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AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 89325-331 (19921

Paleohistology of Pagets Disease in Two Medieval Skeletons


JEAN E. AARON, JULIET ROGERS, AND JOHN A. KANIS
Department of Human Metabolism, Medical School, University of
Sheffield, Sheffield SlO 2RX, England (J.E.A., J.A.K.) and Department of
Medicine, University of Bristol, Bristol Royal Infirmary,
Bristol BS2 SHW, England (J.R.1

KEY WORDS

Paleopathology, Bone histology, Pagets disease

ABSTRACT
Pagets disease has beer, ascribed several times to specimens
of archeological bone but, in the absence of microscopic examination, the
evidence remains insubstantial. Suspected metabolic bone disease is described 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 churchyard at Barton-on-Humber, England. Radiographs showed apparent structural 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. Preservation of the histology was sufficient to permit the assignment of a metabolic
bone disorder and the nature of the sclerosis was consistent with Pagets
disease. o 1992 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,
1933; Wells and Woodhouse, 19753. However, it is generally acknowledged that
much of the evidence is fragmentary and
ambiguous, lacking histological confirmation, and regularly attributing an occurrence where it is either geographically or
ethnically unlikely (Kanis, 1991).As preparative techniques for undecalcified bone histology 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 dimension of microscopy to the gross structural
information derived from the archeological
remains of two abnormal medieval skeletons with suspected metabolic bone disease.
0 1992 WILEY-LISS. INC

Optical comparison with contemporary normal and pathological material is also made.
MATERIALS AND METHODS

The skeletal remains, from two individuals, 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 Cathedral and an isolated medieval sacrum recovered from large deposits of disarticulated
bone, from a churchyard excavation at Barton-on-Humber, South Humberside. Morphological changes were evident; for example, the left femoral shaft was enlarged and
the surface texture of the right and left calcanei 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.

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J E AAROI\J ET AL.

of the individual bones and sites of apparent


abnormality identified. Using a bone biopsy
trephine, 8 m 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 preparative techniques (for example, Aaron, 1976)
the specimens were dehydrated in alcohol,
embedded in methylmethacrylate and undecalcified sections, 8 pm thick, were cut using a heavy d u b Jung K microtome. Sec
tions were stained by the Goldner method
(Schenk et al., 19691, or in 0.1% toluidine
blue stain, pH 3.5, or according to the von
Fig. 1. Radiographs of the sixteenth century os calKossa technique for bone mineral and preces showing the dense and thickened trabecular strucpared for microscopy. The sections were ex- ture
on one side only.
amined in both plain and polarised light.
Using established histomorphometric procedures (Aaron et al., 19871, the trabecular
width, pm, and the extent of resorption cav- era1 resemblance of the sclerotic pathologiities relative to the total trabecular bone cal regions to pagetic bone (Fig. 3b).
surface (% eroded surface) were determined.
The inspection of the sections for possible
Comparisons were also made with contem- non-physiological post-mortem changes inporary specimens of trabecular bone from dicated that some demineralization, evident
the 0s calcis and the iliac crest (the standard with the Goldner and von Kossa stains, had
clinical bone biopsy site) from subjects taken place (Fig. 4a). There was also eviwhose bone status had been reliably diag- dence of a reticulated pattern of destruction
nosed at autopsy or during attendance at within the bone matrix which seemed to
bone clinics.
arise by the specific removal of exposed organic matrix and which some authors have
RESULTS
attributed to past fungal invasion (Stout
While radiographs of much of the skeletal and Teitelbaum. 197613: Fig. 4b). In conseremains appeared normal, X-rays of the quence of these changes, asteoid tissue could
right calcaneus, enlarged left femoral shaft, not be reliably identified. The material reand parts of the sacrum appeared abnor- moved from radiologically normal sites was
mally dense and exceptionally coarse trabe- well-preserved, and in polarised light an
culae were evident. The remaining and ap- undisturbed lamellar organization was obparently normal calcaneus functioned as a served (Fig. 5a). In specimens from the apcontrol for its abnormal partner (Fig. 1).The parently abnormal calcaneus and sacrum,
biopsy specimen from the unaffected calca- the trabeculae were grossly thickened and
neus remained intact, providing good con- although they were continuous (in contrast
trol material (Fig. 2a). In contrast, the spec- with osteoporotic tissue) they contained a
imen taken from the affected calcaneus substantial complement of disorganized or
tended to fragment upon removal and its woven bone (Fig. 5b). In addition, traces of
fragility meant that particular care was re- convoluted cement lines which define the
quired during processing (Fig. 2b). However, mosaicbone pathognomonic of Pagets disthe structure of the sacral specimen was bet- ease were clearly evident (Fig. 5b). At the
ter preserved (Fig. 2c), although its normal same time, deep and well-defined resorption
counterpart was poor. Comparison of the cavities were extensive (Fig. 5c). Moreover,
16th century bone with contemporary mate- a small proportion appeared to contain large
rial showed a close similarity in the normal cells closely juxtaposed to Howships lacutrabecular architecture (Fig. 3a) and a gen- nae and osteoclast-like in profile, though

PALEOHISTOLOGY OF PAGETS DISEASE

Fig. 2. Undecalcified histological sections showing


the trabecular microanatomy of the sixteenth century
bone. a) Normal 0s calcis. b) Abnormal 0s calcis with
thick and irregular trabeculae; fragile trabecular cores
(arrowed) were lost during preparation but their profiles were retained by the embedding medium. c ) Abnorma1 bone from the sacrum with intact thick and irregular trabeculae. Toluidine blue stain, x 10.

cellular detail could not be resolved (Fig.


5c,d). Fragments of marrow tissue (Stout
and Teitelbaum, 197613) adhered to some of
the bone surfaces (Fig. 5a) although the
marrow cavities were largely empty. Osteocyte lacunae were distributed regularly,

327

Fig. 3. Undecalcified histological sections showing


the trabecular microanatomy of twentieth century bone
of established etiology. a) Normal 0s calcis, similar in
structure to 2a. b) Bone from the iliac crest of a patient
with Pagets disease showing the typical thick and irregular trabeculae, similar in structure to 2b and c. Toluidine blue stain, x 10.

throughout both normal and pathological regions and fine details of the fibrous nature
of the collagenous extracellular matrix at
their periphery was still apparent (Fig. 5e).
Some osteocyte lacunae, together with their
canaliculi, were unusually large and had
probably been subjected to processes of at-

328

J.E. AARON ET 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 to ancient
bones provides information which is not resolved by non-invasive procedures. In consequence, a more reliable diagnosis of suspected metabolic bone disease might be
anticipated (Bell and Jones, 1991; Weinstein et al., 1981).An important histological
feature which could not be assessed here
was the status of the osteoid tissue; this was
due to non-physiological mineral density
gradations evident in some regions. Also, it
has been reported that unmineralized bone
matrix or osteoid tissue is rarely, if ever,
preserved (Stout, 1978). Collagen is essentially protected from degradation by the
mineral component of the matrix, the geometric 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 Ascenzi, 1955 and Stout, 1978 for references).
Within this context the fine fibrous nature
of the collagenous matrix described above is
not unusual. At the same time, it may be
because of the protective property of the
bone salt that a proportion of the bone cell
population was unexpectedly conserved.
Both osteocytes and osteoclasts contain
bone mineral during their life cycle. This together with their encapsulation within inaccessible bony cavities and lacunae may have
sufficed to ensure that some escaped the deterioration and loss apparent in the nearby
marrow cells.
Pagets disease is probably most reliably
recognised histologically in bone if its characteristic mosaic pattern can be detected
using polarised light. This feature, the result of deep resorption cavities on the one
hand and exuberant woven bone apposition
on the other, has been described as particularly vulnerable to the pressure of long
burial (Putschar, 1966). However, Stout
(1978) refutes this with descriptions of woven 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 osteopathies such as osteogenic sarcoma
(sometimes a complication of Pagets dis-

PALEOHISTOLOGY OF PAGETS DISEASE

Fig. 5. Histology of the sixteenth century bone. a)


Normal 0s calcis showing the lamellar organization and
remnants of marrow tissue (arrow)adhering to trabecular surfaces. Polarised light; toluidine blue stain, x 125.
b) Abnormal 0s calcis showing disorganized woven bone
with the sites of convoluted cement lines (arrows)outlining the areas of mosaicbone. Polarised light; tolnidine

329

blue stain, x 75. c and d) Abnormal 0s calcis showing


woven bone, resorption cavities (small arrow heads),
and osteoclasts (large arrows). Goldner stain, x 100 and
200, respectively. ef Abnormal 0s calcis showing osteocyte lacunae (large arrows) and bundles of exposed collagen fibres (small arrow head) in the extracellular matrix. Toluidine blue stain, x 480.

330

J.E. AARON ET AL
Trabecular width (micron)
400

Eroded surface (% bone surface)


T

0 s calcis

0 s calcis

Sacrum

Sacrum

Fig. 7. Histomorphometry of sixteenth century bone


comparing the trabecular width in pathological and normal regions and the extent of resorption cavities. The
results are the mean t one standard error. (Copyright
Dr. J . A. Kanis.)
i3 Normal bone on X-ray; Abnormal bone on X-ray

Fig. 6. Osteocyte lacunae in sixteenth century bone.


Some osteocyte lacunae (Oc) were occupied by well preserved 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 metastases may share similar sclerotic histology, 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 discontinuous and localized nature of the abnormality, and the favourable comparison with contemporary pathological preparations, it is
concluded t ha t 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),lacks any histological confirmation of the proposed condition.
ACKNOWLEDGMENT
We are indebted to Monique Beneton for
histological preparation. The support of the

Medical Research Council (PG 8600806) is


gratefully acknowledged.
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