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Contents lists available at ScienceDirect

International Journal of Paleopathology

journal homepage: www.elsevier.com/locate/ijpp

Technical Note

A proposed framework for the study of paleopathological

cases of subadult scurvy
Robert J. Stark ∗
Department of Anthropology, Chester New Hall Room 524, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L9

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

Article history: Paleopathological investigations of subadult scurvy have seen increasing frequency since the introduction
Received 26 November 2012 of the “Ortner criteria” of porotic cranial and infracranial lesions. With the rise in bioarchaeological
Received in revised form 24 January 2014 investigations of subadult scurvy there have also been concerns about the applicability of these lesions.
Accepted 26 January 2014
In an attempt to further address this ongoing debate this study proposes a framework for looking at the
variable stages in which clinical radiological indicators and macroscopically observable skeletal lesions
Keywords:
would be expected to occur in cases of subadult scurvy. This article introduces a three phase system for
paleopathology
considering the timeframe of subadult scurvy onset and resolution.
subadult scurvy
radiological indicators © 2014 Elsevier Inc. All rights reserved.
macroscopic lesions
lesion phases

1. Introduction populations, as humans and other higher primates have always

Scurvy is a painful dietary disorder caused by an inadequate
(<10 mg) daily intake of ascorbic acid resulting in interruption of
collagen and osteoid formation due to the necessity of ascorbic acid
to complete hydroxylation of proline and lysine (Stone and Meister,
1962; Hodges et al., 1971; Hodges, 1976; Myllylä et al., 1978; cf.
Levine et al., 1999). Scurvy can result in the development of a spe-
cific suite of soft tissue and skeletal lesions, and if left untreated,
death may result (Follis, 1942, 1958; Mimasaka et al., 2000; Ortner,
2003; Algahtani et al., 2010; Dolberg et al., 2010). The ability to
identify scurvy in the past is of great paleopathological interest
in light of the insights it provides on food insecurity, preferential
feeding, subsistence economy, and dietary practices. Such insights
can contribute to broader bioarchaeological interpretations of the
human experience (also see Armelagos et al., this issue).
Scurvy has classically been understood as a dietary disorder
(WHO/FAO, 2004). However, a genetic etiology involving varying
heightened susceptibility to scurvy (hypoascorbemia) based on
haptoglobin polymorphisms (Hp 1–1, 2–1, and 2–2) has been pro-
posed, but remains largely uninvestigated (Stone, 1966; Delanghe
et al., 2007; also see Halcrow et al., this issue). Even with an
underlying genetic predisposition, it remains clear that if sufficient
quantities of ascorbic acid are consumed, scurvy will not develop.
It is also unlikely that the underlying biological susceptibility to
scurvy was different in past populations than with contemporary
∗ Tel.: +1 289 442 4712.
E-mail address: starkrj@mcmaster.ca
lacked the ability to endogenously synthesize ascorbic acid (Stone,
1966), due to a mutation in the gene l-gluono-Y-lactone oxidase,
resulting in the inability to complete the final step in ascorbic acid
synthesis (Nishikimi and Udenfriend, 1976; Margittai et al., 2005).
Given this fact, modern clinical data can directly aid investigations
of suspected cases of scurvy in antiquity.
This paper proposes a framework for aligning clinical radiologi-
cal data and macroscopic skeletal evidence from paleopathological
cases to better identify subadult scurvy in antiquity.
The best practice(s) for uniting modern clinical and paleopatho-
logical data in the identification of adult and subadult scurvy
in antiquity remains a debated topic among paleopathologists
(Melikian and Waldron, 2003; Ortner, 2003; Waldron, 2009). Skele-
tal symptoms of subadult scurvy tend to be comparatively quite
distinct and more visible, as they are rooted in pathological effects
of vitamin C deficiency that inhibit developmental biology and
growth processes (Ortner, 2003). As one ages, the skeletal mani-
festations of scurvy become increasingly ambiguous, especially in
adulthood (Van der Merwe et al., 2010b; cf. De Boer et al., 2013).
2. Macroscopic and clinical radiological evidence of
subadult scurvy
A key to the linkage between clinical and paleopathological
methods of identifying subadult scurvy in antiquity is determin-
ing at which point the two methods overlap and provide common
information to thus employ them in tandem. Before addressing
how these approaches can be reconciled, a brief summary of each
approach is reviewed.

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Please cite this article in press as: Stark, R.J., A proposed framework for the study of paleopathological cases of subadult scurvy. Int. J.
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2.1. Clinical approach
Clinical methods for identifying scurvy rely on patient history,
serum ascorbic acid concentration, and radiology (Shore, 2008;
Besbes et al., 2010). As dietary history and serum ascorbic acid con-
centration cannot be examined in paleopathological contexts, only
clinical radiological indicators remain for identification of subadult
scurvy in dry bone.
Subadult scurvy begins to manifest when the body pool of vita-
min C falls below 300 mg, which will occur approximately 6–10
months after the cessation of sufficient ascorbic acid intake (Jaffe,
1972; Algahtani et al., 2010). With the onset of scurvy, a child char-
acteristically adopts a “frog position,” where by they lie on their
back with the upper and lower limbs semi-flexed and externally
rotated to remove pressure from painful joints (McLaren, 1992).
At this time a suite of soft tissue lesions, not all of which may
necessarily develop in concert, begin to manifest. These include
hemorrhage (subperiosteal, purpura, ecchymosis, and potentially
bleeding gums), ocular protrusion (proptosis), joint rattle (crepi-
tus), and impaired wound healing (Jaffe, 1972; McLaren, 1992;
Myllyharju, 2004).
Musculoskeletal alterations occur in approximately 80% of
reported cases. These symptoms result from interruption of col-
lagen and osteoid synthesis, though chondrification generally
continues unabated (Silverman, 1993; Fain, 2005; Besbes et al.,
2010; Smith et al., 2011) (Table 1). This interruption leads to the
development of a series of specific clinical radiological indicators
located in the metaphyseal and epiphyseal regions of long bones
(Jaffe, 1972; Marcove and Arlen, 1992). Jaffe (1972) observed that
even prior to the presence of soft tissue lesions, clinical radiologi-
cal indicators may be present, attesting to the rapid development
of clinical radiological indicators with the onset of scurvy. In
cases of total and long-term deprivation of vitamin C, skeletal
repair, including the formation of reactive bone with the organi-
zation of subperiosteal hematoma, does not take place until the
re-introduction of sufficient ascorbic acid to allow for renewed
ossification (Murray and Kodicek, 1949; Silverman, 1993). Though
no universal timeframe has been established for the resolution of
scurvy, a general pattern is evident. Following the reintroduction
of sufficient levels of ascorbic acid, hemorrhagic tendency usually
ceases within 24 h. After 48 h, bone matrix production resumes,
leading to the onset of skeletal lesion resolution in 2–3 days, and
restoration of normal trabecular architecture in 20–25 days. Com-
plete recovery and normalization of radiological indicators usually
occurs after 3 months of adequate ascorbic acid intake (Phillips,
1971; Tamura et al., 2000; Algahtani et al., 2010; Valentini et al.,
2011).
The clinical literature does not assess how long periosteal
lesions are retained before they are remodeled into the growing
diaphysis; such lesions, being of little structural or pathologic con-
sequence, are not typically of clinical concern (Phillips, 1971; Jaffe,
1972). The same is true of cranial lesions. While paleopathologists
place significant emphasis on the cranium (i.e., the “Ortner crite-
ria”), clinicians do not rely on cranial radiography to make a firm
diagnosis of scurvy (Silverman, 1993; cf. Sloan et al., 1999). It is
clinical radiological indicators of long bones, then, that hold poten-
tial for aiding in examining proposed paleopathological cases of
subadult scurvy (Table 1).
2.2. Paleopathological approach
The use of a suite of porous macroscopically observable skeletal
lesions remains the key method for identifying possible pale-
opathological cases of subadult scurvy in skeletonized human
remains (Table 2). Initial discussions by Ortner (1984), Ortner and
Ericksen (1997) and Ortner et al. (1999, 2001) further developed
Please cite this article in press as: Stark, R.J., A proposed framework for the study of paleopathological cases of subadult scurvy. Int. J.
Paleopathol. (2014), http://dx.doi.org/10.1016/j.ijpp.2014.01.005
criteria to identify a suite of macroscopically observable lesions
believed to result from scurvy. Scurvy promotes significant and
chronic hemorrhaging due to capillary fragility resulting from a
lack of intercellular cement substance in the endothelial layer
(Silverman, 1993; Myllyharju, 2004; Valentini et al., 2011). Under-
standing of the osseous effects of the body’s inflammatory response
to extravasated blood adjacent to bone can aid in paleopatho-
logical examinations of scurvy. The pores represent proliferation
of new blood vessels through bone to deliver white blood cells,
macrophages, and other cells to sites of hematomas in order to
remove them. Porous skeletal lesions are believed to develop at
points of particularly active musculoskeletal activity as a response
to hemorrhagic bleeding, (i.e., on the greater wing of the sphe-
noid bone from mastication-induced hemorrhage induced by the
muscles of mastication) (Ortner and Ericksen, 1997). This premise
resulted in a suite of lesions, referred to here as the “Ortner
criteria,” believed to be indicative of subadult scurvy (see Ortner,
2003). Additional potential sites of scorbutic lesions in the skeleton
include porous foci of endocranial surfaces (Lewis, 2004; cf. Suman
and Dabi, 1998), the occipital bone (Brickley and Ives, 2006), ribs
(Mahoney-Swales and Nystrom, 2009), and the ilium (Brown and
Ortner, 2011).
Such porous foci of the skull and long bone metaphyses are
a result of increased vascularization in the effected areas as a
response to chronic hemorrhagic bleeding (Ortner, 2003). Skeletal
porosity may originate from disorganized attempts at blood vessel
formation under conditions of insufficiency or absence of ascorbic
acid, and may persist following the resolution of scurvy through
renewed angiogenesis (Stolman et al., 1961; Phillips, 1971; Telang
et al., 2007). It is expected that these lesions will begin to develop
and continue formation throughout the duration of the scorbutic
condition, and will persist after the cessation of scurvy until such
time that they are fully remodeled years later (Parfitt, 2002, 2004;
Ortner, 2003). Alternatively, significant periosteal new bone result-
ing from subperiosteal hemorrhaging (i.e., along the long bone
diaphyses, the ilium, scapula, roof of the orbits), will not begin to
form until ascorbic acid is reintroduced. This allows ossification
and appositional new bone deposition on the periosteal surfaces
of bones in the process of hematoma resolution and organization
into bone (Schmorl, 1901; Murray and Kodicek, 1949; Ortner, 2003;
Ratanachu-Ek et al., 2003; Choi et al., 2007; Besbes et al., 2010). It
remains possible that if an individual has <300 mg bodily ascorbic
acid stores, making them clinically scorbutic but not entirely devoid
of ascorbic acid, that some degree of periosteal new bone may form.
The quality and extent of such bone formation in cases of scurvy is
presently not well understood (also see Kwon et al., 2002).
Hemorrhagic reactions in scurvy may be highly variable both in
location and degree of manifestation (Ortner, 2003; Brickley and
Ives, 2008). Such variability can be accounted for by the fact that
scorbutic hemorrhage is often traumatic in origin (Brickley and
Ives, 2008; Smith et al., 2011; Crandall et al., 2012). The location
of porous lesions associated with scurvy is dictated by variabil-
ity in hemorrhage occurrence, and as such, not all macroscopically
observable skeletal lesions may form in every case of subadult
scurvy. In paleopathology, this has resulted in the necessity of
assessing multiple sites of lesion formation to provide confident
assessments of subadult scurvy, reinforcing the necessity to under-
stand scurvy as a fluid and dynamic pathological condition defined
by a suite of lesions, rather than one solitary pathognomonic
expression.
This macroscopic suite of lesions however, has not gone unchal-
lenged. Melikian and Waldron (2003) present concerns that the
“Ortner suite” exhibit only limited similarity to documented clin-
ical cases of scurvy, particularly for cranial lesions. Melikian and
Waldron (2003) found the porous cranial lesions they observed
from archeological specimens to be incomparable in nature to
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Table 1
Clinical radiological indicators of subadult scurvy, with etiology and possible macroscopic appearance.

Lesiona Radiographic appearance Etiology of lesion Macroscopic appearance

White line of Frankel Radiopaque band along the
metaphyses of the long bones and
sternal rib ends
Trümmerfeld zone Radiolucent band along the shaftward
border of the provisional zone of
calcification in long bones and sternal
rib ends
Ground glass Progression from blurring to
appearance disappearance of trabecular markings
in long bone metaphyses
Wimberger’s ring Central rarefaction with radiopaque
ring around the periphery of the
epiphyses and potentially carpal and
tarsal bones
Cortical thinning Abnormal thinness of long bone
cortices
Corner sign Varying extent of clefting at the
margins of the provisional zone of
calcification in the long bones
Pelkan spurs Spur formation at the marginal borders
of the long bones, typically at an angle
approaching perpendicular to the axis
of the shaft
Subperiosteal Evidence of hematoma, ossification
hemorrhage along the raised periosteum, and
deposition of periosteal new bone
Metaphyseal cupping Cupping/mushrooming of the long
and epiphyseal bone metaphyses with possible
invagination invagination/ball-in-socket
appearance of the epiphyses
a
Material in this table was compiled from Follis (1958), Silverman, (1970), Jaffe (1972), Sprague (1976), Edeiken (1981), Greenfield (1990), Silverman et al. (1993), Tamura
et al. (2000), Fain (2005), Brickley and Ives (2008), Shore (2008), and Kozlowski and Witas (2012).
Interruption of calcified cartilage
resorption
Impaired matrix conversion,
disorganized and decreased trabeculae
Atrophy of the spongiosa combined
with micro-fracturing
Thickened zone of provisional
calcification, similar to white line of
Frankel
Due to impairment of osteoblast
activity
Defects in the spongiosa and
micro-fractures
A result of healing micro-fractures
Subperiosteal hemorrhaging
Epiphyseal separation and possible
premature central union of the
epiphysis with metaphysis; this lesion
is very rare
Unobservable in long bones; ribs may
exhibit cupping/flaring at the sternal
ends
Unobservable in long bones; ribs may
exhibit cupping/flaring at the sternal
ends
Unobservable
Unobservable
Unobservable in whole bone, though
possible in section
Unlikely to preserve in
post-depositional environments due to
delicate nature and minuteness of
clefting
Unlikely to survive post-depositional
alteration due to delicate nature of
Pelakan spurs, though may be possible
to observe in cases of good
preservation
Periosteal new bone remains a key
macroscopic indicator of response to
hemorrhage in scurvy
Potentially possible to observe
metaphyseal cupping, but age
dependant as this deformity has the
potential to remodel to normal over
the growth period

those of porous cranial lesions from known scorbutic individuals
preserved in the Royal College of Surgeons. Cranial porosity docu-
mented in clinical cases of scurvy were often several millimeters
thick, contrasting with archeological cases of inferred scurvy. This
brings into question the viability of porous cranial lesions for iden-
tifying subadult scurvy (Table 2). Yet, preserved clinical specimens
are often of the most extreme manifestations of any given patholog-
ical condition, and as such, do not likely represent the full spectrum
of osseous variability seen in subadult scurvy (Ortner, 2003).
To address this perceived disjunction of evidence, Waldron
(2009) recommends an operational definition for scurvy that
includes clinical radiological indictors and periosteal new bone on
the skull. This would allow for the development of a middle ground
where clinical radiological indictors for identifying subadult scurvy
can be paired with paleopathological methods to help provide more
reliable and complementary assessments of subadult scurvy in
antiquity.
2.3. Variability of clinical radiological indicators
It is evident variability exists regarding the onset and degree
of radiological lesion manifestation. Park et al. (1935) serve as one
of the only studies to directly discuss variability of clinical radio-
logical indictors. In a sample of 125 clinical cases of scurvy, this
study showed that clinical radiological indictors are indeed variable
(i.e., where one individual may show radiolucency across an entire
metaphysis, another may only exhibit radiolucency across part of a
metaphysis). Still, Park et al. (1935) do not identify radiographic
variability as a hindrance to the accurate diagnosis of subadult
scurvy, but rather seeks to alert clinicians to the variability therein
and promote more reliable recognition of radiological changes
associated with subadult scurvy (cf. Schwartz, 1927).
Despite the establishment of a standard suite of clinical radio-
logical indictors for recognizing subadult scurvy (Fränkel, 1903/04,
1908; Wimberger, 1923, 1925; Pelakn, 1925; Van Wersch, 1954;
Kottamasu, 2004) and increasingly accurate imaging technology,
considerations of clinical radiological indictor variability have been
comparatively limited. Contemporary clinical literature avoids
developing rigid criteria for the manifestation of clinical radiolog-
ical indictors and instead focuses on the nature of the lesions to
be expected in scurvy, factors associated with onset, co-occurrence
of radiological indicators of scurvy, and eventual resolution (see
Edeiken, 1981; Silverman et al., 1993; Swischuk, 1997; Laor et al.,
1998; Kottamasu, 2004; Hall and Offiah, 2005; Siegel and Coley,
2006; Shore, 2008). This reinforces the notion that clinical radio-
logical indictors of subadult scurvy must be thought of as a
constellation of pathological traits where by, much like macroscop-
ically observable skeletal lesions, a series of indicators are required
to make a firm assessment of scurvy.
In terms of onset, it is typically noted that generalized atrophy
and thickening of the provisional zone of calcification are the first
signs to manifest in scurvy (Silverman, 1993; Kottamasu, 2004).
These signs are non-diagnostic (Silverman, 1993), but following
these initial skeletal alterations, increasingly diagnostic indicators
of subadult scurvy progressively manifest (Table 1). The develop-
ment of clinical radiological indictors occurs rapidly within a period
of days to weeks following the onset of scurvy (Kottamasu, 2004).
Silverman (1993) provides a sequential ordering of locations for the
manifestation of clinical radiological indictors, based on the princi-
ple that clinical radiological indictors manifest first at sights of rapid
growth: sternal rib ends, the distal femur, the proximal humerus,
the proximal and distal tibia and fibula, and the distal radius and
ulna. Of these, the knee appears best suited for observing clinical
radiological indictors of subadult scurvy. The knee is easily imaged

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Table 2
Macroscopically observable skeletal lesions of subadult scurvy, with proposed hemorrhage sites and critiques.

Location Proposed porotic lesionsa Proposed hemorrhage sitesb Critiquec

Mandible Along the coronoid process and
ramus
Greater Wing of the Non-expansive, along the greater
Sphenoid (GWS) wing of the sphenoid
Orbit Lateral and frontal aspect with
pronounced vessel channels. Can
be porous and hypertrophic.
Orbital lesions associated with
scurvy are due to hemorrhage and
new bone formation, not diploëic
expansion
Maxilla Non-expansive along the posterior
and anterior maxilla, the pyriform
aperture, and infraorbital foramen
Temporal Along the squamous portion of the
temporal, often in association with
porous lesions on the GWS
Parietal Along the inferior aspect of the
parietals, often in association with
porous lesions on the GWS
Zygomatic Along the internal/posterior aspect
Palatine porosity along the palatine bones
may be observed, but is often hard
to distinguish from normal
porosity
Alveolard Along the alveolar border and
tooth sockets. Weakening of the
periodontal ligament may lead to
loss of teeth, particularly single
rooted teeth
Scapula Along the supraspinous and
infraspinous fossa
Metaphyseal/diaphyseal >5–10 mm superiorly along the
porosity metaphysis; evidence of localized
periosteal reactions result from
subperiosteal hemorrhaging
Ilium Porosity along the external and
internal ilium
Ribs Porosity along the pleural border
with potential cupping and
bayonet defect along the sternal
end.
a
Porotic lesions were compiled from Park et al. (1935), Ortner (1984), Ortner and Ericksen (1997), Ortner et al. (1999, 2001), Mahoney-Swales and Nystrom (2009), and
Brown and Ortner (2011), where porosity proposed as indicative of scurvy is defined as “. . . a localized, abnormal condition in which fine holes, visible without magnification
but typically less than 1 mm in diameter, penetrate a lamellar bone surface. The lamellar bone may be normal or the result of abnormal (hypertrophic) bone formation”
(Ortner and Ericksen, 1997: 212).
b
Anatomical references were compiled from Gray (1973), Ortner (1984), McMinn and Hutchings (1985), Ortner and Ericksen (1997), Ortner et al. (1999, 2001).
c
Critiques are drawn from material presented in Melikian and Waldron (2003), Waldron (2009), and De Boer et al. (2013).
d
Ortner et al. (1999) do not establish a baseline for differentiating normal growth related alveolar porosity from pathological porosity, rather they state that it could
potentially be observed in cases of scurvy.
Second (pterygoid) branch of the
maxillary artery
Deep temporal arteries along the
temporalis and pterygoid muscles
Anterior deep temporal artery and
lacrimal branch of the ophthalmic
artery
Deep temporal and maxillary
arteries
Deep temporal arteries
Deep temporal arteries
Second (pterygoid) branch of the
maxillary artery
third (pterygopalatine) branch of
maxillary artery
Third (pterygopalatine) branch of
maxillary artery
Subscapular, circumflex and
thoracodorsal arteries along the
supraspinatus and infraspinatus
Inflammation of the periosteum,
hemorrhaging, and hematoma
formation
Iliac arteries
Proximity to pleura, and impaired
collagen synthesis at the sternal
margin
Probable as an important site, though porosity
observed from clinically documented cases of
scurvy in the Royal College of Surgeons
exhibited drastically different porosity, being
raised from the surface by several millimeters
Probable as an important site, though porosity
observed from clinically documented cases of
scurvy in the Royal College of Surgeons
exhibited drastically different porosity, being
raised from the surface by several millimeters
Clinically probable as an important site,
though porosity observed from one of Barlow’s
original cases exhibits drastically different
porosity, being raised from the surface by
several millimeters
Alveolar porosity is often so common that it is
difficult to integrate as a pathological
indicator. Though tooth loss may occur it is
near impossible to confirm or deny its
occurrence being due to scurvy
Ossified hematoma and evidence of
post-cranial porosity are not always present,
nor entirely pathognomonic of scurvy. There is
doubt that paleopathological cases of scurvy in
children can be diagnosed without
pathognomonic radiological signs

and is a major area of longitudinal growth making it a key area
for observing pathological alterations associated with scurvy (Jaffe,
1972; Shore, 2008). Further, though hemorrhage can and does occur
throughout the body, subperiosteal lesions are most likely on the
lower limbs where there is greater weight bearing, shearing strain,
and potential for trauma (Jaffe, 1972; Silverman, 1993; Silverman
et al., 1993; Sloan et al., 1999).
These clinical characteristics suggest that in terms of pale-
opathology, variability among clinical radiological indictors has
little impact on the parallel patterns of osseous lesion formation
(Shore, 2008; cf. Brickley and Ives, 2008). Though variability exists,
the suite of clinical radiological indicators in question all regularly
manifest in cases of scurvy (Shore, 2008). As clinical radiological
indicators of scurvy manifest as a response to impaired collagen
synthesis these pathological indicators will form before macro-
scopically observable lesions, and as such stand to be of significant
benefit to paleopathological assessments of subadult scurvy.
2.4. Moving toward a combined clinical–paleopathological
framework
In attempting to integrate macroscopically observable skele-
tal lesions with clinical radiological indictors, the need remains to
consider variability in terms of lesion development, remodeling,

Please cite this article in press as: Stark, R.J., A proposed framework for the study of paleopathological cases of subadult scurvy. Int. J.
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and resolution. Disjunctions between onset and resolution of clin-
ical radiological indictors and macroscopically observable skeletal
lesions can create a situation in which one set of lesions is more
readily apparent, given the mechanisms responsible for develop-
ment of the respective lesion types. It may be possible to use
this potential timing difference to gauge potential stages of scurvy
onset and resolution and help create stronger links between clin-
ical and paleopathological methods. This paper, thus, proposes a
three-phase framework that can be tested and further amplified in
future research through linking clinical radiological indictors and
macroscopically observable skeletal lesions in paleopathological
investigations of subadult scurvy.
3. Framework
By adopting clinical radiological indictors in paleopathological
investigations of subadult scurvy, it may be possible to cre-
ate stronger links with clinical criteria for identifying subadult
scurvy and a further means for validating proposed macroscopi-
cally observable skeletal lesions. Both clinical radiological indictors
and macroscopically observable skeletal lesions coexist at some
point in most cases of chronic subadult scurvy. Radiological
studies of subadult scurvy make it clear that clinical radiologi-
cal indictors develop before macroscopically observable skeletal
lesions (Silverman, 1993). Clinical radiological indictors develop
as a response to the interruption of collagen formation and
depressed osteoblastic activity, while macroscopically observable
skeletal lesions tend to be characterized by vascular and osteoblas-
tic response to hemorrhaging resulting in porous lesions and
periosteal new bone formation following resumption of sufficient
ascorbic acid intake (McCann, 1962; Akikusa et al., 2003; Brickley
and Ives, 2008; Ortner, 2003; Gupta et al., 2012). Furthermore,
scurvy is often perceived of as a dichotomous condition, either
being present or absent in a skeleton. This leaves little room for
conceptualization and study of the multiple clinical and patho-
physiological stages that scurvy progresses through from onset to
resolution. Given this biological reality, a phase-based system may
help to better categorize the types of lesions observed and provide
more complete assessments of past life histories (Crandall et al.,
2012; also see Armelagos et al., this issue).
4. Proposed model of scorbutic lesion development
The following three-phase system examines the sequence of
subadult scurvy onset and resolution. Variability in the manifes-
tation of both clinical radiological indictors and macroscopically
observable skeletal lesions is considered, and as such, this model
aims for a more inclusive picture from which individual cases
may depart. This phase-based system is relative by necessity, as
establishing precise temporal relationships for lesion formation is
impossible, even in modern clinical contexts (see Silverman, 1993;
Shore, 2008).
4.1. Phase 1: occurrence of clinical radiological indicators
The onset of scurvy results in decreased bone mineral den-
sity and content, decreased number of and thinner trabeculae, and
impaired collagen synthesis with increasing bone fragility (Kipp
et al., 1996). In the absence of sufficient ascorbic acid, osteoblast
function becomes impaired while osteoclast activity continues (Le
Nihouannen et al., 2010). The maintenance of osteoclastic activ-
ity with the interruption of osteoblasitc activity leads to cortical
thinning and bone fragility in the metaphyseal–epiphyseal region,
which may be explained in part by the role ascorbic acid plays
in regulating osteoclast senescence (Le Nihouannen et al., 2010).
Please cite this article in press as: Stark, R.J., A proposed framework for the study of paleopathological cases of subadult scurvy. Int. J.
Paleopathol. (2014), http://dx.doi.org/10.1016/j.ijpp.2014.01.005
5
Park et al. (1935) and Jaffe (1972) both note that clinical radio-
logical indictors were often present before soft-tissue lesions of
scurvy. Though it is difficult to isolate the exact moment of clini-
cal radiological indictor formation since manifestations of scurvy
in humans are variable, it is clear that clinical radiological indictors
are among the first lesions of subadult scurvy to manifest (Caffey,
1978). Unlike macroscopically observable skeletal lesions, clinical
radiological indictors do not require vascular response or formation
of new bone to be apparent. Instead, this first phase represents an
interruption of the longitudinal growth process accompanied by
hematoma formation leading to elevation of the periosteum. For
this reason in the early stages of scurvy clinical radiological indic-
tors will be present, but will be macroscopically invisible in skeletal
remains as osseous involvement has yet to manifest.
4.2. Phase 2: co-occurrence of macroscopically observable
skeletal lesions and clinical radiological indicators
Phase 2 marks the persistence of clinical radiological indictors
with the addition of vascular porous lesions and new bone forma-
tion (macroscopically observable skeletal lesions), developing as a
response to localized hemorrhage, leading to the onset of lesions
considered by the “Ortner criteria,” with periosteal new bone for-
mation and restoration of angiogenesis integrity resuming with the
reintroduction of ascorbic acid (Murray and Kodicek, 1949; Stolman
et al., 1961; Phillips, 1971; Ortner, 2003; Telang et al., 2007; cf.
Barlow, 1883, 1894). Phase 2 bridges the onset of skeletal lesions to
the resolution of radiological indicators, representing a timeframe
in which one would expect to see both active clinical radio-
logical indictors and macroscopically observable skeletal lesions
co-occurring. Individuals in this phase represent the strongest evi-
dence of scurvy, making recognition of potential cases increasingly
likely.
As scurvy progresses, hemorrhage-induced vascular macro-
scopically observable skeletal lesions develop throughout the body
with subperiosteal hemorrhages becoming increasingly radio-
graphically apparent along with other clinical radiological indictors
(Morgan and Eisele, 1992). Porous lesions are believed to form as
a response to focal hemorrhages (Ortner, 2003). The restoration of
structurally sound angiogensis following re-introduction of ascor-
bic acid has been identified as a key factor in the formation and
persistence of porotic lesions (Ortner, 2003; see also Stolman et al.,
1961). It remains possible, however, that porotic lesions consistent
with the Ortner criteria may begin to develop before restoration of
ascorbic acid sufficiency. In cases of scurvy, disorganized and inad-
equate attempts to create new blood vessels do take place (Mettier
and Chew, 1932; Brown and Ortner, 2011). Though new vascula-
ture cannot form properly in scurvy due to the inhibition of proline
and lysine hydroxylation, the formation of new spaces into which
vasculature can extend may occur by way of plasminogen activa-
tor and osteoclast activity (Ashino et al., 2003; Le Nihouannen et al.,
2010; Brown and Ortner, 2011). Plasminogen activator and osteo-
clasts are not effected in the same way as collagen synthesis in the
absence or severe depletion of ascorbic acid, making it possible for
the relatively independent development of initial vascular chan-
nels and porosity in scorbutic individuals prior to restoration of
ascorbic acid sufficiency (Stolman et al., 1961; Ashino et al., 2003).
Brown and Ortner (2011) identify this process as a “troublesome
feedback mechanism,” where the body attempts to generate new
vasculature to aid in removal of hemorrhages, only to spur further
hemorrhage, induced by the instability of the newly created vas-
culature. This closed loop process is believed to initiate the porous
lesions classified under the Ortner criteria.
Following re-introduction of sufficient ascorbic acid and
restoration of successful angiogenesis these porous areas may
become properly vascularized, contributing to hemorrhage
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6 R.J. Stark / International Journal of Paleopathology xxx (2014) xxx–xxx
removal and providing for the retention of porous lesions for
extended periods of time (Stolman et al., 1961; Ashino et al., 2003;
Telang et al., 2007; cf. Ortner, 2003; Brickley and Ives, 2008).
The production of periosteal new bone in subadult scurvy
remains a challenge. It remains possible hat periosteal new bone
could form in cases where individuals are moving toward, or have
achieved a scorbutic state, but receive either low (<10 mg/day), or
intermittent amounts of ascorbic acid (cf. Crandall et al., 2012).
Though potentially possible, it is unlikely for such periosteal new
bone to be substantial given the significant depression of osteoblas-
tic function in scorbutic individuals (Van Wersch, 1954; Jaffe, 1972;
Phan et al., 2004; Le Nihouannen et al., 2010). If periosteal new bone
were to form in an individual in an active scurvy state, the presence
of ongoing hemorrhages would likely prevent the bone from appo-
sitionally settling on the cortex until full healing could take place.
For these reasons, the presence of significant periosteal new bone
formations are more readily expected in the healing phase of scurvy
(Sloan et al., 1999; Shore, 2008).
It is evident from the many pathways for an individual to enter
into a scorbutic state that no one broad categorization is possible.
Rather Phase 2 more readily depicts a mosaic of potentialities of
individuals depleted in their bodily stores of ascorbic acid. Phase 2
remains a clear stage, in that individuals suffering from insufficient
ascorbic acid intake for an extended period will manifest clini-
cal radiological indictors and macroscopically observable skeletal
lesions of scurvy together so long as insufficiency persists, which is
the defining characterization of “Phase 2.”
4.3. Phase 3: predominance of macroscopically observable
skeletal lesions with “remnant” clinical radiological indicators
With re-introduction of ascorbic acid in sufficient quantity,
mineralization and bone (re)modeling resumes, resulting in rapid
resolution of clinical radiological indictors (Brailsford, 1953; Shore,
2008). Clinical studies of subadult scurvy have shown that radio-
logical indictors begin to resolve one to two months after ascorbic
acid reintroduction (Morgan and Eisele, 1992; Ratanachu-Ek et al.,
2003), with restoration to a pre-scorbutic radiographic appearance
as early as three months (Valentini et al., 2011). The exceptions to
this timeframe are Wimberger’s ring and the white line of Frankel
(Shore, 2008). Wimberger’s ring remains radiographically observ-
able due to preservation of the original radiopaque periphery and
central lucency, which appear as an epiphysis-within-an-epiphysis
in the center of the epiphysis as skeletal growth continues (Shore,
2008). Retention of Wimberger’rs ring can provide confirmatory
evidence of a previous episode of scurvy. With renewed longitudi-
nal growth, the white line of Frankel is preserved as a nonspecific
“Harris Line” (Shore, 2008). Both Wimberger’s ring and the white
line of Frankel can remain present for years.
Though rare in cases of scurvy, the presence of metaphyseal flar-
ing and cupping with epiphyseal invagination, if present, may also
persist (Silverman, 1970; Sprague, 1976; Gupta et al., 2012). How-
ever, metaphyseal flaring, cupping, and epiphyseal invagination
typically resolve without intervention following resumed longitu-
dinal growth in the post-scorbutic phase (Silverman, 1993).
Accompanying post-scorbutic hematoma organization, ossifi-
cation along the periphery of the hematoma creates a layer of
subperiosteal new bone that thickens and eventually deposits on
the original bone surface forming the new cortex (i.e., long bone
diaphysis, roof of the orbits), (Sloan et al., 1999; Ortner, 2003;
Shore, 2008). As porotic lesions are believed to develop due to
hemorrhage-induced angiogenesis, these defects may persist for
a significant period, taking years, if not more than a decade to fully
remodel (Front et al., 1978; Parfitt, 2002, 2004).
With restoration of ascorbic acid and the proper balances
between osteoblast and osteoclast activity in bone, (re)modeling
Please cite this article in press as: Stark, R.J., A proposed framework for the study of paleopathological cases of subadult scurvy. Int. J.
Paleopathol. (2014), http://dx.doi.org/10.1016/j.ijpp.2014.01.005
will return to pre-scurvy rates and allow for proper ossification
and bone development, leading to rapid resolution of clinical radio-
logical indictors (Brailsford, 1953; Phan et al., 2004). As the rate
of bone remodeling is fundamentally influenced through a pro-
cess of structural optimization of the biomechanical forces and
strains placed on it (Parfitt, 2002, 2004; Gosman et al., 2011), it
is expected that macroscopically observable skeletal lesions will
resolve more rapidly in areas of ongoing modeling and higher
intensity biomechanical loading (e.g., long bones), where struc-
tural demands are greater than in areas of superficial periosteal and
porotic cranial lesions, locations with less structural imperative to
remodel. In these sites modeling and remodeling is occurring more
frequently to maintain proper longitudinal growth and structural
integrity, whereas such demands differ in the cranium and superfi-
cial periosteal (versus intracortical) envelope of bone (Scheuer and
Black, 2000).
5. Discussion
5.1. Stepwise approach
Though clinical radiological indictors and macroscopically
observable skeletal lesions represent different mechanisms and
components of lesion formation in scurvy, it is possible to link
these lesions through a stepwise approach at the points at
which they overlap. Cranial radiography is not necessary to diag-
nose subadult scurvy, since pathognomonic signs manifest at the
metaphyseal–epiphyseal junction (Shore, 2008). Thus, periosteal
new bone formation and abnormal porosity in the long bones,
which are commonly encountered in paleopathological studies of
scurvy (Nerlich et al., 2000; Nerlich and Zink, 2003; Brickley and
Ives, 2008), provide the bridge between clinical radiological indic-
tors and cranial lesions.
If clinical radiological indictors, periosteal new bone, and abnor-
mal porosity in long bones can be shown to co-occur with cranial
lesions, then a stronger argument can be made to support cranial
porous lesions as being the result of scurvy. If these lesion types
can be shown to co-occur, then it would be possible to assert that
periosteal new bone formation and abnormal porosity in long bones
occurring in conjunction with porous cranial lesions, but in the
absence of clinical radiological indictors, can be taken as signifi-
cantly indicative of subadult scurvy (i.e., Phase 3). By accepting this
premise it is then logical that the Ortner criteria of cranial lesions,
even in the absence of long bone lesions and clinical radiological
indictors, can be taken as sufficiently indicative of subadult scurvy.
This approach thus proposes a middle ground between clinical
and paleopathological indications of subadult scurvy. If strong links
can be made between clinical radiological indictors and macroscop-
ically observable skeletal lesions, it will bring increasing clinical
validation to paleopathological assessments of subadult scurvy.
5.2. Co-morbidity
While individuals are unlikely to suffer exclusively from scurvy,
co-morbidity remains a challenging subject. Iron-deficiency
anemia and scurvy often co-occur due to the role that ascorbic
acid plays in iron-absorption (Besbes et al., 2010). Rickets and
scurvy may co-occur, with predominance of scorbutic traits due
to interruption of collagen production and osteoblastic activity
(Van Wersch, 1954; Kottamasu, 2004; Brickley and Ives, 2008;
cf. O’Donnell et al., 2013). Scorbutic individuals are increasingly
susceptible to infection, which can be fatal under these conditions
(Warkany, 1962; Brickley and Ives, 2008), though Jaffe (1927)
and Schultz (1936) noted that if infection and scurvy develop
together, infection might delay the appearance of scurvy. Kipp
et al. (1996) identified skeletal lesions in guinea pigs that resulted
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R.J. Stark / International Journal of Paleopathology xxx (2014) xxx–xxx
exclusively from ascorbic acid deficiency and not inanition alone.
These lesions are analogous to those observed in humans, allowing
for the dismissal of simple inanition and reinforcement of scurvy
as the causal agent of such skeletal lesions. Further discussion of
co-morbidity is beyond the scope of this article, yet co-morbidity
must always be kept in mind when examining the onset and
resolution of clinical radiological indictors and macroscopically
observable skeletal lesions.
5.3. Inclusion of radiography
To further test and develop the framework presented here, it will
be necessary to integrate radiography in paleopathological studies
of scurvy. Radiographic study has become increasingly accessi-
ble with the advent of portable equipment, digital formatting,
and lower costs. By including radiographic imaging as a standard
practice this would allow for the possibility of identifying radio-
graphic lesions that are apparent before macroscopic lesions (i.e.
Phase 1), as well as providing greater support in cases where macro-
scopic lesions have manifest (i.e. Phase 2), making documentation
of the various phases of scurvy onset and resolution increasingly
possible. As such, promotion of radiography as a standard recording
procedure should be encouraged. By incorporating radiography as a
standard recording procedure it could facilitate compiling a highly
desirable large open-source database of combined macroscopically
observable skeletal lesions and clinical radiological indicators (cf.
Brickley et al., 2009; Wade and Nelson, 2013). This would permit
greater in-depth examination of lesion formation, variation, and co-
occurrence than what is currently possible. Such a database could
also help to further refine the proposed framework presented here,
as it may become necessary to define a number of sub-phases of
scurvy development.
5.4. Histology
In tandem with macroscopic and radiographic methods, the
use of histology may be beneficial in providing stronger evidence
of paleopathological cases of scurvy. The key histological lesion
of scurvy is new appositional bone deposited on the original
perisoteal surface as a result of ossification along the periosteum
during hematoma resolution (Carli-Thiele, 1996; Schultz, 2001;
De Boer et al., 2013). The histological border between the original
periosteal surface and appositional new bone is clearly demarcated
in scurvy (see Carli-Thiele, 1996; De Boer et al., 2013). However,
similar lesions can also manifest as a result of trauma, among
other pathologies, making this indicator non-specific to scurvy
(Schultz, 2001; Van der Merwe et al., 2010a). To date confirmatory
evidence of scurvy based on histological evidence alone has not
been possible (Carli-Thiele, 1996; Schultz, 2001; Maat, 2004; Van
der Merwe et al., 2010a,b; De Boer et al., 2013). Rather, histological
assessments of scurvy have been derived in tandem with macro-
scopic and archival evidence (e.g. Van der Merwe et al., 2010b;
Mays et al., 2013). If histological changes were to be considered
alongside radiological and macroscopic changes in scurvy it may be
possible to develop an increasingly robust system of assessment.
Such an approach would permit for stronger clinical correlates
and earlier recognition of scurvy, as provided by radiology, as well
as increased ability to aid in differential diagnoses of bony lesions
(i.e. bone proliferation vs. bone resorption) through histological
examination. In this way, increasingly robust assessments of
scurvy following this phase system.
6. Conclusions
Though it is not feasible to establish a precise chronology for
development of subadult lesions in scurvy due to its inherent
Please cite this article in press as: Stark, R.J., A proposed framework for the study of paleopathological cases of subadult scurvy. Int. J.
Paleopathol. (2014), http://dx.doi.org/10.1016/j.ijpp.2014.01.005
7
pathogenic variability, a generally linear directionality of progres-
sive lesion formation and resolution is apparent with, formation of
clinical radiological indictors → macroscopically observable skele-
tal lesions → co-occurrence of clinical radiological indictors and
macroscopically observable skeletal lesions → resolution of clinical
radiological indictors → resolution of macroscopically observable
skeletal lesions, as the expected general sequence. It is hoped
that this work will stimulate further radiological and histolog-
ical inquiry into paleopathological evidence of subadult scurvy.
Such continued investigation will provide stronger links between
paleopathological and clinical methods of scurvy assessment, and
ultimately, allow for increasingly robust assessments of subadult
scurvy in antiquity.
Acknowledgments
I would like to acknowledge Dr. Sandra Garvie-Lok, Dr. Ravi
Bhargava, and Dr. Sherry Fox for their assistance in developing this
article. I would also like to thank Dr. Jane Buikstra, John Crandall
and Dr. Haagen Klaus for inviting me to contribute to this special
volume on scurvy, and to the editors and the anonymous reviewers
for their helpful comments on earlier drafts of this manuscript. This
research was funded in part by the Social Sciences and Humanities
Research Council of Canada (SSHRC), the University of Alberta, and
the Wiener Laboratory of the American School of Classical Studies
at Athens (ASCSA).
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