A possible case of Gigantism and/or Acromegaly in a 15th-17th century woman from Đurine Ćelije, Serbia

Abstract

Endocrine disorders during growth and development that occur due to the secretion of excessive growth hormones are very rare in archaeological and modern populations. The human skeletal remains analyzed in this paper belong to an unusually tall woman, approximately 35-40 years of age, buried at the Đurine ćelije site (15th-17th century) in Serbia, who may have suffered from overgrowth syndrome. Individuals with this condition have an unusually tall stature and accompanying pathological changes related to organ systems and joint diseases. The aim of this paper is to show how the aforementioned disorder affected the health status of an individual (grave No. 7a) and the performance of daily activities, but also the attitude of the community towards deformities in the life of that same person and after death. Differential diagnosis was performed since other diseases tend to lead to similar health problems. During the analysis, changes in growth were noticed, and her stature was determined to be 186.42 cm. Compared to the documented stature of the medieval population from this period, the skeletal remains show a significant deviation from the average, especially when it comes to female individuals. Other pathological changes observed in this woman are osteoarthritis, spondyloarthropathy, and periosteal new bone formation.

Full text

IAR Publishing Journal of Bioanthropology
Volume 1, 2021. p. 57-72 ISSN 2787-8201; UDK 572:902
https://doi.org/10.54062/jb.1.1.8
A possible case of Gigantism and/or Acromegaly in a 15th-17th century woman from
Đurine ćelije, Serbia
Maja Miljević-Đajić 1*
1No institutional affiliation
* Corresponding author: maja.miljevic58@gmail.com
Received October 14th, 2021
Accepted for publication December 7th, 2021
Online First December 7th, 2021
Keywords: gigantism/acromegaly, overgrowth syndrome, endocrine disorder, post-Medieval period, Serbia
Introduction
The human skeletal remains analysed in this paper
belong to an unusually tall individual buried at the
Đurine ćelije site (15th-17th century) (Figure 1a, b), who
may have suffered from overgrowth syndrome. The
most common etiology of this syndrome is related to
pituitary dysfunction that produces excessive amounts
of somatropin or growth hormone. In most cases,
growth disorders occur due to pituitary adenoma
(benign tumor) or pituitary tissue hyperplasia
(Aufderheide and Rodríguez-Martín, 1998; Ђурић-
Срејић, 1995; Ortner and Putschar, 1981). Excessive
secretion of this hormone leads to excessively tall
stature and is a serious obstacle to the normal physical
development of the individual. If this disorder occurs
before the fusion of the growth plate, then the
condition is called gigantism, if growth is complete
before the tumor develops, then it is known as
acromegaly (Atanacković, 1990; Roberts and
Manchester, 2010). However, when excessive secretion
of growth hormone occurs in childhood and continues
through adulthood, the result is the simultaneous
development of both disorders related to acromegaly
and gigantism (Ortner, 2003). Such disorders are rare in
ancient people, as well as in modern populations, with
the higher occurrence of acromegaly in modern society.
Today's statistics show that acromegaly occurs in 3:
1,000,000 cases annually worldwide, with a higher
incidence in women than in men (Extabe, et al. 1993),
while gigantism is less common, around 100 cases have
been documented in the literature so far, although this
certainly does not correspond to the real data and this
number is probably underestimated (Sotos, 1996).
Abstract
Endocrine disorders during growth and development that occur due to the secretion of excessive growth hormones are very
rare in archaeological and modern populations. The human skeletal remains analyzed in this paper belong to an unusually
tall woman, approximately 35-40 years of age, buried at the Đurine ćelije site (15th-17th century) in Serbia, who may have
suffered from overgrowth syndrome. Individuals with this condition have an unusually tall stature and accompanying
pathological changes related to organ systems and joint diseases. The aim of this paper is to show how the aforementioned
disorder affected the health status of an individual (grave No. 7a) and the performance of daily activities, but also the
attitude of the community towards deformities during life and after death. Differential diagnosis was performed since other
diseases tend to lead to similar skeletal changes. During the analysis, changes in growth were noticed, and her stature was
determined to be 186.42 cm. Compared to the documented stature of post-medieval population from this period, the
skeletal remains show a significant deviation from the average, especially when it comes to female individuals. Other
pathological changes observed in this woman are osteoarthritis, spondyloarthropathy, and periosteal new bone formation.

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58
Excessive secretion of growth hormone in people
younger than 10 years, suffering from gigantism, leads
to accelerated linear growth. Body proportions are
normal if the balance of linear growth is established by
uniform fusion of the epiphyseal plate, however,
uneven fusion can also occur, resulting in asymmetric
body proportions (Aufderheide and Rodríguez-Martín
1998). In this condition, additionally to the excessively
tall stature, the length and diameter of long bones are
also increased (Ortner and Putschar 1981). If the main
cause of this condition was a tumor then the sella
turcica is enlarged (Weisberg et al. 1976). In
acromegaly, the most noticeable changes are visible on
the facial bones leading to a general enlargement, as
well as an enlargement of the paranasal sinus, and the
bones of the skull vault are thickened. The lower jaw is
elongated and prognathism and dental malocclusion
occur. In the bones of the skull vault, changes leading to
a robust appearance are evident, the superciliary
arches are prominent on the frontal bone, and the
external occipital protuberance of the occipital bone is
pronounced (Ortner and Putschar, 1981; Ortner, 2003).
On the postcranial skeleton, the bones of the hand and
foot as well as the vertebrae are enlarged and the ribs
are broad (Aufderheide and Rodríguez-Martín, 1998;
Waldron 2009). The pathological changes that
accompany these endocrine disorders are related to
organ systems and joint diseases. In ancient and
modern skeletons, in addition to degenerative changes,
spondyloarthropathies lead to difficulties of breathing
and moving, and signs of infectious diseases are often
detected. Altogether, along with other pathologies, this
will shorten the life of the individual (Ortner and
Putschar, 1981; Chanson and Salenave, 2008).
According to the paleopathological literature, a modest
number of certain and potential cases of gigantism and
acromegaly in ancient people have been documented
(Table 1). The commonality linking all these individuals
is primarily extremely tall stature, long bones of the
upper and lower extremities, robust and thickened
skull, large and protruding lower jaw, enlarged sella
turcica, numerous pathologies that accompany this
condition and a short lifespan that rarely exceeds 30
years of age.
Figure 1a: Map of the Republic of Serbia showing the
geographical location of the Đurine ćelije site
Figure 1b: Geographical position of the Republic of Serbia in a
map of Europe

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59
Therefore, the aim of this paper is to show how the
aforementioned disorders affected the health status of
an individual found at Đurine ćelije site (grave No. 7a)
and the performance of daily activities, but also the
attitude of the community towards deformities in the
life of the person and after death. Also, based on the
detected pathological changes on the cranial and
postcranial skeleton, which may indicate the presence
of other diseases, differential diagnosis was performed
here.
Materials and methods
The skeletal remains analyzed in this paper come
from the post-medieval site of Đurine ćelije in the area
of Rudnik, Serbia (Figure 2). Continuous archaeological
excavations of this site took place between 2013-2016
(Радичевић и Миливојевић, 2013; Радичевић и др.,
2015; Гордић и Ћирковић, 2018). During that time, the
remains of a monastery complex with a necropolis were
discovered.
Table 1 Certain and probable cases of gigantism and acromegaly in ancient people that have been documented

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60
The deceased were buried in the immediate vicinity
of the monastery church. Several horizons of the use of
the necropolis have been recorded, dated to the period
from the 15th to the 17th century on the basis of
1
The Sipahis were horsemen in the Ottoman army and could
own a timar (land). They had a high social status among Serbs
during the Ottoman Empire (Радичевић и Миливојевић,
2016).
archaeological findings. According to the tombstone
inscription of grave No. 6 which testifies to the burial of
Jovan Sipahi
1
, archaeological finds from the same grave
and a coin found in grave No. 8, it was possible to date
Figure 2: Site plan of Đurine ćelije site (from Радичевић и др. 2016)

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61
only the youngest burials from the 17th century.
Archaeological excavations have revealed 25 graves
(Радичевић и Миливојевић, 2013; Радичевић и др.,
2015; Гордић и Ћирковић, 2018). The deceased were
buried in an extended position on their backs, usually
with their hands on their chests or stomachs,
orientation west-east (Радичевић и др., 2015). There
were some deviations and the orientationthe
orientation of some burials was northwest-southeast
(Гордић и Ћирковић 2018). North of the church,
burials were located under the tombstones (Figure 3)
and they are dated to the 17th century (Радичевић и
др., 2015). Below one of the tombstones, marked as
grave No. 7 there were two buried individuals. The first
buried deceased (7b) was in the primary position, while
the skeletal remains of the second buried individual (7a)
2
Đurine ćelije-report 2015, December 15th 2015.
were disturbed, i.e. in the secondary position (Figure 4).
According to the researchers of this site, the grave was
disturbed before archaeological excavations took
place.
2
The state of preservation of skeletal remains was
observed according to the categories proposed by Mikić
(Mikić 1978). Determination of the sex was based on
the morphological characteristics of the pelvic bones, as
well as the morphological characteristics of the skull
(Workshop of European Anthropologists, 1980; Buikstra
and Ubelaker, 1994). The auricular surface of the ilium
(Lovejoy et al., 1985b) and the degree of closure of the
cranial sutures were observed to determine age at the
time of death (Workshop of European Anthropologists,
1980). The standard tooth numbering system was used
in the analysis of dentition (Federation Dentaire
Figure 3: Tombstones north of the monastery church (from Радичевић и др. 2016)

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62
Internationale, 1971). Metric analyzes were applied in
this paper to obtain data on stature based on maximum
length of long bones, according to the formulae of
Trotter and Gleser (1958) and body weight was
calculated based on the maximum diameter of the
femoral head, according to the formula of Ruff et al.
(1991). Existing standards (Ortner and Putschar, 1981;
Aufderheide and Rodríguez-Martín, 1998; Ortner, 2003)
were used to identify and diagnose pathological
changes. In this paper, the analysis of macroscopic
examination of musculoskeletal stress markers was also
performed (Mariotti et al., 2017).
Results
The analyzed human skeletal remains in this paper
belong to the category of well – preserved, incomplete
skeletal remains. In Figure 5 the state of preservation of
skeletal remains is presented. Table 2 provides the
skeletal measurements buried in grave No. 7a.
Morphological characteristics of the skull (os frontale,
arcus superciliaris, tuber frontale et parietale, planum
nuchale, total aspect of the mandible, mentum, angulus
mandible) and postcranial skeleton (incisura ischiadica
major) showed that the skeletal remains belong to a
female individual. Her age at the time of death, based
on morphological changes of the auricular surface of
the ilium, was 35-39 years (stage IV), and based on the
degree of closure of the cranial sutures from 35-40
Figure 4: Grave No. 7 with two buried individuals (photo credit: V. Milivojević)

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63
years of age.
3
According to the method of Trotter and
Gleser (1958), the maximum lengths of long bones were
measured and her body height was calculated (Table 3).
Stature values ranged from 189.93 cm for the right tibia
3
Although cranial suture closure is used for decades as an
indicator of age it is an unreliable method. Diseases or
genetic disorders can lead to faster or slower suture closure.
and 182.92 cm for the right femur, with an average
value of 186.42 cm. According to the formula of Ruff et
al. (1991) her body weight was 80.9 kg.
Figure 5: Inventory of burial No. 7a. Bones shaded in black are present.

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Table 4 presents an overview of estimated stature of
medieval populations on the territory of Serbia during
the late Middle Ages. The range of estimated stature for
men ranged from 153-181 cm, and for women from
146-172 cm (Живановић, 1985; Живановић, 1987;
Ђурић-Срејић, 1997; Миладиновић-Радмиловић,
2007; Вуловић и Бизјак, 2019). At the Đurine ćelije site,
the average stature for males was 179.19 cm, and for
Table 2 Measurements of the cranial and postcranial skeleton
Bones marked with * have two measurements, the upper is for the left, and the lower is for the right side of the body
Table 3 Measurements of the long bones and estimated stature (grave No. 7а)

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females 165.32 cm
4
. In individual No. 7a estimated
stature was 20 cm higher than the average height of
females. This is most evident in this case, abnormal
height and proportional growth, significantly long
bones of the upper and lower extremities (Figure 6) and
pathological changes in the cranial and postcranial
skeleton. Robust characteristics were noticed on the
skull, a pronounced external occipital protuberance and
4
It was possible to calculate stature only for three women.
However, the individual from grave No 7a was excluded from
this analysis due to growth disorder (Miljević, 2018).
large mastoid process. Prognathism-protrusion and
obtuse angle are noticeable on the mandible (Figure 7a)
and a significant number of teeth lost antemortem
5
(Figure 7b).
Anatomical variation such as bilateral perforatio fossa
olecrani, also known as septal aperture, was detected
on both humeri (Figure 8). The pathological changes
5
FDI numbering system for the permanent teeth: Teeth lost
antemortem: 37, 38, 44, 46-48.
Table 4 Estimated stature for late Medieval population from Serbian sites. (aM-9, F-2; bM-25, F-10; cM-9, F-13; dM-32, F-24; eM-4, F-0;
fM-5; F-0).
a-f Number of male (M) and female (F) individuals
1 Authors used formula of Trotter and Gleser (1952)
2 Authors used formula of Pearson (1899)
Figure 6: Comparison of the long bones of the lower limbs between 7a and normal body height of the femalе individual (grave
No. 6) (photo credit: author)

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observed in this individual are: osteoarthritis,
spondyloarthropathy, and periostitis. Osteoarthritis has
been observed in almost every joint, most often in the
form of osteophytes and eburnation. The new bone
formation or osteophytes were found on the proximal
ends of the left and right humerus, radius, femur, tibia
and preserved distal ends of fibulae, on the distal ends
of clavicles, metatarsal, and tarsal bones. On the right
clavicle and acromion of the right scapula, in addition to
osteophytes, eburnation also occurs (Figure 9). Fusion
of the right rib with the vertebra was observed on one
thoracic vertebra (T4) (Figure 10). Traces of fusion are
also noticeable in other thoracic vertebrae, but during
the excavation it was separated. Fusion also occurs in
the area of the spinous process, i.e. in the articular
surfaces of the lumbar vertebrae (from L3 to L5) and
thoracic vertebrae (from T9 to T12) with the
intervertebral space between the bodies of the thoracic
vertebrae (Figure 11). Significant curvature and
sacralization with L5 was observed in the sacrum. The
missing sacroiliac joint probably existed and was lost
Figure 7a: Protrusion and obtuse angle on the mandible
(photo: author)
Figure 7b: Teeth lost antemortem (photo: аuthor)
Figure 8: Bilateral epigenetic variation perforatio fossa olecrani
on the distal ends of both humerus (photo credit: author)
Figure 9: Osteoarthritic changes (eburnation) on the acromion of
right scapula (photo credit: author)

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67
during or after excavation. Excessive bone growth on
the remaining parts of the left pelvic and sacral bone
parts indicate an ossification, probably an ankylosing
spondylitis. Periosteal reactions occur on almost all long
bones of the upper and lower extremities (humerus,
femur, tibia, fibula). These are healed periosteal
reactions, none of which were active at the time of
death. In the left femur, due to this disorder, there was
never an adhesion of the proximal end (femoral head)
with the diaphysis (Figure 12), although ossification on
all bones showed that the growth was complete.
Bilateral indentations on the lateral sides of both
proximal femurs were observed (Figure 13), as well as
narrowing of the iliac bone on the left preserved pelvic
Figure 10: Costovertebral joint on the thoracic vertebrae (T4)
(photo credit: аuthor)
Figure 11: Fusion of articular surface of thoracic and lumbar vertebrae (photo credit: аuthor)
Figure 12: Nonunion of the proximal epiphysis with diaphysiѕ
of the left femur (photo credit: author)

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bone. Musculoskeletal stress markers were observed
on the postcranial skeleton, and the most pronounced
muscle attachments were present on the right side of
the skeleton (Table 5).
Discussion and Conclusion
Discussion
Growth and development disorders that lead to tall
stature rarely occur in archaeological and modern
populations, and they are especially difficult to
diagnose on osteological material. However, if
abnormal stature is not associated only with excessive
secretion of growth hormone from the pituitary gland,
these changes can also occur due to other similar
disorders. Diseases that lead to similar development
and growth disorders are Marfan’s syndrome (Petitt
and Adamec, 2005; Aufderheide and Rodríguez-Martín,
1998), Sotos syndrome (Parker and Parker, 2007),
Weaver syndrome (Bansal and Bansal, 2009) and
Beckwith-Wiedemann syndrome (DeBaun and Horst,
2011). Marfan’s syndrome is a genetic disorder that
affects the cardiovascular, ocular and skeletal systems
(Petitt and Adamec, 2005). The skeletal changes that
dominate due to Marfan’s syndrome are excessively
long upper and lower extremities, especially the upper
ones. In addition, dental anomalies and malocclusion
occur, scoliosis, kyphosis or pectus carinatum (pigeon
breast) are common in the area of the chest and spine
(Aufderheide and Rodríguez-Martín, 1998). Sotos
syndrome is another disorder that affects the skeletal
system and where growth is accelerated. Affected
babies and children tend to grow faster and they are
taller than children of the same age. However, their
Figure 13: Bilateral indentations on the lateral sides of both proximal femurs (photo credit: author)
Table 5 Degree of musculoskeletal stress markers on the upper
and lower limb bones (grave No. 7a)

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adult height is quite normal. An abnormal curvature of
the spine (scoliosis) can also be the sign of Sotos
syndrome (Parker and Parker, 2007). Weaver syndrome
is a disorder that usually starts with rapid growth before
birth of the baby and continues through childhood. It is
characterized by accelerated bone maturation,
craniofacial, skeletal and neurological abnormalities.
The mandibule can be smaller than normal. Fingers of
people affected with this syndrome are usually broad
(Bansal and Bansal, 2009). Beckwith-Wiedemann
syndrome is an overgrowth syndrome of the prenatal
period and it is characterized by congenital
malformations, and predisposition to cancer. Children
with this syndrome can have asymmetry of the limbs or
face, as well as joint laxity, scoliosis, and thoracic cage
abnormalities (DeBaun and Horst, 2011).
Despite the differential diagnosis, where none of the
above examples completely fit into the presented
pathological picture, and the insufficient preservation
of skeletal remains (especially facial bones and sella
turcica), which would facilitate and confirm the
diagnosis that this is an overgrowth syndrome due to
pituitary adenoma, we can only assume that the
observed changes in the osteological material may have
been due to excessive secretion of this hormone. The
results of the anthropological analysis which may
indicate that the individual from grave No. 7a was
suffering from gigantism and / or acromegaly are as
follows:
1. The appearance of the skull which has robust
characteristics, as indicated by the prominent external
occipital protuberance, large mastoid processus.
Protrusion-prognathism and obtuse angle of the
mandible were observed on the mandible.
2. On the postcranial skeleton, increased longitudinal
growth of the upper and lower extremities, nonunion of
the proximal epiphysis with the diaphysis of the left,
abnormal stature for period and sex and accompanying
pathologies (degenerative joint diseases,
spondyloarthropathy of the spine, periosteal changes
on the long bones) were detected.
Although the skull has robust characteristics,
morphological changes of the pelvis indicate a female
individual. Mandibular prognathism occurs in these
disorders leading to remodeling of bites, malocclusions,
and large numbers of teeth lost antemortem
(Aufderheide and Rodríguez-Martín, 1998; Ortner,
2003). Incomplete fusion of the proximal end with the
diaphysis occurs in younger individuals who have been
diagnosed with gigantism, because this disease leads to
growth disorder (Waldron, 2009). However, in this
individual (grave No. 7a) the growth on all the bones
was complete, so we cannot speak of a younger person.
It is obvious that the excessive secretion of growth
hormone that developed in youth continued in
adulthood, which could have resulted in both gigantism
and acromegaly. This is also indicated by her tall stature
(186.42 cm), which stopped at one point. If the
increased secretion of hormones continued in youth
(before the complete fusion of the pineal gland), this
individual would certainly have a height of over 200 cm
(Aufderheide and Rodriguez-Martin 1998). Pathologies
observed in No. 7a belong to the group of pathologies
that are standardly associated with constant excessive
growth disorder (Aufderheide and Rodriguez-Martin,
1998; Hošovski, 1991; Mulhern, 2005; Ozdemir et al.,
2017). Patients with gigantism rarely or never live
longer than 30 years, because of the progression of
other diseases (Minozzi et al., 2012), while in patients
diagnosed with acromegaly life expectancy exceeds 50
years of age (de Herder, 2008; de Herder, 2014).
Possible ankylosing spondylitis in No. 7a was detected
in the form of fusion which affected the lumbar and
thoracic vertebrae in the area of the spinous process
and joint surfaces, as well as the costovertebral joints
on the thoracic vertebrae. The sacroiliac joint also
existed, but during or after the excavation, this joint
was damaged and separated. According to Olivieri et al.
(2009), Waldron (2009) and Ortner and Putschar (1981)
the disease usually begins in the lumbar vertebrae and
sacroiliac joint and progressively affects the thoracic
vertebrae and their costovertebral joints. Also, for a full
list of diagnostic criteria follow up Šlaus et al. (2012).
Perforatio fossa olecrani, which is observed on the
distal ends of the humeri, may be related to this
disorder. It has been observed that this epigenetic
anomaly occurs with a higher frequency in the female
population (Mays, 2008). The hypothesis is that weaker
muscles can lead to increased joint looseness, which
results in hypermobility and the appearance of

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70
perforatio fossa olecrani, and that it occurs in a higher
percentage in older individuals. There have been
attempts to compare the incidence of osteoarthritis
with this anomaly (Myszka and Trzcinski, 2015; Myszka,
2015), but it has been concluded that it develops in
youth and not as osteoarthritis in old age. The question
of the cause of this anomaly remains open. In addition
to the observed pathological changes, changes in the
form of indentations on the lateral sides of both femurs
were recorded, as well as narrowing of the iliac bone of
the left pelvic wing. It was not possible to observe the
right one because it was fragmented.
This case showed that, despite the aggravated
pathological picture and indisputably different physical
appearance and development, she was not separated
and isolated from other graves, but received the same
treatment in funeral practice as all the deceased,
including burial below the tombstone. Although this is
not an isolated example, it is known from previous
research that the caring attitude of the society towards
deformities and weaknesses of people with gigantism
and acromegaly did not always extend to posthumous
customs (Gladykowska-Rzeczycka et al., 1998). The
analysis of the skeletal remains of a giant woman from
the Ostrow Lednicki site showed that, once or probably
several times, she received medical care throughout her
life during the repair of the limb fracture. However,
during the mortuary treatment, she was not buried in
the same necropolis as the others, but in another
former necropolis that ceased to be used, but was
previously reserved for the burial of the elite. Also, she
was not buried in the same position. Her body was
placed in an unusual position and out of order. Her
skeleton was lying on the left side, with her left hand
close to her head. The right upper limb was bent at the
elbow, the left lower limb was bent at the knee, and
apparently without care. This does not mean that the
woman from Ostrow Lednicki was completely rejected,
but in the contrast to the case presented in this paper
from Đurine ćelije, she was probaly not a full member
of the community (Gladykowska-Rzeczycka et al., 1998;
Matczak and Kozlowski, 2017).
Conclusion
Abnormally enlarged long bones of the upper and
lower extremities, robust skull, mandibular
prognathism, numerous pathologies and tall stature
above the average for the post-medieval population
and sex were recorded in a female individual (grave No.
7a) from the Đurine ćelije site. These changes observed
on skeletal remains may indicate the presence of
gigantism and acromegaly at the same time. However,
although the pathological picture indicates a difficult
life for the infected person, this disorder did not
prevent her from performing physical activities during
her lifetime, since there is a noticeable absence of
muscle atrophy and pronounced enthesis on the upper
and lower extremities. It is difficult or almost impossible
to find out to what extent this woman suffered from
pain at all, but it seems very likely that she went through
some periods of pain or discomfort during her life. The
results of the anthropological analysis indicate that
during her life, and after her death, she was treated
equally by her contemporaries, despite obvious
differences in physical appearance and needs for a
functional life.
Acknowledgements
The author wishes to thank prof. Dejan Radičević
(Faculty of Philosophy, University of Belgrade) and
history curator Vladan Milivojević (National museum in
Aranđelovac) on provided osteological material, and
prof. Sofija Stefanović (Laboratory for Bioarchaeology,
Faculty of Philosophy, University of Belgrade; Biosens
Institute, University of Novi Sad) for valuable
comments. The author declares that no funding was
received for this research.
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