Review paper
The diabetic foot: Charcot joint and osteomyelitis
Laura Giurato and Luigi Uccioli
Foot problems are common causes of disability in
diabetic patients with as many as 25% expected to develop
severe foot or leg problems during their lifetimes. Although
skin ulceration is the most frequent problem, bones may
also be involved in two different clinical conditions:
osteomyelitis and Charcot osteoarthropathy. Osteomyelitis
causes complications in up to one third of diabetic foot
c 2006 Lippincott Williams & Wilkins.
infections and is due to direct contamination from a
soft-tissue ulcer. Osteoarthropathy Charcot foot is a
chronic and progressive disease of the bone and joints.
Both osteomyelitis and Charcot joint are conditions with an
increased risk of lower limb amputation, both may have a
successful outcome when recognized and treated in
the early stages. The major diagnostic difficulty is
in distinguishing bone infection (osteomyelitis) from
non-infectious neuropathic bony disorders as in
osteoarthropathy Charcot foot. An additional difficulty is
found when a bone infection superimposes a Charcot
Charcot neuroarthropathy in the diabetic foot
A possible manifestation of the neuropathic foot is
neuropathic osteoarthropathy, commonly referred to as
Charcot’s joint. It is a chronic and progressive disease of
the bone and joints. This pathological process culminates
in bone and joint destruction and subsequent foot
deformity, which predisposes to ulceration. The patho-
genic mechanism(s) for the development of the Charcot
foot have been the subject of a number of competing
theories, but the pathogenesis remains unclear. It is
certain that the cause is multifactorial [1,2].
A number of the mechanisms operate simultaneously:
peripheral sensory and motor neuropathy, biomechanical
factors, autonomic neuropathy are all considered poten-
tial causes in the development of the Charcot foot [3].
Motor neuropathy leads to changes in the integrity of the
arches of the foot, with increased pressure loading at
certain points. The concomitant sensory neuropathy
leads to these pressure loads remaining unnoticed, which
can induce microfractures and bone deformity. The
repeated trauma in an insensitive foot leads to laxity of
ligaments and instability of joints with resultant bone
damage (neurotraumatic theory) [4,5].
According to neurovascular theory, sympathetic denerva-
tion is the leading cause through the induction of active
bone resorption and osteopenia by osteoclasts. Autonomic
neuropathy is responsible for impairment of vascular
0143-3636
c 2006 Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
osteopathy. This condition, which can be clinically
suspected when foot ulceration appears in Charcot foot,
needs to be diagnosed because it implies a different
therapeutic strategy. This article aims to summarize
both these two clinical conditions and give indications to
make a timely and correct diagnosis. Nucl Med Commun
27:745–749
Nuclear Medicine Communications 2006, 27:745–749
Keywords: osteomyelitis, Charcot neuroarthropathy, foot ulcers, infection
Department of Internal Medicine, ‘Tor Vergata’ University of Rome, Italy.
Correspondence to Dr Luigi Uccioli, Department of Internal Medicine, ‘Tor
Vergata’ University of Rome, Viale Oxford 81, 00133 Rome, Italy.
Tel: + 0039 06 2090 2784; fax: + 0039 06 2090 2804;
e-mail: luigi.uccioli@ptvonline.it
Received 12 July 2005 Accepted 10 May 2006
smooth muscle tone and, consequently, it produces a
vasodilatory condition in the small arteries and an
increase in bone blood flow. The resultant osteolysis,
demineralization of bone, can predispose to the develop-
ment of Charcot osteoarthropathy [4,5].
It is likely that the pathogenesis of Charcot foot is a
combined effect of these theories.
However, neuropathic osteoarthropathy (acute Charcot
foot) is also characterized by uncontrolled inflammation.
It has been suggested that the disorder arises by abnormal
expression of nuclear transcription factor NF-kB
in diabetic neuropathy, associated with the increased
release of proinflammatory cytokines, such as tumour
necrosis factor alpha and interleukin 1 beta, and this
cascade results in increased osteoclastogenesis. Osteo-
clasts cause progressive bone lysis, leading to further
fracture, which in turn potentiates the inflammatory
process [6,7].
Clinical features
The Charcot foot is characterized by acute and chronic
phases. In acute Charcot neuroarthropathy, the foot is
warm, oedematous, markedly erythematous, and with
temperature difference > 21C between the affected and
non-affected foot and can be associated with a history of
traumas even if under-reported [8,9]. There is always
some degree of sensory neuropathy in which reflexes,
 746 Nuclear Medicine Communications 2006, Vol 27 No 9
vibratory sense and proprioception are either diminished
or absent. Autonomic neuropathy, which co-exists with
somatosensory neuropathy, can be clinically appreciated
by the presence of anhydrosis with very dry skin. Pain
may or may not be present.
The chronic phase is characterized by deformity of
the foot with abnormal pressure on the plantar surface
due to the collapse of the plantar arch and the
development of a rocker bottom deformity. Continued
weight-bearing will cause increasing damage with pro-
gressive destruction of the foot. The skin overlying new
bony prominences is associated with callus formation,
which is liable to ulceration especially in the mid-foot. A
concomitant ulceration will therefore raise the risk of
contiguous osteomyelitis. Charcot deformities have been
described for all the foot bones therefore an anatomical
classification has been proposed, as given in Table 1.
Investigations
The diagnosis of the Charcot foot remains primarily
clinical, particularly in the early stages. Plain radiographs
are not helpful for ascertaining the presence of osteoar-
thropathy in a warm, swollen and insensate foot. In
advanced stages the typical radiology RX signs are:
demineralization, bone destruction and periosteal reac-
tion, ‘pencil and cup’ deformity at the metatarso-
phalangeal joints or fragmentation of the metatarsal
heads, especially in the forefoot Charcot and dislocation
or fracture in the mid-foot and atypical calcaneal
fractures. Plain films are useful for anatomical information
but are neither sensitive nor specific for separating
Charcot changes from infection [10,11].
Other investigations for the diagnosis of acute Charcot
neuroarthropathy are represented by computerized to-
mography (CT) and magnetic resonance (MR). An MR
scan of a Charcot foot is extremely sensitive, having a
100% detection of abnormalities [12].
Diagnosis of underlying osteomyelitis can be difficult in
chronic Charcot osteoarthropathy with foot ulcers.
Scintigraphic methods such as combined 111In-leuko-
cyte/bone or leukocyte/marrow scintigraphy are extremely
useful in making differential diagnosis between a Charcot
joint with and without osteomyelitis [13–15].
Table 1 Anatomical classification* of Charcot deformities
Type Joints involved
I Metatarso-phalangeal and interphalan-
geal
II Tarso-metatarsal
III Tarsal
IV Sub-talar
V Calcaneum
*
From Sanders LJ, Frykberg RG; Charcot foot in Levin ME, O’Neal LW, Bowker
JH. (Eds.): The Diabetic foot. Ed 5. St Lovis Hosby Book, 1993.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
In this particular condition MRI seems not to be able to
distinguish the marrow oedema associated with Charcot
and that associated with osteomyelitis.
Osteomyelitis in the diabetic foot
Foot infections are among the most frequent and serious
consequences of foot ulceration in diabetic patients and
they are responsible for more hospital days than any other
complications of diabetes and contribute up to 25–50% of
lower-extremity amputations in diabetic patients [16,17].
An estimated 10–30% of diabetic patients with a foot
ulcer will eventually require an amputation, approxi-
mately 60% of which are preceded by an infected ulcer
[18,19]. Although the true prevalence of osteomyelitis in
diabetic foot ulcers is not known, studies have shown that
it may be present in more than 60% of infected diabetic
foot ulcers [20,21].
Osteomyelitis is secondary complication of diabetic foot
ulceration. It is a bone infection that induces a
progressive destruction of the bone. In the diabetic ulcer
the infection develops by spreading from contiguous soft-
tissue to underlying bone. It may involve any bone of the
foot, but it mostly affects forefoot bones [22].
Clinical manifestation
The first approach to diagnosis is a clinical evaluation.
Skin ulceration with soft-tissue infections that have been
present for more than a week or two, especially if they are
located over a bony prominence, are at high risk for
contiguous bone involvement. The typical signs of local
infection are swelling, erythema, warm with or without
discharging pus and or fragments of bone [23,24].
Systemic signs, such as fever and malaise, are unusual
in any form of foot infection, including chronic osteo-
myelitis.
The larger and deeper the skin ulceration the more likely
the underlying bone will be infected [25]. All of the
ulcers in which bone exposed, either visibly or by probing,
have underlying osteomyelitis with a sensitivity of 66%, a
specificity of 89% and a positive predictive value of 89%
[26]. Moreover, it has proposed that clinically the
‘sausage toe’ deformity, due to local soft tissue infection
and inflammation and underlying bony changes, is highly
suggestive of osteomyelitis [27].
Ulcers of long duration are probably more often
associated with underlying osteomyelitis as are those
which overlie bony prominences.
A systemic reaction to osteomyelitis of blood tests,
including C-reactive protein (CRP) and white blood cell
(WBC) count, are non-specific; in fact, both a neutrophil
count and CRP were higher in soft-tissue infections than
in osteomyelitis.
 Charcot joint and osteomyelitis Giurato and Uccioli 747

Fig. 1

(a) Charcot foot

Foot with swollen, warm, erythematous skin, with elevated temperature

without a history or presence of ulcer in the neuropathic diabetic patient

Highly suspected for acute Charcot

Plain X-ray
negative

Compatible with Charcot MRI foot

(b) Charcot Joint with ulcer in mid/hindfoot

Clinical suspicion of bone infection

MRI foot

Combined leukocyte/marrow scintigraphy

(c) Osteomyelitis of the fore/midfoot

Ulcer with bone exposed Ulcer with bone probing

Presumptive osteomyelitis high probability of osteomyelitis

Plain X-ray
Bone culture positive negative
Plain X-ray and/or MRI foot
In 111WBC scan
and /or
Follow-up with plain X-ray MRI foot

(d) Ulcer with soft-tissue infection

Plain X-ray

highly suspected

Compatible with osteomyelitis In 111WBC scan

or/and
MRI foot
Follow-up with plain X-ray
A possible approach to the diagnostic evaluation of different clinical conditions of the diabetic foot.

In contrast, an elevated erythrocyte sedimentation rate Imaging studies

(ESR) may be a better marker of bone infection. In fact, Plain films are routinely used in imaging to diagnose
studies found a high ESR in 96% of cases in which bone osteomyelitis in the diabetic foot but it is difficult to
was involved [28]. interpret them in the early stages. In fact, bony

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 748 Nuclear Medicine Communications 2006, Vol 27 No 9
abnormalities related to osteomyelitis are generally not
evident on plain films until 10–20 days after infection.
Although plain X-ray changes are not pathognomonic for
infection a diagnosis of probable osteomyelitis can be
made when classic findings are associated with the
presence of typical clinical signs [29,30]. Plain films are
diagnostically useful to monitor the treatment of
osteomyelitis [30].
Radionuclide bone scanning with 99mTc-diphosphonates
in three or four phases is certainly more diagnostic than
X-ray in early osteomyelitis. The sensitivity is of 86%
(68–100%) but its specificity of about 45% (0–79%) is
poor because any type of bone disease (including
neuropathic osteoarthropathy and healing infections)
may be able to increase uptake of isotope [31,32].
A 111In-WBC scan gives better results in the diagnosis of
infection with a sensitivity of 89% (45–100%) and
specificity of 78% (29–100%). When the infection
resolves, this scan normalizes. This makes it a potentially
useful tool to follow the response to therapy. The major
limitation of this scan in the foot is that the lower
resolution may not differentiate infection of the bone
from that of adjacent soft tissues [33]. Moreover, the
sensitivity can be limited in the presence of peripheral
ischaemia.
However, a WBC scan or scans using other infection-
specific radiopharmaceuticals combined with a bone scan
or 99mTc-labelled sulfur colloid (which localizes to the
marrow) can increase specificity and this approach may be
evaluable in excluding osteomyelitis when Charcot
osteoarthropathy has been complicated by secondary
neuropathic ulceration [13,14,34].
Although there have been some promising results in early
studies this technique with a double scan is relatively
expensive, technically demanding and requires with-
drawal and re-infusion of blood [35].
Most specialists agree that MRI offers the greatest
diagnostic support in clinical practice to diagnose
osteomyelitis in the diabetic foot. In addition, MRI has
a better resolution and better sensitivity in differentiat-
ing bone infection from soft-tissue infection than do
other diagnostic techniques. The diagnostic sensitivity of
MRI is 90–100%, while its specificity is 83% [35,36],
although this is limited by the fact that the technique is
not able to distinguish between marrow oedema, which is
characteristic of osteomyelitis, and other conditions that
are able to increase bone marrow oedema, such as acute
Charcot osteoarthropathy. However, MRI has a positive
predictive power of 93% and a negative predictive power
of 100% according to a study that compared its results to
those of bone biopsy, which is considered the ‘gold
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
standard’ technique in this context [36]. In addition, in
some studies evaluating diabetic patients with a clinical
suspicion of osteomyelitis secondary to an infection of
soft tissues, MRI performed better in the diagnosis of
osteomyelitis than did plain X-ray, bone scans and WBC
scans [37,38]. Recent evidence suggests a possible role of
positron emission tomography (PET) and PET/CT using
2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) for the
diagnosis of diabetic foot osteomyelitis. 18F-FDG is a
non-specific tracer for increased intracellular glucose
metabolism and accumulates in sites of infection and
inflammation [39,40].
However, bone biopsy remains the ‘gold standard’
in diagnosing osteomyelitis because it has 95% sensitivity
and 99% specificity [41]. Moreover, it has the advantage
of providing culture and antimicrobial susceptibility
results which can guide the choice of antibiotic
therapy. A possible approach in the diagnosis of different
clinical conditions of the diabetic foot is outlined in
Fig. 1.
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