Diagnosis and Evaluation of Causative Factors for the Presence of Endemic Treponemal Disease in a Japanese Sub-Tropical Island Population from the Tokugawa Period

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Diagnosis and evaluation of causative factors for the presence of endemic treponemal disease in a Japanese sub-tropical island population from the Tokugawa period

Article in International Journal of Paleopathology · September 2015 DOI: 10.1016/j.ijpp.2015.04.001

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International Journal of Paleopathology 10 (2015) 16–25

Contents lists available at ScienceDirect

International Journal of Paleopathology

j ournal homepage: www.elsevier.com/locate/ijpp

Diagnosis and evaluation of causative factors for the presence of

endemic treponemal disease in a Japanese sub-tropical island

ଝ

population from the Tokugawa period

a, b

Mauricio Hernandez ∗, Mark J. Hudson

Division of Biological Anthropology, Department of Archaeology and Anthropology, University of Cambridge, Cambridge CB2 3DZ, United Kingdom

Research Institute for Sustainable Environments and Cultures, Nishikyushu University, Kanzaki 842-8585, Japan

a r t i c l e i n f o a b s t r a c t

Article history: We present a description and differential diagnosis of pathological lesions observed on skeletal ele-

Received 1 June 2014

ments found during surface surveys of the Nagabaka site on Miyako-jima Island, Japan. The Nagabaka

Received in revised form 5 April 2015

site served as a bone depository during the Early Modern period (c. AD 1600–1870). We evaluated remains

Accepted 6 April 2015

via macroscopic inspection to classify infectious lesions according to criteria in Weston (2008). We also

obtained CT scans of three bone elements for more extensive lesion analysis and carried out a differential

Keywords:

diagnosis utilizing paleopathological literature. Subsequent investigation yielded convincing evidence

Yaws

of treponemal infection on 23 skeletal elements. Based on known geographical spread and morpholog-

Treponemal disease

Paleopathology ical comparisons of lesion patterning, we identiﬁed yaws as the pathogen most likely responsible, but

refrained from calculating site-wide prevalence due to the taphonomical nature of the sample. Lastly, we

Ryukyu Islands

Japan review treponemal infection rates in other archaeological sites throughout Southeast Asia and Oceania,

and assess similar ecological and cultural factors contributing to the observed pathologies. Nagabaka is

the northernmost site in the world where yaws has so far been identiﬁed. Located between sites between

Mainland China and Western Micronesia where this infection has been previously identiﬁed, Miyako-jima

holds an important geographical position for research into the historical spread of pathogens.

1. Introduction Miyako-jima is the largest of the Miyako Islands, located approx-

imately 270 km southwest of Okinawa Island. It forms part of a

The global history of treponemal disease is constantly being chain of islands stretching from Taiwan to Kyushu, collectively

reﬁned with new temporal and geographic data points emerging known as the Ryukyu Islands (see Fig. 1). Miyako-jima is triangular

through ongoing research in the ﬁelds of archaeology, paleopathol- in shape, with a total area of approximately 158.70 km . The island

ogy, history and genetics. During the course of surface surveys and is largely ﬂat, with a maximum elevation of only 115 m above sea

excavation at the Nagabaka site on Miyako-jima, Japan, we discov- level. At present, the terrain is mostly covered with arable ﬁelds and

ered evidence that could extend the geographic range of infection the principal cash crop is sugarcane for brown sugar production.

prevalence northeast, into Japanese territory. This paper reports the The climate of Miyako-jima is considered to be sub-tropical due to

site context and procedures we used to deﬁne most probable dis- the warm waters of the Kuroshio ocean current that passes through

ease identiﬁcation, including both macroscopic and radiographic this region, known as the Indomalaya eco-zone. Since Medieval

analysis, along with an extensive differential diagnosis. times, Miyako-jima has been home to speakers of Ryukuan lan-

guages who likely migrated south from Japan (Pellard, 2015).

The Nagabaka site located at 24◦ 51# N, 125◦ 17# E in the Shimajiri

district of northern Miyako-jima. It is situated within 50-m long

ଝ rock shelter, which rests on a ridge approximately 26–27 m above

Grant Sponsorship: Grant-in-aid for Scientiﬁc Research on Innovative Areas,

MEXT, Japan for the project ‘Environmental and cultural changes in the Ryukyu sea level within a densely wooded area. This rock shelter was used

archipelago during prehistoric and proto-historic times’ (No. 21101005), Downing as a depository for human remains during the Early Modern era.

College Graduate Travel Grant, Ridgeway-Venn Travel Studentship, Worts Traveling

Although artifacts found at the site suggest that its main period of

Scholar Fund, and JSPS Core-to-Core Program.

use occurred during the 17–18th centuries, some skeletons may

∗ Corresponding author at: Downing College, Regent Street, Cambridge CB2 1DQ,

date as late as the 19th century (Nagabaka Archaeology Project,

United Kingdom. Tel.: +44 7494 360 251; fax: +44 1223 764 710.

E-mail address: [email protected] (M. Hernandez). 2013).

http://dx.doi.org/10.1016/j.ijpp.2015.04.001

M. Hernandez, M.J. Hudson / International Journal of Paleopathology 10 (2015) 16–25 17

Fig. 1. Regional map of the Ryukyu Islands and the location of Miyako-jima. Inset shows the location of the Nagabaka site within the island.

Nagabaka is composed of three sections (running north to south) broken epiphyses due to taphonomic processes including animal

demarcated by low limestone-block walls that prevent the skele- activity, and several have been stained green from algae growth.

tal remains and accompanying cultural implements from rolling Lastly, a small percentage of remains also display mineral deposits

down the ridge. The North and South sections of the site where from being under driplines, which indicates that the site, as well as

most skeletal remains are found are the longest, measuring approx- the remains, are largely undisturbed.

imately 23 m each. An overhanging rock shelter covers the South The Nagabaka site is an example of a type of cemetery known

and Central sections (see Fig. 2), whereas the overhang in the in the Ryukyu Islands as a fus¯ obo¯ or fus¯ obaka¯ , terms with the lit-

North section is less pronounced, making it more open to the ele- eral meaning of “wind burial”. Corpses were deposited in caves

ments. Within each section of the site, there are many scattered or rock shelters and left until the ﬂesh decayed, a process that

human remains, both exposed and partially buried. Bone preserva- was often accelerated by hermit crabs. Once the ﬂesh was gone,

tion varies, depending on location within the rock shelter. Bones bones were often placed in ceramic urns or wooden cofﬁns. No

within the North section are generally more weathered, whereas such ceramic urns are present at Nagabaka. Pieces of wood found

in the Central and South sections, they generally display good cor- in the North and South sections of the site are likely to be fragments

tical preservation, as they are protected from direct sunlight and of the boat-shaped cofﬁn mentioned by Ikeda (1974). However, it

the low overhang helped to maintain humidity and soil moisture. seems unlikely that all of the skeletal remains from Nagabaka were

About 60–70% of long bones have partially damaged or completely originally contained in just one cofﬁn, suggesting that the method

Fig. 2. Map of the Nagabaka site showing the shelter’s North, Central and South sections, as well as the retaining wall. Inset A – South section viewed from the north. Inset B

– southern portion of the North section. Inset C – adjacent area of the North section. Photos taken during ﬁeldwork in July, 2012.

18 M. Hernandez, M.J. Hudson / International Journal of Paleopathology 10 (2015) 16–25

Table 1

Distribution of major skeletal elements at the Nagabaka site divided by section and

side.

Bone North Central South

L/R L/R L/R

Cranium 75 16 88

Mandible 32 5 30

Humerus 34/16 2/4 38/43

Radius 11/10 0/2 16/9

Ulna 9/8 1/0 29/17

Femur 56/61 6/4 68/47

Tibia 46/51 5/3 52/64

of body disposal varied and the site may have been used for both

primary and secondary body disposal. No historical records of the

Nagabaka cemetery are known and current residents of the island

do not consider themselves related to the individuals deposited

within the shelter. Although we cannot verify the identity of the

commingled remains at Nagabaka, as Ikeda (1974) notes, the gen-

erally isolated history of Miyako-jima makes it almost certain that

these skeletons represent the local population in the early modern period.

2. Materials

Since the early 1970s, all three sections of the Nagabaka

rock shelter have been subject to anthropological investigation

by several scholars (Ikeda, 1974; Dodo et al., 1998, 2000, 2001;

Pietrusewsky, 1999). Recently, ﬁeldwork was conducted by M.J.

Hudson in nine annual seasons from 2005 to 2013. A 2010 surface

survey of all the commingled remains at the site, led to the inference

that the site’s three sections house a minimum of 172 individuals

(Nagabaka Archaeology Project, 2013). In 2012, a second survey

of the site and the surrounding area recovered 179 complete or

mostly complete crania and 67 mandibles, along with 137 humerii,

48 radii, 163 ulnae, 296 femora and 221 tibiae, some complete and

some missing epiphyses. More fragile elements such as the ﬁbula or

smaller parts of the skeleton such as the vertebrae and phalanges

were inspected but not counted and many more limb bone frag-

Fig. 3. Graphs displaying MNI by bone element and side for each of Nagabaka’s three

ments were found scattered throughout the three sections. For a sections.

more thorough description of the skeletal elements, which were

collected for analysis and then replaced, please refer to Table 1.

This state of preservation and commingling is likely due to ani- commingled. The primary method for analyzing the remains was

mal activity and the natural incline of the ridge where the site is macroscopic inspection to identify all bones displaying lesions.

located, rather than differential mortuary treatment. Fig. 3 (after Weathered remains, or those with extensive taphonomic damage

Osterholtz et al., 2014) displays the distribution of bone elements to the cortical surface that would prevent accurate assessment

divided by side, comparing each of the shelter’s three sections. were excluded. Descriptions focused on lesion appearance, loca-

We note that crania are the most numerous, followed by femora tion on the bone, lesion distribution on the body (axial skeleton,

and tibiae. Concurrent with Willey and Scott’s (1997) observation upper or lower limb), and lesion distribution throughout the pop-

favoring the preservation of larger bone elements, we posit that ulation (adult v. sub-adult). Detailed assessment of every affected

this consistent result for each section reﬂects previous exhuma- bone follows Weston’s (2008) tri-partite method for pinpointing

tion as well as scavengers and other animals eventually carrying off the speciﬁcity of periosteal lesions, which utilizes criteria from

smaller, less cumbersome elements, or water runoff being respon- Cook (1976), Lallo (1973) and Hackett (1976) to recognize the hard

sible for burying the smaller skeletal elements. From the maximum tissue changes of the cranial vault and long bones. We also divided

number of crania, we calculated approximately 179 individuals. each bone into quarters for assessing the extent of lesions and

During this second survey, we also observed a number of cranial separated lesion areas on each bone into three categories: small

2 2 2

and postcranial remains that displayed ante-mortem pathological (<4 cm ), medium (4–20 cm ), and large (>20 cm ).

lesions appearing systemic in nature. These remains prompted a Computed tomography (CT) scans and X-rays have been used

collection and reassessment of every bone scattered on the surface to make a stronger case for systemic infectious diseases such as

of the rock shelter’s three sections and further inquiry to disease leprosy, tuberculosis or treponemal disease, as they can discern

etiology. changes in the bone cortex (Ortner, 2003, Chapter 4). Therefore, we

obtained scans of three bone elements – two femora and a cranial

3. Methods fragment, which displayed some of the most prominent reactive

changes on the periosteal surface, in order to assess the nature

Age or sex estimations could not be accomplished for the of osteoclastic and osteoblastic activity. For more extensive anal-

majority of postcrania as all skeletal elements at Nagabaka were ysis of the lesions, each element was scanned with 3.9 mm slices

M. Hernandez, M.J. Hudson / International Journal of Paleopathology 10 (2015) 16–25 19

Fig. 4. Affected cranium 2 (occipital). (A) Outer vault displays cavitation and focal

destruction. (B) Inner vault displays lesions perforating the vault.

at approximately 4 h per scan, using an Alphard VEGA 3030 X-ray

CT machine, made by the Asahi Roentgen Ind. Co., Ltd, Japan. We

processed images using OsiriX Imaging Software v.5.7, an open-

source Digital Imaging and Communications in Medicine (DICOM)

viewer to arrange them into composite coronal, transverse and

sagittal views.

We then proceeded to make a differential diagnosis of all

affected skeletal elements utilizing various paleopathology man-

Fig. 6. Affected distal right humerus displaying moderate expansion and rugose

uals (Steinbock, 1976; Aufderheide and Rodríguez Martín, 1998;

nodes. (A) Anterior view. (B) Posterior view.

Ortner, 2003), which provide detailed descriptions and images

of lesion patterning and disease progression. Moreover, we

brieﬂy review bioarchaeological literature from Southeast Asia and

fragment from a right rib was found on the south section of the shel-

Oceania to understand the timing of spread and geographical dis-

ter. From percentage of observable remains, we note that the lower

tribution of infectious disease in the vicinity of Miyako-jima. Lastly,

limb was the region most frequently affected by lesions. There were

we consulted historical records in order to draw cross-cultural

eight affected femora, ﬁve left and three right (see Fig. 7), includ-

and ecological parallels to other regional societies that may have

ing one from a sub-adult and a pair likely belonging to the same

suffered from similar infections and which would clarify our diag-

young individual as their epiphyseal fusion schedules matched.

noses.

There were 13 tibiae, eight left and ﬁve right (see Fig. 8) that dis-

played lesions of infectious appearance. One tibia also displayed

4. Results severe medial bowing (see Fig. 9). Lastly, there was a fragment

of ﬁbula midshaft that could not be sided due to cortical pathol-

4.1. Description of bone elements via macroscopic observation ogy. A summary of pathological changes observed in each element,

and CT scans along with more detailed descriptions of the affected remains can

be found on Table 1 within the supplementary information for this

From surface surveys of the three sections at Nagabaka under- article.

taken in 2011 and 2012, we found a total of 29 skeletal elements Fig. 10 shows CT scans of femurs 4 and 6 and cranial fragment

displaying suspected pathology of potentially infectious etiology. 3 displaying areas of different cortical bone density along the mid-

There were three cranial fragments suspected of systemic infec- shaft and cranial vault, with dense bone in white and less dense

tion, all of which were found in the south sector of the rock shelter bone in yellow and red. Sagittal slices of femurs 4 (Fig. 10A) and

(see Figs. 4 and 5). From the upper limb, there is a right humerus 6 (Fig. 10B) display extensive cavitations penetrating deep into

from the south section of the shelter (see Fig. 6) and a complete the cortex, as well as regions of thickened cortex that decrease

right ulna from the north section with evidence of infection. There is the area of the medullary cavity. Coronal slices of all three bones

also a complete left radius from the south section displaying severe also display these cavitations with rounded edges, with a gumma-

medial bowing. The axial skeleton is represented only by a large tous, “worm-eaten” appearance, most discernible on the occipital

Fig. 5. Affected cranium 3 (left frontal fragment). (A) Anterior view displays several jagged, destructive lesions. (B) Lateral view displays additional lesions. (C) Inner vault

displays thickening and lesions perforating the vault.

20 M. Hernandez, M.J. Hudson / International Journal of Paleopathology 10 (2015) 16–25

Fig. 9. Tibia 13 displaying medial bowing. (A) posterior view, (B) anterior view.

4.2. Differential diagnosis of skeletal elements at the Nagabaka

Site

Each of the 29 skeletal elements at Nagabaka was assessed

separately; thus possible diagnoses are carried out on different

elements exhibiting similar characteristic abnormalities. Described

in detail within the supplementary information, these cranial and

postcranial elements display lesions that may be the result of sev-

Fig. 7. Affected femora, anterior views. (A) Femur 2. (B) Femur 3. (C) Femur 6.

eral soft and hard tissue diseases. Possible differential diagnoses

for the observed pathological conditions include traumatic injury,

metabolic diseases such as skeletal ﬂuorosis, scurvy or rickets,

(Fig. 10C). Additionally, both the sagittal and coronal views of all malignant tumors like osteolytic metastatic carcinoma or multi-

three elements display brighter, more dense regions of cortex, ple myeloma, hypertrophic osteoarthropathy as a secondary result

suggesting limited but active reactive bone near the lesions. Lesions of lung cancer or infection, reticuloendothelial diseases such as

on each of bones were separately evaluated in a differential diag- eosinophilic granuloma (Langerhans cell histiocytosis), develop-

nosis below. More extensive background information about each of mental anomalies such as melorheostosis or even Paget’s disease.

these conditions/disorders may also be found within the additional Chronic conditions as a result of pyogenic bacteria or mycotic

supplementary materials. infection may also be responsible for pathological lesions on

Fig. 8. Affected tibiae, medial views. (A) Tibia 3, (B) Tibia 5, (C) Tibia 7, (D) Tibia 8.

M. Hernandez, M.J. Hudson / International Journal of Paleopathology 10 (2015) 16–25 21

skeletal elements at Nagabaka. These infections include hematoge- may have affected a subset of the population at Nagabaka. It is

nous osteomyelitis, leprosy, tuberculosis, as well as venereal or important to note that the tibial curves the knee outward and not

endemic treponemal disease. inward, as seen in cases of rickets ‘tibia vara’, and the femoral neck

Pseudopathology is certainly of concern when diagnosing of femur 8 does not display ‘coxa vara’ (heightened angulation).

pathology at Nagabaka, due to the context in which the bones were No other adult skeletal elements display angulation deformities

found. Except when noted, the cortical surfaces of all vault and limb are apparent at the site, so the condition is not widespread. It is

bones on which lesions were detected were not weathered and possible that the radius and the tibia displaying angulation defor-

matched the general color pattern of the rest of the bone element. mities originated from the same individual, since both were found

We thus conclude that post-depositional taphonomical changes on the south section of the site. Lastly, there are a large number

were not causative factor for the observed hard tissue changes on of acquired and inherited conditions that cause rickets in children

these 29 elements. (Pettifor and Prentice, 2011) so we cannot assume that if these

Several elements portray lesions that may be non-speciﬁc indi- three skeletal elements were affected by rickets, that the etiology is

cators of chronic infections or trauma (as a secondary inﬂammatory dietary. Therefore, other diagnoses must be explored for the rest of

response) due to the presence of periosteal reaction. Weston (2008) the pathologies that may also include the bowing changes apparent

notes that disease progression rather than disease type is the on these bones.

most important determinant of overall lesion appearance. How- Multiple myeloma (MM): At Nagabaka, again cranial frag-

ever, from the descriptions of at three tibiae (tibiae 2, 9 and 10), ment 3 and the lone rib display lytic lesions that penetrate into

relatively slight lesion severity is simply insufﬁcient to make a more marrow or through to the endocranium, in contrast to other

conﬁdent diagnosis for these particular elements. bones with pathological lesions that consist of cortical expansion,

Trauma: Some elements display cortex expansion from cavitation and periosteal reaction, which are not characteris-

osteoblastic activity during healing. Cranium 1 displays likely tic of MM. Furthermore, as Japan is well-known for its long

periosteal remodeling, as the lesion occurs near healed cranial life expectancy, inhabitants of Miyako-jima likely lived past 50

trauma on the left region of the frontal. Moreover, periosteal years, judging from the edentulous mandibles and crania with

remodeling visible on the nasal ﬂoor and left maxilla along the completely obliterated sutures, so that MM presence may be

rim of the nasal aperture on the same cranium appears to be the possible. However, the multiple lytic lesions on both, cranial frag-

result of periapical dental disease and will not be considered fur- ment 3 and the lone rib do not have the round, “punched out”

ther. Femur 1 displays an abnormally short neck surrounded by an appearance of cases of MM. Instead, cranial fragment 3 (simi-

area of woven bone. We thus determine that the periosteal reaction larly to cranial fragment 1) displays reactive bone around the

on this element is likely the aftermath of a femoral neck fracture. lesion edges, which are not round, and the lesions evident on

Lastly, femur 8 displays thickened cortex extending from the prox- the lone rib do not penetrate the endocranium. Unfortunately,

imal metaphysis down to the midshaft. This feature resembles a as the rib is incomplete, not all lesions can be clearly evalu-

callus as the result of a traumatic fracture, although the cortex ated.

appears continuous and the femoral neck angle is unaffected. We Osteolytic metastatic carcinoma (LMC): At Nagabaka, cranial

posit the fracture may have occurred in very early childhood and fragment 3 and the lone rib display lytic lesions that do not occur

remodeled by the time of death. As the skeletal element belonged to in high density within the affected skeletal element and are not

a child of 5–6 years, according to the maximum femur length tables round. However, Ortner (2003, Chapter 20) notes that reactive bone

of Fazekas and Kósa (1978 in Scheuer and Black, 2000, Chapter 11), formation in a differential diagnosis helps to discount lesions orig-

this fracture likely occurred much earlier in life. inating from a craniopharyngeal carcinoma (a type of LMC) as the

Fluorosis: Although abnormal bone deposition can be discerned possible cause. Instead, he suggests that the lesion patterning seen

on several bones at Nagabaka, and tibia 13 and radius 1 are curved, in cranial fragment 3 may be more akin to leprosy, lupus vulgaris

CT scans from some elements do not show evidence of osteoscle- or tertiary treponemal disease than metastatic cancer. Lastly, since

rotic or osteoporotic bone, leading us to conclude that groundwater no affected nasal regions were discerned, we decided not to include

in Miyako-jima has not been naturally high in ﬂuoride in the lupus vulgaris in the differential diagnosis.

past and thus, skeletons at Nagabaka are likely not suffering from Hypertrophic Osteoarthropathy (Marie-Bamberger Syndrome):

endemic skeletal ﬂuorosis. At Nagabaka, several lower limb elements showed periosteal reac-

Scurvy: Miyako-jima’s relative proximity to the mainland and tion along their cortex, and if the lesions on the incomplete lone rib

historic records of active trading would mean that fresh produce, as could be shown to be the result of a LMC, then certainly these limbs

well as ﬁsh should have maintained the population’s vitamin C lev- could be affected by hypertrophic osteoarthropathy. However, it

els relatively stable. At Nagabaka, there are several adult limb bones should be noted that none of the affected long bones display the

with periosteal new bone formation, and some, such as femur 1, classic dense, uneven periosteal reaction and most reactive bone

additionally display trauma near the new bone. Also, the presence occurred proximally or near the midshaft, which argues against

of several edentulous mandibles may correspond to ante-mortem hypertrophic osteoarthropathy, as the reaction should proceed

tooth loss as a result of adult scurvy. However, as previously stated, proximally along the shaft. Lastly, it should also be mentioned that

the island’s location and history of contact with the mainland, as although substantial commingling occurred at Nagabaka, none of

well as the ambiguity of evidence for adult scurvy means that we the elements displaying periosteal reaction showed similar reac-

do not believe that the population suffered from vitamin C deﬁ- tion patterning on left and right sides.

ciency. Lastly, since only single-rooted teeth are generally affected Eosinophilic granuloma (Langerhans cell histiocytosis): Cranial

by scurvy and the mandible were missing all teeth, we believe fragment 3 (frontal) and the rib display small more than one lytic

this may be the result of a carbohydrate-rich diet compounded by lesion and they may belong to individuals under 20 years of age,

advanced age. increasing the chances of a diagnosis of eosinophilic granuloma.

Rickets: At Nagabaka, both the lone adult radius and tibia 13 However, the lesion margins show reactive bone, especially on the

display substantial angulation of the shaft, with the radius display- frontal bone, and the rib is not sufﬁciently complete to determine

ing the deformity distally and the tibia displaying it proximally. lesion appearance or age of the individual, also casting doubt on

In addition, subadult femur 8 displays metaphyseal ﬂaring at both a positive diagnosis of this condition. Lastly, every other bone dis-

the proximal and distal ends, along with evidence of a healed frac- playing lytic lesions also shows reactive bone formation, indicating

ture that occurred in very early childhood, suggesting that rickets that eosinophilic granuloma was likely not present.

22 M. Hernandez, M.J. Hudson / International Journal of Paleopathology 10 (2015) 16–25

Fig. 10. CT scans of affected bones elements displaying focal destruction and cavitation. (A) Femur 2, 3D anterior view, with sagittal and coronal slices of lesions. (B) Femur

6, 3D anterior view, with sagittal and coronal slices of lesions. (C) Cranial fragment 2, 3D outer vault, with a coronal slice of the lesions.

Melorheostosis (Leri’s disease): At Nagabaka, femurs 3 and 6 of the lower Yangtze region. The “boils of Guangdong”, as the dis-

display irregular bone deposition on the cortical surface. However, ease was called, was likely spread due to trade with Portuguese

their appearance suggests that lytic processes were involved unlike ships beginning in the early 16th century (Leung, 1993, Chapter

in melorheostosis, and images from CT scans do not show abnormal 7.2). Documentary evidence of the ﬁrst Japanese outbreak of vene-

cortical thickening. real syphilis dates to 1512–13, only a decade after the disease was

Osteitis deformans (Paget’s Disease): At Nagabaka, several ele- ﬁrst reported in China (Fujikawa, 1902; Dohi, 1902, both in Suzuki,

ments display lytic lesions or a mixture of lytic and sclerotic lesions, 1984). Known at the time as the Tau-mo (Chinese eruption) or the

which can suggest different stages of Paget’s disease. However, CT Ryukyu-mo (Ryukuan eruption), due to the regions where it was

scans do not display abnormal thickening of the bone cortex, espe- ﬁrst noticed, the epidemic began in western Japan and spread to

cially on the frontal. Furthermore, assuming that the geographic the northeast within a year.

distribution of Paget’s disease has remained constant from the 17th Miyako-jima is part of the Ryukyu Islands, where those early

century to the present, the rarity of this condition in Asia also makes outbreaks occurred nearly a century before the Nagabaka rock shel-

it unlikely that individuals deposited at the Nagabaka site would ter would have come into use, thus it is a good starting point to

have been affected. look for evidence of syphilis in the region. From the 23 skeletal ele-

Leprosy: Affected remains at Nagabaka include parts of the cra- ments suspected to have systemic infection, 11 of them, seven left

nium, the upper limb and several femora, which are areas normally and three right, are tibiae. In syphilis, the tibia is often 10 times

spared by leprosy. Furthermore, the bone addition and cavitation as likely to display syphilitic lesions (Ortner, 2003, Chapter 11).

seen in many of the skeletal elements at the site are not consistent This is due to its proximity to the skin and hence, the higher like-

with this disease. Lastly, from the 179 crania or the few hand and lihood of being transferred to osseous tissue. However, the tibia

foot bones located in the shelter’s three sections, none displayed is also the most affected bone in yaws, so this does not say much

characteristic destructive or resorptive lesions noted in diagnostic about which treponemal infection may have affected inhabitants

cases of leprosy. of Miyako-jima. From the 179 crania surveyed in 2012, there were

Tuberculosis: At Nagabaka, although articular surfaces are gen- only two cranial fragments that displayed vault changes resem-

erally missing from several of the commingled remains found on bling caries sicca. Since the cranial vault is the main location on

the surface, none displayed resorptive lesions consistent with this the body where late-stage syphilitic disease most commonly dis-

disease. A thorough inspection of the most common location of plays characteristic lesions after the tibia (Ortner, 2003, Chapter

skeletal lesions such as the vertebral column, hip and knee, as well 11), this low prevalence at Nagabaka suggests that a treponeme

as less common areas such as the shoulders, elbows, hands and other than syphilis may be responsible for the osseous changes

feet (Steinbock, 1976, Chapter 5) failed to yield any evidence for noted.

characteristic tuberculosis lesions. Yaws: One fundamental difference between syphilis and yaws

Osteomyelitis: None of the affected remains at Nagabaka display is the timing of ﬁrst exposure, as the former is primarily transmit-

a sequestrum or involucrum, and those with abnormal, expanded ted by sexual contact and the latter can be acquired earlier in life,

cortical bone lack the hypervascularized surface or medium to large via an open lesion (Aufderheide and Rodríguez Martín, 1998, Part

cloacal opening seen in bones affected with osteomyelitis. 7). Whilst assessing lesion morphology in the affected elements, we

Treponemal disease: From the four manifestations of trepone- noted distinctive nodes in four adult femora, as well as the pattern-

mal infection, we evaluated Nagabaka remains for bejel, syphilis, ing of periosteal expansion in two femora and four tibiae, which we

and yaws, as pinta does not leave behind osteological evidence. A had previously conﬁrmed via an analysis of CT scans. Additionally,

diagnosis of bejel was also quickly discarded due to the warm and there was also slight anterior bowing present in three to four tibiae

humid climate of Miyako-jima, which is incompatible for infection. (see Fig. 8). From the descriptions found in diagnostic textbooks, we

Therefore, only the last two treponemes are evaluated at length consider these changes not to be true bowing but rather, “pseudo-

below. bowing,” more characteristic of later teen age/adult treponemal

Syphilis: In East Asia, venereal syphilis is ﬁrst mentioned in a infection. However, a radius and a tibia were severely bowed, the

1502 Ming Dynasty medical work as being present in the people latter implying that the affected person had a distinctive waddling

M. Hernandez, M.J. Hudson / International Journal of Paleopathology 10 (2015) 16–25 23

appropriate contextual information to our tentative diagnosis of

the affected skeletal elements in Miyako-jima. Also, we brieﬂy dis-

cuss how shared cultural practices in the region may contribute to

the prevalence of disease in these populations.

5. Discussion

Harper et al. (2008a) examined 26 Treponema spp. genetic strains

from around the world to track the evolution and spread of this

spirochete. They note a single Old World TPE 1 (yaws) strain to be

present throughout the region of Southeast Asia, North Oceania and

the Western Paciﬁc Islands, as far north as Taiwan and Mainland

China in the region of Fujian province, echoing the global distribu-

tion of treponemes proposed by Hackett (1976, Fig. A). The authors

concur with Cockburn’s (1967) hypothesis that yaws is an “heir-

loom disease” in humans, which has co-evolved with our ancestors,

and is not a recent split from the spirochetes that cause bejel and

syphilis.

Table 2 provides a general overview of osteological studies that

have identiﬁed treponemal disease in Southeast Asia and Ocea-

nia, as this is the region where yaws infection is endemic. Starting

in Fujian province, the northern margin of geographical distribu-

tion, Zhang (1994) notes a possible case in an adult female skull

dating to the Song Dynasty (AD 960–1279). The author describes

a lesion extending from the glabella to the frontal bone and dis-

playing extensive irregular traces of gummatous destruction and

typical “worm-eaten” appearance. A tibia associated to this same

individual exhibits extensive porous gummatous periosteal reac-

Fig. 11. Diagrams displaying patterns of skeletal involvement in venereal syphilis tion throughout the surface of the shaft. However, no images are

versus yaws infections. Areas affected more often are shaded black, and areas

provided for the specimens. In the Philippines, Borobia Melendo

affected less often are shaded gray – after Steinbock (1976, Chapter 4).

and Mora Postigo (1995) report an adult female cranium from

Samar Cave with lesions characteristic of treponemal disease on

gait, perhaps due to secondary lesions on the foot soles occurring the frontal, left parietal and malar bones, but they unfortunately

during childhood – a condition called crab yaws (Steinbock, 1976). do no provide radiocarbon dates.

Moreover, the most severely affected elements were often Several osteological studies have identiﬁed yaws at sites across

part of the lower limb, principally the tibia, although several Micronesia in the Western Paciﬁc, an area settled by Chamorro

femora (which seldom develop syphilitic lesions) also displayed indigenous groups as early as 4000 years ago. The Chamorro share

advanced stages of infection. This would differ from the pattern the Austronesian language that originally migrated from Taiwan,

of venereal syphilis, where the face and cranial vault are the most south to the Philippines and east to cover the Paciﬁc (Gray et al.,

often-affected elements (see Fig. 11 for comparisons of lesion distri- 2009). In the Mariana Islands, Stewart and Spoehr (1952, 1967)

bution for both treponemes). The distal humerus displaying rugose have identiﬁed yaws-like infections at Chamorro sites on the island

changes to the cortical surface seems to exhibit reactive bone of Tinian, dating to as early as AD 700. Similar ﬁnds have also

remodeling, which does not occur in syphilis, and has been used been made in Guam at the sites of Hyatt Hotel, Sandcastle Club,

to contrast the infection from yaws (Ortner, 1992). Gognga-Gun Beach, and Camp Watkins (Rothschild and Heathcote,

No evidence for treponemal disease, including congenital 1993; Stodder, 1997; Stodder et al., 1991a,b, 1992; Trembly, 1996),

syphilis, was found in sub-adult dental remains at the site. From at Apurguan (Douglas et al., 1997; Pietrusewsky et al., 1997), and

the 23 elements we identiﬁed as being affected by an infectious the Hornbostel and Thomson collections (Suzuki, 1986). From dat-

pathogen, 20 had fused, fully obliterated epiphyses, which signi- ing of the earliest cases, Trembly (1996) posits that yaws has

ﬁes that either, (1) the infection was contracted mainly during late prevalent in the region from as early as the 9th century AD. It

teens through adulthood (which traditionally occurs in syphilis), is noteworthy to mention that the Chamorro at Tinian practiced

or (2) the disease was contracted during childhood but was not secondary burials, just like the population responsible for the skele-

fatal and allowed for survival into adulthood. Non-venereal infec- tal remains at Nagabaka. While speculative, this shared cultural

tions could, in theory, proceed slowly and reach secondary stage in practice may have contributed to the prevalence of treponemal dis-

late teen age or adulthood, depending on the severity of the initial ease if haematophagous ﬂies frequented bone depositories such as

infection, or vice versa – allowing for lesions to heal in those indi- the rock shelter at Nagabaka or places utilized by the Chamorro,

viduals who survived into adulthood. Therefore, the second option facilitating the spread of the pathogen.

is more likely to explain why most of the bones displaying lesions Although syphilis was present in Southeast Asia after the 16th

came from adults and why very little direct evidence of sub-adult century (as its early Japanese name, the Ryukuan eruption, would

infection was found. These observations, along with the presence of suggest), Suzuki (1984) researched six cranial series from different

an affected sub-adult femur merit a provisional diagnosis of yaws sites in Japan during the Edo period, and noted a paucity of his-

for the skeletal elements at Nagabaka with discernable, systemic torical or medical evidence of non-venereal treponemal disease,

lesion patterning. likely because it would have been limited to the less developed

In the following section, we synthesize evidence of treponemal areas of the southern Ryukyus, which experience a warmer climate.

disease from Southeast Asia and Oceania to assess the geographi- Thus, he considered it unnecessary for endemic treponemes to be

cal and historical spread of this infectious disease to provide more included into differential diagnoses of paleopathological cases from

24 M. Hernandez, M.J. Hudson / International Journal of Paleopathology 10 (2015) 16–25

Table 2

Literature review of osteological evidence for treponemal disease in Southeast Asia and Oceania.

Region Date Probable treponeme Source

Tinian, Northern Marianas c. AD 700–1200 Yaws Stewart and Spoehr (1952, 1967)

Guam, Southern Marianas (US) c. AD 700–1500 Yaws Stodder (1997), Trembly (1996)

Guam, Southern Marianas (US) c. AD 800–1668 Yaws Suzuki (1986)

Guam, Southern Marianas (US) c. AD 815–1500 Yaws Stodder et al. (1991a,b, 1992)

Guam, Southern Marianas (US) AD 880–1660 Yaws Rothschild and Heathcote (1993)

Wanfugong, Fujian, China AD 960–1279 Yaws Zhang (1994)

Guam, Southern Marianas (US) AD 1046–1663 Yaws Douglas et al. (1997), Pietrusewsky et al. (1997)

Sarawak, Malaysia AD 1368–1644 Yaws?/Syphilis? Brothwell (1976)

Honshu Island, Japan AD 1603–1868 Syphilis Suzuki (1984)

Ishigaki, Ryukyus, Japan AD 1603–1868 Yaws?/Syphilis? Zukeran et al. (2002)

Queensland, Australia AD 1660–1820 Bejel Domett et al. (2006)

Samar, Philippines N/A Yaws?/Syphilis? Borobia Melendo and Mora Postigo (1995)

the region. However, it should be noted that all six sites were situ- led in this warm and humid climate, likely allowed for yaws bacte-

ated near Tokyo on the island of Honshu, located 1840 km northeast ria to remain prevalent in the population for a long time. This in

of Miyako-jima and experiencing much cooler winters. As Miyako- turn resulted in the wide array of affected bone elements at the site

jima itself is near the northernmost range of the distribution map where infective processes were evident. The geographical location

of endemic treponemal disease presented by Harper et al. (2008a), and historical record of the Ryukyus in general make Miyako-jima

it is unlikely that any cases would have been present on Hon- an important place for researching the themes of population migra-

shu. However, further south in the Ryukyu Islands, Zukeran et al. tion and contact, along with the spread of infectious disease. We

(2002) describe two adult female tibiae with osteomyelitis and vis- encourage future demographic, osteological, and paleoparasitolog-

ible cloaca at the Kabira site of northwest Ishigaki Island. Dating to ical studies of archaeological populations throughout the greater

the same time period and located approximately halfway between region of East and Southeast Asia as it is a promising way to eluci-

Miyako-jima Island and Taiwan, this is the closest site to Nagabaka date the origin, and track the dynamics by which tropical diseases

for which there could be evidence for non-venereal treponemal likely spread.

disease.

In Oceania, on the island of Borneo, Brothwell (1976) describes

Acknowledgements

a burial cave at Lobang Kudih, Sarawak from the 15–16th century

based on associated Ming period ceramics. The author suggests that

The authors would like to express their gratitude to Hajime

the infection is most likely yaws, which may be present due to trade

Ishida of the University of the Ryukyus and Ogasawara Kunishige

from China. However, the cranial evidence for osteitis/caries sicca

from the Haneji Dental and Oral Surgery Hospital in Hirara, Miyako-

may suggest syphilis (which would ﬁt with the spread of syphilis

jima, for facilitating access to relevant literature and providing us

to Japan due to trade with China during the same period). Hackett’s

with CT scans free of charge, and lastly to Prof. Mary Lucas Powell,

(1936) monograph on boomerang leg of Australian Aborigines is

Dr. Piers Mitchell, Samantha Cox, Rodrigo Retamal Yermani, and

one of the earliest manuscripts describing the tissue changes in

one anonymous reviewer who all provided useful comments on

individuals infected by yaws. It indicates that the disease was

earlier drafts of this manuscript that greatly improved its clarity

prevalent in indigenous populations within Oceania, which is in

and quality.

close proximity to the rest of Southeast Asia; allowing for seafaring

populations to come into contact with the aborigines at one point or

another. Lastly, Domett et al. (2006) describe a middle-aged Aborig- Appendix A. Supplementary data

inal female skeleton from inland northwest Queensland, Australia

displaying saber-shin tibia with radiographically thickened cortex Supplementary data associated with this article can be found, in

and periosteal lesions also present on the ﬁbula. Due to the burial the online version, at doi:10.1016/j.ijpp.2015.04.001

being dated to just before European contact, the authors dismiss a

diagnosis for venereal syphilis, and settle on treponarid (bejel) due

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Paciﬁc. Anthropol. Sci. 107 (4), 255–281. Japan. Anthropol. Sci. 110, 421–436. Bone%% Skeletal% Lesion% Type%of%periosteal% Periosteal%lesion%severity% Periosteal%new%bone% Periosteal% Likely% Section% Disease%staging1 number element number/%size reaction/caries%sicca%series1 stage2 production3 vascularization3 systemic? Cranium% 1 N medium focal,destruction n/a isolated,,elevated,plaque multiple(small(striae N/A (complete) Cranium%2% extensive,serpiginous,cavitation, isolated,,elevated,plaque, multiple,large, 2 S large n/a tertiary,,active? + (occipital)% with,focal,destruction covering,1/3,to,2/3,of,area foramina Cranium%3% focal,cavitation,with,jagged, multiple,small, 3 S 4+,small n/a normal tertiary,,active + (frontal%frag.) edges,D,perforating,lesions, foramina moderate,expansion,,rugose, uniform,elevation,of,2/3,of, mixed,,abnormal, 4 Humerus%(R) N large Stage,6,D,swelling,and,scaling, tertiary,,active + nodes the,vascular,surface vascularization moderate,changes,D,rugose, uniform,elevation,of,2/3,of, 5 Ulna%(R) N large Stage,4,D,moderate,swelling multiple,small,striae secondary,,active? + expansion,,coarse,striation the,vascular,surface

6 Radius%(L) S n/a bowing Stage,2,D,longitudinal,striations normal multiple,small,striae primary/secondary?

focal,destruction,D,nodes,with, multiple,small, 7 Rib%(R) S 3,small Stage,1,D,normal normal tertiary,,active? + superficial,cavitation foramina isolated,,elevated,plaque, mixed,,abnormal, 8 Femur%1%(L) N large fine,striation Stage,2,D,longitudinal,striations N/A covering,1/3,of,the,area vascularization focal,destruction,–,metaphyseal, Stage,8,D,heavy,pitting,in,two, uniform,elevation,over,2/3, multiple,large, 9 Femur%2%(L) S large tertiary,,active + expansion,,superficial,cavitation quarters of,,the,vascular,surface foramina uniform,elevation,over,2/3, focal,destruction,–,metaphyseal, Stage,7,D,heavy,pitting,in,at, mixed,,abnormal, 10 Femur%3%(L) S large of,area,with,moderate, tertiary,,active? + expansion,and,cavitation least,one,zone vascularization increase,in,diameter moderate,changes,D,rugose, Stage,6,D,two,continuous, uniform,elevation,of,2/3,of, mixed,,abnormal, 11 Femur%4%(L)* N large secondary,,active + expansions quarters,exhibit,swelling the,vascular,surface vascularization moderate,changes,D,rugose, Stage,6,D,two,continuous, uniform,elevation,of,2/3,of, mixed,,abnormal, 12 Femur%5%(R)* N large secondary,,active + expansions quarters,exhibit,swelling the,vascular,surface vascularization uniform,elevation,of,2/3,of, focal,destruction,D,nodes,with, Stage,9,D,heavy,pitting,over,the, mixed,,abnormal, 13 Femur%6%(R) S large the,area,with,moderate, tertiary,,active + superficial,cavitation entire,cortical,area vascularization increase,in,diameter moderate,changes,D,rugose, Stage,6,D,three,nonDcontinuous, uniform,elevation,of,2/3,of, mixed,,abnormal, 14 Femur%7%(R) S large secondary,,latent? + expansions quarters,exhibit,swelling the,vascular,surface vascularization moderate,changes,D,rugose, Stage,3,D,one,to,two,quarters, uniform,elevation,of,2/3,of, mixed,,abnormal, 15 Femur%8%(L) S large secondary,,active? expansion with,swelling the,vascular,surface vascularization rugose,changes,D,expansion,, Stage,3,D,one,to,two,,quarters, isolated,,elevated,plaque,on, 16 Tibia%1%(L) N large multiple,large,striae secondary,,latent + coarse,striae,and,pitting with,mild,pitting one,third,of,vascular,surface Stage,2,D,longitudinal,striations, 17 Tibia%2%(L) N medium fine,striation normal multiple,small,striae N/A in,three,quarters fine,striation,,nodes,,pseudoD Stage,6,D,three,quarters,exhibit, uniform,elevation,of,two, 18 Tibia%3%(L) N large multiple,large,striae secondary,,latent + bowing swelling thirds,of,the,vascular,surface Stage,5,D,one,local,large, isolated,,elevated,plaque,on, 19 Tibia%4%(L) N large nodes/expansion,with,plaques multiple,large,striae secondary,,latent + swelling,with,moderate,pitting one,to,two,thirds,of,the,area Stage,3,D,two,to,three,quarters, isolated,,elevated,plaque,on, 20 Tibia%5%(L) N large coarse,striation,,pseudoDbowing multiple,large,striae primary/secondary? + with,mild,pitting,and,swelling one,third,of,the,area Stage,6,D,three,nonDcontinuous, uniform,elevation,of,two, mixed,,abnormal, 21 Tibia%6%(L) N large moderate,periosteal,reaction secondary,,active + quarters,exhibit,swelling thirds,of,the,vascular,surface vascularization nodes/expansion,with,plaque,, Stage,5,D,one,local,large, isolated,,elevated,plaque,on, mixed,,abnormal, 22 Tibia%7%(L) S large secondary,,latent + pseudoDbowing swelling,with,moderate,pitting one,to,two,thirds,of,the,area vascularization gross,changes,D,rugose, Stage,7,D,heavy,pitting,in,at, uniform,elevation,of,more, mixed,,abnormal, 23 Tibia%8%(R) N large tertiary,,latent + nodes/expansion least,two,continuous,quarters than,two,thirds,of,the,area vascularization Stage,2,D,longitudinal,striations, 24 Tibia%9%(R) N medium fine,striation normal multiple,small,striae primary/secondary? in,two,continuous,quarters Stage,2,D,fine,,longitudinal, 25 Tibia%10%(R) N medium normal,bone,with,fine,striation normal multiple,small,striae N/A striations coarse,striation,, Stage,6,D,Three,quarters,exhibit, uniform,elevation,of,two, 26 Tibia%11%(R) S large multiple,large,striae secondary,,latent + nodes/expansion swelling thirds,of,the,vascular,surface Stage,2,D,Longitudinal,striations, 27 Tibia%12%(R) N large fine,striation normal multiple,small,striae primary/secondary? + in,three,quarters Stage,2,D,longitudinal,striations, 28 Tibia%13%(L) S large bowing,,fine,striation normal multiple,small,striae primary/secondary? in,two,continuous,quarters gross,changes,D,rugose, Stage,6,D,one,zone,exhibits, uniform,elevation,of,two, mixed,,abnormal, 29 Fibula S large tertiary,,active + nodes/expansion swelling,and,scaling, thirds,of,the,vascular,surface vascularization Additional supplementary material for the differential diagnosis

Pseudopathology

Soil pressure can warp bones and erode the cortex, resulting in misdiagnoses of metabolic conditions, or infectious processes (Buikstra and Ubelaker, 1994 Chapter 9). Wet sub-tropical environment are especially detrimental to taphonomic changes and open-air ossuaries are prone to animal activity that results in missing small bones and broken epiphyses.

Metabolic disease

Endemic skeletal fluorosis

A chronic condition resulting from unusually high fluoride content in the drinking water of a particular region (Krishnamachari, 1986). Normally added to water in countries such as the United States to increase caries protection on human dental enamel, high concentrations of this element can affect the structure and appearance of bones and teeth as it substitutes the hydroxyl ion in the hydroxyapatite crystals of mineralized tissues to form fluoroapatite, a more stable structure whilst also promoting osteoblast activity

(Resnick, 1995b in Ortner, 2003 Chapter 15). As fluoride is a cumulative toxin, the clinical course of the disease depends on the amount of fluoride ingested, and long-standing cases of feature bone deposition in any cortical surface, most commonly at the insertion sites of tendons and ligaments, resulting in a combination of exostosis formation and osteosclerosis (Krishnamachari, 1986). Furthermore, bone made up of high proportions of fluoroapatite is mechanically inferior, so fractures can be a common problem, as well as osteomalacia and osteoporosis (Ortner, 2003 Chapter 15).

Scurvy

A metabolic disease caused by prolonged vitamin C (ascorbic acid) deficiency in both children and adults.

With the exception of humans, other primates, guinea pigs and the fruit-eating bat, all other mammals are able to synthesize their own vitamin C. Therefore, it must be obtained from dietary sources such as fresh fruits and vegetables, as well as milk, meat and fish (Fain, 2005; Brickley and Ives, 2008 Chapter 4). Vitamin C is closely linked to blood formation, as well as the metabolism of iron and folate. Particularly important for growth and development, vitamin C also maintains the formation of collagen, which is the main protein making up our connective tissues (Jaffe, 1972 in Brickley and Ives, 2008 Chapter 4). Vitamin

C is water-soluble and does not remain in the body for long, so it is critical to constantly replenish it.

Symptoms of scurvy can become evident between 29-90 days after vitamin C is removed from the diet.

Defective collagen synthesis leads to weakened vessel walls, hemorrhaging and delayed would healing causing anemia, petechiae, purpura and reduced bone deposition (Fain, 2005). Cases of scurvy in very young infants, both in contemporary and archaeological populations are rare, due to vitamin C provisioning from mothers during pregnancy. Children and adolescents with scurvy display characteristic bone remodeling near growth centers and reduced osteoblastic activity, resulting in arrested deposition of osteoid at the epiphyses. Comparatively, adults will experience a mixture of bone changes such as fractures, osteopenia, and in severe cases, tooth loss - none of which are sufficiently characteristic for identifying the condition (Brickley and Ives, 2006; Pimentel, 2003 in Brickley and Ives, 2008 Chapter 4).

In general, rates of scurvy do not significantly increase in warmer latitudes (although see Klaus, 2014) until the ‘Age of Discovery’ when sailors who spent extended periods at sea did not have enough fresh food available to obtain adequate amounts of vitamin C in their diet. From their study on skeletal remains of

Lapita peoples in Vanuatu, Buckley et al. (2014) also note that similar processes occurred during the initial human colonization of isolated island chains across the Pacific Ocean.

Rickets

Caused by a prolonged lack of vitamin D, which plays a substantial role in many physiological processes including immune reaction, metabolism of minerals, cell growth and cardiovascular health (Brickley and

Ives, 2008 Chapter 5). For the body to synthesize vitamin D, it needs to be exposed to ultraviolet radiation, which naturally comes from sunlight. Humans can also obtain vitamin D from dietary sources such as eggs, fortified milk, liver, and oily fish. Vitamin D is crucial for skeletal development and health, as it regulates renal absorption and excretion of calcium and phosphorus, allowing for adequate levels to remain in the blood serum for normal ossification of the growth plate and mineralization of the osteoid on trabecular and cortical bone (Pettifor and Prentice, 2011). The growth plates of children lacking minimum amounts of vitamin D for extended periods continue to promote cartilage development that leads to disordered cartilage to form. The poor cartilage arrangement is exacerbated by mechanical forces due to normal locomotion and body weight that further spreads the cartilage into wider, horizontal orientations than expected with normal progressive growth (Brickley and Ives, 2008 Chapter 5). When bone mineralization eventually occurs following small acquisition of vitamin D or complete recovery, the bone can only form on top of the existing affected cartilage template. Therefore, children and juveniles affected by rickets most frequently display widespread bending deformities of the skeleton affecting growth centers (Bullough, 2010 Chapter

8). Bone deformation in rickets is dependent on the stage of development at which the individual was affected. For example, crawling motions earlier in life would result in softening and eventual bending of forearm bones, whereas older children can experience similar processes, and even fractures of the ribs or lower limbs as a result of weight bearing stresses. In paleopathological methodology, the term rickets is used to refer to vitamin D deficiency in childhood and residual evidence of the healed childhood condition detected on adult bones, whereas osteomalacia refers to vitamin D deficiency that began/occurred during adulthood (Brickley and Ives, 2008 Chapter 5).

Neoplastic disease

Multiple Myeloma (MM)

A hematological bone malignancy associated with the development of osteolytic bone disease (Fowler et al,

2011). Is the most common tumor type found on skeletal tissue, affecting individuals over 50 years of age.

It occasionally appears in younger individuals, with males suffering from the condition approximately twice as often as women (Bullough, 2010 Chapter 20). As it prefers marrow-containing bones, it almost always involves the vertebral column, although primary sites can include the skull, ribs, sternum or pelvis.

Although MM is associated with an increase in osteoclastic resorption and suppression of osteoblastic activity, other cell types within the bone marrow can also contribute to its development (Fowler et al,

2011). MM lesions appear as characteristic round, sharply-defined lytic defects on the bone table ranging from 5 mm to 2 cm in diameters that can often be detected by an imaging study (Aufderheide and Rodríguez-Martín, 1998 Part 11). Sclerotic changes are seen very rarely. At times, when the lytic lesion is not apparent on radiographs, a differential diagnosis from osteoporosis must be made by further laboratory analysis. As the lytic lesions eventually break down the structural integrity of marrow-containing bones, pathologic fractures lead to overall loss of vertebral body height, with swelling of adjacent intervertebral discs into the affected bodies in over 50% of sufferers (Bullough, 2010 Chapter 20). This condition is often aggressive and would have led to an early death in the past.

Osteolytic metastatic carcinoma (LMC)

A malignant non-matrix producing neoplasm that occurs more commonly than primary bone tumors. Most tumors that metastasize are carcinomas, although rarely, sarcomas have also been known to spread from the site of origin (Ortner, 2003 Chapter 20). Most metastatic bone lesions result from a primary carcinoma that originates on the breast, prostate, lung, kidney, thyroid, or colon (Bullough, 2010 Chapter 20). Although in the majority of cases, metastasis to bone will appear within the medullary cavity, in rare cases, it can also appear on the cortex. For diagnosis, it helps to know that 75% of metastatic tumors are osteolytic, 15% are osteoblastic, and the remaining 10% are a combination of both processes (Greenspan and Remagen, 1998 in Ortner, 2003 Chapter 20). LMC progress by eroding cortical tissue from within the marrow cavity whilst destroying cancellous bone, and in a differential diagnosis of dry bone, can appear indistinguishable from

MM (Ortner, 2003 Chapter 20). However, Strouhal (1991) lists eight general features that can help to differentiate MM from LMC in a possible diagnosis, including that MM lesion density is higher than for

LMC, which presents more localized lesions, MM lesions are round and LMC lesions are irregular, and that

MM lesion size is small to medium and LMC lesions appear in more irregular sizes, among others.

Hypertrophic Osteoarthropathy (Marie-Bamberger Syndrome)

Occurs in association with chronic inflammatory conditions and neoplastic diseases, primarily of the lungs, although other types of cancers can also trigger it (Ortner, 2003 Chapter 13). It involves the formation of symmetric, marked periosteal reaction on the appendicular skeleton, progressing proximally along the shaft

(Bullough, 2010 Chapter 5). The appearance of the periosteal formation is variable, but the classic expression results in a dense, uneven surface. This condition has no known etiology and has been noted to disappear when the causative lesion is extracted from a living patient (Ortner, 2003 Chapter 13).

Eosinophilic granuloma (Langerhans cell histiocytosis)

A reticuloendothelial disorder consisting of histiocytes known as Lagerhans cells that contain abnormal cytoplasmic granules (Bullough, 2010 Chapter 19). The condition is normally present in the first decade of life and 75% of cases occur before 20 years. Males are affected roughly twice as often as females with the most commonly affected region being the skull, after which are flat bones, vertebrae and ribs, with the limb bones seldom involved (Ortner, 2003 Chapter 14). Upon imaging, a single (in about 80% of cases) or multiple well-demarcated lytic lesions lacking sclerotic margins may be discernible on bone. Three clinical disorders grouped under the histiocytoses, due to similar lesions, although each has a different clinical progression, also include Hand-Schuller̈ -Christian disease and Letterer-Siwe disease (Bullough, 2010

Chapter 19).

Melorheostosis (Leri’s disease)

A rare developmental anomaly consisting of sclerosing bone dysplasia with no known etiology (Greenspan and Azouz, 1999). Derived from the Greek words melos for limb and rhein for flow, it features a deposition of irregular, dense cortical bone akin to a dripping candlewax effect that is usually diagnosed via radiograph (Leri and Joanny, 1922; Azouz and Greenspan, 2005). The condition primarily affects the appendicular skeleton and is most commonly discernible on long bones of the upper and lower extremities, usually occurring on only one element (Bansal, 2008).

Osteitis deformans (Paget’s Disease)

Originally described by Paget (1877), osteitis deformans is a chronic condition of unknown etiology that results in gross remodeling of osseous tissue. It occurs commonly in European populations, but is rare in people of African or Asian descent. Males are more often affected than females. It may involve a single, several, or many bones, but never the entire skeleton, and about 90% of cases occur in people over 40 years of age (Ortner, 2003 Chapter 17). Primarily affecting the axial skeleton, the disease process is best characterized as a pathological increase in the rate of remodeling, which reaches 20% above normal, due to larger-than-normal osteoclasts that appear to contain virus-like inclusion bodies (Mundy 1999 in Ortner,

2003 Chapter 17). Juvenile Paget’s disease, known as idiopathic hyperphosphatasia occurs as a metabolic bone dysplasia that is inherited as an autosomal recessive trait. Unrelated in etiology to the classic condition that affects adults, it is characterized by increased osteoclastic activity and bone tissue turnover

(Bae et al, 2008). On the cranium, early Paget’s disease lesions feature single or multiple resorptive areas with wavy margins and a porous surface. As the disease progresses, extreme cortical and trabecular thickening/expansion, as well as a mixture of lytic and sclerotic areas on the vault and other noncontiguous bones become apparent (Ortner, 2003 Chapter 17).

Infectious disease

Leprosy

A slow-progressing, chronic, infectious disease caused by Mycobacterium leprae, which is spread via direct contact, or by inhaling the bacilli in the oral mucosa of an infected person (Ortner, 2003). The disease has high rates of bone involvement and depending on the stage of infection, the skeleton may exhibit 1) osteomyelitis and periostitis, 2) neurotrophic bone and joint lesions, and 3) ordinary osteomyelitis and septic arthritis. Long-term skeletal lesions feature absorptive changes in the phalanges of the upper and lower limb and destruction of facial bones, and the disease has also been occasionally known to affect the tibia and fibula (Ortner, 2003).

Tuberculosis

A chronic infection caused by Mycobacterium tuberculosis, which is closely related to the bacterium responsible for leprosy. The principal mode of transmission is via tubercle bacilli entering the respiratory tract from direct or indirect contact with an infected person, with the infection beginning in the lungs

(Ortner, 2003). In post-primary infection, the bacilli then cross into the bloodstream from the lymphatic system and eventually relocate within the skeleton, particularly in areas with high circulatory and metabolic rate such as epiphyses for children, which are filled with cancellous bone, or joint capsules for adults. In the 3-5% of untreated individuals that develop skeletal lesions of tuberculosis, the spine is the most common site of osteological changes, and the hip and knee, the joints most often affected, with the rest of the bone being generally spared (Roberts and Buikstra, 2008). Resorptive lesions in the spine leading to vertebral collapse and eventual fusion occur in late stages of disseminated disease, so positive diagnosis of infection relies on identification of this characteristic skeletal lesion, affecting 25-50% of individuals affected by skeletal tuberculosis (Ortner, 2003). In children, long bone destructive changes are seen in the metaphyses, with formation of sequestra and periosteal new bone on a thinned cortex. In adults, secondary hypertrophic osteoarthropathy can also develop on the long bones (Roberts and Buikstra, 2008).

Osteomyelitis

An infection which occurs when pathogens, namely pyogenic bacteria, enter the medullary cavity either through traumatic injury, proximity to infected soft tissue or via sepsis, and can lead to a systemic condition. Osteomyelitis presents itself mainly in juveniles in any bone element, but is generally localized to a bone or joint, and may be limited in scope to the periosteum and cortex (Ortner, 2003 Chapter 9).

Acute osteomyelitis occurs when a subperiosteal abscess forms a layer of infectious exudate on the cortex, creating necrotic tissue along the surface and resulting in a sequestrum, which preserves the infection. The infected, raised periosteum continues to create bone as a shell of hypervascularized hard tissue known as the involucrum.

Treponemal disease

A chronic/sub-acute granulomatous infection caused by spirochete bacteria of the genus Treponema

(Aufderheide and Rodríguez-Martín, 1998 Part 7; Warrell, 2010). Of the four clinically recognized treponematoses—yaws, bejel (treponarid), pinta and syphilis—only the last one is transmitted venerally. It is generally agreed that while syphilis has a worldwide occurrence, non-venereal forms of treponemal infection are confined by geographical and climactic boundaries (Arrizabalaga, 1993; Steinbock, 1976,

Chapter 4), although in areas of large ranges of temperature and humidity, a mixed occurrence of diseases is found (Grin, 1961 in Hackett, 1963). Pinta is the only one to not produce bone tissue changes and is thus invisible to osteological assessment.

In paleopathology, diagnostic criteria have been developed to diagnose treponemal disease from patterns seen in dry bone (Hackett, 1976) as well as via histological analysis (Schultz, 2001). Serologically and morphologically, the strains that cause treponemal disease are virtually indistinguishable and as they share common antigens - infection by one species produces varying degrees of cross-immunity to the others in both rabbits and humans (Turner et al., 1947; Hackett, 1963; Baker and Armelagos, 1988; Warrell, 2010).

Furthermore, several authors (Arrizabalaga, 1993; Baker and Armelagos, 1988; Morse 1967, 1978 in

Aufderheide and Rodríguez-Martín, 2000 Part 7) have emphasized the difficulty in diagnosing treponemal disease; with yaws sometimes being confused with venereal syphilis (Koch, 1900 in Brothwell, 1993).

However, thanks to newly developed methods of genetic sequencing for the study of archaeological samples, it may now be possible to tell whether treponemal disease was present, and if so, which subspecies is the infectious agent responsible (Ortner, 2003 Chapter 11). In a recent study, Harper and colleagues (2008b) performed a genetic analysis of the arp gene found in all T. pallidum spirochetes and note repeat motifs that were used for distinguishing venereal from non-venereal strains. Smajs et al. (2012) propose further genetic discrimination approaches based on inter- and intra-group variation of Treponema strains in order to detect the relative virulence of a particular strain, or the ability of a strain to elude the immune system of a host due to its capability for wide genetic variance. Indeed, variation of the Treponema tprK gene via a particular gene conversion mechanism (Centurion-Lara et al, 2004) is what allows successful immune system evasion and the reinfection of a host by the spirochete Palmer et al. (2009).

-Bejel

Also, called endemic syphilis, is restricted to temperate and subtropical arid regions such as Central

Australia, Central and Southwest Asia, as well as North Africa. Caused by T. pallidum ssp. endemicum

(TEN), bejel strikes early in life and affects people living in rural settings with limited hygiene. The infection is highly transmissible and although lesions in early stages are rarely seen, the disease does eventually affect skin and bone tissues in its latter stages and it is principally visible around the mouth, armpits, and inguinal regions of the body where there is sufficient moisture (Hackett, 1963; Steinbock,

1976 Chapter 4).

-Syphilis

This is the only one of the treponemal syndromes that is primarily transmitted through sexual contact, although there are clinical accounts of non-venereal transmission of syphilis through non-sexual contact between infants or children and infected adults (e.g., wet nurses) or vice versa (Powell and Cook, 2005a).

This treponeme is widely considered the most severe of all, as it eventually attacks the central nervous system and cardiovascular system and thus be fatal (Steinbock 1976 Chapter 4; LaFond and Lukehart,

2006). Caused by T. pallidum ssp. pallidum (TPA), syphilis principally affects older teenagers and adults due to its mode of transmission, although the infection may pass from mother to fetus in utero or at birth if the mother’s infection has progressed to the secondary stage, resulting in congenital syphilis (Steinbock,

1976 Chapter 4). As the only treponemal syndrome with such ability, congenital syphilis can lead to spontaneous abortion, stillbirth, death of the neonate, or a myriad of physical deformities and health issues in the infant, depending on their immune response (LaFond and Lukehart, 2006). Late-stage syphilitic infection features the characteristic “caries sicca” lesions appearing on the cranial vault. Caries sicca form via a process consisting of a gumma which results in a large area of destroyed and remodeled bone tissue, most frequently in the parietal or frontal regions of the cranium (Hackett, 1976 Figs. B and C).

Theories regarding the New World origin and spread of venereal syphilis have been contested since the early 20th century starting with Holcomb (1934,1935), but see reviews by Meyer et al. (2002) and the volume by Powell and Cook (2005). However, recent studies utilizing novel methods have been successful in addressing these issues. An assessment of five different Treponema strains by Gray and colleagues

(2006) showed that TPA is older than 500 years, the time of European contact with the New World. Further phylogenetic analyses utilizing paleopathological evidence and evolutionary rate assessments of different

T. pallidum strains by de Melo and colleagues (2010) showed that venereal syphilis had arisen approximately 5,000 years ago, long after the 16,500 yr BP colonization of the Americas. Furthermore, in an extensive and systematic assessment of reports detailing evidence for Pre-Columbian cases of congenital or acquired syphilis in the Old World, Harper and colleagues (2011) discount each one based on one or several factors, including faulty dating methodology, faulty or inconsistent descriptive analysis or the lack of photographic evidence. These data suggest that non-venereal treponemes originally migrated into the

New World where a venereal strain then evolved and was subsequently carried to the Old World after

European contact.

-Yaws

Caused by the spirochete T. pallidum ssp. pertenue (TPE), is the humid tropical and sub-tropical counterpart of bejel, found similarly in rural settings throughout South America, Central Africa, Southeast

Asia, Oceania and the Western Pacific, where the mean temperature is around 26°C and annual rainfall is about 127-190 cm (Hackett, 1963, 1976; Brothwell, 1993; Aufderheide and Rodríguez-Martín, 1998 Part

7). As populations living in these environments often wear only minimal clothing, one of the principal modes of transmission is skin-to-skin contact between infected wounds and open sores. Skin lesions resulting from treponemal infection are highly virulent and have the capacity to spread the spirochetes easily. The haematophagous flies of the genus Hippelates, can also spread the spirochete among people, as they are attracted to exudate from open lesions (Barnard, 1952; Cockburn, 1961; Howe, 1981 in

Aufderheide and Rodríguez-Martín, 1998 Part 7). Unlike syphilis, yaws is most often contracted during childhood, as children often play with one another, increasing the likelihood of minor contact of skin abrasions with infected friends.

Steinbock (1976) states that bone lesions in yaws are more common than in the other treponemal syndromes, beginning in the secondary stage and affecting 5-15% of cases. The extent of bony lesions occurs principally in the lower limbs, namely the tibia – although other limb bones can be affected.

However, unlike syphilitic infections, involvement of the cranial vault in yaws is less common and when present, it is less severe than in the former (Aufderheide and Rodríguez-Martín, 1998 Part 7). It is noteworthy to mention that if a child survives into adulthood, bone lesions from yaws have been known to heal completely without leaving permanent bone changes (Ortner, 2003 Chapter 11).

A skeletal feature often seen in yaws cases is tibial bowing in the anterior direction, a phenomenon that

Hackett (1936) termed “forward convexity.” It is a characteristic sign that the infection was contracted during childhood. This “true” tibial bowing, also known as “boomerang leg”, is similar to what is termed

“saber-shaped” tibia in cases of congenital syphilis (Steinbock, 1976). Its occurrence may be correlated to the dynamics of growth of the tibia, when epiphyseal fusion occurs and how the bacteria affect the weight bearing cortical and trabecular structures (Steinbock, 1976; Buckley and Tayles, 2003). This characteristic should not be confused with “pseudo-bowing,” a result of periosteal reaction occurring on the anterior and medial surface of the tibial mid-shaft, but lacking true distortion in the longitudinal plane (Jaffe, 1972 in

Ortner, 2003). Lastly, Ortner (2003) notes that the radius and the ulna may occasionally bend in a similar way than the tibia, which also denotes sub-adult infection.

Lastly, there is also a fundamental difference between the time the treponemal syndrome is first contracted and when bone lesions begin to appear. Hackett (1951) in his review of cases in Lango, Uganda, notes that

60 percent of persons displaying bone lesions from tertiary yaws were over 15 years of age, and the summary of clinical findings of slight (Table XV) and moderate (Table XIV) “boomerang leg” found in

Hackett (1936) show that more than 50% of the cases in each table were aged between 18 and 60 years.

These observations imply that in the case of treponemal infection, or at the very least, non-venereal syndromes, there is, as Ortner (2003 Table 11-1) explains, a differential expression of the pathogen due to several factors such as the general health of the host, their immune response, population density, age of onset, size of inoculum, etc. This is confirmed by Hackett’s (1936) monograph, where several photos documenting the progression of yaws display children with tertiary infection, as well as adults of different ages with signs of moderate and severe tibial bowing.

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