CT and micro CT analysis of a case of Pagey's desease in the Grant Skeletal collection

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CT and Micro-CT Analysis of a Case of
Paget’s Disease (Osteitis Deformans) in
the Grant Skeletal Collection
A. D. WADE,a* D. W. HOLDSWORTHb AND G. J. GARVINc
a Department of Anthropology, University of Western Ontario, London, Ontario N6A 5C2, Canada
b Robarts Research Institute, University of Western Ontario, London, Ontario N6A 5K8, Canada
c St. Joseph’s Health Care, London, Ontario N6A 4V2, Canada
ABSTRACT This paper presents a case study in which Paget’s disease of bone is differentially diagnosed in an individual
from the Grant skeletal collection using non-destructive computed tomography (CT) and micro-computed
tomography (micro-CT) analyses of the pubis, in addition to plain film radiography and macroscopic
examination. In archaeological and modern osteological samples diagnosis frequently relies on macroscopic
examination, plain film radiography and histological examination of bone samples. CT and micro-CT
modalities provide researchers with a non-destructive view of the internal structure of bone unhampered
by the superimposition that is characteristic of plain film radiographs. Given the importance of the increased
cortical and trabecular thickness in the differential diagnosis of Paget’s disease, these techniques are ideal
means by which to non-destructively examine culturally-sensitive and scientifically-valuable human remains
for signs of Paget’s disease of bone. Copyright � 2009 John Wiley & Sons, Ltd.
Key words: Paget’s disease of bone; osteitis deformans; computed tomography (CT); micro-CT;
palaeopathology
Introduction
The accurate diagnosis of Paget’s disease of bone
(osteitis deformans) in the living relies not only on passive
radiographic techniques but also on studies that can
only be performed in the living, including bone scans
(requiring the injection of radiopharmaceuticals) and
biochemical tests indicative of increased bone turnover.
In archaeological and modern osteological samples
dynamic tests cannot be performed, so differential
diagnosis frequently relies on macroscopic examin-
ation, plain film radiography and histological exam-
ination of bone samples. Radiographic modalities,
including plain film radiography, computed tomogra-
phy (CT) and micro-CT provide investigators with
non-destructive options for assessment of many patho-
logical conditions in remains that are incompatible with
macroscopic techniques (i.e. fragmentary remains, wrapped
mummies) and are more appropriate for culturally-sensitive
archaeological and forensic materials which must remain
unmodified for future researchers or for repatriation and
reburial. Given the importance of the increased cortical
and trabecular thickness in the differential diagnosis of
Paget’s disease, CT and micro-CT modalities provide
researchers with an ideal means by which to non-
destructively examine bone for signs of Paget’s disease; a
view of the internal structure of bone unhampered by the
superimposition that is characteristic of plain film
radiographs. This paper presents a case study in which
Paget’s disease of bone is differentially diagnosed using
CT and micro-CT analyses, in addition to plain film
radiography and macroscopic examination, of an
individual from the Grant skeletal collection.
Paget’s disease of bone
First formally described by Sir James Paget to the Royal
Medical and Chirurgical Society in 1876 (Paget, 1877),
Paget’s disease is a disruption of the normal process of
bone remodelling. It is characterised by an increase in
International Journal of Osteoarchaeology
Int. J. Osteoarchaeol. 21: 127–135 (2011)
Published online 15 October 2009 in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/oa.1111
* Correspondence to: Department of Anthropology, University of Western
Ontario, London, ON, N6A 5C2, Canada.
e-mail: awade4@uwo.ca
Copyright # 2009 John Wiley & Sons, Ltd. Received 3 August 2008
Revised 22 March 2009
Accepted 13 July 2009
osteoclast-mediated bone resorption and a compensa-
tory increase in new bone formation (Dona´th et al.,
2004) resulting in the increased formation of osteoid
that is softer and weaker than normal (Kanis, 1998).
Present in approximately 3–4% of the population
(Resnick, 1988) and most common in males (Roches
et al., 2002) over the age of 40 years (Davie et al., 1999),
Paget’s disease generally affects two or more bones
(Schneider et al., 2002). The proportion of monostotic
forms (single element affected), often a precursor to
polyostotic forms (multiple elements affected)
(Resnick, 1988), is between one quarter and one third
of cases (Monfort et al., 1999; Schneider et al., 2002).
Paget’s disease is most commonly encountered in the
pelvis (Table 1), with the greater proportion of cases in
the right innominate (Monfort et al., 1999).
The exact cause of Paget’s disease is, as yet, unknown
but geographic distributions, particularly in light of
migration, imply a genetic component. Present in as
much as 6% of the population in areas of Great Britain
(Monfort et al., 1999) and similarly common in
populations and emigrants from Western Europe
(Resnick, 1988; Cooper et al., 1999), the disease is
rare in indigenous populations in China, Japan and
Africa (Resnick, 1988; Ralston, 2002). While there is
no single, clear mode of inheritance, studies suggest
connections to genes on chromosomes 5, 6 and 18
(Ralston, 2002) and it has been further suggested that
the genetic component of the disease may be a
predisposition, which becomes active with exposure to
an environmental factor (Mee, 1999; Ralston &
Helfrich, 1999; van Hul, 1999). Paramyxoviruses, such
as measles and canine distemper virus (CDV), have
been suggested as activating factors since ‘most pagetic
osteoclasts contain intracellular virus-like particles. . .’
(Meunier, 2002: p. 105) resembling CDV and a study
using reverse transcriptase in situ hybridisation has
found CDV present in all such cases (Ralston, 2002).
Paget’s disease is frequently diagnosed incidentally
on plain film X-rays (Singer, 2002). In suspected cases,
Pagetic involvement can be confirmed by biochemical
markers, such as total alkaline phosphatase and urinary
hydroxyproline (Eastell, 1999), and by CT and bone
scans (Singer, 2002). Since Paget’s disease is usually
asymptomatic, treatment is rarely required. If symp-
toms are disabling, bisphosphonates can be used to
inhibit the hydroxyapatite dissolution that triggers the
deposition of abnormal bone (Kanis, 1998).
In contrast, the diagnosis of Paget’s disease in
archaeological samples (Wells & Woodhouse, 1959;
Bell & Jones, 1991; Stirland, 1991; Molleson & Cox,
1993), some as ancient as the Neolithic (Roches et al.,
2002), frequently relies only on macroscopic and plain
film radiological assessment, as biochemical markers
are absent and radio-isotopes cannot be carried to bone
in the absence of a bloodstream. Paget’s disease is
generally indicated macroscopically by the presence of
skeletal elements thickened by the deposition of a
porous or ‘coral-like’ periosteal bone (Wells & Wood-
house, 1959; Stirland, 1991; Molleson & Cox, 1993)
and investigated further using thin-section microscopy
and radiography. The case of Paget’s disease here,
noted incidentally in a radiographic study of the pubis
(Wade, 2008), demonstrates the diagnostic power of
CT and micro-CT where biochemistry and bone scans
are impossible, particularly as applied to sensitive
remains that preclude destructive thin-section micro-
scopy. CT and its higher resolution counterpart micro-
CT can image the trabecular micro structures internal
to skeletal elements in three dimensions. The proces-
sing of CT andmicro-CT data provides volumetric data
that avoid the confusion of superimposing cortical and
cancellous structures and the apparent increases in
density with element thickness that characterise plain
film radiography.
Materials and methods
The Grant skeletal collection,of which this individual
(669) is a part, consists of skeletal elements of 202
individuals collected by the University of Toronto’s
Anatomy Department, under Dr JCB Grant, using
unclaimed bodies as per the Anatomy Act of Ontario
(1888). The collection consists mostly of males over 40
years of age almost entirely of European ancestry, with
one exception, and samples, largely, the transient and
migrant worker population of southern and central
Ontario (Bedford et al., 1993). Cause of death is noted
in collection documents but detailed notes on
pathological conditions are absent.
The left pubis of individual 669 was examined
radiographically, using plain film radiographs, CT and
Table 1. Frequency of most commonly affected sites (after
Schneider et al., 2002: p. 2069)
Site Frequency (%)
Pelvis 72
Lumbar spine 58
Femur 55
Thoracic spine 45
Skull 42
Tibia 35
Humerus 31
Cervical spine 14
Copyright # 2009 John Wiley & Sons, Ltd. Int. J. Osteoarchaeol. 21: 127–135 (2011)
128 A. D. Wade, D. W. Holdsworth and G. J. Garvin
micro-CT, as part of a study of pubic trabeculation
(Wade, 2008). The pubis was X-rayed in the antero-
posterior view (posterior toward source) for 2min at
60 kV and 0.2mA using Kodak Ektavision 5 (EVG5) X-
ray film in a Faxitron model 43855A cabinet X-ray
machine (Faxitron X-ray Corporation, Wheeling, IL).
The film, developed in Pro-Plus premixed X-ray film
fixer and developer was then scanned at 600 dpi, using
a UMAX Powerlook 2100XL flatbed scanner and
Magic Scan v.4 software. Using scanning time donated
by St. Joseph’s Health Care, London, ON, the dry
bone innominate was scanned in a GE lightspeed
volumetric computed tomography (VCT) 64 slice
scanner at a slice thickness of 0.625mm (120 kV,
200mA, axial). The ilium was supported on foam
wedges to keep the antero-posterior plane of the pubis
parallel and the medio-lateral and supero-inferior
planes perpendicular to the scanner bed, with the
medial end of the pubis facing into the scanning gantry.
The scan was then saved in DICOM (Digital Imaging
and Communications in Medicine) format for proces-
sing in the GE Microview CT/micro-CT analysis
software (ver. 2.1.2). The innominate was also scanned
at the John P. Robarts Research Institute (University of
Western Ontario) in a GE Locus Ultra 150mm micro-
CT scanner (120 kV, 20.0mA, 16.0 s). A volumetric
reconstruction was calculated from the raw scanning
data and saved in VFF (volume file format) format for
processing in the GE Microview analysis software.
Finally, a follow-up digital radiography and CT scan
session was performed at The Hospital for Sick
Children, Toronto, ON to examine both innominates,
both femurs, the spine and the skull. Scanning time
donated by the hospital permitted scans in a Philips
Gemini GLX16 PET/CT scanner at a slice thickness of
0.75mm (120 kV, 200mA, axial). These scans were
also saved in DICOM format for processing in the GE
Microview analysis software.
Individual 669
Grant collection individual 669 was a male of western
European ancestry living in southern Ontario until
January 1944. Cause of death was determined to be
coronary thrombosis associated with arteriosclerosis,
and verified age-at-death records indicate that this
individual was 66 years old at time of death.
Initial macroscopic examination of the left pubis of
individual 669 found no distinct indicators of a
pathological condition of bone. Initial screening for
gross indicators of pathological conditions primarily
focused on pitting which can be indicative of
tuberculosis (Zink et al., 2005), a disease prevalent in
the Grant collection (DeLaurier, 1998). Measurements
of the thickness of the pubic body were high (14.5mm
at midbody, 19.45mm at maximum) but fell within the
range of variation of the sample (midbody: Avg.
11.1mm, SD 2.0mm, 669 z-score¼ 1.7; maximum:
Avg. 18.13mm, SD 2.43mm, 669 z-score¼ 0.54). A
second macroscopic examination, subsequent to the
appreciation of pathology, revealed an area on the
anterior surface of the pubis potentially indicative of
bony expansion (Figure 1) and significant expansion of
the right iliac tuberosity (Figure 2). Additionally, the
ninth and tenth thoracic vertebrae and the tenth left rib
are fused (Figure 3) and the roof of the left orbit is
almost entirely absent with a related perforation of the
left frontal sinus (Figure 4).
Figure 1. Region of potential bony expansion apparent on the
anterior of the left pubis. This figure is available in colour online at
wileyonlinelibrary.com/journal/oa.
Figure 2. Expansion of the right iliac tuberosity. This figure is
available in colour online at wileyonlinelibrary.com/journal/oa.
Copyright # 2009 John Wiley & Sons, Ltd. Int. J. Osteoarchaeol. 21: 127–135 (2011)
CT and Micro-CT Analysis of Paget’s Disease of Bone 129
Radiographic findings
Innominates
The innominates were first examined radiologically
using plain film radiographs and exhibit diffuse
sclerosis, well-defined lucencies, cortical thickening
and significant trabecular thickening; with fewer but
thicker trabeculae (Figure 5). This chaotic sclerotic
appearance, often referred to as a jigsaw or mosaic
pattern, was the primary indication that this individual
suffered from a pathological condition, likely Paget’s
disease of bone (Cushing & Bone, 2002). CT scans of
the innominates and a micro-CT scan of the left pubis
additionally demonstrate foci of greatly increased
sclerosis, areas of marrow with little or no trabeculation,
and areas of greatly increased and greatly decreased
radiodensity relative to otherwise normal innominates
(Figure 6).
Examination of the CT and micro-CT scans
(Figures 6 and 7) showed greatly increased cortical
thickness and a dramatic rarification of trabeculae.
Micro-CT stereology produced average trabecular
thickness (mm) and connectivity density (-Euler#/
Volume) values of 0.406 and 0.130, respectively. The
trabecular thickness is significantly greater (z¼ 3.54)
than the mean for the Grant collection sample (Avg.
0.314, SD 0.026). The degree to which trabeculae
remain connected falls within the lower end (z¼�1.05)
of normal variability for the same sample (Avg. 0.724, SD
0.565). The thickened cortical bone was also less dense
than that of normal pubes, showing up as irregular and
darker (less radiodense) in the CT and micro-CT scans.
The cortical bone of individual 669 demonstrated
reduced radiodensity values approximately 350 units
less (CT greyscale and micro-CTHounsfield Units) than
that typical of the other 65 individuals scanned in this
Figure 3. Fused ninth and tenth thoracic vertebrae and tenth left
rib. This figure is available in colour online at wileyonlinelibrary.
com/journal/oa.
Figure 4. Basal cranium with absent left orbital roof and perfor-
ation to frontal sinus. This figure is available in colour online at
wileyonlinelibrary.com/journal/oa.
Figure 5. AP plain film radiograph of a normal pubis (left, Grant
127) and the pubis of individual 669 (right).
Figure 6. Sagittal CT slice of a normal pubis (left, Grant 222) and
the pubis of individual 669 (right).
Figure 7. Oblique coronal micro-CT reconstruction of a normal
pubis (left, Grant 111) and the pubis of individual 669 (right).
Copyright # 2009 John Wiley & Sons, Ltd. Int. J. Osteoarchaeol. 21: 127–135 (2011)
130 A. D. Wade, D. W. Holdsworth and G. J. Garvin
series. The CT and micro-CT values for individual 669
were 1850 (CT units) and 1200 (HU) units, respectively,
while the average CT and micro-CT values were 2232
and 1561 units, respectively, with associated SDs of 121
and 103 units. These produce a z-score of�3.16 for the
CT greyscale radiodensity and a z-score of �3.50 for
the micro-CT Hounsfield radiodensity.
Femora
The right femur is radiographically normal, without
qualitative indications of increased or decreased bone
mineral density. The plain film radiographs(Figure 8)
and the CT scan of the left femur, however, indicate
pathological involvement of the proximal half of the
bone. Relative to the contralateral femur, the cortex is
thickened, as are the trabeculae and subchondral plate
of the femoral head. There is diffuse sclerosis of the
greater trochanter with small well-defined lucencies
superiorly.
Spine
The vertebrae demonstrate pathological involvement
at multiple levels of the cervical, thoracic and lumbar
spine (Figure 9). Marginal osteophytic lipping,
indicative of multilevel degenerative disk disease is
noted incidentally, decreasing in severity from the
lumbar to cervical spine. Plain film radiographs of the
cervical vertebrae showminimal to mild sclerosis of the
atlas (C1) and mild sclerosis of the axis (C2). Cervical
vertebrae C4 and C7 are diffusely sclerotic with bubbly
lucencies supero-posteriorly. The CT scan of the
cervical spine also reveals increased density of the dens,
greatly thickened cortex in C4 and C7, and very
sclerotic pedicles and coarse, irregular trabeculae in C7
(Figure 10).
Figure 8. AP plain film radiographs of the femora.
Figure 9. Composite AP and lateral plain film radiographs of the
spine.
Figure 10. Axial CT slice of C7.
Copyright # 2009 John Wiley & Sons, Ltd. Int. J. Osteoarchaeol. 21: 127–135 (2011)
CT and Micro-CT Analysis of Paget’s Disease of Bone 131
The majority of the thoracic spine appears normal,
with pathological changes present in T7, T9 and T10.
Plain film radiographs (Figure 9) show the dramatic
fusion of the ninth and tenth thoracic vertebrae and the
tenth left rib, with two sets of posterior vertebral
elements attached to a single-waisted, anteriorly-
wedged body. While vertebral fusion may occur
congenitally, the CT scan (Figure 11) shows complete
fusion with the tenth rib and remnants of vertebral
endplates bracketed by remaining marginal osteo-
phytes (now located mid-body) indicating a collapse
following presumably normal formation. The single
body of the fused vertebrae appears otherwise normal
and this complex was most likely the result of a
compression fracture with healing, fusion of the bodies
and secondary fusion of the rib. Remnants of body
cortex are present at the edge of the rib fusion on the
left and on the right, possibly indicating near fusion of
the right tenth rib to this complex. In the CT scan, note
was also made of a number of slightly craggy, lytic
lucencies in the body of T7.
Plain film radiographs of the lumbar spine (Figure 9)
show involvement of the first and third lumbar
vertebrae. While L3 demonstrates very slight sclerosis,
L1 is highly sclerotic, with increased thickness of both
trabeculae and end plates.
Skull
Plain film radiographs of the skull (Figure 12)
demonstrate minimal pathological involvement. The
skull base appears questionably sclerotic and the right
frontal bone demonstrates a region of patchy sclerosis
laterally. CT scans of the skull (Figure 13, left) show
patchy bilateral sclerosis, with well-defined surround-
ing lucency and associated cranial thickening at the
areas of involvement. The margins of the absent left
orbital roof appear too sharply defined to be the result
of a natural lytic process, particularly in the absence of
indications of pathological bone surrounding the
affected area (Figure 13, right). This feature is favoured
to represent post-mortem damage, likely in relation to
the sagittal sectioning of the basal cranium by saw
(Figure 4).
Summary
The entirety of both innominates, the proximal half of
the left femur, the first lumbar vertebra and the fourth
and seventh cervical vertebrae demonstrate a pattern of
bilateral, asymmetric, diffuse mild-to-severe sclerosis,
trabecular thickening and rarification and cortical
thickening. The fused thoracic vertebrae likely
represent the activity of a degenerative process or an
infectious agent and the absent orbital roof likely
represents post-mortem damage.
Differential diagnosis
No diagnostic indicators of bony pathology were
noted in the macroscopic examination of the left pubis.
During examination of the entire skeleton, for signs of
Figure 11. Coronal CT slice of the fused T9/T10 showing end-
plate (arrow) and marginal osteophyte (ovals) remnants.
Figure 12. AP and lateral plain films of the skull with patchy
sclerosis in frontal indicated.
Figure 13. Axial CT slice (left) of the frontal showing an area of
sclerosis with surrounding lucency indicated and oblique cor-
onal CT slice (right) with sharp orbital roof margin indicated.
Copyright # 2009 John Wiley & Sons, Ltd. Int. J. Osteoarchaeol. 21: 127–135 (2011)
132 A. D. Wade, D. W. Holdsworth and G. J. Garvin
the pathological involvement indicated radiographi-
cally, potential expansion of the left pubis (Figure 1)
and significant expansion of the right iliac tuberosity
(Figure 2) were noted. Neither expansion is pathog-
nomonic for a particular disease, nor is the fused vertebrae/
rib complex (Figure 3) which likely represents the collapse
of vertebrae following a compression fracture likely caused
by trauma or, less likely but possibly, infection. This
scenario is more likely, in retrospect, as the vertebrae
do not radiographically exhibit remodelling with softer
Pagetic osteoid that would lead one to suspect this to
be one of the 4.4% of cases (Marcelli et al., 1995;
Saifuddin & Hassan, 2003) in which Paget’s disease
results in vertebral ankylosis. Neither femur showed
macroscopic signs of disease. The skull exhibited
absence of the roof of the left orbit. However, the lack
of involvement of surrounding bone, the presence of
sharp margins and the proximity to the dissection cut,
point to post-mortem damage.
Radiographically, the pathologically involved
elements exhibit regional involvement with mild
expansion, cortical thickening and fewer but thicker
trabeculae; diagnostic radiographic characteristics of
Paget’s disease of bone. While several conditions share
some of these features with Paget’s disease (Table 2),
they do not include all of them. Osteitis ilii condensans
results in increased density of the ilium and is often
problematic in differential diagnosis of Paget’s disease.
In this case, however, involvement is throughout the
innominate and present in non-pelvic elements.
Additionally, osteitis ilii condensans does not result in
the trabecular rarification (Cushing & Bone, 2002) seen
in Paget’s disease. Fibrous dysplasia is similar to Paget’s
disease in the characteristic expansion and variable
density of bone, but is often marked by ground-glass
opacity in plain films and may actually result in cortical
thinning. Metastatic cancer (i.e. metastatic carcinoma
of the prostate) may also result in isolated sclerotic
lesions of the pubis (Kanis, 1998; Cushing & Bone,
2002). Bone expansion in sclerotic metastases, how-
ever, rarely retains the shape of the affected element
and the metastases rarely have more than one of the
radiographic features characteristic of Paget’s disease
(Kanis, 1998). CT scans are recommended in
differentiating between these conditions (Cushing &
Bone, 2002). The condition most radiographically like
Paget’s disease, however, is hyperphosphatasia but this
is an early onset disease resulting in generalised skeletal
involvement and shortened stature (Kanis, 1998) not
seen in this individual. Measures of the femoral,
humeral and tibial lengths (Right: 43.25 cm, 29.80 cm
and 34.00 cm; Left: 42.00 cm, 29.50 cm and 33.80 cm,
respectively) were applied to stature estimation
formulae for American White males (Trotter & Gleser,
1952) and provide an estimated height of 5’5’’.
Individual 669 has all of the characteristic signs and,
given the age (66 years old) and ancestry (western
European) of this individual, was most likely affected
by Paget’s disease of bone.
Effects
It is important, from a bioarchaeological/osteobio-graphic standpoint, to understand not simply the signs
and presence of a pathological condition, but what it
means for a person to suffer from this condition. It
should be noted that approximately 70–80% (Cushing
& Bone, 2002; Schneider et al., 2002) of modern
patients with Paget’s disease are asymptomatic. It is not
Table 2. Differential diagnosis of pathological conditions sharing indicators with Paget’s disease
Pathological condition Indicators Presence
Paget’s disease of bone � Regional involvement with mild expansion þ
� Cortical thickening þ
� Trabecular thickening þ
� Trabecular rarification þ
Osteitis ilii condensans � Increased density of ilium only �
� No trabecular rarification �
Fibrous dysplasia � Expansion of bone þ
� Variable density þ
� Ground glass opacity �
� Cortical thinning �
Metastatic cancer � Isolated sclerotic lesions �
� Bony expansion does not retain shape of affected element �
� Rarely more than one characteristic feature of Paget’s �
Hyperphosphatism � Similar to Paget’s þ
� Early onset disease resulting in shortened stature �
See references in text.
Copyright # 2009 John Wiley & Sons, Ltd. Int. J. Osteoarchaeol. 21: 127–135 (2011)
CT and Micro-CT Analysis of Paget’s Disease of Bone 133
surprising, therefore, that many modern diagnoses
result from incidental findings on radiographs (Singer,
2002). Of those who do become symptomatic, the
most common symptom is pain in the hip joints
(coxalgia) and lower back (lumbalgia) (Monfort et al.,
1999). In more severe cases, such as those described by
Paget (1877), affected individuals suffer skeletal
expansion that bows already brittle long bones,
decreases joint space leading to osteoarthritis and
constricts the brain and nerves of the cranium (Resnick,
1988; Kanis, 1998; Meunier, 2002; Schneider et al.,
2002; Trojanowska et al., 2004). Pagetic bone pain
‘increases with rest, on weight bearing, when the limbs
are warmed and at night’ (Schneider et al., 2002: p.
2070) and coupled with arthritic joint pain can result in
considerable suffering for the individual affected by
this disease. The individual presented here shows no
signs of long bone deformation, decreased acetabular
space or dramatic cranial expansion leading to the
more severe effects of the disease. The collapsed
thoracic vertebrae, likely unrelated to Paget’s disease in
this case, and the expanded iliac tuberosity may each
have resulted in decreased mobility and significant
back pain. While bisphosphonate treatment of Paget’s
disease of bone is a simple answer to the disease in
modern times, the same cannot be said in antiquity.
Advanced symptoms, therefore, will be most relevant
to individuals who suffered this condition in the
archaeological past, when treatment was not possible.
Conclusion
Palaeopathological diagnosis is complicated by the
lack of bone scan and biochemical indications present
only in the living or recently deceased and by the
cultural and scientific importance of archaeological
remains that precludes their modification or destruc-
tion for the sake of analysis. Non-destructive options
for assessment, used to assist or extend macroscopic
examination, are essential in the accurate diagnosis of
palaeopathological conditions. CT and micro-CT, in
addition to traditional plain film radiography, are
powerful tools in the assessment of pathology and
provide researchers with three dimensional and truly
volumetric reconstructions of skeletal remains. These
volumetric radiographic modalities are, as demon-
strated in this case study, of particular importance in
the diagnosis of Paget’s disease of bone where the
ability to examine the thickness and quality of cortical
bone and trabeculae is the key to an accurate
differential diagnosis and where macroscopic findings
are ambiguous at best.
References
Bedford ME, Russell KF, Lovejoy CO, Meindl RS, Simpson
SW, Stuart-Macadam PL. 1993. Test of the multifactorial
aging method using skeletons with known ages-at-death
from the Grant collection. American Journal of Physical
Anthropology 91(3): 287–297.
Bell LS, Jones SJ. 1991. Macroscopic and microscopic
evaluation of archaeological pathological bone: Backscat-
tered electron imaging of putative Pagetic bone. Inter-
national Journal of Osteoarchaeology 1: 179–184.
Cooper C, Dennison E, Schafheutle K, Kellingray S, Guyer
P, Barker D. 1999. Epidemiology of Paget’s disease of
bone. Bone 24(5): 3S–5S.
Cushing FR, Bone HG. 2002. Radiographic diagnosis and
laboratory evaluation of Paget’s disease of bone. Clinical
Review in Bone and Mineral Metabolism 1(2): 115–134.
Davie M, Davies M, Francis R, Fraser W, Hosking D,
Tansley R. 1999. Paget’s disease of bone: a review of
889 patients. Bone 24(5): 11S–12S.
DeLaurier A. 1998. The effects of habitual biochemical
stress, trauma and pathology on the development and
age-related degeneration of the male pubic symphysis.
MA Thesis. University of Western Ontario.
Dona´th J, Krasznai M, Fornet B, Gergely P Jr, Poo´r G. 2004.
Effect of bisphosphonate treatment in patients with
Paget’s disease of the skull. Rheumatology 43(1): 89–94.
Eastell R. 1999. Biochemical markers of bone turnover in
Paget’s disease of bone. Bone 24(5): 49S–50S.
Kanis JA. 1998. Pathophysiology and Treatment of Paget’s Disease of
Bone (2nd edn). Martin Dunitz: London, UK.
Marcelli C, Yates AJ, Barjon M-C, Pansard E, Angelloz-
Pessey L, Simon L. 1995. Pagetic vertebral ankylosis and
diffuse idiopathic skeletal hyperostosis. Spine 20(4): 454–459.
Mee AP. 1999. Paramyxoviruses and Paget’s disease: the
affirmative view. Bone 24(5): 19S–21S.
Meunier PJ. 2002. The Pagetic lesion. Clinical Review in Bone
and Mineral Metabolism 1(2): 103–107.
Molleson T, Cox M. 1993. The Spitalfields Project, Volume 2: The
Anthropology. Council for British Archaeology: York, UK.
Monfort J, Rotes Sala D, Romero AB, Duro JC, Maymo J,
Carbonell J. 1999. Epidemiological, clinical, biochemical,
and imaging characteristics of monostotic and polyostotic
Paget’s disease. Bone 24(5): 13S–14S.
Paget J. 1877. On a form of chronic inflammation of bones
(osteitis deformans).Medico-Chirurgical Transactions 60: 37–64.
Ralston SH. 2002. Pathogenesis of Paget’s disease of bone.
Clinical Review in Bone and Mineral Metabolism 1(2): 109–114.
Ralston SH, HelfrichMH. 1999. Are paramyxoviruses involved
in Paget’s disease? A negative view. Bone 24(5): 17S–18S.
Resnick D. 1988. Paget disease of bone: current status and a
look back to 1943 and earlier. American Journal of Roent-
genology 150: 249–256.
Roches E, Blondiaux J, Cotton A, Chastanet P, Flipo R-M.
2002. Microscopic evidence for Paget’s disease in two
osteoarchaeological samples from early northern France.
International Journal of Osteoarchaeology 12: 229–234.
Copyright # 2009 John Wiley & Sons, Ltd. Int. J. Osteoarchaeol. 21: 127–135 (2011)
134 A. D. Wade, D. W. Holdsworth and G. J. Garvin
Saifuddin A, Hassan A. 2003. Paget’s disease of the spine:
unusual features and complications. Clinical Radiology 58:
102–111.
Schneider D, Hofmann MT, Peterson JA. 2002. Diagnosis
and treatment of Paget’s disease of bone. American Family
Physician 65(10): 2069–2072.
Singer FR. 2002. Evolution of the clinical presentation of
Paget’s disease of bone. Clinical Review in Bone and Mineral
Metabolism 1(2): 95–98.
Stirland A. 1991. Paget’s disease (osteitis deformans): a classic
case? International Journal of Osteoarchaeology 1: 173–177.
Trojanowska A, Czekajska-Chehab E, Trojanowski P, Ois-
zanski W, Golabek W, Drop A. 2004. Diagnostic possi-
bilities of multi-slice computed tomography in Paget’s
disease of skull – case report. Advanced CT 8789: 37–39.
Trotter M, Gleser GC. 1952. Estimation of stature from long
bones of American whites and negroes. American Journal of
Physical Anthropology 10(4): 463–514.
van Hul W. 1999. Paget’s disease froma genetic perspective.
Bone 24(5): 29S–30S.
Wade AD. 2008. Radiological assessment of age-related
change in the trabecular structure of the human
os pubis. MA Thesis. University of Western Ontario.
Wells C, Woodhouse N. 1959. Paget’s disease in an Anglo-
Saxon. Medical History 19: 369–400.
Zink AR, Grabner W, Nerlich AG. 2005. Molecular identi-
fication of human tuberculosis in recent and historic bone
tissue samples: the role of molecular techniques for the
study of historic tuberculosis. American Journal of Physical
Anthropology 126(1): 32–47.
Copyright # 2009 John Wiley & Sons, Ltd. Int. J. Osteoarchaeol. 21: 127–135 (2011)
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