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7/25/2019 American Journal of Physical Anthropology Volume 89 Issue 3 1992 [Doi 10.1002%2Fajpa.1330890306] Dr. Jean E. Aaron; Juliet Rogers; John a. Kanis -- P
1/7
AMERICAN
JOURNAL
OF PHYSICAL ANTHROPOLOGY 89325-331 19921
Paleohistology
of
Pagets Disease in
Two
Medieval Skeletons
JEA N E. AARON, JULIE T ROGERS,
AND JOHN A. KANIS
Department of Hu m an Metabolism Medical School Universi ty of
Sheffield Sheffield SlO 2RX, England J.E.A., J.A.K.) and Department o
Medicine University of Bristo l B ristol Royal Inf irm ary
Bristol BS2 SHW, England J.R.1
KEY W O R D S
Paleopathology, Bone histology, Pagets disease
ABSTRACT Pagets disease has beer, ascribed several times
t o
specimens
of archeological bone but, in the absence of microscopic examination, the
evidence remains insubstantial. Suspected metabolic bone disease is de-
scribed here in the archeological remains of a skeleton from a 16th century
burial ground at Wells Cathedral, England and from a single medieval
sacrum recovered from a large deposit of disarticulated bones from a church-
yard at Barton-on-Humber, England. Radiographs showed apparent struc-
tural abnormality in one femoral shaft and calcaneus and in the isolated
sacrum. Histomorphometry on undecalcified bone cores confirmed the regions
of abnormality and showed not only increased trabecular width but also areas
of mosaic woven bone together with extensive resorption cavities; these
features contrasted with the normal structure and organized lamellar bone
from sites elsewhere. Despite post-interment changes in surrounding tissues,
the morphological stability of some of the osteocytes was remarkable. Preser-
vation of the histology was sufficient
t o
permit the assignment of a metabolic
bone disorder and the nature of the sclerosis was consistent with Pagets
disease.
992
Wiley-Liss,
Inc.
Although Pagets disease was recognised
as a clinical condition only one hundred
years ago, there are reports describing the
existence from neolithic times (Denniger,
Optical comparison with contemporary nor-
mal and pathological material is also made.
MATERIALS AND M ETHODS
1933; Wells and Woodhouse, 19753. How-
ever, it is generally acknowledged that
much of the evidence is fragmentary and
ambiguous, lacking histological confirma-
tion, and regularly attributing an occur-
rence where it is either geographically or
ethnically unlikely (Kanis, 1991).A s prepar-
ative techniques for undecalcified bone his-
tology have improved,
so
the use of the small
trephine sample
for
the optical microscopy
of ancient skeletal remains has increased
(Smith et al., 1981; Stout and Teitelbaum,
1976a,b; Stout, 1978; Weinstein et al.,
1981). By applying histological techniques
this communication seeks
to
add the dimen-
sion
of
microscopy
t o
the gross structural
information derived from the archeological
remains of two abnormal medieval skele-
tons with suspected metabolic bone disease.
The skeletal remains, from two individu-
als, consisted of the lower half of the male
skeleton (SK270), probably aged over
45
years, discovered in
a
16th century grave in
an excavated burial ground at Wells Cathe-
dral and an isolated medieval sacrum recov-
ered from large deposits of disarticulated
bone, from a churchyard excavation at Bar-
ton-on-Humber, South Humberside. Mor-
phological changes were evident; for exam-
ple, the left femoral shaft was enlarged and
the surface texture of the right and left cal-
canei differed. Radiographs were prepared
Received October 22,1991: accepted May 4,1992.
Address correspondence to Dr. J
E.
Aaron, Department of
Anatomy, Medical and Dental Building, University of Leeds,
Leeds LS2 9JT. England.
992 WILEY-LISS. INC
7/25/2019 American Journal of Physical Anthropology Volume 89 Issue 3 1992 [Doi 10.1002%2Fajpa.1330890306] Dr. Jean E. Aaron; Juliet Rogers; John a. Kanis -- P
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326 J E
AAROI
of the individual bones and sites of apparent
abnormality identified. Using a bone biopsy
trephine, 8m m in diameter, cylinders of
bone were removed from the representative
radiologically normal and abnormal sites,
including the left and right 0s calces and the
sacrum. By means of established prepara-
tive techniques (for example, Aaron, 1976)
the specimens were dehydrated in alcohol,
embedded in methylmethacrylate and unde-
calcified sections,
8
pm thick, were cut us-
ing
a
heavy d u b Jung
K
microtome. Sec
tions were stained by the Goldner method
(Schenk et al., 19691,
o r
in 0.1 toluidine
blue stain, pH 3.5, or according
t o
the von
Kossa technique for bone mineral and pre-
pared for microscopy. The sections were ex-
amined in both plain and polarised light.
Using established histomorphometric proce-
dures (Aaron et al., 19871, the trabecular
width,
pm,
and the extent
of
resorption cav-
ities relative to the total trabecular bone
surface ( eroded surface) were determined.
Comparisons were also made with contem-
porary specimens
of
trabecular bone from
the 0s calcis and the iliac crest (the standard
clinical bone biopsy site) from subjects
whose bone status had been reliably diag-
nosed at autopsy or during attendance at
bone clinics.
RESULTS
While radiographs of much of the skeletal
remains appeared normal, X-rays of the
right calcaneus, enlarged left femoral shaft,
and parts of the sacrum appeared abnor-
mally dense and exceptionally coarse trabe-
culae were evident. The remaining and ap-
parently normal calcaneus functioned as a
control for its abnormal partner (Fig. 1).The
biopsy specimen from the unaffected calca-
neus remained intact, providing good con-
trol material (Fig. 2a). In contrast, the spec-
imen taken from the affected calcaneus
tended to fragment upon removal and its
fragility meant that particular care was re-
quired during processing (Fig. 2b). However,
the structure of the sacral specimen was bet-
ter preserved (Fig. 2c), although its normal
counterpart was poor. Comparison of the
16th century bone with contemporary mate-
rial showed a close similarity in the normal
trabecular architecture (Fig. 3a) and a gen-
\J
ET
AL.
Fig.
1
Radiographs of the sixteenth century
os
cal-
ces showing the dense and thickened trabecular struc-
ture on one side only.
era1 resemblance of the sclerotic pathologi-
cal regions to pagetic bone (Fig. 3b).
The inspection of the sections for possible
non-physiological post-mortem changes in-
dicated th at some demineralization, evident
with the Goldner and von Kossa stains, had
taken place (Fig. 4a). There was also evi-
dence of a reticulated pattern of destruction
within the bone matrix which seemed to
arise by the specific removal
of
exposed or-
ganic matrix and which some authors have
attributed to past fungal invasion (Stout
and Teitelbaum. 197613: Fig. 4b). In conse-
quence of these changes, asteoid tissue could
not be reliably identified. The material re-
moved from radiologically normal sites was
well-preserved, and in polarised light an
undisturbed lamellar organization was ob-
served (Fig. 5a). In specimens from the ap-
parently abnormal calcaneus and sacrum,
the trabeculae were grossly thickened and
although they were continuous (in contrast
with osteoporotic tissue) they contained a
substantial complement of disorganized or
woven bone (Fig. 5b). In addition, traces
of
convoluted cement lines which define the
mosaicbone pathognomonic of Pagets dis-
ease were clearly evident (Fig. 5b). At the
same time, deep and well-defined resorption
cavities were extensive (Fig. 5c). Moreover,
a small proportion appeared to contain large
cells closely juxtaposed
t o
Howships lacu-
nae and osteoclast-like in profile, though
7/25/2019 American Journal of Physical Anthropology Volume 89 Issue 3 1992 [Doi 10.1002%2Fajpa.1330890306] Dr. Jean E. Aaron; Juliet Rogers; John a. Kanis -- P
3/7
PALEOHISTOLOGYO F PA G E T S DISEASE
327
Fig. 2. Undecalcified histological sections showing Fig.
3 .
Undecalcified histological sections showing
the trabecular microanatomy of twentieth century bone
of established etiology. a Normal
0s
calcis, similar in
structure t o 2a.
b
Bone from the iliac crest of a patient
with Pagets disease showing the typical thick and irreg-
ular trabeculae, similar in str ucture to
2b
and c Tolu-
idine blue stain,
x
10.
the trabecular microanatomy of the sixteenth century
bone. a) Normal
0s
calcis. b Abnormal
0s
calcis with
thick and irre gular trabeculae; fragile trabecular cores
(arrowed) were lost during preparation but their pro-
files were retained by the embedding medium.c Abnor-
ma1 bone from the sacrum with intac t thick an d irregu-
lar trabeculae. Toluidine blue stain , x 10.
throughout both normal and pathological re-
cellular detail could not be resolved (Fig. gions and fine details
of
the fibrous nature
5c,d). Fragments of marrow tissue (Stout of the collagenous extracellular matrix at
and Teitelbaum, 197613) adhered to some
of
their periphery was still apparent (Fig. 5e).
the bone surfaces (Fig. 5a) although the Some osteocyte lacunae, together with their
marrow cavities were largely empty. Osteo- canaliculi, were unusually large and had
cyte lacunae were distributed regularly, probably been subjected to processes of at -
7/25/2019 American Journal of Physical Anthropology Volume 89 Issue 3 1992 [Doi 10.1002%2Fajpa.1330890306] Dr. Jean E. Aaron; Juliet Rogers; John a. Kanis -- P
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328
J.E. AARON
T
AL.
Fig.
4
Non-physiologicalchanges in the sixteenth century bone. a) Sharply defined irregular areas of
demineralization (arrows); von Kossa stain, x 50.
b
A trabecula exhibiting a reticulated mineralized
matrix (arrow) surrounding clear areas
of
attrition. Goldner stain,
x
375
trition due to diagenic changes (Bell, 1990)
during prolonged interment (Fig. 6). While
many lacunae were devoid of cells, others
contained osteocytes in a remarkable state
of preservation with nuclei and fine cellular
processes remaining structurally intact
(Figs. 5e, 6). The quantitative analysis is
summarised in Fig. 7.
DISCUSSION
Pagets disease occurs in Western races
after the age of forty. It may be localized in
any part of the skeleton including the long
bones and sacrum and in more severe cases
there is bone enlargement and deformity.
The application
of
bone histology
t o
ancient
bones provides information which is not re-
solved by non-invasive procedures. In conse-
quence, a more reliable diagnosis of sus-
pected metabolic bone disease might be
anticipated (Bell and Jones, 1991; Wein-
stein et al., 1981).An important histological
feature which could not be assessed here
was the status of the osteoid tissue; this was
due t o non-physiological mineral density
gradations evident in some regions. Also, it
has been reported tha t unmineralized bone
matrix o r osteoid tissue is rarely, if ever,
preserved (Stout, 1978). Collagen is essen-
tially protected from degradation by the
mineral component of the matrix, the geo-
metric structure
of
which is unchanged by
fossilization and replacement with fluorides
and carbonates (Posner, 1969). The conser-
vation of collagen by bone salt is
so
effective
that the typical 640A periodic banding of
collagen has been observed in the electron
microscope in Pleistocene bones (see As-
cenzi, 1955 and Stout, 1978 for references).
Within this context the fine fibrous nature
of the collagenous matrix described above is
not unusual.
A t
the same time, it may be
because of the protective property of the
bone salt tha t a proportion of the bone cell
population was unexpectedly conserved.
Both osteocytes and osteoclasts contain
bone mineral during their life cycle. This to-
gether with their encapsulation within inac-
cessible bony cavities and lacunae may have
sufficed t o ensure tha t some escaped the de-
terioration and loss apparent in the nearby
marrow cells.
Pagets disease is probably most reliably
recognised histologically in bone
if
its char-
acteristic mosaic pattern can be detected
using polarised light. This feature, the re-
sult of deep resorption cavities on the one
hand and exuberant woven bone apposition
on the other, has been described as particu-
larly vulnerable to the pressure of long
burial (Putschar, 1966). However, Stout
(1978) refutes this with descriptions of wo-
ven bone as generally well preserved in the
ancient skeleton. This view is confirmed by
the persistence of mosaic bone, described
above. It follows that , while a number
of os-
teopathies such as osteogenic sarcoma
(sometimes a complication of Pagets dis-
7/25/2019 American Journal of Physical Anthropology Volume 89 Issue 3 1992 [Doi 10.1002%2Fajpa.1330890306] Dr. Jean E. Aaron; Juliet Rogers; John a. Kanis -- P
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PALEOHISTOLOGY OF PAGETS DISEASE
3 9
Fig. 5. Histology of the sixteenth century bone.
a
Normal 0s calcis showing th e lamellar organization and
remnants of marrow tissue (arrow)adhering to trabecu-
lar surfaces. Polarised light; toluidine blue stain, x 125.
b
Abnormal
0s
calcis showing disorganized woven bone
with the sites of convoluted cement lines (arrows)outlin-
ing the areas
of
mosaicbone. Polarised light; tolnidine
blue stain, x 75.
c
and
d
Abnormal
0s
calcis showing
woven bone, resorption cavities (small arrow heads),
and osteoclasts (large arrows). Goldner stai n,
x
100 and
200, respectively. f Abnormal
s
calcis showing osteo-
cyte lacunae (large arrows) and bundles
of
exposed colla-
gen fibres (small arrow head) in the extracellular ma-
trix. Toluidine blue stain , x 480.
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330
J.E. AARON ET
AL
Trabecular width micron )
400
Fig. 6.
Osteocyte lacunae in sixteenth century bone.
Some osteocyte lacunae (Oc) were occupied by well pre-
served osteocytes with
a
nucleus (diagonal arrow) and
fine cell processes (horizontal arrow). The canaliculi
(Ca)were enlarged. Toluidine blue stain, x 850.
ease; Nordin 1973) and osteoblastic me-
tastases may share similar sclerotic histol-
ogy,
only one condition apparently presents
with thick trabeculae of mosaic bone in the
adult male On the basis of the thick and
irregular trabecular structure the deeply
defined resorption cavities the significant
areas of mosaic woven bone the discontin-
uous and localized nature of the abnormal-
ity and the favourable comparison with con-
temporary pathological preparations it is
concluded that the bone disease manifest in
these medieval remains is Pagets disease.
This may be the first incidence of Pagets
disease to be assigned histologically since
even one of the most reliable studies that of
Wells and Woodhouse (1975), acks any his-
tological confirmation of the proposed condi-
tion.
ACKNOWLEDGMENT
We are indebted to Monique Beneton for
histological preparation. The support of the
Eroded surface
(
bone surface)
s
calcis
0 s
calcis Sacrum Sacrum
Fig. 7. Histomorphometry of sixteenth century bone
comparing the trabecular width in pathological and nor-
mal regions and the exten t of resorption cavities. The
resul ts are th e mean one standard error. (Copyright
Dr. J . A. Kanis.)
i 3Normal bone on X-ray; Abnormal bone on X-ray
Medical Research Council PG 8600806)
is
gratefully acknowledged.
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PALEOHISTOLOGY
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