Chapter 5
Abnormal Bone: Considerations for
Documentation, Disease Process
Identification, and Differential Diagnosis
Haagen D. Klaus1 and Niels Lynnerup2
1
Department of Sociology and Anthropology, George Mason University, Fairfax, VA, United States, 2Department of Forensic Medicine, University of
Copenhagen, Copenhagen, Denmark
The overview of normal bone biology in Chapter 4 pro-
vides a context for considering pathological alterations to
the human skeleton. Many, if not all, of these phenomena
can be understood in terms of alterations, transformations,
or deviations of underlying mechanisms involving normal
osteoblast osteoclast coordination, bone growth, mainte-
nance, and metabolic functions. Here, discussion moves
to an overview of key issues surrounding abnormal bone
tissue. This chapter outlines the basics of abnormal bone,
from gross appearance to documentation, disease process
identification, and differential diagnoses of skeletal
abnormalities.
ABNORMAL BONE: GENERAL
CONSIDERATIONS AND GROSS
APPEARANCE
As noted in Chapter 4, bone is paradoxical—remarkably
complex in its biology but evolutionarily and functionally
constrained in its phenotypic responses to many diseases.
Bones can only respond in three ways to pathological pro-
cesses: formation of abnormal tissue, abnormal loss of tis-
sue, or a combination of formation/loss. In some
syndromes, these responses are nonspecific, while in
others the patterns of bone alteration can lead to a possi-
ble or probable differential diagnosis (Appleby et al.,
2015; Aufderheide and Rodrı́guez-Martı́n, 1998; Buikstra
et al., 2017; Lewis, 2018; Ortner, 2003, 2012; Ragsdale
and Lehmer, 2012; Roberts and Manchester, 2007;
Weston, 2012).
Linking gross appearance and molecular signaling
mechanisms are the osteoblasts and osteoclasts discussed
in Chapter 4. The behavior of these cells produce skeletal
Ortner’s Identification of Pathological Conditions in Human Skeletal Remains. DOI: https://doi.org/10.1016/B978-0-12-809738-0.00005-3
© 2019 Elsevier Inc. All rights reserved.
lesions that characterize many disease states (Schinz
et al., 1951 1952; Resnick, 2002: 609 651). Local and
systemic factors interacting with bacteria, viruses, proto-
zoa, multicellular parasites, fungi, external nutritional fac-
tors, and innate genetic disorders can all pathologically
modify normal osteoblast and osteoclast functioning and
behavior (see below, and Chapter 4; also see chapters in
Anderson et al., 2011).
In human skeletal paleopathology, a crucial first step
in the study of disease is distinguishing normal from
abnormal bone, which necessitates understanding the full
range of normal (or otherwise nonpathological) anatomi-
cal variation and physiological functions that produce dif-
ferences of size, shape, and morphology that do not lead
to functional impairment. Within this “range of normal,”
some examples include anomalies such as cranial ossicles,
persistence of the metopic suture into adulthood, the sep-
tal aperture of the olecranon fossa, or the presence of ses-
amoid bones in the hands and feet. A definitive source to
consult on nonpathological nonmetric cranial and postcra-
nial variation is Mann et al. (2016; also Hauser and De
Stephano, 1989). Such normal variation also changes
throughout the life course. For instance, the presence of
highly vascular and porous new bone formation is normal
in a fetal and infant skeleton and reflects the rapid pace
of growth (Lewis, 2018). However, bone tissue of a simi-
lar gross appearance in an individual over the age of two
is likely indicative of a pathological process. In another
example involving the need to carefully distinguish nor-
mal from abnormal, a slight degree of superficial porosity
may often be present on the ectocranial surfaces of the
parietal and frontal bones in adulthood. Such features rep-
resent fine arrays of nonpathological nutrient foramina
59
60 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

FIGURE 5.1 Postmortem damage to bones can often resemble perimortem or antemortem pathological processes. In these cases, careful observation
of margin morphology and coloration demonstrates a range of postmortem features including: (A) depressed parietal bone fracture; (B) incomplete post-
mortem breakage of a proximal ulna resulting from a torsional force; (C) penetrating puncture wound to a parietal bone; (D) penetrating chop damage to
a lumbar vertebral body; and (E) oblique chop/slicing damage to the diaphysis of a humerus. These bones were damaged in antiquity as their respective
skeletons were exhumed and placed in a large collective secondary burial (Mórrope, Peru, Middle/Late Colonial Period; photos: HDK).

and are not necessarily healed porotic hyperostosis
lesions. To evaluate the possibility of porotic hyperosto-
sis, further observations regarding the location, morphol-
ogy, density, and size of porous features are required.
Paleopathologists must also distinguish between
changes in bone produced during life and the range of
pseudopathological postmortem alterations that can mimic
disease conditions. These are produced either by factors
within the immediate depositional environment or through
excavation. Within a burial setting, various biotic pro-
cesses can alter bone, and include the growth of plant
roots around and through bones, burrowing insects or
rodents, and the action of fungi (Henderson, 1987; Child,
1995). Abiotic factors are typically geological, which can
include variations in temperature, salinity, pH, pressure of
the overburden, and so forth. For example, growth of salt
crystals within bone can produce damage at first glance
quite similar to gummatous caries sicca lesions produced
by treponemal disease. Careful observation, however, can
rule out disease (Verano, 2012). Also, the chemistry of
specific soil microenvironments even within a single
burial can produce variations in preservation that might
be confused with abnormal bone tissue. For example,
bone in contact with wood from a coffin tends to break
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5 61

down faster than other elements in a burial, leading to

erosion on the anterior aspect of vertebral bodies that has
been confused with the influence of infectious disease.
Careless excavation can produce alterations to bone
that may be confused with pathological processes. So-
called examples of “trowel trauma” resemble, and must
be differentiated from, sharp force injuries. The accidental
swipe of a shovel might produce damage analogous to a
wound from a bladed weapon. Natural taphonomic forces,
such as the pressure exerted by the overburden on a skele-
ton or precipitation of salt crystals, can also break bone in
a wide variety of ways (Fig. 5.1A E). At least three crite-
ria can be considered to distinguish genuine pathological
processes from postmortem artifacts.
First, postmortem destructive processes generally pro-
duce jagged, sharp, or otherwise highly irregular edges.
Second, the coloration of the defect margin is especially
important to consider. In virtually any kind of postmortem
bone breakage, the edges of the defect are often more
lightly colored than the outer cortical bone surface. More
recently exposed inner surfaces of the bone have not been
in contact with the surrounding depositional environment
for the same amount of time. Therefore, they are lighter in
color. While wooden digging tools are optimal when exca-
vating skeletons, subtle examples of damage can occur
when a fine-tipped implement (such as a bamboo skewer)
comes into contact with bone and produce features resem-
bling cut-marks. The postmortem nature of such damage
can be discerned as postmortem due to the shiny or slightly
reflective bone surface within the defect, particularly
FIGURE 5.2 Some types of skeletal lesions require extremely careful
evident at low magnification. Authentic, perimortem
examination to include the distribution of lesions in the skeleton and
cut-marks display no such polish. Along these lines, key radiographic characterization to distinguish it from pseudopathological
features to look for on the edge of “cuts include evidence or taphonomic processes, such as this case of metastatic cancer (primary
that the bone at the edge of the cut has been altered in color site unknown) affecting the vertebral column and os coxae (left supero-
to resemble external bone surface color. Bright, light- posterior ilium pictured here) (34 year-old male, Terry Anatomical
Collection, NMNH P0001606; photo: HDK).
colored edges are evidence of recent taphonomic events.
Third, biologic processes experienced in life, espe-
cially those involving chronic conditions promoting bone taphonomic changes. Of course, when applying their taph-
loss, will demonstrate comparatively greater degrees of onomic terms, using the additional adjective “postmor-
smoothed or rounded margins. With the exception of only tem” is quite important (Buikstra et al., 2017).
the most aggressive osteoclastic chronic diseases, bone Incorrect identification of a postmortem artifact of
destruction is commonly accompanied by reparative new taphonomy as an antemortem process is bad science and
bone formation surrounding the margins of the defect that certainly embarrassing. That said, some cases of altered
involves an inflammatory/reparative axis in response to bone present significant challenges, even for experienced
bone destruction. Still, in the case of aggressive disease paleopathologists. Very careful and nuanced observation
processes such as certain metastasized cancers, careful may be required, and further use of tools such as micros-
examination of lesion characteristics, distribution of copy or medical imaging technologies (e.g., radiographs,
lesions in the skeleton, and its radiographic appearance CT scanning) can often provide definitive diagnostic
are required to distinguish it from any pseudopathological information. Sometimes, even after all that effort, a case
process (Fig. 5.2; see Chapters 15 and 20). Additionally, may still be ambiguous. Still, a few guidelines can be con-
when describing postmortem taphonomic changes, sidered that can assist in the macroscopic differentiation
Manchester et al. (2016) offer an outstanding set of struc- between a postmortem pseudopathological condition and an
tured lists of descriptive terminology including abnormality that arose in living bone (Ortner, 2003, 2012).
62 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains
DESCRIPTION OF ABNORMAL BONE
When an antemortem or perimortem bone abnormality
has been identified, goals turn to reconstructing pathologi-
cal processes and the most likely causes of the abnormal-
ity. In paleopathology, traditional reliance is placed upon
visual (gross) examination of bone that is the focus of this
chapter. Of course, the more lines of available evidence,
the better, and gross examination is often best comple-
mented by radiography (Chapter 7; Wanek et al., 2012),
various forms of microscopy (e.g., Schultz, 2001;
Ragsdale and Lehmer, 2012), chemical or isotopic analy-
ses (Koon, 2012), and increasingly, ancient pathogen and
microbiome DNA analysis (Chapter 8; Bos et al., 2014;
Rasmussen et al., 2015; Vågene et al., 2018; Warinner
et al., 2014).
Description in paleopathology. Best practices in 21st
century paleopathology rely on a multitiered logical
framework that first describes an abnormality. Second,
these features are used to identify diseases most likely to
have caused this change. Third, one engages in differen-
tial diagnosis. Of course, in many cases, it may be impos-
sible to determine the ultimate cause or exact disease
(e.g., Weston, 2008). For example, while there are more
than 100 known conditions that can produce enamel
hypoplasias (Schultz et al., 1998), they are nonetheless
among the most valuable windows on early life stress and
physiological disruption. While the exact trigger for hypo-
plasia formation is not observable in skeletal tissue alone,
the fact that a stress-induced physiological state occurred
is what matters. In other situations, a combination of care-
ful description and differential diagnosis can identify a
disease process, especially when the types and patterns of
bone involvement tend toward unique patterning.
As Ortner (1991, 2003, 2011, 2012) and others
(Buikstra and Ubelaker, 1994) have emphasized, a clear
and detailed description is one of the most important and
fundamental elements to proper practice of paleopathology.
Ortner defined four key components to a descriptive system
for abnormal bone conditions. First, standardized and
unambiguous terminology must be used. Second, a com-
plete inventory of all skeletal material observed must be
made. Third, abnormalities are then precisely described in
terms of the size, shape, and other morphologic characteris-
tics such as the characteristics of the defect margins.
Fourth, the location(s) and distribution of the pathological
features are described. Ortner framed description as being
conceptually anchored by thinking about bone abnormali-
ties in terms of altered osteoclast and osteoblast activity.
The strength of any descriptive system is only as good
as its descriptive terminology. In a very concrete sense,
words matter. Ortner (2011, 2012) argued that in
paleopathological description and differential diagnosis,
the terms we use “. . .often make a big difference between
confusion and understanding. Indeed, a basic component
of any scientific discipline is rigor in defining and using
terms” (Ortner, 2012: 250). Critiques from both within
and outside our discipline have aimed at improving our
descriptive terminological rigor (Manchester et al., 2016).
Particularly those who work in the anatomical sciences
provide good models for paleopathologists to follow, as
their exacting and rigorous use of terminology helps in
getting the highest achievable precision in the observation
and description of anatomical structures.
Specifically, the foundation of a common descriptive
system in paleopathology can and should consistently
embrace the international terminological standards estab-
lished by the Nomina Anatomica (NA) and its successor,
the Terminologica Anatomica (TA). These works are the
officially approved nomenclature for anatomy as desig-
nated by the International Congress of Anatomists. The
NA had its origins in 1955 and represented an effort to
better standardize the earlier Basle Nomina Anatomica.
The NA was continuously revised in 5-year intervals until
1985. Technically, the yet further streamlined TA suc-
ceeded the NA in 1998, although the NA is still very
widely used (International Anatomical Nomenclature
Committee, 1989).
For example, a paleopathologist using the TA or NA
would not varyingly use any of the multiple, imprecise, or
confusing terms for the orbit seen in paleopathological lit-
erature (referred to as many things, such as the eye orbit,
ocular orbit, orbital plate). Beyond the simple fact that the
TA/NA identify this structure as the orbit, there is a consis-
tent logic to this: there is only one structure in the skeleton
that is an anatomical orbit, so the use of any other adjec-
tives is redundant or misleading. Likewise, according to
these standards, there are no such structures in the human
body as “the frontal,” “the parietal,” or “the sphenoid” as is
so often written in paleopathological descriptions. As
named structures, these features do not exist in the natural
world. However, the sphenoid bone (the os spehnoidale),
along with the frontal bone (os frontale), and the parietal
bone (os paretale) are recognized. Other descriptive termi-
nological errors are even more common, such as the sur-
prisingly frequent misuse of the term skull when the
anatomical cranium is being explicitly described (and see
Knüsel (2014) for more on this issue, including thoughtful
perspectives derived from funerary archaeology).
Using the human anatomical terminology in the
Terminologica Anatomica (1998) as its foundation,
Manchester et al. (2016) developed systematic termino-
logical conventions tailored specifically to paleopatholog-
ical documentation and interpretation. They drew upon
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5
the experiences and lessons learned from a series of work-
shops hosted by Donald Ortner and Bruce Ragsdale
beginning in 1985 (Powell, 2012; Ragsdale, 1992). This
effort initially involved the need to counter the use of
inconsistent or inappropriate terms when describing nor-
mal and abnormal structures, as well as the fundamental
importance of the correct use of widely held descriptive
conventions. Manchester and colleagues (2016) add to
this further refinement and systemization of terms to the
ends of increasing consensus, replicability of observation,
and accuracy in paleopathology. Their schema spans gen-
eral terms, systemic and functional anatomy and physiol-
ogy, systematic anatomy (bones, joints, muscles,
cardiovascular, lymphoid, and neural), pathological, clini-
cal, radiological, and taphonomic descriptive categories.
The broader point is that the use of anatomical descrip-
tive standards lends greater precision, reduces ambiguity
and interobserver error, and builds cross-disciplinary credi-
bility. Further, we would argue even further that such
terminological rigor enhances how we observe and docu-
ment anatomical structures and their deviations from
normal anatomy. The language that we use directly shapes
our thinking and perception. Descriptive terminological
quality is not just about a state of mind, but it helps foster
better practice, tying together the description process
recognition differential diagnosis process.
Rooted within a rigorous terminological foundation
(see Chapter 2; Buikstra et al., 2017; PPA Website) the
initial descriptive analysis then attempts to determine
whether a skeletal abnormality is: (1) a solitary abnormal-
ity possessing a single or solitary focus; (2) a bilateral
multifocal abnormality in which abnormal bone is located
in two or more sites of the skeleton; (3) a randomly dis-
tributed multifocal pathological phenomenon; (4) a dif-
fuse abnormal reduction of bone mass throughout the
skeleton (but not necessarily equally reduced in all areas,
and; (5) a local or generalized disturbance of normal size
and shape of bone that may be accompanied by abnormal
bone (Ortner, 2003: 49). In the case of solitary lesions,
the lesion itself should be described minimally in terms of
size, shape, depth or height, bone quality (e.g., reactive
new bone, remodeled bone), and characteristics of the
margins of the abnormality. In the case of bilateral multi-
focal abnormalities, the contralateral lesion may be of a
perceptively different size, shape, and position. In this
case, it is best to measure each lesion and discuss the var-
iation in size. Of course, more than one pathological con-
dition may be at play in a skeleton, and beginning with
the process of documentation and description, the poten-
tial of comorbid conditions must always be considered.
Further, a descriptive analysis of an abnormal skeleton
should be highly specific in regard to the bones involved
63
and the location of the abnormalities within the skeleton.
Basic directional terminology drawn from the TA/NA
should always be used consistently when describing
defect locations (e.g., anterior, posterior, anterolateral,
inferoposterior, distal, proximal, and so forth). Then,
observations are to be mapped onto an anatomical organi-
zational framework. This framework provides a system-
atic nomenclature and can be expanded with as much
anatomic specificity as required or dictated by preserva-
tion, research design, or other factors (Buikstra and
Ubelaker, 1994; Ortner, 2003; Wilczak and Dudar, 2011).
Process recognition in paleopathology. Once the
abnormality is described, the work then turns to distin-
guishing the potential biological process or processes
responsible for the abnormality. Abnormal bone can be
described in terms of possibilities of altered bone forma-
tion, bone loss, bone size, or bone shape. Again, all of
this comes back to basic bone biology and variations of
abnormally elevated or depressed osteoblast or osteo-
clast activity. Another option involves normal osteoclast
function but depressed osteoblast activity that cannot
mineralize normally osteoid matrix. Since unmineralized
osteoid decomposes along with the rest of the soft tissue,
this last phenomenon might visually appear as a case of
elevated osteoclastic responses. Again, the following
categories again are not intended to be comprehensive
but to serve as a framework than can be expanded upon
as needed:
1. Abnormal bone size
a. Abnormally small size for age and/or sex
b. Abnormally large size for age and/or sex
2. Abnormal bone or bone group shape
a. Abnormal shape resulting from defects in growth
and development
b. Abnormal shape resulting from poorly mineralized
bone or biomechanical loading
c. Abnormal shape resulting from poor alignment fol-
lowing fracture
3. Abnormal bone formation
a. Abnormal new bone formation
i. Immature reactive new bone (no discernable
pattern or organization of vascular pores or
striations)
ii. Porous bone
iii. Striated bone
iv. Spiculated bone
b. Abnormal formation of compact (lamellar) bone
i. Smooth compact bone (nonplaque-like forma-
tions (e.g., osteomas))
ii. Porous compact bone
iii. Striated compact bone
64 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains
iv. Spiculated compact bone
v. Plaque-like formations (relatively thin and flat
formations of smooth compact new bone atop
a normal bone surface)
4. Abnormal bone destruction
a. No margin or clearly defined border
b. Clear border but no evidence of repair (marginal
new bone formation absent)
c. Clear border with evidence of repair (marginal
new bone formation present)
d. Defined focus with centralized destruction accom-
panied by marginal new bone formation
e. Repair of defined focus with centralized destruc-
tion accompanied by marginal new bone formation
f. Focal porous destruction
g. Generalized porous destruction
h. Destructive remodeling
i. Osteopenia
j. Fracture
Pathophysiology and disease processes—defining
mechanisms of abnormal bone. The pathological varia-
tions of abnormal bone size, shape, formation, and
destruction varyingly span several biologic phenomenon:
vascular disturbances, innervation/biomechanical disease,
trauma/repair, errors in growth, metabolic diseases,
inflammatory processes, and neoplastic disorders (see
Chapters 10 23). For an additionally key overview of
this topic, we recommend Ragsdale and Lehmer (2012).
Further, Donald Resnick’s (2002) five-volume Diagnosis
of Bone and Joint Disorders, Fourth Edition, is a vital ref-
erence work. While Resnick’s emphasis is skeletal radiol-
ogy, it also provides excellent coverage on the
pathogenesis and patterning of skeletal diseases extending
down to the cellular level and should be a standard refer-
ence for anyone engaging in the study of ancient disease.
The broader message here is that integrating these
explicitly biological perspectives encourages rigorous and
informed disease process identification, and thus, differ-
ential diagnosis (Mays, 2018). Pathophysiology is the
holistic study of disease physiology, at the center of
which are the structural and functional changes to the
body caused by disease or anatomical alteration. Key
components to the broader perspectives pursued by patho-
physiology are its additional foci involving defining vari-
ous etiologies and the progression of disease
pathogenesis—the sequence of nested or contingent cau-
salities spanning cellular, tissue-level, system-wide, and
body-level events beginning with the initial exposure or
manifestation of a disease state to its conclusion (Kumar
et al., 2014; Porth, 2014). These events influence morpho-
logical changes to underlying tissues that are often
characteristic or diagnostic of specific disorders which
themselves are products of yet more fundamental molecu-
lar or genetic phenomena.
The human body can endure a range of abnormal or
altered physiological stimuli that can produce diverse phe-
nomena. Many states reflect physiological plasticity and
are reversible. They can be identified as consistent with a
few broad pathophysiologic categories that then are pro-
gressively narrowed down to specific conditions (see
Kumar et al., 2014). For example, an increased demand
or tissue-level stimulation can promote hypertrophy or
hyperplasia. Hypertrophy involves an increase in the size
of cells as more cellular protein is synthesized to meet a
functional demand. In contrast, hyperplasia is an increase
in the number of cells to similarly meet a perceived func-
tional demand, resulting in increased tissue or organ
mass. Abnormal production of hormones or growth fac-
tors is one driver, while compensatory hyperplasias gener-
ate increased tissue mass following tissue damage (e.g., a
bone callous following fracture). Atrophy represents an
opposite process where tissue or organ size decreases due
to an abnormal loss of cells or a reduction of cell size.
Atrophy can be subdivided into several pathologic catego-
ries such as disuse atrophy, denervation atrophy (damage
to nerve fibers that affect muscles and bone mass), inade-
quate blood supply (ischemia), inadequate protein/calorie
nutrition (cachexia), depressed endocrine signaling, and
tissue compression (pressure) (Kumar et al., 2014).
Cell injury and death can relate to either acute or
chronic reduced oxygen supply (hypoxia), microbial
infection (fungal, parasitic, bacterial, and viral agents),
external physical causes (mechanical trauma, thermal
trauma), and chemical insults (excess fluoride, poisons,
drugs, pollutants). These produce myriad forms of cell
injury that may be varyingly reversible or irreversible.
Generally, they all involve changes to cell morphology,
from initial exposure to crossing over so-called “points of
no return” leading to cell death (Kumar et al., 2014).
Cellular swelling is a near universal feature of cell injury
and occurs when ion pumps in the plasma membrane can
no longer maintain fluid homeostasis. This produces fatty
swelling of the endoplasmic reticulum and mitochondria
as well as swollen outpouchings of the cell membrane
(blebs). Persistent or excessive injury or cell death may
produce necrosis spanning coagulative, liquefactive, gan-
grenous, caseous, fatty, and fibrinoid forms (Kumar et al.,
2014: 15, 16). An inflammatory response, degradation of
the cell membrane, and leakage of the cellular contents
all characterize necrosis. Apoptosis is another reaction
involving a regulated form of preprogrammed, noninflam-
matory cell death. For a look at the nature, processes, and
variations of inflammatory responses, we direct the reader
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5
to Kumar and colleagues’ (2014) overview of acute and
chronic inflammation.
Another component of pathophysiology is to consider
how cellular responses play out on larger tissue- or organ-
level scales. This is not only intrinsically valuable to the
study of disease progression but further assists paleopa-
thology in the identification and differential diagnosis of
skeletal lesions. That is to say the combination of an
understanding of cell and tissue-level physiology and
related anatomical features is important to rigorous paleo-
pathological practice. For example, it was long held that
porotic hyperostosis lesions were a product of chronic
childhood iron-deficiency anemia (e.g., Stuart-Macadam,
1987, 1992). Walker and colleagues (2009) took a patho-
physiological approach to the behavior of marrow cells
and the process of erythropoiesis and suggest that megalo-
blastic anemias (vitamin B9 and B12 deficiencies) are at
the roots of its etiology, though iron deficiency or comor-
bidity between megaloblastic and iron-deficiency anemia
65
still remain as possible interpretations (Oxenham and
Cavill, 2010; McIlvaine, 2015).
Abnormal size and shape. Based on these pathophysio-
logical mechanisms outlined above, disease processes can
produce abnormal bone sizes, shapes, formation, and loss
(Fig. 5.3). A spectrum of abnormalities in bone size can
be linked to genetic, developmental, mechanical, or envi-
ronmental factors. Errors in growth, or dysplasias, involve
abnormal bone size and shapes, and are often found in
developmental disorders occurring in embryological
development and that play out over development, such as
scoliosis (Fig. 5.4). Skeletal dysplasias can be seen as a
spectrum of connective tissue disorders (Chapter 19).
Rubin (1964) proposed that the various disorders could be
organized according to the anatomic site of the potential
defect: epiphyseal, metaphyseal, and diaphyseal. Some
errors are triggered by environmental cues, such as the
link between maternal folate deficiency and neural tube
defects (spina bifida) (Pitkin, 2007). Likewise, chronic
FIGURE 5.3 Examples of abnormal
bone shape. Left: distinctive anterior
pseudo-bowing of the tibia produced by
pathological apposition of new bone on
the anterior surfaces of the diaphysis in a
clinically documented case of venereal
syphilis (79-year-old female, Terry
Anatomical Collection, NMNH
P0000172). Right: medial bowing and
marked anteroposterior flattening of a left
tibial diaphysis possibly attributable to
rickets or osteomalacia (adult individual;
Huntington Anatomical Collection 850,
NMNH; photo: HDK).
66 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains
FIGURE 5.4 Scoliosis of the vertebral column resulting from develop-
mental errors producing wedge-shaped vertebral bodies and characteristic
abnormal spinal curvature; also note fusion of right inferior rib (59-year-
old female, Terry Anatomical Collection, NMNH P0001636; photo: HDK).
vitamin D deficiency (rickets in children and osteomala-
cia in adults) where elements such as the long bones, cra-
nial base, and pelvic girdle bow or flattened due to their
inability to resist normal weight-bearing owing to insuffi-
ciently mineralized osteoid content (Fig. 5.5).
Other size abnormalities have genetic origins such as
improper expression of Wnt3 in tetra-amelia syndrome
that inhibits the formation of the appendicular skeleton
(Niemann et al., 2004). Achondroplasia (Fig. 5.6) is
another example resulting from a mutation of the fibro-
blast growth factor receptor gene FGFR3. This leads to a
failure of normal endochondral ossification at the level of
proliferating and maturing cartilage, along with impacts
to intramembranous ossification (DiRocco et al., 2014),
but most of the axial skeleton forms and develops rela-
tively normally. Such errors may be understood less as a
“malfunction” of chondroblasts, osteoblasts, and osteo-
clasts, but as those cells faithfully executing impaired
instructions.
Abnormal bone size can also result from elevated
osteoblast activity in a range of morphological forms of
hypertrophy (Fig. 5.7). These conditions may relate to a
state where there is disequilibrium between bone forma-
tion and bone resorption in a bone environment where:
(1) osteoblast and osteoclast formation are both ele-
vated; (2) osteoblast activity is elevated while osteoclast
functioning is normal; and (3) osteoblast activity is
either normal or elevated while osteoclast functioning is
depressed.
Importantly, size/shape variations and abnormal new
bone production do not represent mutually exclusive
phenomena. Hypertrophic conditions can be products of
pathologic processes producing abnormal new bone,
including alteration of the shape of the anterior tibia in
treponemal disease, or localized hyperostosis of the cra-
nium under conditions of chronic anemia, or the general-
ized skeleton-wide hyperostosis of the skeleton in
pachydermia. The other side of this coin included osteo-
petrosis, or Albers Schönberg disease. This features
normal osteoblast functioning but virtually nonexistent
osteoclast activity. Extensive abnormal bone formation
in the endosteal envelope (Fig. 5.8) formed as osteo-
clasts fails to remove bone enlarging the marrow cavity
during growth.
Anatomical factors may produce pathological size
and shape variations. Altered or insufficient vascular
supply to bone can produce necrosis or ischemia. A
compromised arterial blood supply to bone in Calve-
Legg-Perthe disease involves the idiopathic blockage of
arterial supply to the femoral head, which is delivered
almost exclusively from major arteries running by the
neck of the femur (the circumflex arteries). The growing
femoral head cannot receive enough blood from the aux-
iliary artery that passes through the round ligament of
 FIGURE 5.5 Medial bowing of the
left and right femoral diaphyses (left)
(48-year-old male, Terry Anatomical
Collection, NMNH P0000828; photo:
HDK) and tibial diaphyses (right) (65-
year-old female, Terry Anatomical
Collection, NMNH P0000770 charac-
teristic of healed (inactive) rickets.
Photo: HDK).

FIGURE 5.6 Normal adult femur size and morphology (left) and achondroplastic femoral (right). Also note the flaring distal femoral metaphyses and
epiphyses, which is also characteristic of achondroplastic dysplasias (37-year-old female, Terry Anatomical Collection, NMNH P0000512 (left), and 59-
year-old female, Terry Anatomical Collection, NMNH P0001636; photo: HDK).
68 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains
FIGURE 5.7 Hypertrophy of the left and right femoral diaphyses attribut-
able to Paget’s disease. Contralateral lesions on the right femur are clearly
not as severe but abnormal bone formation is still clearly present (75-year-
old male, Terry Anatomical Collection, NMNH P0000531; photo: HDK).
FIGURE 5.8 An example of abnormal bone formation in the endosteal
envelope of a right proximal femoral diaphysis leading to near total
obliteration of the medullary cavity (Huntington Anatomical Collection,
NMNH; photo: HDK).
FIGURE 5.9 Skeletal disuse atrophy (humerus, left; femur; right) asso-
ciated with quadriplegic paralysis for at least the final 16 years of this
individual’s life (21-year-old male, NMNH 6087; photo: HDK).
the head of the femur. The shape of the femoral head
progressively changes as bone tissue necrotizes and
adjacent bone atrophies.
Additional size and shape abnormalities relate to
innervation and biomechanical disease. These alterations
generally follow Wolff’s law. These can involve a spec-
trum of abnormally hypertrophied bone emerging from
excessive strain from high levels of physical activity to a
pathological loss of bone mass/strength and resultant atro-
phy in contexts of disuse or paralysis (Fig. 5.9).
Traumatic injuries span a wide array of abnormal
bone shape/size, bone formation, and bone loss stemming
from fractures, dislocations, cuts, blunt force injuries, dis-
memberment, trepanations, cranial deformation, and burn
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5 69

FIGURE 5.10 Complete fracture of the distal femoral diaphysis. While poorly reduced (aligned), the bone demonstrates very advanced healing
(enlarged view, right) (adult male, NMNH (169) Huntington Anatomical Collection 321053; photo: HDK).

injuries (Redfern, 2016) (Figs. 5.10 5.17). Immediately
following sublethal bone fractures, a repair process begins
with the formation of a hematoma and a cascade of
molecular signaling mechanisms including the master
organizer Runx2 that begin to direct the organization of
the clot into a semistable fibrous mass that is further orga-
nized into bone as repair proceeds (Fig. 5.18) (Lieberman
and Friedlaender, 2005).
Abnormal bone formation and destruction. Abnormal
new bone formation may occur as both periosteal and
endosteal envelopes. On the molecular level, a host of
bone-forming signaling mechanisms can be at play, from
Wnt expression to RANK and OPG ratios. On a tissue
level, conditions that produce passive hyperemia elevate
blood oxygen tension such that the locally negatively
charged environment stimulates osteoblasts (MacGintie
et al., 1993). Abnormal periosteal new bone formation
can be morphologically quite variable (Ragsdale et al.,
1981; Resnick, 2002). While the timing of response is
variable, injury or inflammation to the periosteum will
activate its osteogenic potential such as with treponemal
disease, localized trauma, staphylococcal or
70 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

FIGURE 5.11 Femoral diaphyseal fracture exhibiting a large and relatively well-organized and extensively remodeled bony callous that originated
as a hematoma surrounding the traumatic injury (48-year-old female, Terry Anatomical Collection, NMNH P0000016R; photo: HDK).

streptococcal infection, or scurvy (Figs. 5.19 and 5.20)
as new, reactive bone is rapidly formed. It is initially
highly vascularized and poorly organized but is destined
for remodeling (Figs. 5.21 and 5.22). Contrary to com-
mon use in paleopathology, it is probably incorrect to
refer to such new bone formation as “woven bone” since
usage of that term should be based on histological
identification.
The faster new bone formation occurs, the less orga-
nized the new tissue will be (Figs. 5.23 and 5.24). So-
called “sunburst” formations of spiculated new bone pro-
duced by an adrenoneuroblastoma, for instance, represent
high-velocity abnormal new bone formation when
compared to plaque-like periostosis. New bone formation
typically produces defects with persistent well-defined
borders. New bone formation may also be fundamentally
reparative in function, from callous formation in fracture
repair to inflammation or bone destruction in osteoarthri-
tis, vertebral tuberculosis, or intervertebral disk herniation
(osteophytosis) (Fig. 5.25). In that sense, abnormal new
bone formation in degenerative joint disease is not pro-
duced by the disorder, but rather, it is an attempted repar-
ative response to the underlying pathological condition.
Neoplasms represent accelerated proliferation of
abnormal cells (Brothwell, 2012; Resnick, 2002) that may
be either localized and benign or systemic and malignant
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5 71

FIGURE 5.13 Well-healed depressed cranial fracture affecting the

right posteroinferior parietal bone (adult individual; Huntington
Anatomical Collection, NMNH; photo: HDK).

FIGURE 5.14 Crush fracture affecting the left lateral aspect of the L-5
vertebral body; subsequent remodeling and fusion to the bony sacrum
FIGURE 5.12 Complete fracture of the right humerus characterized by
can be observed (adult individual; Huntington Anatomical Collection
successful union and significant remodeling of the callous (79-year-old
213, NMNH; photo: HDK).
female, Terry Anatomical Collection, NMNH P0000047R; photo: HDK).
72 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

FIGURE 5.15 Abnormal bone loss owing to a surgical intervention

seen here in an example of trepanation; little to no remodeling can be
observed and it is likely this individual did not survive long after the
procedure was concluded (adult male individual, pre-Hispanic Peru,
NMNH 204254; photo: HDK).

(Figs. 5.26 and 5.27). Neoplasms or osteopenia can also

compromise normal bone size, shape, or strength. Bone
tumor types are numerous (Ragsdale and Lehmer, 2012:
Fig. 13.1) but generally can be characterized by the loca-
tion of the types of cells in which they arise (chondro-
blasts, osteoblasts, and osteoclasts) and by their products
(cartilage, fibrous tissue, or bone). Metastatic cancer,
especially breast, prostate, lung, and kidney tumors have
a special affinity for bone (Resnick, 2002; and see below
in Case Study 2: Abnormal Bone Destruction and
Formation discussed at the end of this chapter).
Depending on the neoplasm, resulting bone involvement
can be lytic (e.g., multiple myeloma), blastic (e.g., sarco-
mas), or mixed (leukemia, prostate/pancreatic/bladder/car-
cinoid metastases) (e.g., Klaus, 2016, 2018b). Other more
exotic neoplasms can include bone- and tooth-forming
teratomas that arise from errors in embryological develop-
ment (Wasterlain et al., 2017), and depending on their
size, can become malignant (Charlier et al., 2009; Klaus
and Ericksen, 2013).
Abnormal bone loss can relate to either a failure of
formation or the destruction of preexisting tissue. The for-
mer can include embryological errors such as an epider-
mal inclusion cyst (Ortner, 2003), where epidermal tissue
is improperly sequestered in the mesoderm and bone can-
not form. Destruction or removal of preexisting bone
occurs far more commonly as seen in pathogenic pro-
cesses including the fine vascular response to scurvy in FIGURE 5.16 Abnormal bone size resulting from bilateral amputation
of the lower limbs approximately at the midpoint in the tibia and fibula
the sphenoid bone to more wide-ranging and larger associated with clinically documented chronic syphilis (right side shown
volumes of bone loss seen in brucellosis, tuberculosis, here) (approximately 42-year-old female, Terry Anatomical Collection,
and various metastatic diseases. In these processes, there NMNH P0000745; photo: HDK).
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5
FIGURE 5.17 Pronounced fronto-occipital style of artificial cranial
deformation produced by application of chronic low-grade pressure dur-
ing childhood when the cranium is incompletely ossified (adult female
individual, pre-Hispanic Bolivia, NMNH 390818; photo: HDK).
FIGURE 5.18 Abnormal periosteal new bone formation on the anterior
diaphysis of a right femur; size, shape, and sharply defined margin char-
acteristics, along with the abnormal medial angulation of the superior
diaphysis, are together suggestive of the abnormality’s origin as subper-
iosteal bleeding is associated with a fracture (adult male individual;
Huntington Anatomical Collection (144) 318956, NMNH; photo: HDK).
FIGURE 5.19 Abnormal periosteal new bone formation located on the
anterior crest of the tibia, exhibiting fine, highly vascularized new bone
formation and associated sclerotic activity. Abnormal periosteal new
bone formation (adult individual; Huntington Anatomical Collection,
NMNH; photo: HDK).
73
FIGURE 5.20 New bone formation present on the right zygomatic
bone indicative of an abnormal osteoblastic phenomenon (63-year-old
female, Terry Anatomical Collection, NMNH P0000240R; photo: HDK).
again is a spectrum of predicable responses in relation
aggressiveness and speed of progression. Slowly progres-
sive lytic lesions can feature partially remodeled and rela-
tively regular borders, whereas more acute and
destructive processes will produce highly irregular,
“punched-out,” or “moth-eaten” lesions in appearance
that do not elicit marginal inflammation (Fig. 5.28).
Bone destruction can be seen as a net increase in oste-
oclastic activity, itself a downstream state of the funda-
mental cellular signaling mechanisms that emerge during
a chronic inflammatory event in or around bone (Gosman,
2012). Simply stated, inflammation causes bone to
destroy itself. Related active hyperemia increases tissue
oxygen tension and positively charged solutes in blood
are optimal for osteoclast activity (MacGintie et al.,
1993). Inflammatory disorders are the result of an
immune response to infectious agents such as bacteria,
viruses, parasites, fungi, and autoimmune disorders (Ward
and Lentsch, 1999; Straub and Schradin, 2016). The
inflammatory process begins with a standard, coordinated
vascular cellular response, but bone itself is incapable of
swelling (one of the three biologic manifestations of
inflammation). Inflammation involves an exaggerated
form of normal cell turnover, encompassing elaborate cas-
cades of cell signaling factors and pro- and antiinflamma-
tory signals. Inflammation triggers the recruitment of
leukocytes, activation of macrophages, neutrophils, pha-
gocytes, regulatory interleukins, and other factors that
may ultimately conclude inflammatory and healing pro-
cesses. Importantly, inflammation-driven bone destruction
and reactive new bone formation can coexist in bone, and
represent two adjacent bone microenvironments with con-
trasting osteoblast and osteoclast activity. This is dis-
cussed further later in this chapter. Many such
inflammatory disorders follow these patterns, though a
few exceedingly rare osteoclastic disorders follow their

FIGURE 5.22 As abnormal periosteal new bone is progressively remo-
deled, impressions of blood vessels in the periosteal membrane may
form as the remodeling processes occurs around the adjacent vasculature
(adult male individual; Huntington Anatomical Collection (448) 132316,
NMNH; photo: HDK).
FIGURE 5.21 Abnormal periosteal new
bone formation affecting much of the
diaphysis of this right tibia. Bottom close-
up image demonstrates the presence of
newer, more vascularized tissue (A) and
lesion surfaces exhibiting a greater degree
of age and remodeling (B) (63-year-old
female, Terry Anatomical Collection,
NMNH P0000240R; photo: HDK).
FIGURE 5.23 Exuberant, relatively poorly organized, and generally
rapid idiopathic new bone formation and partial ossification of the inter-
osseous membrane affecting the left tibia and fibula (60-year-old male,
Terry Anatomical Collection, NMNH P0000868; photo: HDK).
 FIGURE 5.24 Manifestations of periosteal new
bone formation on the same tibial diaphysis, demon-
strating a highly vascularized active state of new
bone formation on the left anterior aspect of the
bone (A) simultaneously accompanied by a more
inactive, healing, and remodeling surface on the left
posterior aspect (B) (adult male individual;
Huntington Anatomical Collection (1556) 227958,
NMNH; photo: HDK).

FIGURE 5.25 Examples of abnormal joint morphology. Left: Extensive vertebral osteophytosis and partial fusion between the T12 and L1 vertebral
bodies can often be understood in terms of the pathophysiological response and reparative attempt in response to underlying inflammatory disorders
(Burial 2007-2 DIST, 35 45-year-old individual of indeterminate sex, late pre-Hispanic Peru). Right: similarly, marginal lipping can be observed in
the superior and anterior borders of the glenoid fossa, while purely lytic joint surface porosity of the joint surface itself is related to subchondral bone
death (adult individual; Huntington Anatomical Collection (22.2) ‘93-‘4. NMNH). Photos: HDK).
76 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains
own unique rules, such as Gorham Stout syndrome. Also
known as vanishing bone disease or progressive massive
osteolysis, a still-unknown mechanism(s) abnormally sti-
mulates osteoclasts in the absence of an inflammatory
trigger whereby bone is resorbed and replaced by hyper-
vascular connective and lymphatic tissue (Nickolaou
et al., 2014) (Fig. 5.29).
The five modes of inflammation are septic, granulo-
matous, angiitic, toxic, and reactive (Ragsdale and
FIGURE 5.26 A benign and localized neoplasm in the form of a well-
defined and circumscribed “button” osteoma observed on the anterior
aspect of the right parietal bone (70-year-old male, Terry Anatomical
Collection, NMNH P00000061; photo: HDK).
FIGURE 5.27 Aggressive and purely osteolytic processes affecting the ilium (A) and scapula (B) associated with clinically identified metastasized
breast cancer (48-year-old female, Terry Anatomical Collection, NMNH P0000016R; photo: HDK).
Lehmer, 2012). Septic inflammation is dominated by
polymorphonuclear immune cells that rapidly produce
exudate (pus) that can fill a marrow cavity, strip perios-
teum, and kill bone. Septic inflammation, such as that
seen in osteomyelitis (Fig. 5.30), can generate swelling
and edema in the medullary cavity with increasing pres-
sure, promoting infarction of cortical tissue. The result is
a sequestrum (necrotic bone destined for resorption) and
accompanying involucrum (a shell of new, reparative
periosteal bone). Granulomatous inflammation is a
slower, histiocyte-moderated mode of inflammatory
response. It involves the accumulation of rounded aggre-
gates of macrophages and lymphocytes around a necrotic
focus that spread and can lead primarily to bone destruc-
tion such as with tuberculosis. Angiitic inflammation is
driven by antibody-producing cells (plasma cells, lym-
phocytes) that accumulate around blood vessels and pro-
duce a necrotizing gumma as seen in treponemal
diseases. Toxic inflammation includes rheumatoid arthri-
tis when fluid effusion in a joint triggers an inflamma-
tory response. Reactive inflammation, associated with
viruses and parasitic infection, tends to be the most
localized and least severe in skeletal tissue (Ragsdale
and Lehmer, 2012).
Other disorders feature both abnormal bone loss and
formation. These are associated with biphasic hyperemia
with the disease beginning as active hyperemia but later
transitioning to a passive state such as chronic
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5 77

FIGURE 5.28 Contrasting processes: (A) an example of a chronic and inflammatory condition involving both bone destruction and new bone forma-
tion, particularly notable along the margins of the destructive focus attributable to tertiary syphilis (adult individual, NMNH (1263) Huntington
Anatomical Collection 317848; photo: HDK); (B) a more acute and purely lytic phenomenon producing so-called “moth-eaten” irregular margins in a
case of probable subadult tuberculosis (Burial U10 05-29, Middle/Late Colonial Period, Mórrope, Peru; photo: HDK).
78 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains
FIGURE 5.29 Radiographic view of Gorham Stout syndrome (also
known as vanishing bone disease or progressive massive osteolysis).
This rare osteoclastic disorder involves abnormally stimulated osteoclasts
in the absence of an inflammatory trigger whereby bone (in this case, the
entire mandible) is resorbed and replaced by hypervascular connective
and lymphatic tissue (image courtesy of Dr. Aditya Shetty, Radiopaedia.
org).
osteomyelitis, Paget’s disease, or pulmonary hypertrophic
osteoarthropathy. In the case of gummatous treponemal
lesions, a region of reactive abnormal periosteal new bone
formation surrounds a central destructive focus.
Tuberculosis lesions in vertebral bodies produce signifi-
cant bone loss and mechanical fragility. Reparative new
bone attempts to offset the destruction (Fig. 5.31), but
since osteoclastic activity is far more rapid, greater net
bone loss always occurs, leading to Pott’s disease and
kyphosis. Recognizing a biphasic phenomenon may be
very valuable to disease process identification, such as
with Paget’s disease (Fig. 5.32) and metastasized prostate
cancer both featuring initial lytic activity that later
switches over to abnormal new bone formation.
Metabolic diseases also produce a host of atypical
bone phenotypes through abnormal production, minerali-
zation, maintenance, or as secondary sequellae to meta-
bolic deficiencies. For instance, rickets and ostemalacia
stem from chronic vitamin D deficiency in subadults and
adults, respectively. Improper mineralization of osteoid
leads to mechanically insufficient bone that can bend,
flatten, or otherwise become distorted under conditions of
normal loading. Rachitic bone may also feature “slit/strut”
morphology in metaphyseal regions. These formations
represent parallel zones of alternatingly mineralized and
unmineralized osteoid that provide both greater resistance
to bending and a basis for rapid mineralization when suf-
ficient vitamin D becomes available (Ortner and Mays,
1998: 53).
Skeletal signs of scurvy can be understood as a mani-
festation of vitamin C deficiency that leads to poor-
quality type-I collagen, which produces weakened blood
vessels prone to tearing and hemorrhage. With bleeding
occurring in the periosteal envelope, various osteoblastic
and osteoclastic-related responses occur, including the
removal of bone to make way for new blood vessels and
the formation of new bone from subperiosteal hematomas
(see papers in Crandall and Klaus, 2014). Beyond tradi-
tionally recognized nutritional, hormonal, and environ-
mental factors, other deeper systemic and genetic factors
may underlie generalized disorders of the skeleton are
considered “metabolic” regardless of immediate cause,
including hereditary diseases such as osteogenesis imper-
fecta or osteopetrosis. Yet, a metabolic disorder such as
osteoporosis is probably best understood as a syndrome or
group of diseases resulting in a reduction of bone mass.
Similarly, drawing distinctions between endocrine dis-
eases, nutritional deficiencies, and hereditary syndromes
can logically organize and distinguish such disorders and
is advantageous in terms of diagnostic logic; the underly-
ing pathophysiological processes of systemic skeletal dis-
eases very much form a continuum.
Ultimately, all pathological variations of bone size,
shape, formation, and loss are multicomponent phenom-
ena. To understand them in the most complete way possi-
ble, cultural/behavioral influences to the physiological
components of inflammation, hyperemia, and osteoblast
and osteoclast activity must also be considered. An under-
standing of these conditions ultimately must rest with the
body of knowledge regarding: molecular signaling
mechanisms and gene expressions—and how particular
disease states change, alter, or manipulate osteoblast and
osteoclast signaling to their own ends (see examples at
the end of this chapter). The fundamental factor is the
behavior of the RANKL/RANK/OPG regulatory axis, the
RANKL:OPG ratio, and the expressions of Wnt/β-catenin
pathway (also known as the canonical pathway) (Porth,
2014; Gosman, 2012; also see Chapter 4 and various
chapters in Rosen et al., 2014). This is critical to how
paleopathologists think about identifying and understand-
ing disease processes.
Classify with caution (see Chapter 1). Classification
systems are useful tools but also involve perils. While
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5 79

FIGURE 5.30 Fracture of the left femur demonstrating advanced yet incomplete healing with swelling of the diaphysis and extensive reparative new
bone formation (left); posterior close-up view of the fracture with a single, large draining cloaca resulting from chronic osteomyelitis (21-year-old
male, Terry Anatomical Collection, NMNH P000128; photo: HDK).

they can minimize ambiguity and error in assigning a
given disorder to any of the categories in the system,
they are typologies and do not guarantee unambiguous
assignment (Ortner, 2012). Therefore, the most prudent
way to pursue the necessary classification of abnormal
bone is considering causation and pathogenesis at the
center as the guiding principles for understanding the
disease process (see examples below). The pathologic
and radiographic features of skeletal disorders at various
stages of a disease known from living patients are vital
FIGURE 5.31 Two views of osteoclast-driven bone destruction and osteoblast-mediated responses, including putative attempts at stabilization via
ossification of adjacent connective tissue, are seen here in a case of extensive chronic tuberculosis affecting the T7 L5 vertebral bodies (23-year-old
male, Terry Anatomical Collection, NMNH P000468; photo: HDK).

FIGURE 5.32 Bone destruction and formation can be observed in cases of Paget’s disease, which is a biphasic disorder. Initial and persistent bone
loss affecting the posterior cranium (right) can be contrasted with subsequent abnormal bone formation that has altered the geometry of the facial skel-
eton (adult male, NMNH, Historic New York; photos: HDK).
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5
factors in differential diagnosis, but paleopathology can
only reconstruct disease processes in bone most often
confined only to the last moments of a person’s afflic-
tion and may or may not be the immediate cause of
death (Ortner, 2011). Also, while we depend on analo-
gies with clinical literature for interpreting skeletal evi-
dence of disease, we must recognize that we are making
a uniformitarian assumption (Buikstra et al., 2017). That
is, we would be wise to question whether or not a patho-
logic process unfolded in the past as it does in the clini-
cally observed present, especially when there are
significant discontinuities in ecogeographic space and
evolutionary time. This gives us at least some critical
understandings to evaluate the strengths of any classifi-
catory analogies we may draw.
DIFFERENTIAL DIAGNOSIS
The process of description and process identification in
paleopathology builds toward the final goal—the differ-
ential diagnosis of abnormal skeletal tissue. Quick visual
examination is never sufficient to securely identify a
pathological process. Given the multitude of distinct dis-
eases that can produce similar or overlapping patterns of
pathological bone formation or destruction, the method
of differential diagnosis is a necessary tool in the study
of abnormal bone. A survey of the literature uncovers
multiple “styles” of differential diagnosis. As Buikstra
et al. (2017) emphasize, there are clinical approaches
that focus upon individual skeletons, while in other
cases, a population-based approach may be followed. In
the latter case, key diagrams or pattern-fit methods may
be applied.
Modern paleopathology aims to practice rigorous dif-
ferential diagnosis (Buikstra et al., 2017; Klaus, 2017;
Mays, 2018). Some investigators have sought confirma-
tion of what they deem is a likely diagnosis. Others con-
duct what could be called “snap” diagnoses, drawing on
intuition or appealing to “expert opinion.” Instead, the
most advisable approach is to adapt the methods and epis-
temology using the hypothetico-deductive method of dif-
ferential diagnosis as used in clinical practice.
The relationship between disease and skeletal lesions
is not isomorphic. Accordingly, differential diagnosis is
by nature a probabilistic endeavor. First, one gathers all
available information in the description of a pathological
condition. Second, possible etiological and pathogenic
conditions are identified. Third, the observed abnormal
bone is compared to known disease patterns and contrast-
ing forms of disease are systematically removed from
consideration. Diagnostic options are thus progressively
narrowed down in an exclusionary fashion. As in hypoth-
esis testing, the most likely diagnostic option(s) is that
which cannot be ruled out or rejected. In other words,
81
differential diagnosis is a method that involves a process
of elimination that reduces the probability of candidate
conditions until one or more conditions are concordant
with observations and cannot be excluded.
Plurality, creativity, and differing opinions should
always be encouraged in science, but when it comes to dif-
ferential diagnosis, there is arguably less flexibility regard-
ing best practice. An increasingly rigorous, streamlined,
and systematic approach can reduce interobserver error,
enhance comparability across studies, and produce more
certain and accurate differential diagnoses of skeletal dis-
ease. This can be possible through operationalizing a few
different elements. First, it is key to comparatively and
visually map the anatomical distribution of lesions in an
individual or across a sample. Then, process identification
and pattern matching can make equal use of this frame-
work or rubric to rank potential differential diagnoses to
the progressive exclusion of unlikely diagnostic options.
Once again, the use of rigorous and explicit terminol-
ogy plays a key role in differential diagnosis and the confi-
dence of the assessment. A review of the literature reveals
a wide range of often-ambiguous terminology used in diag-
nosis, from considerations of a lesion being perhaps a
likely candidate condition to claims of pathognomonic cer-
tainty. For the sake of both standardization and logical
rigor, we concur with Appleby et al. (2015) and find great
value in their recommendation to adapt the logic and orga-
nization of the Istanbul Protocol Manual on the Effective
Investigation and Documentation of Torture and other
Cruel, Inhuman or Degrading Treatment or Punishment
(UN, 2004). Appleby et al. (2015: 20) replaced the
Istanbul Protocol’s use of “trauma” with “condition(s)”
and proposed the following criteria:
G Not consistent: the abnormality could not have been
caused by the condition(s) described;
G Consistent with: the abnormality could have been
caused by the condition(s) described, but it is nonspe-
cific and there are many other possible causes;
G Highly consistent: the abnormality could have been
caused by the condition(s) described, and there are
few other possible causes;
G Typical of: the abnormality is usually found with this
type of condition(s), but there are other possible
causes;
G Diagnostic of: the abnormality could not have been
caused in any way other than by the condition(s)
described (i.e., it is pathognomonic).
This system possesses several advantages, including
making the degree of diagnostic confidence overt.
Naturally, we seek the most specific identification of
ancient disease. Ortner (2011, 2012) always stressed that
differential diagnoses must always be restrained—never
to exceed the evidence. Ragsdale and Lehmer (2012) also
82 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains
emphasized the need for a conservative practice of differ-
ential diagnosis. For them, the greatest diagnostic confi-
dence and comparability can be found in the level of
disease identification (see also Miller et al., 1996). In one
example, Klaus and Ortner’s (2014) study of treponemal-
like lesions in a skeleton from early postcontact Peru are
highly concordant with those produced by known cases of
venereal syphilis. Still, there is highly significant overlap
with lesions produced by yaws (another treponemal mani-
festation) with no one specific feature to argue the lesions
were diagnostic of either candidate condition. Therefore,
the differential diagnosis can reject a variety of abnormal
proliferative and lytic conditions but can only say the
lesions are either typical of yaws or venereal syphilis.
It is also equally important to avoid careless diagnos-
tic comparisons between an archeological skeletal abnor-
mality and radiographic or gross images of clinical
patients with skeletal disorders. The legendary American
orthopedic pathologist Lent Johnson, M.D., decried what
he called “ribbon matching” in which he referred to diag-
nostic efforts that attempted to match either a pathologi-
cal gross specimen or a radiograph with an image in an
orthopedic pathology or skeletal radiology text (Ortner,
2011: 6). Instead, Johnson urged paleopathologists to
base their diagnoses in the reconstruction of the patholog-
ical history of a skeletal disorder and then to seek an
understanding of the pathogenesis of the abnormality.
Ortner (2011) extended this excellent advice to all possi-
ble analyses of archaeological examples of skeletal
pathology. When examining a lesion in dry bone, close
examination will allow the observed to identify the prog-
ress of a disease. As part of differential diagnosis, one
should consider the disease process in both soft and hard
tissue, as it culminates in the observed lesion. While this
will not always be possible in every skeleton, it should
still be attempted based upon a reasonably comprehensive
knowledge of basic osteoblastic and osteoclastic
processes.
We end this section by considering a number of epis-
temological and theoretical observations regarding differ-
ential diagnosis offered by Mays (2018). Ultimately,
differential diagnosis involves an attempt to bridge
unknown to known, but we must always question and
improve the ways in which we generate this knowledge.
These include the relationships between heuristic (intui-
tive) and formal analogies, the limitations of comparabil-
ity of archaeological material with the medical, clinical,
and paraclinical literature, and the benefits and shortcom-
ings from comparisons with anatomical reference samples
(Mays, 2018). In particular, Mays (2018: 17) argues for a
greater metacognizance that can prevent “the unthinking
empiricism that reliance on a reference/target sample
methodology can engender.” Of course, reference data
and collections will always be useful, but combining them
with other lines of information is often wise. At the same
time, we need to increase the explicit biological (patho-
physiological) emphasis in understanding of skeletal
lesions, further practical and philosophical evaluation
regarding our uses of analogy, and the potential of
Bayesian methods to reduce diagnostic ambiguity. Further
thinking regarding any uniformitarian notions should be
critically assessed. Continuing advances in genomics,
metagenomics, and proteomics are permitting increasingly
unambiguous forms of direct identification, which may
eventually transcend many of the challenges that currently
face paleopathological differential diagnosis.
CASES OF ABNORMAL BONE: MODELING
DESCRIPTION, IDENTIFICATION, AND
DIFFERENTIAL DIAGNOSES
We close this chapter with a summary of two abbreviated
case studies involving archeological examples of ancient
bone from a site in Peru that attempts to apply examples
of the frameworks described in this chapter. We review
one case dominated by abnormal bone loss and one case
featuring abnormal bone destruction and formation.
Case Study 1: Abnormal Bone Destruction. The arche-
ological site of Ventarrón is located in the Lambayeque
Valley Complex on the arid north coast of Peru.
Ventarrón was a prominent monumental site during
Peru’s precocious Formative era beginning around 2800
BCE (Alva Meneses, 2012). Though abandoned for mil-
lennia, the complex was seen as a sacred locus by later
societies who continued to bury their dead among the
ruins (Klaus, 2018a). Burial 2007-2 DIST-A was a
35 45-year-old individual of indeterminate sex. This
context likely dates to the late pre-Hispanic Middle Sicán
culture (AD 900 1050/1100). The vertebral column dem-
onstrated significant bone destruction between the sixth
and eighth thoracic vertebrae (Fig. 5.33).
The greatest degree of destruction was centralized at
the T7 vertebrae. More than 95% of the vertebral body
had been destroyed, leaving only small intact portions of
the superior vertebral endplates anterior to the left and
right pedicles. The T8 vertebra demonstrated a large
defect present in the anterior aspect of the vertebral body
that had extended anteriorly to destroy nearly all of the
superior vertebral endplate. Well-organized sclerotic new
bone formation was present on the remaining anterior, left
lateral, and right lateral surfaces of the T8 vertebral body.
The left lateral side of the T6 vertebral body was missing
as a large cavity-like defect exposed the trabecular struc-
ture all the way to the anatomical center of the vertebral
body. Well-organized sclerotic new bone formation was
similarly present on the remaining anterior and right lat-
eral surfaces of the T6 vertebral body.
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5 83

FIGURE 5.33 Two views of affected vertebrae diagnostic of pre-Hispanic tuberculosis on the north coast of Peru, with a detailed view of the extent
of bone destruction and osteoclastic activity affecting the T6, T7, and T8 vertebral bodies (right) (Burial 2007-2 DIST, 35 45-year-old individual of
indeterminate sex, late pre-Hispanic Peru; photo: HDK).

Before the differential diagnosis can proceed, we must
evaluate whether these defects are taphonomic in nature.
We can reject the pseudopathological options. These fea-
tures are not consistent with patterns of salt crystal precip-
itation in bone in the region (Verano, 2012; Klaus and
Ortner, 2014). They do not conform to any form of post-
depositional damage caused by looting. There is no evi-
dence of fungal growth, bioturbation (animal or root
activity), or other geological cause (e.g., high water table,
high acidity). These abnormalities were from a biological
process incurred during life. New bone formation on the
T6 and T8 vertebral bodies further validates this
interpretation.
Disease process identification involves these defects
narrowed down to that of a primarily osteoclastic phe-
nomenon of the vertebral column that can be accompa-
nied by some reactive bone. The lack of more extensive
reparative or reactive new bone appears to reflect a rap-
idly progressing, though chronic, condition. Within this
category, the most likely diagnostic options are brucello-
sis, echinococcosis, paracoccidoidomycosis, and tubercu-
losis (see Resnick, 2002; Ortner, 2003, this volume).
Brucellosis is a zoonosis caused by ingesting the milk
or meat of an animal infected by one of three species of
this Gram-negative bacteria. Pulmonary infection fre-
quently disseminates to the skeleton, mainly affecting
noncontiguous vertebrae and frequently destroying verte-
bral endplates and the intervertebral disc. Brucellosis is
not a consistent diagnostic option due to the involvement
of contiguous vertebrae and that endplate destruction here
appears as collateral damage due to the progression of an
osteoclastic process focused in vertebral bodies.
Echinococcosis tapeworms are transmitted to humans via
contaminated meat, crops, or drinking water. Infection
generally begins in the liver with disseminated cases
involving the growth of cysts in bone as part of the para-
site’s lifecycle. Here, these lesions are highly inconsistent
with echinococcosis, including lesion size, the presence of
marginal repair, and the fact that vertebral transverse pro-
cesses and neural arches were spared.
Paracoccidoidomycosis is a fungal infection that pro-
duces either singular or multiple destructive lesions in
marrow spaces. Again, this condition is inconsistent with
these observations, as paracoccidoidomycosis tends to
produce relatively rounded lesions that are far more
numerous, better defined, and distributed on noncontigu-
ous vertebrae. Tuberculosis is acquired by either aerosol-
ized transmission or via consumption of infected animal
84 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains
meat or milk. Disease progression consists of primary
infection and later reactivation with the potential of hema-
togenous dissemination to hematopoietic marrow.
Vertebral lesions associated with tuberculosis are predom-
inantly osteoclastic but as the infection persists and pro-
gresses, increased venous blood flow with reduced
oxygen tension produces a contrasting anoxic bone micro-
environment around the margins of a destructive focus.
Thus, osteoblasts can be stimulated to produce reactive or
reparative new bone around and within the margins of
lytic foci (Resnick, 2002).
Using the modified Istanbul Protocol (Appleby et al.,
2015), we would argue that lesions in Ventarrón Burial
2007-2 DIST-A are diagnostic of tuberculosis.
Mycobacterial infection cannot be ruled out. It is the most
probable diagnostic option. Still, much of the skeleton of
this individual was missing, and one of the bases for a
confident differential diagnosis involves evaluation of
lesion distribution throughout the entire skeleton. The
missing elements here prohibit this broader perspective,
so we may state the lesions are tentatively diagnostic of
tuberculosis. It is, however, always better to err on the
side of caution. In general, however, this set of changes is
consistent with findings from prior, rigorously established
differential diagnoses of tuberculosis (Buikstra, 1981;
Buikstra et al., 2017; Roberts and Buikstra, 2003).
If the differential diagnosis leads to tuberculosis, it is
useful to evaluate the degree of consistency between these
lesions and the known pathophysiology and molecular
signaling mechanisms of mycobacterial disease. Here, we
find high consistency. When tuberculosis disseminates
from the lungs, the bacilli take a hematogenous route
aided by the venous plexus of Baston to the vertebrae. As
an iron-loving bacterium, the rich hematopoietic marrow
inside the vertebral bodies represents the most optimal
environment for bacilli colonization and growth (Wilbur
et al., 2008). A granuloma then forms around infectious
foci in the bone marrow microenvironment. The granu-
loma is surrounded by numerous multinucleated
osteoclast-like and osteoclast precursor cells. These and
other innate immune cells are activated to manage the
infection. They release multiple inflammatory factors
such as IFN-γ, TNF-α, and IL-1. In particular, the
cytokines TNF-α and IL-1 locally disregulate the normal
balance between osteoclasts and osteoblasts. The
RANKL-OPG ratio is altered in the context of tuberculo-
sis infection (OPG downregulated; RANKL upregulated).
In fact, osteoblasts are in charge of the downstream effect
of increased osteoclastogenesis (Li et al., 2016; Zhang
et al., 2015). Pathological bone loss then follows.
Further, experimental evidence suggests that bone
destruction in tuberculosis goes beyond the release of
inflammatory factors. Tuberculosis reprograms osteoclasts.
Hoshino et al. (2014) infected cultured osteoclasts with
tuberculosis bacilli. Their results showed that intracellular
infection of multinucleated osteoclasts resulted in a rapid
advance of tuberculosis infection and prompted an osteoly-
tic response. Tuberculosis bacteria were also able to escape
from the infected osteoclast. This triggered an abnormal
pattern of osteoclast activation rooted in the bacteria’s
manipulation of the osteoclast itself, with development via
dysregulation of cytokine and chemokine expression—the
purposes of which require additional investigation.
Of course, abnormal new bone formation also occurs
in tuberculosis immediately adjacent to the margins of
destructive foci. This means that pathogenic and molecu-
lar signaling pathways within a lytic lesion are more or
less the diametric opposite of what is occurring just
beyond its margins as an attempt at sclerotic repair is
made. Certainly, we may suspect responsible agents are
upregulated Wnt, BMP, and related signaling involving
the RANKL-OPG axis. This also helps highlight the fact
that disease processes may not be characterized in terms
of binary molecular signaling processes (also see
Chapter 8).
Case Study 2: Abnormal Bone Destruction and
Formation. One of the other structures at the Ventarrón
Archaeological Complex involved another Middle Sicán
occupation at the truncated pyramid of Zarpán (Alva
Meneses, 2012). There, 43 funerary contexts were docu-
mented. Zarpán Burial 9 possessed abnormal patterns of
bone loss and bone formation on their L5 vertebra and S1
sacral segment (Klaus, 2018b). This adult male was
40 45 1 years old at the time of death and was generally
very well preserved and complete except for the missing
left and right feet. A complex mixture of bone resorption
and new bone formation were observed on the anterior
and lateral surfaces of the L5 vertebra and S1 segment of
the bony sacrum (Figs. 5.34 and 5.35). These abnormali-
ties featured a mixed reaction involving bone loss and
bone formation. On the anterior aspect of the L5 and S1,
dozens of focal points of bone loss involved well-
circumscribed oval or circular defects, some of the smal-
lest examples of which could be mistaken for enlarged
nutrient foramina. A larger area of contiguous bone loss
destroyed the right anteroinferior margin of the L5 verte-
bra. These lytic loci were accompanied by areas of fine
reactive new bone formation initiated on the right anterior
aspect of the L5, more advanced spiculated bone forma-
tion on the left anterior aspect of the L5, and areas of fine
new abnormal bone formation on the S1 sacral segment,
especially on the left side.
The inferior portion of the L5 vertebra exhibited bone
destruction affecting most of the inferior vertebral end-
plate. Anteriorly, substantial irregular areas of bone had
been resorbed, and were generally surrounded by errati-
cally distributed additional circular or oval foci of pene-
trating bone loss. Additional vertebral margin bone loss
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5 85

FIGURE 5.34 Mixed abnormal bone

resorption and new bone formation on
anterior and lateral surfaces of the L5
vertebra and S1 segment of the bony
sacrum, highly consistent with metastatic
prostate cancer (adult male, Zarpán
Burial 9; photo: HDK).

FIGURE 5.35 (a) Detailed left anterolateral view of the L5 lumbar vertebrae; (b) abnormal multifocal bone loss affecting the inferior vertebral end-
plate of the L5 vertebral body; and (c) abnormal multifocal bone loss affecting the superior vertebral endplate of the S1 vertebral segment of the bony
sacrum (adult male, Zarpán Burial 9; photo: HDK).
86 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains
was present on the left posteroinferior aspect of the L5
body. This lytic process extended into the superior end-
plate of the S1 segment of the bony sacrum. There, the
most significant destruction was again localized on the
left side, and extended into the superior left wing of the
bony sacrum. Vertebral endplate destruction of the L5
and S1 sacral segment was not associated with marginal
new bone formation. The only other pathological pro-
cesses in this individual’s skeleton included well-healed
cribra orbitalia and porotic hyperostosis lesions, as well
as active periodontal disease.
Pseudopathology can be convincingly excluded, as
there are clearly multiple antemortem processes of de
novo bone proliferation and bone resorption. Process iden-
tification of these lesions falls into the range of disorders
that can produce mixed blastic and lytic phenomena in the
inferior vertebral column. These lesions are inconsistent
with osteomyelitis due to the lack of necrotizing foci or
cloaca. Nonspecific periostosis is equally inconsistent as
anterior vertebrae are an extraordinarily rare anatomical
location for nonspecific lesions. Brucellosis should be con-
sidered but can be ruled out as not consistent the basis that
brucellosis is intensely osteolytic, has a predilection for
thoracic vertebrae, and rarely involves new bone formation
(Ortner, 2003). Tuberculosis is inconsistent due to the infe-
rior anatomical location, lack of large destructive foci, and
the presence of endplate involvement. Chronic fungal
infections such as coccidoidomycosis or paracoccidoido-
mycosis are rejected as they are characterized by well-
defined lytic foci, often coupled with sclerotic margins on
noncontiguous vertebrae, clavicles, ribs, and long bones
(Long and Merbs, 1981; Ortner, 2003; Temple, 2006).
An evaluation of sclerosing bone disorders, such as
hypertrophic (pulmonary) osteoarthropathy, melorheosto-
sis, and fluorosis can each be ruled out on the basis of a
clear mismatch of lesion morphology, distribution, and
cooccurrence of lytic foci. Metastatic disorders, however,
can produce a variety of mixed blastic and lytic bone
involvement (Johnson and Sterling, 2013). Most metasta-
ses, such as metastasized breast cancer, are highly osteo-
lytic (Resnick, 2002). Potential diagnostic options such as
multiple myeloma, leukemia, and Hodgkin’s and non-
Hodgkin’s lymphomas can be rejected based on differing
lesion morphology and distribution (Resnick and
Haghighi, 2002). Of all metastatic diseases, prostate can-
cer is by far the most likely to produce osteoblastic
lesions (Resnick, 2002).
The distribution of metastatic prostate cancer is dis-
tinct from the majority of hematogenous metastases, as
this condition has a clear anatomical preference for the
lumbar vertebrae, bony sacrum, and ossa coxae (Resnick,
2002; Ortner, 2003; Coleman, 2006). Related osteosclero-
tic new bone formation may possess radial, sunburst-like
formations. Single or multiple vertebrae may be involved,
and when lesions are confluent over multiple vertebrae,
intervertebral disk spaces may be invaded by cancer cells
(Resnick, 2002: 4304). Clinical findings of abnormal scle-
rosing bone formation on vertebral bodies of older adult
men are nearly always correlated to metastasized prostate
cancer (Resnick, 2002: 4293). New bone proliferation on
the os coxae is highly unique though not quite diagnostic
for disseminated prostate cancer (Ortner, 2003), and diag-
nosis does not oblige pelvic involvement. Any related
bone destruction is characterized by poorly defined,
highly irregular loci (Resnick, 2002; Johnson and
Sterling, 2013). On these bases, we argue that these
lesions are highly consistent with metastatic prostate can-
cer. We are cautious because bladder, pancreatic, and car-
cinoid caners may not be differentiated from prostate
metastases via either visual or radiographic means.
However, differential diagnosis is a probabilistic exer-
cise, and bone involvement in these other cancers is far
less common, especially for carcinoid and pancreatic
malignancies. Even further, the former tends to be pre-
dominantly lytic, while the latter preferentially involves
both thoracic and lumbar vertebrae (see discussion in
Resnick, 2002). The solitary lesion in the T4 vertebra is
very likely to represent another kind of disease process
such as tuberculosis. Thus, comorbidity is possible, if not
likely, in this individual (independent differential diagno-
sis of that abnormality is required, but is a bit beyond the
scope and space that we have here).
Again, we can check our most probable differential
diagnosis of metastasized prostate cancer against anatomi-
cal, clinical, and molecular factors. Anatomical structure
is consistent. In the case of a primary prostate cancer
tumor, the paravertebral plexus of Baston is the most
likely vascular intake point for prostate cancer cells that
seed them directly to lumbar vertebral bodies (Resnick,
2002). The rich hematopoietic marrow, large capillary
networks, and sluggish blood flow in lumbar vertebrae
represent an appealing environment for tumor metastases.
Experimental and therapeutic perspectives demon-
strate disseminated prostate cancer lesions likely begin
with a strong bone resorption component, and as the dis-
ease progresses, the formation/resorption control axis flips
dramatically (Johnson and Sterling, 2013). The patho-
physiology of sustained metastasized prostate tumor
growth requires secretion of osteoblast-derived growth
factors. Prostate cancer cells themselves appear to secrete
multiple Wnt ligands to activate the canonical Wnt path-
way along with multiple other bone-forming factors
within the cancer microenvironment (Klaus, 2018b). In
other words, once the cancer establishes a foothold, osteo-
blasts become the “master switches” manipulated by the
malignant cells for their survival and growth. Also, dis-
seminated cancer cells likely home-in toward specific
organs that provide the most ideal microenvironments for
 Considerations for Documentation, Disease Process Identification, and Differential Diagnosis Chapter | 5
tumor development. The anatomical specificity for lum-
bar, sacral, or pelvic lesions associated with prostate car-
cinomas may reveal the existence of unique and
preexisting molecular “addresses” in these bones for pros-
tate metastases—following the evolving theoretical con-
cept of the premetastatic niche (Clines, 2013).
CONCLUSION
This chapter has provided an overview of key paleopatho-
logical considerations of abnormal bone. The discussion
examined considerations of terminology, the abnormal
behavior of bone cells, general mechanisms of pathology,
and systems for the rigorous description, disease process
identification, and differential diagnosis of skeletal abnor-
malities. Our discipline is grounded by long-established
core competencies involving observational/diagnostic
proficiency and the ability to study disease across broad
geographic, temporal, and evolutionary contexts.
Simultaneously, new developments including clinical, the-
oretical, and methodological advances are emergent
(Crespo et al., 2017; Gosman et al., 2011; Lorenzo et al.,
2015; Thakker et al., 2018). It is hard to envision that
in the future, at least in the near term, where aDNA or
proteomic analyses will truly render obsolete the funda-
mental competencies of description, identification, and
differential diagnosis. These new frontiers represent com-
plementary and synergistic domains for human skeletal
paleopathology, pointing toward diverse new horizons in
the study of abnormal bone.
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