pathological fractures are caused by malignancy. Other
causes of pathological fractures include osteoporosis, osteogenesis
imperfecta, bisphosphonate use, hyperparathyroidism, Pagets
disease of bone, and a variety of benign tumours (including
unicameral bone cyst, aneurysmal bone cyst and giant cell tumour
of bone). The focus of this review is on malignant pathologies
(principally metastatic). The initial approach should however be
the same with any patient suspected of having a pathological
fracture.
With advances in the medical management of malignancy,
cancer patients are living longer increasing the risk of bony
metastases [1,2]. Palliation, not cure, is usually the objective of
treatment for metastatic bone disease [3,4] with the main aims
being pain relief, restoration of function, and improvement in
quality of life. The management of pathological fractures differs
from fractures in disease-free bone [5] and inappropriate
treatment can lead to xation failure or, at worst, result in the
dissemination of a potentially curable primary malignancy.
The pathological fracture
The axial skeleton is the most common site for skeletal
metastases but most pathological fractures arise in the long bones
of the appendicular skeleton [6]. Two-thirds of non-vertebral
fractures occur in the femur with the remainder most commonly
seen in the proximal humerus [7] (Fig. 1). Osteolytic lesions, lesions
larger than 25 mm, areas subject to high anatomical stress, and
areas with resorption exceeding more than 5075% of the original
bone diameter are at greatest risk of pathological fracture [810].
Skeletal metastases are seldom a cause of cancer mortality
[11,12] but result in considerable morbidity including pain,
hypercalcaemia, reduced mobility, neurology from spinal cord
or nerve root compression and pathological fractures [13]. Lower
limb fractures affect mobility and fractures of the upper limb can
compromise functional independence [14]. In some cases,
pathological fractures may represent the end-stage of the
malignant disease or the limits of medical management [15]. Half
of patients who undergo surgery for a pathological fracture will die
within 6 months [16]. Visceral metastases, a haemoglobin level
less than 70 g/L, lung cancer and pathological fractures are all
negative prognostic indicators for overall survival in patients with
metastatic bone disease [17].

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.

000
000
000
000
000
000
000
000
000

between 300 and 400 new cases of bone sarcoma each year in
the UK [19], with osteosarcoma the most common type followed
by chondrosarcoma and Ewings sarcoma [20]. The incidence of
pathological fractures in patients with osteosarcoma is between
5 and 10% [21,22]. With a bimodal distribution, incidences peak in
children and adolescents, and in the elderly [23].
Pathological fractures arise because of bone destruction and
mechanical weakness wrought by the underlying malignancy, but
biopsy induced weakness, radiotherapy induced necrosis and
chemotherapy induced osteoporosis can also contribute [24].
Approaching the patient with a possible primary bone
malignancy
A detailed review of pathological fractures in primary bone
malignancy is outside the scope of this review. The following
guidance is given to avoid the pitfalls of inappropriate initial
management of potential primary malignancy.
In patients with a suspicious bone lesion or pathological
fracture, in the absence of known malignancy and the absence of
widespread metastatic disease, a cautious but expeditious
approach must be undertaken. Fixation should be avoided until
a denitive diagnosis is established, because inappropriate xation
of a primary bone cancer can lead to dissemination of tumour cells,
potentially precluding a curative procedure, and culminate with an
unsalvageable limb requiring mutilating proximal amputations,
including hindquarter amputations for femoral tumours [24,25].
Pathological fractures are frequently low energy injuries and do
not require emergent xation. Expeditious appropriate investigation is requiredsuspect and detect should be the mantra. Biopsy
is necessary for tissue diagnosis and must be considered in all cases

Primary bone malignancy

Primary bone sarcomas are rare, with all sarcomas representing
approximately 1% of all malignant tumours [18]. There are

Fig. 1. 73 year old lady with metastatic breast cancer and right hip pain.
Radiographs demonstrate a large lytic metastasis of the femoral neck and represent
an impending pathologic fracture

Please cite this article in press as: Bryson DJ, et al. The investigation and management of suspected malignant pathological fractures: A
review for the general orthopaedic surgeon. Injury (2015), http://dx.doi.org/10.1016/j.injury.2015.07.028

G Model

JINJ-6312; No. of Pages 9

D.J. Bryson et al. / Injury, Int. J. Care Injured xxx (2015) xxxxxx

where the diagnosis is uncertain. Where there is suspicion of

primary bone malignancy patients should be referred to supraregional bone tumour centres prior to biopsy. In England these
centres are Stanmore, Birmingham, Oxford, Oswestry and Newcastle.
In patients with fractures suspicious of malignancy, the affected
limb may be immobilised in a cast, traction or a brace while further
investigations are undertaken or even while chemotherapy is
instituted. Fracture stabilisation with external xation may be
utlilised [26]. The pins should be placed outside the pathological
segment of bone.
Metastatic disease
Skeletal metastases are more common than primary bone
tumours and represent the third most common site of metastases
after the lung and liver [7,8,27]. More than 50% of all primary
cancers will spread to the skeleton [27] with primary malignancy
of the breast, lung, prostate, kidney and thyroid being the
commonest [28]. In advanced breast and prostate cancer, bony
metastases can be present in almost 100% of patients [29]. Pathological fractures occur in up to 30% of patients with bony
metastases with the femur, proximal humerus and tibia the most
common sites for long bone fractures [30].
Multiple myeloma
Multiple myeloma is a B-cell lympho-proliferative disease,
characterised by involvement of the skeleton at multiple sites. It is
more common in men, people of African origin and the peak
incidence is 5060 years of age. Most patients will present with
multiple lesions but some will present with a single lesion and
negative bone marrow aspirate which carries a better prognosis.
Patients also have a high risk of developing fractures, and this risk
can be increased through treatment with corticosteroids [31].
When to be suspicious
Failure to recognise the pathological nature of a fracture is likely
to result in mistreatment. Key features in the history and
examination of the patient such as prodromal pain, along with
initial radiographs should raise sufcient suspicion to alter the
investigation and subsequent management of the patient.
Previous malignancy, recent weight loss, general malaise and a
smoking history should all be established and a general systemic
history obtained. The mechanism of injury, a prior history of
malignancy and, importantly, identifying a period of pain
preceding the fracture can raise concerns before any kind of
investigation is performed. Characteristically dull or aching in
nature, metastatic bone pain is commonly well localised,
progressive, unresponsive to rest and analgesia, and persistent
at night [32]. No individual test is capable of identifying the
underlying primary. Instead, a comprehensive history, examination and a combination of investigations will be required.
Examination
A systemic approach to examining the patient may aid in the
diagnosis of a primary malignancy and allow proper assessment of
the patients general health. A digital rectal examination should be
performed, as should breast examination in women. If the fracture
is a result of a primary bone malignancy, or direct invasion from an
adjacent tumour, there may be a detectable soft tissue mass on
clinical examination. However, this is unlikely in metastatic
disease.

Table 1
Efcacy of investigative modalities in identifying primary site of
malignancy [33,34].
History and physical examination
Chest X-ray
Chest CT
Abdominal CT
Biopsy

8%
43%
15%
13%
8%

Aims of investigations
In cases of suspected primary malignancy, computerised
tomography (CT) of the chest, MRI of the affected bone and whole
body isotope scan or PET-CT scan are the investigations of choice.
Urgent referral to a supra-regional bone tumour centre is
mandatory. Referral should not be delayed pending completion
of imaging.
If the diagnosis is likely metastatic, further investigations may
be required to identify the primary pathology (Table 1), visceral
involvement and to stage the disease [33,34]. Knowing the primary
diagnosis and stage of the disease in metastatic disease can also
affect the surgical management of a patient. For example,
pathological fracture in renal cell carcinoma (RCC) may represent
an isolated metastatic lesion and needs to be approached with care.
Often hypervascular, embolisation of the tumour preoperatively
may reduce blood loss if surgical xation is planned [35]. Although
minimally radiosensitive, and showing a variable response to
chemotherapy, a RCC metastasis may be fully excised, potentially
resulting in a prolonged life expectancy for the patient [36,37].
Tables 2 and 3 outline recommended haematological and
radiological investigations that may be used in the workup of
patients with suspected metastatic bone disease.

Radiographs
The location of a fracture and associated changes to the quality
of bone in that area can raise the suspicion of a pathological
fracture. Subtrochanteric femoral fractures should be considered
pathological in nature until proven otherwise. Most appendicular
metastases occur proximally. In suspicious fractures occurring
more distally, a primary bone tumour or metastatic lung
carcinoma should be considered [6].
Radiographic changes may be subtle. Metastatic lesions may be
blastic (prostate or occasionally breast), lytic (thyroid, lung, kidney
and the majority of breast primaries) or mixed (breast) in
appearance depending on the primary malignancy (Fig. 2).
Table 2
Routine investigations in patients with suspected metastatic bone disease.
Investigation
Full blood count
Bone prole
Liver function tests
& coagulation screen
Erythrocyte sedimentation
rate
& C-reactive protein
Prostate specic antigen
(in males)
Myeloma screen (including
24 h urine collection for
Bence Jones Proteins)
Other tumour markers

Reason for test

Anaemia
Hypercalcaemia
Raised alkaline phosphatase
Derangement, suggestive of
visceral involvement
Markers of systemic
inammatory process (but will
not differentiate between
malignancy and infection)
Less than10 ng/ml essentially
rules out bone metastases due
to prostate carcinoma [38]
To assess for multiple myeloma

As appropriate

Please cite this article in press as: Bryson DJ, et al. The investigation and management of suspected malignant pathological fractures: A
review for the general orthopaedic surgeon. Injury (2015), http://dx.doi.org/10.1016/j.injury.2015.07.028

G Model

JINJ-6312; No. of Pages 9

D.J. Bryson et al. / Injury, Int. J. Care Injured xxx (2015) xxxxxx

Table 3
Radiological imaging in patients with suspected metastatic bone disease.
Modality
Plain radiographs (AP and Lateral)
Magnetic Resonance Imaging (MRI)
Computed tomography (CT) chest,
abdomen and pelvis
Isotope bone scan
PET-CT

Rationale
Image the whole length of a bone with suspected malignancy, to look for other critical lesions
A chest radiograph may aid in diagnosis of the primary malignancy or detect lung metastases [33,34]
When there is suspicion of the fracture resulting from a primary tumour, MRI of the whole bone outlines
the extent of a tumour in both the bone and soft tissues, and also detects skip lesions.
Stages disease (visceral & nodal involvement) and can identify the primary tumour
To determine location and extent of skeletal spread and singularity versus multiplicity
Can determine extent of tumour burden, detect occult metastatic disease, and may help identify the most
active part of tumour in preparation for biopsy [39]

Biopsy

Surgical management of metastatic pathological fractures

If other investigations have left uncertainty, a biopsy must be

performed to establish the diagnosis [40]. Both open biopsy and
radiologically guided needle biopsy are highly accurate but should
be performed by the team planning denitive treatment and, in the
case of a potential primary malignancy, at a specialist bone tumour
unit [41]. Fracture haematoma and callus may have similar
histology to osteosarcoma. Therefore, the histology sample must
be analysed by an experienced pathologist who also has access to
the patients radiological investigations.
There are some key principles that must be followed to ensure
adequate and safe biopsy of musculoskeletal tumours:

The surgical management of pathological fractures should be

individualised, taking into consideration the nature and location of
the fracture and associated lesion(s), any risk of impending
fracture, and also the patients general health and prognosis.
Damron and Sim [43] proposed several basic principles that should
underpin metastatic fracture management:

1) If the lesion is potentially a primary bone sarcoma the biopsy

should be performed at a specialist bone tumour centre.
2) Needle biopsy is preferable.
3) The site of biopsy should allow excision of the biopsy tract at the
time of denitive surgery.
4) Only one compartment should be breached.
5) Meticulous haemostasis and avoidance of drains is ideal.
Biopsy should be considered in all cases where the diagnosis is
uncertain. This is of critical importance in cases of suspected
primary malignancy. The question should not be does this patient
require a biopsy?, rather why doesnt this patient need a biopsy?
Management: generic principles
The management of patients with metastatic bone disease and
pathological fractures should be via a multidisciplinary team
approach. Emergent intervention is rarely required, except in cases
of spinal cord compression [25]. Instead, a planned approach built
upon early recognition, expeditious investigation, and individualised intervention should underpin all investigative and management strategies. The Rizzoli institute [30] has produced a helpful
algorithm to guide to the assessment and management of any long
bone pathological fracture (Fig. 3).
In cases where co-morbidities preclude surgery, palliative
treatment may be the only option [25]. Patients with established
fractures, or those at high risk of fracture, and who are t for
surgery, should usually be offered operative intervention. Surgical
intervention, in palliative patients, by the orthopaedic surgeon will
generally take one of three forms [42]:
1) Prophylactic xation of impending fractures.
2) Stabilisation or reconstruction of bones affected by pathological
fracture.
3) In spinal disease, decompression and mechanical stabilisation
of the spinal cord, nerve roots and vertebral column.
The goal of surgery is relief of pain, achievement of skeletal
stability, restoration of function and mobility, and improvement in
quality of life [2,14].

1) The prognosis should exceed the anticipated recovery time from

surgery.
2) Intervention should address all areas of weakened bone, along
with any likely to weaken subsequently.
3) The construct employed should allow immediate full weightbearing.
4) All patients should be considered for post-operative radiotherapy.
Bone cement
Polymethylmethacrylate (PMMA) cement is a key component
in the surgical management of pathological fractures. It can be
used percutaneously to prevent vertebral collapse in patients with
metastatic spinal disease, as a lone stabilisation device in cases of
focal disease following curettage, and is an important augment for
internal xation including intramedullary or plate xation [44]
(Fig. 4), and also arthroplasty procedures.
Cemented arthroplasty is preferred to uncemented. Postoperative radiotherapy is indicated for almost all patients;
radiotherapy may negatively affect bone ingrowth or ongrowth
predisposing to failure in uncemented prostheses [7].
Pathological fractures of the femoral neck
The proximal femur is the most common site for pathological
fractures of the appendicular skeleton, with one-third occurring in
the femoral neck [45]. Prosthetic replacement is the preferred
treatment strategy [16] either with hemiarthroplasty or total hip
replacement. Conventional internal xation is not advised [43] as
these fractures have poor healing potential [12] and the load
sharing capabilities of osteosynthetic xation may fail if the bone
does not heal [5]. In addition, osteonecrosis as a result of both the
fracture and post-operative radiotherapy, coupled with high
mechanical stresses predisposes to implant failure and cut out [8].
Wedin et al. reported a failure rate of 14% in patients treated
with osteosynthesis compared with a failure rate of 2% in cases of
endoprosthetic replacement (EPR) [46]. Cemented long-stem
femoral implants, either hemiarthroplasty or total hip replacement, should be considered to reinforce the medullary canal and to
protect the entire femur. Haberman et al. recommended routine
total hip replacement in patients undergoing arthroplasty for
proximal femoral lesions because of the identication of acetabular involvement in 83% of cases [47]. However, the dislocation rate

Please cite this article in press as: Bryson DJ, et al. The investigation and management of suspected malignant pathological fractures: A
review for the general orthopaedic surgeon. Injury (2015), http://dx.doi.org/10.1016/j.injury.2015.07.028

G Model

JINJ-6312; No. of Pages 9

D.J. Bryson et al. / Injury, Int. J. Care Injured xxx (2015) xxxxxx

in total hip arthroplasty has been reported at 22%, ve times higher

than with hemiarthroplasty [48]; for proximal femoral replacement the dislocation rate can be as high as 35% [49].
The femoral stem should bypass the distal part of the lesion by
two bone diameters. Failure to do so risks xation failure
secondary to periprosthetic fracture or disease progression.
However, long-stem prosthesis and intramedullary devices have
been associated with cardiorespiratory events including pulmonary emboli, cardiac arrest and death [5052]. In a review of
96 patients treated with long-stem arthroplasty or intramedullary
whole bone xation, Alvi and Damron found the incidence of
disease progression to be lower than the physiological complication rate, suggesting that the risks may not outweigh the benets
[53]. In high-risk patients, such as those with severe cardiopulmonary disease or a short life expectancy, Weber et
al.
recommended that short stem prostheses and expedient surgery,
with less blood loss, is advisable [2].
Peritrochanteric fractures
Plate and screw osteosynthesis, augmented with polymethylmethacrylate (PMMA) cement injected into the defect has been a
traditional method of xation. Cephalo-medullary nails can also be
used. They have the biomechanical advantage of a centromedullary position that resists medialisation of the distal fragment, a
common cause of failure of the sliding hip screw [54]. However,
femoral head and neck involvement should be assessed to reduce
risk of failure.
The use of long-stemmed prosthesis or proximal femoral
replacement in patients with peritrochanteric lesions or fracture
has also been advocated [2,48,49]. As already discussed, prostheses
should be cemented and stems should bypass any remaining lesion
by at least two cortical diameters [7].
Subtrochanteric and diaphyseal femoral fractures

Fig. 2. (a) AP radiograph of proximal femur showing mixed appearance. (b) Sclerotic
lesion in left proximal femur. (c) Lytic lesion of the distal femur

Locked cephalomedullary nails protect the femoral neck,

diaphysis and distal femur in a single procedure [55]. They are
safe, effective and reliable, providing pain relief and early postoperative mobilisation and weight-bearing [51,56,57].
There are signicant risks associated with intramedullary
nailing of impending and actual pathological fractures. Cardiopulmonary compromise following embolisation of marrow contents
during reaming is well described [58,59]. The highest intramedullary pressures are achieved during the initial reaming [60] and
can generate pressures over 450 mmHg (pressures of 100 mgHg
are sufcient to cause intravasation of marrow [61,62], with
subsequent activation of the coagulation and brinolytic cascades
[59]).
Cortical venting, unreamed nails, and reamer irrigation aspiration systems (RIA) may all reduce the risk of embolic phenomenon.
Venting may lead to extra-skeletal spread of disease [7]. Time to
union has been shown to be longer using unreamed, compared to
reamed, femoral nails in trauma patients [63,64]. However,
satisfactory outcomes have been demonstrated using unreamed
femoral nails in the stabilisation of pathological fractures
[65,66]. Negative pressure reaming and irrigation have been
developed to reduce intramedullary pressures and the systemic
effects of reaming [67]. In animal studies, RIA reduced intramedullary pressures from 188 mmHg to 33 mmHg in porcine femora
[68] and produced lower D-dimer levels and pulmonary permeability in lung-injured sheep femora compared to standard reamed
nailing [69]. The use of RIA preparation of the femur may prove
important in reducing embolic phenomenon and tumour disbursement in patients with pathological lesions [70].

Please cite this article in press as: Bryson DJ, et al. The investigation and management of suspected malignant pathological fractures: A
review for the general orthopaedic surgeon. Injury (2015), http://dx.doi.org/10.1016/j.injury.2015.07.028

G Model

JINJ-6312; No. of Pages 9

D.J. Bryson et al. / Injury, Int. J. Care Injured xxx (2015) xxxxxx

Fig. 3. The Rizzoli Institute Algorithm [30] for patients with pathological fractures. *When limb salvage is not feasible due to extent of lesion, neurovascular involvement, and/
or massive contamination.
**Radiation therapy rarely given; only if margins are not wide, or contaminated.
***Wide resection if xation is not feasible.
****Wide resection only if xation is not feasible due to extent of the lesion or meta-epiphyseal involvement.
y
Chemotherapy in patients with skeletal metastases only if feasible depending on age, general condition and expected survival.

The distal femur

Distal femoral lesions or fractures can be managed by
retrograde nailing; curettage and internal xation augmented
with PMMA, or by endoprosthetic replacement (EPR) depending on
the extent of disease and the exact anatomical location. When bone
stock is adequate, conventional xation with locking plates [2,5,7],
or retrograde nailing [71,72], augmented with PMMA is usually
sufcient.
In cases where more than half of the epiphyseal or metaphyseal
region is involved, resection and replacement with a cemented
distal femoral replacement may be indicated [7,8].
The humerus
The humerus is second most common long bone site of
metastatic disease with the proximal third and diaphysis
frequently affected [73]. An incidence of pathological fracture
between 16 and 27% has been reported [74], resulting in
considerable pain and disability. Frassica and Frassica proposed
a management strategy based upon division of the humerus into
three regions [75] (Fig. 5).
Disease conned to the humeral head and proximal metaphysis
can be managed with either endoprosthetic replacement (EPR)

[74,76], or locking plate with cement augmentation [44]. EPR can

provide good pain relief and acceptable function in selected cases
[74,76]. A cemented, long stem prosthesis spanning the diathesis
to the supracondylar region is advised to protect the entire
humeral shaft [75]. Shoulder function will often be compromised
because of disruption to soft tissues and their anchoring points, but
this is tempered by achievement of a painless limb [77]. Locking
plate constructs with cement augmentation may provide a more
favourable outcome in terms of function [44].
In cases of diaphyseal involvement, both intramedullary nailing
and plate and screw xation (with or without cement augmentation) have shown good results in terms of pain relief and
restoration of function [74,7880]. Plate xation avoids violation
of the rotator cuff but requires greater surgical exposure, risks
damage to the radial nerve, fails to protect as much humeral length
[74] and can lead to stress risers [77]. Intramedullary nails provides
rigid xation to the length of the humerus with minimal morbidity
and early return of function to the extremity [79,81,82].
Distal humeral involvement is rare and can be challenging.
Fractures at this level are best managed with locking plate and
screw osteosynthesis. In very distal fractures, or cases of extensive
disease, exible intramedullary nails have been utilised [75,83].
Endoprosthetic reconstruction of the elbow after distal humerus
tumour excision has shown good functional outcome and pain

Please cite this article in press as: Bryson DJ, et al. The investigation and management of suspected malignant pathological fractures: A
review for the general orthopaedic surgeon. Injury (2015), http://dx.doi.org/10.1016/j.injury.2015.07.028

G Model

JINJ-6312; No. of Pages 9

D.J. Bryson et al. / Injury, Int. J. Care Injured xxx (2015) xxxxxx

Fig. 5. Fixation techniques based upon anatomical location of pathological fractures

in the humerus.
Fig. 4. Distal tibial renal cell carcinoma metastasis managed with curettage and
internal xation with cement augmentation.

relief in the small cohort of patients who have undergone such

procedures [84,85].
The tibia, foot and ankle
Metastatic fractures of the tibia are rare [86]. In a multicentre
study of 592 bony metastases only 26 (4.4%) were in the tibia [87].
Proximal disease is often best managed with curettage, PMMA
augmentation and locking plate xation. Endoprosthetic replacement is an option but necessitates major soft tissue reconstructive
procedures [7] including gastrocnemius aps and split skin
grafting because of the subcutaneous nature of the tibia. Patella
tendon reconstruction is also a challenge. In cases of diaphyseal
disease, locked antegrade intramedullary nailing is preferred
[5,7,86] and may be augmented with PMMA cement. With distal
tibial involvement not amenable to intramedullary nailing,
curettage and internal xation with cement augmentation is
indicated (Fig. 4).
Focal lesions of the talus or calcaneum may be amenable to
curettage and cementation [25]. Below knee amputation or partial
amputation of the foot may sometimes be required in cases of
acrometastases or metastatic disease involving the ankle.
Amputation
Indications for amputation in metastatic disease include failure
of internal xation with painful non-union, local recurrence,
involvement of the skin, soft tissues and neurovascular structures,
severe lymphoedema, post-radiation neuropathy and brosis,

tumours not amenable to excision and reconstruction, and

acrometastases [7,25,42].
Non-surgical managementradiotherapy
Radiotherapy is a vital adjunct in the management of patients
with metastatic disease [43]. Radiotherapy to the entire surgical
eld should be the default position and considered in every case. Up
to 90% of patients can expect some pain relief with 5060%
experiencing complete pain relief. Failure to undertake radiotherapy
is not only likely to result in less effective pain relief, but also
increases the risk of tumour progression and subsequent failure of
xation or reconstruction. A failure to irradiate the whole surgical
eld may further result in the development of periprosthetic
metastases [7,25].
Single fraction therapy regimes are as effective as multifraction for palliative treatment and are more convenient for
patients, necessitating fewer visits to outpatient clinics and are less
costly [88].
Medical therapy
Bisphosphonates, denosumab, chemotherapy, radiopharmaceuticals and hormonal therapy may all have a role to play in
the medical management of patients with metastatic bone disease
or pathological fracture. This aspect of management is beyond the
scope of this review. However, these additional treatments should
be considered by the multi-disciplinary team.
Summary
The management of patients presenting with a pathological
fracture can be challenging. Adherence to basic principles can

Please cite this article in press as: Bryson DJ, et al. The investigation and management of suspected malignant pathological fractures: A
review for the general orthopaedic surgeon. Injury (2015), http://dx.doi.org/10.1016/j.injury.2015.07.028

G Model

JINJ-6312; No. of Pages 9

D.J. Bryson et al. / Injury, Int. J. Care Injured xxx (2015) xxxxxx

reduce the risk of failing to detect, or inappropriate management

of, a pathological fracture.
A history of malignancy, preceding pain, and minimal trauma,
or the absence of trauma should raise the suspicion of the fracture
being pathologicalsuspect and detect should be the mantra. The
investigation and diagnosis of a skeletal lesion must be comprehensive, particularly in the absence of a known metastatic
malignancydo not hesitate to investigate and for all patients.
In cases of possible primary bone sarcoma advice should be sought
from a supra-regional bone tumour centre. In cases where the
diagnosis is unclear, the question should be why doesnt this
patient need a biopsy? In the majority of cases routine
investigations (plain radiographs, CT, MRI, isotope bone scan) will
reveal the underlying cause, but if uncertainty persists, biopsy
should be undertaken. In cases of possible primary malignancy this
should be performed at the supra-regional bone tumour centre.
When surgical intervention is performed, it should be remembered
that standard methods of trauma xation may not be appropriate.
It should be assumed that a pathological fracture will not unite.
Non-union, radiotherapy-related complications, and the possibility of disease progression all predispose to xation failure. Fixation
should be planned based on this assumption. Arthroplasty has, in
general, lower failure rates than internal xation. The goals of
surgery in patients with metastatic disease are pain relief,
maintenance of function and mobility, and improvement in quality
of life, for that time remaining. Multidisciplinary input is crucial in
achieving these goals. All surgical patients should be offered
radiotherapy and when administered it should be given to the
entire surgical eld. Single fraction regimes are more convenient
for patients and less costly.
Conict of interest
The authors have no conict of interest to declare.
References
[1] Biermann JS, Holt GE, Lewis VO, Schwartz HS, Yaszemski MJ. Metastatic bone
disease: diagnosis, evaluation, and treatment. J Bone Joint Surg Am 2009;91:
151830.
[2] Weber KL, Randall RL, Grossman S, Parvizi J. Management of lower-extremity
bone metastases. J Bone Joint Surg Am 2006;88(Suppl. 4):119.
[3] Goodman MA, Weiss KR. Surgical approach to metastatic bone disease. Oper
Tech Orthop 2014;24:8590.
[4] Katagari H, Takahashi M, Wakai K, Sugiura H, Katoka T, Nakanishi K. Prognostic
factors and a scoring system for patients with skeletal metastasis. J Bone Joint
Surg Br 2005;87:698703.
[5] Scolaro JA, Lackman RD. Surgical management of metastatic long bone fractures: principles and techniques. J Am Acad Orthop Surg 2014;22(2):90100.
[6] Hage WD, Aboulaa AJ, Abouaa DM. Incidence, location and disgnositc
evlauation of metastatic bone disease. Orthop Clin North Am 2000;31(4):
51528.
[7] Ashford RU, Benjamin L, Pendlebury S, Stalley PD. The modern surgical and
non-surgical management of appendicular skeletal metastases. Orthop Trauma 2012;26(3):18499.
[8] Capanna R, Camanacci DA. The treatment of metastases in the appendicular
skeleton. J Bone Joint Surg Br 2001;83(4):47181.
[9] Van der Linden YM, Dijkstra PDS, Kroon HM, Lok JJ, Noordijk EM, Leer JWH,
et al. Comparative analysis of risk factors for pathological fracture with
femoral metastases. J Bone Joint Surg Br 2004;86:56673.
[10] Fidler M. Incidence of fracture through metastases in long bones. Act Orthop
Scand 1981;52(6):6237.
[11] Edwards SA, Pandit HG, Clarke HJ. The treatment of impending and existing
pathological femoral fractures using the long gamma nail. Injury 2001;32(4):
299306.
[12] Wedin R. Surgical treatment for pathological fracture. Acta Orthop Scand
Suppl 2001;72(302):129.
[13] Bohm P, Huber J. The surgical treatment of bony metastases of the spine and
limbs. J Bone Joint Surg Br 2002;84B:5219.
[14] Tillman RM. The role of the orthopaedic surgeon in metastatic disease of the
appendicular skeleton. Working party on metastatic bone disease in breast
cancer in the UK. J Bone Joint Surg Br 1999;81(1):12.
[15] Bauer HCF, Wedin R. Survival after surgery for spinal and extremity metastases. Acta Orthop Scand 1995;66(2):1436.

[16] Bauer HCF. Controversies in the surgical management of skeletal metastases. J

Bone Joint Surg Br 2005;87(5):60817.
[17] Hansen BH, Keller J, Laitinen M, Berg P, Skjeldal S, Trovik C, et al. The
Scandinavian Sarcoma Group skeletal metastases register Survival after surgery for bone metastases in the pelvis and extremities. Acta Orthop Scand
Suppl 2004;75(311):115.
[18] Grimer RJ, Briggs TWR. Earlier diagnosis of bone and soft-tissue tumours. J
Bone Joint Surg Br 2010;92(11):148992.
[19] Dean BJF, Whitwell D. Epidemiology of bone and soft-tissue sarcomas. Orthop
Trauma 2009;23(4):22330.
[20] Maheshwari AV, Cheng EY. Ewing sarcoma family of tumors. J Am Acad Orthop
Surg 2010;18(2):94107.
[21] Abudu A, Sferopoulos NK, Tillman RM, Carter SR, Grimer RJ. The surgical
treatment and outcome of pathological fractures in localised osteosarcoma. J
Bone Joint Surg Br 1996;78:6948.
[22] Scully SP, Ghert MA, Zurakowski D, Thompson RC, Gebhardt MC. Pathological
fracture in osteosarcoma: prognostic importance and treatment options. J
Bone Joint Surg Am 2002;84A(1):4957.
[23] Bramer JAM, Somford MP. The epidemiology of primary skeletal malignancy.
Orthop Trauma 2010;24:24751.
[24] Papagelopoulos PJ, Mavrogenis AF, Savvidou OD, Benetos IS, Galanis EC,
Soucacos PN. Pathological fractures in primary bone sarcomas. Injury 2008;
39(4):395403.
[25] Ashford RU. Palliative orthopaedic surgery for skeletal metastases. Eur Oncol
2009;51:304.
adell J, San-Julian M, Cara J, Forriol F. External xation in tumour patholo[26] Can
gy. Int Orthop 1998;22(2):12630.
[27] Swanson KC, Pritchard DJ, Sim FH. Surgical treatment of metastatic disease of
the femur. J Am Acad Orthop Surg 2000;8(1):5665.
[28] Coleman RE. Skeletal complications of malignancy. Cancer 1997;80:158894.
[29] Bischel OE, Bohm PM. The use of a femoral revision stem in the treatment of
primary or secondary bone tumours of the proximal femur. J Bone Joint Surg Br
2010;92(10):143541.
[30] Ruggieri P, Mavrogenis AF, Casadei R, Errani C, Angelini A, Calabro` T, et al.
Protocol of surgical treatment of long bone pathological fractures. Injury 2010;
41(11):11617.
[31] Melton III LJ, Kyle RA, Achenbach SJ, Oberg AL, Rajkumar SV. Fracture risk with
multiple myeloma: a population-based study. J Bone Miner Res 2005;20(3):
48793.
[32] Wilkinson AN, Viola R, Brundage MD. Managing skeletal related events
resulting from bone metastases. BMJ 2008;337. http://dx.doi.org/10.1136/
bmj.a2041 [Nov 3, a2041].
[33] Rougraff BT, Kneisl JS, Simon MA. Skeletal metastases of unknown origin. A
prospective study of a diagnostic strategy. J Bone Joint Surg Am 1993;75(9):
127681.
[34] Rougraff BT. Evaluation of the patient with carcinoma of unknown origin
metastatic to bone. Clin Orthop Relat Res 2003;415(Suppl.):S1059.
[35] Barton PP, Warneck RE, Karnel FJ, Ritschl P, Kramer J, Lechner GL. Embolization
of bone metastases. J Vasc Interv Radiol 1996;7(1):818.
[36] Baloch KG, Grimer RJ, Carter SR, Tillman RM. Radical surgery for the solitary
bone metastases from renal-cell carcinoma. J Bone Joint Surg Br 2000;82(1):
627.
[37] Lin PP, Mirza AN, Lewis VO, Cannon CP, Tu SM, Tannir NM, et al. Patient
survival after surgery for osseous metastases from renal cell carcinoma. J Bone
Joint Surg Am 2007;89(8):1749801.
nder AU, Sonmezoglu K, Erozenci A, Solok V. The value of
[38] Ataus S, Citci A, O
serum prostate specic antigen and other paramaters in detecting metastases
in prostate cancer. Int Urol Nephron 1999;31(4):4819.
[39] Ashford RU, Fairbain KJ. Investigation of musculoskeletal malignancy. Orthop
Trauma 2009;23(4):2319.
[40] British Orthopaedic Association and British Orthopaedic Oncology Society
Publication. Metastatic bone disease: a guide to good practice British Orthopaedic Association, London; 2000
[41] Saifuddin A, Mitchell R, Burnett SJD, Sandison A, Pringle JA. Ultrasoundguided needle biopsy of primary bone tumours. J Bone Joint Surg Br 2000;
82(1):504.
[42] Eastley NC, Newey M, Ashford RU. Skeletal metastases the role of the
orthopaedic and spinal surgeon. Surg Oncol 2012;21:2126.
[43] Damron TA, Sim FH. Operative treatment for metastatic disease of the pelvis
and proximal end of the femur. J Bone Joint Surg Am 2000;49(1):11426.
[44] Gregory JJ, Ockendon M, Cribb GL, Cool PW, Williams DH. The outcome of
locking plate xation for the treatment of periarticular metastases. Acta
Orthop Belg 2011;77(3):36270.
[45] Ramisetty NM, Pynsent PB, Abudu A. Fracture of the femoral neck, the risk of
serious underlying pathology. Injury 2005;36(5):6226.
[46] Wedin R, Bauer HC, Wersall P. Failures after operation for skeletal metastatic
lesions of long bones. Clin Orthop Relat Res 1999;358:12839.
[47] Haberman ET, Sachs R, Stern RE, Hirsh DM, Anderson Jr WJ. The pathology
and treatment of metastatic disease of the femur. Clin Orthop 1982;169:
7082.
[48] Wedin R, Bauer HC. Surgical treatment of skeletal metastatic lesions of the
proximal femur: endoprosthesis or reconstruction nail? J Bone Joint Surg Br
2005;87B:16537.
[49] Ashford RU, Hanna SA, Park DH, Pollock RC, Skinner JA, Briggs TW, et al.
Proximal femoral replacements for metastatic bone disease: nancial implications for sarcoma units. Int Orthop 2010;34:70913.

Please cite this article in press as: Bryson DJ, et al. The investigation and management of suspected malignant pathological fractures: A
review for the general orthopaedic surgeon. Injury (2015), http://dx.doi.org/10.1016/j.injury.2015.07.028

G Model

JINJ-6312; No. of Pages 9

D.J. Bryson et al. / Injury, Int. J. Care Injured xxx (2015) xxxxxx
[50] Herrenbruck T, Erickson EW, Damron TA, Heiner J. Adverse clinical events
during cemented long-stem femoral arthroplasty. Clin Orthop Relat Res
2002;395:15463.
[51] Patterson BM, Healey JH, Cornell CN, Shamrock NE. Cardiac arrest during hip
arthroplasty with a cemented long-stem component. A report of seven cases. J
Bone Joint Surg Am 1991;73(2):2717.
[52] Leddy LR. Rationale for reduced pressure reaming when stabilizing actual or
impending pathological femoral fractures: a review of the literature. Injury
2010;41(Suppl. 2):S4850.
[53] Alvi HM, Damron TA. Prophylactic stabilization for bone metastases, myeloma
or lymphoma: do we need to protect the enitre bone? Clin Orthop Relat Res
2013;471(3):70614.
[54] Kokoroghiannis C, Aktselis I, Deligeorgis A, Fragkomichalos E, Papadimas D,
Pappadas I. Evolving concepts of stability and intramedullary xation of
intertrochanteric fracturesa review. Injury 2012;43(6):68693.
[55] Ramakrishnan M, Prasad SS, Parkinson RW, Kaye JC. Management of subtrochanteric femoral fractures and metastases using long proximal femoral
nail. Injury 2004;35(2):18490.
[56] Sharma H, Bhagat S, McCaul J, Macdonald D, Rana B, Naik M. Intramedullary
nailing for pathological femoral fractures. J Orthop Surg (Hong Kong) 2007;
15(3):2914.
[57] Nilsson J, Gustafson P. Surgery for metastatic lesions of the femur: Good
outcome after 245 operations in 216 patients. Injury 2008;39(4):40410.
[58] Kerr PS, Jackson M, Atkins RM. Cardiac arrest during intramedullary nailing for
femoral metastases. J Bone Joint Surg Br 1993;75(6):9723.
[59] Robinson CM, Ludlam CA, Ray DC. The coagulative and cardiorespiratory
response to reamed intramedullary nailing of isolated fractures. J Bone Joint
Surg Br 2001;83(7):96373.
[60] Pape HC, Giannoudis P. The biological and physiological effects of intramedullary reaming. J Bone Joint Surg Br 2007;89(11):14216.
[61] Peter RE, Seiz T, Koestli A. Inuence of the reamer shape on intraosseus
pressure during closed intramedullary nailing of the unbroken femur: a
preliminary report. Injury 1993;24(Suppl. 3):S4855.
[62] Peter RE, Schopfer A, Le Coultre B, Hoffmeyer P. Fat embolism and death during
prophylactic osteosynthesis of a metastatic femur using an unreamed nail. J
Orthop Trauma 1997;11(3):2334.
[63] Giannoudis PV, Furlong AJ, Macdonald DA, Smith RM. Reamed against
unreamed nailing of the femoral diaphysis: a retrospective study of healing
time. Injury 1997;28(1):158.
[64] Clatworthy MG, Clark DI, Gray DH, Hardy AE. Reamed versus unreamed
femoral nails a randomised, prospective trial. J Bone Joint Surg Br 1998;
80(3):4859.
[65] Giannoudis PV, Bastawrous SS, Bunola JA, Macdonaid DA, Smith RM.
Unreamed intramedullary nailing for pathological femoral fractures: good
results in 30 cases. Acta Orthop 1999;70(1):2932.
[66] Cole AS, Hill GA, Theologis TN, Gibbons CLMH, Willett K. Femoral nailing for
metastatic disease of the femur: a comparison of reamed and unreamed
femoral nailing. Injury 2000;31(1):2531.
[67] Kanakaris NK, Morell D, Gudipati S, Britten S, Giannoudis PVl. Reaming
Irrigator Aspirator system: early experience of its multipurpose use. Injury
2011;42(Suppl. 4):S2834.
[68] Husebye EE, Lyberg T, Eriksen M, Rise O. The inuence of a one-step reamerirrigator-aspirator technique on the intramedullary pressure in the pig femur.
Injury 2006;37(10):93540.

[69] Pape HC, Zelle BA, Hildebrand F, Giannoudis PV, Krettek Cm van Griensven
M. Reamed femoral nailing in sheep: does irrigation and aspiration of
intramedullary contents alter the systemic response? J Bone Joint Surg
Am 2005;87(11):251522.
[70] Muller CA, Green J, Sudkamp NP. Physical and technical aspects of intramedullary reaming. Injury 2006;37(Suppl. 4):S3949.
[71] Healey JH, Lane JM. Treatment of pathological fractures of the distal femur
with the Zickel supracondylar nail. Clin Orthop Relat Res 1990;250:
21620.
[72] Scholl BM, Jaffe KA. Oncologic uses of the retrograde femoral nail. Clin Orthop
Relat Res 2002;394:21926.
[73] Frassica FJ, Frassica DA. Evaluation and treatment of metastases to the
humerus. Clin Orthop Relat Res 2003;415(Suppl.):S2128.
[74] Picciolo A, Maccauro G, Rossi B, Scaramuzzo L, Frenos F, Capanna R. Surgical
treatment of pathologic fractures of humerus. Injury 2010;41(11):11126.
[75] Frassica FJ, Frassica DA. Metastatic bone disease of the humerus. J Am Acad
Orthop Surg 2003;11(4):2828.
[76] Kumar D, Grimer RJ, Abudu A, Carter SR, Tillman RM. Endoprosthetic replacement of the proximal humerus: long term results. J Bone Joint Surg Br
2003;85(5):71722.
[77] Bashore CJ, Temple HT. Management of metastatic lesions of the humerus.
Orthop Clin North Am 2000;31(4):597609.
[78] Weiss KR, Bhumbra R, Biau DJ, Grifn AM, Deheshi B, Wunder JS, et al. Fixation
of pathological humeral fractures by the cemented plate technique. J Bone
Joint Surg Br 2011;93(8):10937.
[79] Thai DM, Kitagawa Y, Choong PF. Outcome of surgical management of bony
metastases to the humerus and shoulder girdle: a retrospective analysis of
93 patients. Int Semin Surg Oncol 2006;3:5.
[80] Dijkstra S, Stapert J, Boxma H, Wiggers T. Treatment of pathological fractures
of the humeral shaft due to bone metastases: a comparison of intramedullary
locking nail and plate osteosyntheis with adjunctive bone cement. Eur J Surg
Oncol 1996;22(6):6216.
[81] Redmond BJ, Biermann JS, Blassier RB. Interlocking intramedullary nailing of
pathological fractures of the shaft of the humerus. J Bone Joint Surg Am 1996;
78(6):8916.
[82] Sarahrudi K, Wolf H, Funovics P, Pajenda G, Hausmann JT, Vecsei V. Surgical
treatment of pathological fractures of the shaft of the humerus. J Trauma
2009;66:78994.
[83] Dala S, Gibson RJ. Pathological fracture of the distal humerus treated with
Nancy nails. Injury 2004;35(3):3278.
[84] Hanna SA, David LA, Aston WJ, Gikas PD, Blunn GW, Cannon SR, et al.
Endoprosthetic replacement of the distal humerus following resection of bone
tumours. J Bone Joint Surg Br 2007;89(11):1498503.
[85] Kulkarni A, Fiorenza F, Grimer RJ, Carter SR, Tillman RM. The results of
endoprosthetic replacement for tumours of the distal humerus. J Bone Joint
Surg Br 2003;85(2):2403.
[86] De Geeter K, Reynders P, Samson I. Metastatic fractures of the tibia. Acta
Orthop Belg 2001;67(1):549.
[87] Kelly CM, Wilkins RM, Eckardt, Ward WG. Treatment of metastatic disease of
the tibia. Clin Orthop Relat Res 2003;415:S21929.
[88] van den Hout WB, van der Linden YM, Steenland E, Wiggenraad RG, Keivit J, de
Haes H, et al. Single- versus multiple-fraction radiotherapy in patients with
painful bone metastases: cost-utility analysis based on a randomized trial. J
Natl Cancer Inst 2003;95(3):2229.

Please cite this article in press as: Bryson DJ, et al. The investigation and management of suspected malignant pathological fractures: A
review for the general orthopaedic surgeon. Injury (2015), http://dx.doi.org/10.1016/j.injury.2015.07.028