Metabolic Disease

Chapter 15

Metabolic Disease

Megan B. Brickley1 and Simon Mays2 1Department of Anthropology, McMaster University, Hamilton, ON, Canada, 2Historic England, Portsmouth, United Kingdom

INTRODUCTION often a tendency toward collection of the spectacular or unusual (Alberti, 2011; Stephens, 2011). This bias in the Metabolic bone diseases are conditions that cause an reference group may mean that the manifestations of dis- alteration in normal bone formation, resorption, or miner- ease may differ from those likely to be encountered in an alization, or a combination of these; in most conditions archeological target group. In addition, specimens gath- these alterations are systemic. Metabolic bone disease ered for medical pathology museum collections may have may arise due to nutritional problems, hormonal imbal- come from individuals who suffered from multiple condi- ance, or other causes. In this section we consider disease tions, some of which may have affected the skeleton and associated with vitamin C deficiency (scurvy) and vitamin only one of which was diagnosed by physicians. These D deficiency (rickets and osteomalacia), osteoporosis considerations should always be borne in mind when (which normally arises from age-related hormonal using reference material in paleopathology, but are espe- changes), together with certain other conditions arising cially to the fore in metabolic bone disease. For example, from imbalances in bone metabolism. most pathology museum specimens showing vitamin C The classical approach to diagnosis of disease in and vitamin D deficiency show much more severe bony paleopathology is essentially to use lesions in a reference alteration than will usually be encountered in archeologi- group or groups to help us interpret lesions in a target cal material (Brickley and Ives, 2008: 118; Mays, 2008a). individual or population. The target group is archeological It has long been recognized (e.g., Barlow, 1883) that, remains showing pathological lesions. The reference especially in infants, deficiencies of vitamin C and vita- group comprises individuals showing skeletal lesions and min D may often coexist, and some medical museum spe- with independent evidence concerning which disease was cimens diagnosed with rickets also appear to show lesions present. Reference materials comprise specimens from due to scurvy (Brickley and Ives, 2008: 11). Recent medical pathology museums; radiographic and other paleopathological work directed at identification of vita- imaging studies of living individuals also contribute. min C and vitamin D deficiencies has emphasized an Whilst having clear strengths, using lesions observed in a alternative approach, involving careful reading of primary reference population to interpret alterations in a target clinical sources coupled with a close understanding of the group or individual also has limitations. Ideally, we would pathophysiology of the bony alterations, as a means of wish a reference group to be representative of the full augmenting and refining our diagnostic criteria (Ortner, range of skeletal expression of the disease of interest. 2011; Crandall and Klaus, 2014). We therefore use not Medical pathology museum specimens collected prior to only documented cases, but also archeological material to the mid-20th century predate the advent of effective drug illustrate pathology typical of these diseases. For another and other treatments which radically altered the natural major condition discussed in this section, osteoporosis, history of many diseases, an advantage when acting as we are forced to step away from the reference/target pop- reference material for archeological target groups. ulation, lesion-based approach. Osteoporosis is a condition, However, pathology museum collections were assembled often age-related, that involves a decline in bone mass and for a variety of didactic and other purposes, none of in microstructural integrity of bone. Osteoporosis is identi- which were concerned with facilitating paleopathological fied in skeletal remains by direct measures of bone mass or

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright diagnosis. Accessioning and deaccessioning policies were microstructural integrity; in our discussion we emphasize often rather idiosyncratic, and heavily dependent upon the the strengths and weaknesses of applying various methods interests of individual curators (Arnold, 1999). There was to assess these parameters in ancient remains.

Ortner’s Identification of Pathological Conditions in Human Skeletal Remains. DOI: https://doi.org/10.1016/B978-0-12-809738-0.00015-6 © 2019 Elsevier Inc. All rights reserved. 531 Ortner's Identification of Pathological Conditions in Human Skeletal Remains, edited by Jane E. Buikstra, Elsevier Science & Technology, 2019. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/harvard-ebooks/detail.action?docID=5673624. Created from harvard-ebooks on 2020-11-08 16:07:31. 532 Ortner’s Identification of Pathological Conditions in Human Skeletal Remains

VITAMIN C DEFICIENCY long bone. There may also be osteopenia of the trabecular bone of the epiphysis. Mineralization in the provisional Scurvy is a disease caused by inadequate vitamin C. zone of calcification at the growth plate margin is main- Unlike most other animals, humans are unable to synthe- tained and is visible as a thin, more radiodense line at the size their own vitamin C, so are reliant on dietary intake. metaphyseal surface immediately beneath the growth Fresh fruit and vegetables are rich in vitamin C, and smal- plate. This is known as the white line of Fra¨nkel. ler amounts are available in meat, fish, and dairy pro- Similarly, the radiolucent epiphyseal spongiosa tends to ducts. Vitamin C content of foods is diminished by be surrounded by a thin, more radiodense line termed heating (Igwemmar et al., 2013) and, unless air is Wimberger’s ring (Noordin et al., 2012; Agarwal et al., excluded, by prolonged storage (Montan˜o et al., 2006). 2015). The poorly mineralized growing end of the bone Vitamin C deficiency principally reflects faulty diet, food may yield to mechanical forces, resulting in microfracture preparation, or storage. of the spongiosa beneath the growth plate. This may be evident as irregularity or concavity (“cupping”) of the growing end of the bone (Duggan et al., 2007). Repair of SUBADULT SCURVY microfractures may lead to bony spur formation at meta- Neonatal levels of vitamin C are related to maternal physeal margins (Pelkan’s spurs) (McCann, 1962; Tamura levels, and vitamin C is present in breast milk (Agarwal et al., 2000). Some of these alterations are shown dia- et al., 2015). Scurvy is rarely observed before age 4 grammatically in Fig. 15.1, and radiographically in months (unless the mother is deficient in the vitamin) and Fig. 15.2. The most frequent of the bony alterations asso- is most frequent in later infancy and early childhood, ciated with the direct effects of vitamin C deficiency is although it can occur at any age (Gulko et al., 2015). generalized osteopenia (Weinstein et al., 2001), which is Prolonged deficiency is necessary to produce scurvy, per- too nonspecific to aid diagnosis. The other changes are haps for a matter of months, although research in humans less frequent and may not form at all, even in advanced on this point relates to adult rather than subadult cases disease (Tamura et al., 2000; Weinstein et al., 2001; (e.g., Hodges et al., 1971). Akikusa et al., 2003). Most of the above alterations are Historical sources mainly discuss adult scurvy. The removed by remodeling following restoration of adequate first good description of subadult scurvy dates from 17th- vitamin C, but metaphyseal deformity may persist in century England (Still, 1935). It only began to be noted as severe cases (Sprague, 1976). In buried bone, care is a widespread problem in the 1870s when the wealthy began to feed their infants on bread and milk sterilized by heating, which destroyed the vitamin C (Carpenter, 1986: 158172). In 1914, Hess demonstrated that scurvy could be cured by including raw milk, or fresh fruit and vegetables, in the diet, and as the benefits of these dietary com- ponents became more widely known, the frequency of the disease fell (Carpenter, 1986: 172). Vitamin C is a critical modulator of the production of collagen, the main structural protein of bone and other connective tissue. In bone, the effects of vitamin C are complex and incompletely understood, but as well as pro- moting collagen matrix formation, it also (inter alia) pro- motes osteoblastic differentiation and proliferation in osteogenic cells (Aghajanian et al., 2015). Deficient vitamin C results in reduced bone formation, with consequent rarification of trabecular bone and cortical thinning. Although the metabolic effects of scurvy are systemic, in the growing skeleton, alterations are most pronounced at rapidly growing long-bone ends, particularly the distal femur, and at the sternal rib ends. These alterations, most of which are best visualized using radiographic or other medical imaging techniques, are described below.

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright There may be a transverse band of decreased density, visible as a radiolucent line (termed a scurvy line or FIGURE 15.1 Radiographic alterations that may be observed in sub- Tru¨mmerfeld zone) adjacent to the metaphyseal end of a adult scurvy (Brickley and Ives 2008, Fig. 4.7).

Ortner's Identification of Pathological Conditions in Human Skeletal Remains, edited by Jane E. Buikstra, Elsevier Science & Technology, 2019. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/harvard-ebooks/detail.action?docID=5673624. Created from harvard-ebooks on 2020-11-08 16:07:31. Metabolic Disease Chapter | 15 533

describe such lesions (Brickley et al., 2016:93;Klaus, 2017: 6), but in this chapter the term mixed lesion is used. The cranium is a frequent site of hemorrhagic lesions in subadult scurvy, but lesions may also be seen postcranially. The most typical sites for changes are item- ized in Table 15.1, and illustrated in Figs. 15.315.7. Perhaps the most consistent cranial location for osteological hemorrhagic lesions in scurvy is the external surface of the greater wing of the sphenoid bone (Ortner and Ericksen, 1997). Here, major blood vessels lie between the temporalis muscle (one of the major muscles involved in mastication) and the bone. Minor traumata due to con- traction of the muscle would potentially cause bleeding that might elicit an osteological response. Lesions at locations 26inTable 15.1 may also be associated with minor traumata associated with mastication (Ortner et al., 1999). Lesions on the orbital walls may be elicited by eye movement, and cranial vault lesions by minor scalp FIGURE 15.2 Anteroposterior radiograph of the left knee in a modern trauma. Foramina, such as the foramen rotundum of the case of scurvy. In addition to generalized osteopenia, there are radiolu- sphenoid bone and the infraorbital foramen of the maxilla, cent “scurvy” lines running transversely in the metaphyseal bone beneath convey nerves and blood vessels, so bleeding at these the growth plate, and irregularity of the metaphyseal end of the femur structures might potentially be responsible for localization due to microfracturing. Illustration courtesy of Michael Weinstein and the American Academy of Pediatrics. Pediatrics (2001), 108: E55. of hemorrhagic alterations in these locations. Although some vitamin C is required for new bone formation, animal studies (Bourne, 1942, 1943; Murray needed in evaluating radiographic changes. Soil erosion and Kodicek, 1949a,b) suggest that only very small of bone ends or superficial soil infiltration may potentially amounts of the vitamin (2%5% of the dose required to remove or mimic the Fra¨nkel and Wimberger signs. maintain vitamin C saturation) are needed to enable an Collagen is the major structural protein in blood vessel osteoblastic response. Other than in starvation, total walls, so deficiency of vitamin C leads to hemorrhage. absence of vitamin C from the diet is rare. Therefore, pro- When hemorrhage occurs close to bone it may potentially liferative lesions are expected not only in the recovery cause osteological lesions. Outside the circulatory system, phase but also in active disease, and this has been con- blood elicits an inflammatory response (Klaus, 2017). firmed radiographically in humans (Joffe, 1961). Inflammation, or mechanical pressure on the periosteum In the identification of hemorrhagic lesions in subadult from localized bleeding, may provoke an osteoblastic scurvy, care is needed to distinguish abnormal porosity response (Weston, 2012), resulting in new bone deposi- from normal skeletal morphology. It is only once an tion upon the existing cortex. The vascular component of infant reaches about 1 year of age that the fiber bone that the inflammatory response to hemorrhage results in prolif- formed the fetal skeleton is fully replaced by lamellar eration of capillaries in the affected area. This may result bone. Therefore, bones of infants are often rather porous. in localized porosity of cortex to provide pathways for the Even in older individuals, bone at some locations, includ- vessels through bone (Ortner et al., 1999). These pores ing the alveoli, the inferior surface of the hard palate and are characteristically ,1 mm diameter and fully penetrate long bone metaphyses, retains a porous appearance. In the outer cortex (Brown and Ortner, 2011). In addition, such cases, as well as detailed morphological examina- deposits of new bone may show small branching channels tion, comparison with elements from remains of indivi- indicating capillary proliferation, and such “branched duals of similar age at death may help resolve whether or lysis” may also be seen on the normal cortical surface not porosity is abnormal. In addition, care is needed to (Mays, 2008b; Brown and Ortner, 2011). Although distinguish hemorrhagic lesions in the orbit and cranial lesions may take the form of subperiosteal new bone for- vault from lesions due to rickets or anemia. It should be mation and/or porosity of existing cortex, the latter is remembered that these conditions frequently cooccur more frequent (Ortner et al., 2001; Krenz-Niedbała, (Weinstein et al., 2001; Lewis et al., 2006). In any event, 2016). In some instances, both types of alteration may none of the alterations listed in Table 15.1 is diagnostic in

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright occur, with new bone formation upon cortex which itself isolation, but, in combination, they are strongly sugges- shows porosis. A range of terminology has been used to tive of scurvy.

TABLE 15.1 Typical Sites for Hemorrhagic Lesions in Infantile Scurvy

Lesion Location Comments Cranial 1. Sphenoid, external surface, greater wing Generally bilateral and symmetric 2. Zygomatic bone, medial surface/posteromedial surface of maxillary zygomatic process 3. Posterior surface of maxilla 4. Coronoid process of mandible, medial surface 5. Inferior surface, palatine processes of maxillae 6. Maxillary and/or mandibular alveolar bone 7. Orbital walls Superior wall most often affected Alterations may show left/right asymmetry 8. Cranial vault Ectocranial surface more often affected than endocranial 9. Infraorbital foramen of maxilla 10. Foramen rotundum of sphenoid bone Postcranial 1. Long bones Especially metaphyses 2. Scapulae, supra- and infraspinous fossae 3. Ilia

Sources: Ortner and Ericksen (1997); Ortner et al. (1999, 2001); Brown and Ortner (2011); Geber and Murphy (2012); Klaus (2017).

FIGURE 15.3 Left side of the cranium of a child aged about 2 years. There is an area of abnormal porosity focused on the greater wing of the sphenoid bone. (Archeological individual, Pachacamac, Peru.)

Paleopathology Starting in the 1980s, some paleopathological cases of subadult scurvy were reported, diagnosed on the basis of

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright FIGURE 15.4 Posterior part of right maxilla of a 9 10-year-old child the microscopic appearance of subperiosteal new bone showing abnormal porosity (arrowed). (Archeological individual, deposits (e.g., Schultz, 1989; Schultz et al., 1998). Kilkenny, Ireland.) (Geber and Murphy, 2012, Fig. 15.2B.)

FIGURE 15.5 Medial surface, right hemimandible from a child aged about 18 months. There is an area of abnormal porosity at the base of the coronoid process (indicated by arrows). (Archeological individual, Alikianos, Greece.) (Bourbou, 2014, Fig. 15.4.)

FIGURE 15.7 Endocranial surface of left sphenoid of a 3-year-old child showing new bone formation around the foramen rotundum. (Archeological individual, Kilkenny, Ireland.) This figure was kindly supplied by Dr. Jonny Geber.

the dominant approach has been to use his macroscopic criteria (augmented by later authors—see Table 15.1)to identify the disease. On this basis, cases have been identified from early populations in North America (Ortner et al., 2001), South America (Klaus, 2014), Europe (Mays, 2014), Asia (Ortner and Ericksen, 1997; Halcrow et al., 2014), Africa (Pitre et al., 2016), and Oceania (Buckley et al., 2014). In most large collections that have been examined, few cases have been found. Reviewing the European evidence, Mays (2014) concluded from this relative rarity, that in a temperate environment, seasonal fluctuations in vitamin C availability, and year- on-year variations in crop yields must not normally have been enough to induce serious vitamin C deficiency in subadults. Occasional findings of groups with high FIGURE 15.6 Cranial vault of an infant with scurvy showing new prevalences ( . 20%) of subadults showing lesions bone formation on frontal and parietal bones. (WM RCSE S56.4.) suggestive of scurvy were associated with famine or other historic events that disrupted normal food supply However, the value of this diagnostic approach has been (Mays, 2014). questioned, so that until they are reviewed using more A Bronze Age round barrow at Barrow Clump recent diagnostic criteria, their status remains uncertain (Mays, 2008b) provides an early case of scurvy from (Mays, 2014). Little use has been made of radiographic England. The remains date from 2200 to 1970 BC and are diagnostic criteria for identifying scurvy in paleopathol- of a child aged about 2 years. The postcrania survive ogy, perhaps because the fragile metaphyseal ends and poorly, precluding radiographic or other study of the Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright epiphyses are often missing or poorly preserved in arche- metaphyses for signs of scurvy, but the skull was in ological material. Since Ortner’s work in the late 1990s, good condition and shows a constellation of hemorrhagic

lesions. These are summarized in Table 15.2 and illus- Turning to postcranial lesions, scapular alterations are trated in Figs. 15.815.11. Some alterations were slight, illustrated by another European case, from medieval and needed to be carefully evaluated against nonpatholo- Serbia (Brown and Ortner, 2011). This individual (aged gical skeletons from the same site to ascertain that they about two years at death) showed porosis/new bone for- lay beyond the range of normal morphological variation mation at most of the cranial locations listed in (Figs. 15.8 and 15.10). Taken as a whole, the cranial Table 15.1. There were also porotic alterations in the lesions are as expected in vitamin C deficiency, and infraspinatus and supraspinatus fossae of the scapulae the array of alterations cannot credibly support another (Fig. 15.12). These sites underlie the major muscles of the diagnosis. rotator cuff; minor traumata due to arm movements may

TABLE 15.2 Lesions in Burial 6010 From Barrow Clump, England

Feature Type of Alteration Present Sphenoid, external surface, greater wing P Zygomatic bone, medial surface/posteromedial surface of maxillary zygomatic process P Posterior surface of maxilla P Coronoid process of mandible, medial surface P Inferior surfaces of palatine processes of maxillae P Alveolar bone Orbital walls NB, P Cranial vault Ectocranial: P; endocranial NB, P, BrL Infraorbital foramen of maxilla Foramen rotundum of sphenoid N

, no observation possible; BrL, branched lysis; N, no pathological change; NB, new bone formation; P, porosity.

FIGURE 15.8 Barrow Clump, burial 6010. (A) Greater wing of sphenoid bone, showing porosity. (B) A normal bone from a child of similar age for comparison. Although the normal bone shows some pores they are fewer and larger than in the Barrow Clump individual and tend to enter the cortex at oblique angles. Although the alterations in the Barrow Clump sphenoid are less severe than in Fig. 15.3, comparison with a reference bone indicates that the porosis is clearly

FIGURE 15.9 Barrow Clump, burial 6010. Right orbital roof showing new bone formation. FIGURE 15.11 Barrow Clump, burial 6010. Endocranial surface of the right parietal bone showing multiple contiguous bony channels (“branched lysis”). Areas of most intense channeling link with channels whose morphology indicates they conveyed blood vessels, supporting the notion that “branched lysis” alterations reflect proliferation of capillaries on the bone surface.

supplies caused by conflict and natural disasters (see Hess, 1920; Carpenter, 1986). Once growth has ceased, changes in the skeleton due to the presence of scurvy will be limited and subtle. Pathological lesions that develop secondary to hemorrhage will be the primary change found in adult skeletal remains (Brickley et al., 2016). If the condition persists for any time, reduced bone formation will lead to the development of osteopenia, but this type of change is nondiagnostic and poses problems for interpretation in FIGURE 15.10 Barrow Clump burial 6010. (A) Inferior surface of the hard palate of the right maxilla showing porosis. (B) Normal bone from paleopathology (Ortner, 2012). The first reports of possi- a child of similar age at death for comparison. Although the inferior sur- ble cases of scurvy in paleopathology were in adults (e.g., face of the hard palate is normally somewhat porotic, the Barrow Clump Wells, 1967; Saul, 1972). Recognition of the limitations bone is outside of the normal range of morphology. of paleopathology led to extensive research on subadults where pathological changes develop more rapidly, but recently further work on possible cases of scurvy in adult have elicited the lesions. A New World Case, from the skeletal material has been undertaken. Although some of 16th to 17th-centuries AD Shannon site, Virginia, shows the pathological changes found in the subadult skeletal abnormal porosity of the metaphyses of several long bones remains also develop in adults, these lesions occur less (Fig. 15.13). Clinical cases of scurvy often show bleeding frequently and their expression is less clear (Mays, 2014). around the joints (Fain, 2005), and the lesions in this 12- Skeletal changes associated with scurvy include porosity month-old child, who also showed cranial signs of scurvy, at sites of blood vessels in the cranial bones and periosteal are probably in response to periarticular hemorrhage. new bone formation (PNBF) on the cranial and long bones. Mixed lesions occasionally also develop in the cranial bones. ADULT SCURVY In adults, scurvy tends to occur in individuals that have restricted access to food. Food sources can become Paleopathology restricted for various reasons including practicalities of Possible cases of changes in adult skeletons linked to

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright long sea voyages, problems of provisioning armies, pris- scurvy have been proposed in individuals buried at an ons, and other institutions, lack of familiarity with avail- Arctic whaling station at Spitsbergen (Maat, 1982; Maat able foods for those that move, and disruption of food and Uyttershaut, 1984), inmates who died in a workhouse

FIGURE 15.12 Zidine, Serbia, burial LZIDS 18, left scapula. (A) Posterior view, showing porosity in infraspinous fossa. (B) Superior view showing porosity in supraspinous fossa. (Brown and Ortner, 2011, Fig. 15.8.)

during the Great Irish Famine (Geber and Murphy, 2012), early European colonists in North America (Crist and Sorg, 2014), prisoners in an early North American colonial settlement (Brickley et al., 2016), individuals voyag- ing from Europe to the Americas buried on La Isabela, in what is now the Dominican Republic (Tiesler et al., 2014), and workers from a South African mining community (Van der Merwe et al., 2010). In all cases careful evaluation of contextual information was key to using the skeletal changes identified to suggest cases of scurvy. There have been two investigations at archeological sites with good contextual information for the presence of scurvy in which no pathological changes that would allow cases of scurvy to be suggested were identified (Brickley et al., 2006; Cook, 2012). It is likely that many cases of scurvy in past communities will not produce clear pathological changes, and without good contextual information the lack of specificity in the pathological lesions produced may make it difficult to suggest scurvy as a likely diagnosis. In light of the nature of pathological lesions, investigations of attritional cemeteries are unlikely to produce many clear cases of scurvy (Brickley et al., 2016). Comparisons between evidence of pathological conditions in adult and subadult individuals have the potential to provide more nuanced information on social and cultural factors operating in past societies (Mays, 2014). In the case of scurvy, differences in the speed and frequency of development of recognizable skeletal lesions between adults and subadults are sufficiently large that comparisons using currently available techniques are unlikely to produce useful results. Recognition of the earliest cases of scurvy in adult skeletal material relied heavily on PNBF, particularly in

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright FIGURE 15.13 Shannon site, NMNH 382489. (A) Anterior view the postcranial skeleton (e.g., Saul, 1972). Work by Geber proximal humeri. (B) Anterior view, distal femora. Each bone shows and Murphy (2012) on skeletal remains of both adult and abnormal metaphyseal porosity. subadult individuals known to have died during the Great

FIGURE 15.14 Porosity of the greater wing of the sphenoid bone in an adult male (estimated age of death of ./ 5 46 years) from the Kilkenny Union workhouse intramural mass burial ground, Ireland. This figure was kindly supplied by Dr. Jonny Geber.

Irish Famine, during which scurvy was known to have FIGURE 15.15 Slight deposits of subperiosteal new bone formation been a serious problem, identified some of the character- around the infraorbital foramen in an adult female (estimated age at istic changes in adults (see Table 15.1). Amongst the death 2635 years). Slight porosity is also present in the area of the changes found in adults were porotic lesions of the greater alveolar process marked. The individual pictured was excavated from the Kilkenny Union workhouse intramural mass burial ground, Ireland. wing of the sphenoid bone (Fig. 15.14). The pathological This figure was kindly supplied by Dr. Jonny Geber. changes are not as marked as some reported in subadults, but as in other reported cases in adults and subadults the porosity extends onto the temporal bone. Active areas of porosity with small deposits of sub-PNBF were present at a number of cranial areas including the infraorbital foramina (Fig. 15.15). In Fig. 15.15, slight porosity can also be seen along the alveolar process. Pathological changes to the gums are commonly mentioned in both contemporary and past texts covering scurvy in adults (Fain, 2005). In adults, dental eruption can be excluded as a cause for such change, but extensive dental pathology present in many past communities makes it hard to be certain that porosity observed is linked to scurvy (Brickley et al., 2016). The medial surface of the mandibular rami, in the region above the mandibular foramen, is another area in which porosity, hypertrophy, and slight areas of new bone formation have been reported in the skeletal remains of individuals suggested to have had scurvy. The very slight deposits of new

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright bone formation in this region in an individual with other FIGURE 15.16 The medial surface of the mandibular ramus foramen in an adult male (estimated age at death 2635 years). The individual clear changes suggesting the presence of scurvy illustrate pictured was excavated from the Kilkenny Union workhouse intramural the very slight nature of some of the pathological changes mass burial ground, Ireland. This figure was kindly supplied by Dr. formed in cases of scurvy in adults (Fig. 15.16). Jonny Geber.

VITAMIN D DEFICIENCY of the gut, liver, and kidney (Resnick and Niwayama, 1988: 20892126). Most of these conditions are rare and/ Vitamin D is essential for calcium and phosphorus metab- or would not have been survivable for prolonged periods olism. In the absence of adequate levels of the vitamin, in the absence of modern medical care. Historically, the there is reduced absorption of these minerals from the gut. most important cause of vitamin D deficiency was inade- The resultant serum hypocalcemia stimulates the release of quate acquisition of the vitamin. Given the importance of parathyroid hormone. This has the effect of mobilizing cal- ultraviolet light in its synthesis, exposure of the skin to cium stores from the skeleton, and there is increased loss sunlight is crucial. Although there is less solar ultraviolet of phosphorus in the urine (Holick, 2006, 2007). The effect at higher latitudes, cultural factors that limit the exposure of vitamin D deficiency is therefore poor mineralization of of skin to sunlight are of prime importance in determining bone formed during growth and remodeling. the frequency of the disease in populations. The adoption Most foods naturally contain little vitamin D, but it is of indoor lifestyles, the use of enveloping clothing, or liv- synthesized in the body via the action of ultraviolet light ing in an urban industrial environment where tall, closely upon the skin. This produces a chemical precursor, 7- spaced buildings and atmospheric pollution combine to dehydrocholesterol, which then undergoes successive limit sunlight reaching ground level are key variables hydroxylation in the liver and kidney to produce 1,25 (Brickley et al., 2014). dihydroxyvitamin D, which is the most physiologically Historical sources are a rich body of evidence con- active form (Henry and Norman, 1992). cerning rickets in the past. The first convincing descrip- In subadults the term rickets is commonly used to refer tions come from 1st-century AD Rome (Jackson, 1988: to diseases caused by lack of availability of vitamin D, in 38). The first clinical treatises come from mid-17th- adults it is termed osteomalacia. century England (O’Riordan, 2006), and it was then that it seems first to have become a regular problem. The prevalence of the disease increased sharply with industri- RICKETS alization, so that by the early 20th century, it affected up Rickets may be produced by a variety of conditions that to 90% of children of the poor in some cities in northern affect vitamin D metabolism, including various disorders Europe (Steinbock, 1993). By the mid-20th century it had

TABLE 15.3 Some Macroscopic Abnormalities That May Occur in Rickets

Feature Active/Healed 1. Cranial vault porosity A 2. Orbital roof porosity A 3. Cranial vault thickening H 4. Deformed mandibular ramus 5. Rib bending deformity 6. Costochondral rib flaring 7. Costochondral rib porosity A 8. Ilium concavity 9. Bending deformity—upper-limb long bones 10. Bending deformity—lower-limb long bones 11. Long-bone metaphyseal flaring/cupping of ends 12. Long-bone general thickening H 13. Long-bone cortical (especially metaphyseal) porosity A 14. Superior flattening femoral metaphysis 15. Coxa vara

16. Porosis/roughening on bone underlying growth plates A Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright A, presence denotes disease active at time of death; feature generally removed by remodeling in healed cases. H, presence denotes healed/healing disease. Remaining features may be seen in both active and healed cases.

become rare once more, as a result of treatment and pro- phylaxis using vitamin D-rich cod liver oil (Loomis, 1970). Rickets rarely appears before 4 months of age unless the mother was herself vitamin D-deficient (Maiyegun et al., 2002), and cases rarely develop after 4 years. Bone changes may be divided into those that arise directly due to metabolic disturbance, which leads to inadequate mineralization of bone deposited during growth, and biomechanical deformation of the weakened, poorly mineralized bone. The former are seen most readily at bone surfaces undergoing rapid endochondral or appositional growth. The latter are usually most pronounced in weight-bearing elements. Some of the bony changes most useful in identification of rickets are listed in Table 15.3 and are described below. Defective mineralization of bone deposited beneath the growth plate leads to subchondral porosis and irregularity. Where severe, this may be visible in radiographs of living patients (Fig. 15.17) as “fraying” of bone ends (Thacher et al., 2000; Pettifor, 2003). Changes are most often seen at the diaphysial ends of long bones (Fig. 15.18), but in archeological material care is needed to distinguish this from postdepositional erosion. Deficient mineralization of bone deposited in appositional growth leads to porosity of external cortical surfaces. In vivo, the pores and other defects on growing surfaces are filled with osteoid. Cortical porosity may occur at most subperiosteal surfaces but is often most evident on the external cranial vault (Fig. 15.19), orbital roofs (Fig. 15.20), and in metaphyseal parts of long bones; at FIGURE 15.17 Rickets in a 5-year-old child. There is widening, cup- the latter locations care is needed to distinguish pathology ping, and fraying of the distal ends of radius and ulna. Courtesy of the from the normal slight porosity seen there. When ade- University of Virginia. quate vitamin D is restored, the pores are filled in with bone and obliterated, so the presence of porosity denotes disease active at death (Table 15.3). Because much oste- when upper limbs may be more affected. In the femur, oid may accumulate, ossification on recovery often results diaphyseal bending most often takes the form of accentua- in thickening of bones. In the cranium this thickening is tion of the normal anterior curvature, and the area of shar- often greatest at the frontal and parietal bosses pest angulation is often in the subtrochanteric area. There (Fig. 15.21). Flaring of long-bone metaphyses may also be flattening of the superior surface of the proxi- (Fig. 15.22) and sternal rib ends (Fig. 15.23) may occur, mal metaphysis and/or coxa vara (Fig. 15.22). Tibiae and and seems to reflect both increased width of the growth fibulae most often show medial and/or anterior bowing; in plate and biomechanical deformation of the weakened the tibia there may be localized medial tilting of the distal bone. Mechanical forces may also result in concavity end, and the fibula shaft is often flattened. Sometimes (cupping) of diaphyseal ends; the distal ends of the tibia new bone is deposited on the concave side of bending and forearm bones and the sternal rib ends are favored deformities, thickening the cortex on that side. Upon sites (Figs. 15.17 and 15.23). Bending deformity (or less recovery, bone deformity may be progressively removed often, pathological fracture) is most often seen in the long by growth and modeling, but in some cases it may remain bones, but sometimes in other elements, particularly the into adult life. The frequency with which residual defor- ribs and mandibular condyles. Among the long bones, mity remains depends upon the severity and timing of deformity tends to be greatest in the lower limb, unless childhood disease, but Hess (1930) suggests 10%25%

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright disease was active when the infant was still crawling of cases of rickets may retain noticeable deformity.

FIGURE 15.18 Sequence to show increasing severity of porosity and roughening of diaphyseal bone underlying the epiphyseal growth plate in active rickets. (A) Proximal end of a tibia of a 9-month-old infant showing normal morphology. (B) Distal radius, 1824-month-old child showing slight roughening, giving a “velvety” texture (the exposed trabecular bone toward the bottom in the photograph is a postdepositional artifact). (C) Distal end of a femur from a 3-month-old infant showing more marked roughening. (D) Distal end of a tibia from a 3-year-old child showing marked porosis. There is also concavity (“cupping”) of the bone end. (E) Distal end of a radius from a 612-month-old infant showing extreme roughening and porosis. (Archeological bones, (A), (C), (E) from Wharram Percy, UK; (B), (D) from St Martin’s Birmingham, UK.)

FIGURE 15.19 Ectocranial surface of a cranial vault fragment from an infant aged 68 months showing severe porotic alterations. FIGURE 15.20 Left orbital roof from an infant aged about 8 months, (Archeological individual, Wharram Percy, UK.) showing marked porosis. (Archeological individual, Wharram Percy, UK.) Radiographic signs of active rickets include diffuse osteopenia, coarsening and thinning of the trabecular struc- (qv) are present (Goodman et al., 1994; Adams, 1997; ture, and loss of corticomedullary distinction (Thacher Mays et al., 2007). These alterations are gradually removed

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright et al., 2000; Pettifor, 2003; Mays et al., 2006). Upon as the child recovers. microscopic study, evidence of defective mineralization Some of the more subtle alterations seen in dry bone should be visible, and indications of hyperparathyroidism would not be visible on clinical imaging, but the

FIGURE 15.23 Sternal rib-ends. The top three bones from a child aged about 8 months showing signs of rickets, displaying porosity of cortex and “cupping” of their ends. The lower bone is a normal example for comparison. (Archeological bones from Wharram Percy, UK.) FIGURE 15.21 Cranium of a 7-month-old infant with rickets, showing porotic bone deposition focussed on the frontal and parietal bosses (PMUG 2465, autopsy 6115, 1874). mechanical deformities, and the more severe grades of porotic change seen at growing surfaces, appear to be the dry bone manifestation of alterations that have been documented radiographically in living patients (e.g., Thacher et al., 2000; Pettifor, 2003). In combination, the alterations described above represent compelling evidence of childhood vitamin D deficiency.

Paleopathology Sporadic paleopathological cases of rickets have been noted from around the world (Littleton, 1998; Angel et al., 1987; Pfeiffer and Crowder, 2004), but most come from Europe. A few European cases date back to the prehistoric or Roman periods (Bennike, 1985: 213214; Blondiaux et al., 2002), but frequencies in populations increase (up to c. 34% in some cases) in post-medieval urban industrialized groups (e.g., Clevis and Constandse- Westermann, 1992; Brickley et al., 2006; Henderson et al., 2013; Ellis, 2014). Clusters of cases occurring earlier than this, or in post-medieval rural groups, have occasionally been reported, with factors such as swaddling of infants (Veselka et al., 2015), sickly infants being con- fined indoors (Ortner and Mays, 1998), or cultural avoid- Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright FIGURE 15.22 Femur from a 2 3-year-old child showing signs of ance of exposure of skin to sunlight (Littleton, 1998) rickets (left), together with a normal comparative bone (right). The dis- being invoked as explanations. eased bone shows marked flaring and cortical porosis of the distal metaphysis, and, at the proximal end, coxa vara and superior flattening of the There are 21 cases of rickets among 164 subadults metaphysis. (Archeological individual, St Martins, Birmingham, UK.) from 19th-century St Martin’s churchyard, Birmingham,

FIGURE 15.24 St Martin’s Birmingham, UK, burial HB772. Distal FIGURE 15.26 St Martin’s Birmingham, UK, burial HB772. Scanning ends of radius and ulna, showing flaring and cortical porosis. electron micrograph, trabecular bone. Some areas of newly formed bone (A) are darker, indicating poor mineralization. Defective cement lines (open arrows) are also evident. The long arrows indicate areas of erosion of trabecular bone within trabecular elements.

mineralization of more recently formed bone and defective cement lines (Fig. 15.26). Taken together, these alterations are consistent with rickets; the porotic alterations, and the radiographic and microscopic changes suggest disease active at time of death. There are also indications of hyperparathyroidism. Radiographically, lin- ear radiolucencies were evident within cortical bone, giving it a longitudinally striated appearance (Fig. 15.25). Microscopically, there is erosion of trabecular bone from within trabecular elements (Fig. 15.26). These alterations are consistent with the skeletal effects of hyperparathyroidism, which is expected secondary to vitamin D deficiency. Two medieval subadult cases from medieval Wharram Percy illustrate biomechanical deformities characteristic of rickets. Burial V57 is an infant aged 612 months. The skeleton is rather incomplete but shows abnormal porosity of cortex, and of bone underlying the growth plates on long-bone diaphyses, indicative of active vitamin D deficiency. The only intact long bone is the left FIGURE 15.25 St Martin’s Birmingham, UK, radius burial HB772 (at radius, which shows marked angulation of the distal end left) with a normal radius for comparison (right). (Fig. 15.27). Consistent with the age of the individual, this suggests active vitamin D deficiency, whilst the England. Among these is burial HB772, a child of about infant was still crawling. Lower-limb bone deformity is 3 years. The distal metaphyses of all long bones, save the evidence on an older infant (burial SA070, approximately humeri, showed flaring and abnormal porosity of cortex 18 months). This child shows predominantly healed (Fig. 15.24), as did some sternal rib ends. There was lesions (thickened ribs, long bones), but there is some roughening of the bone underlying the endochondral porosity of the cranial bones suggesting that disease growth plate at the distal ends of the tibiae (Fig. 15.18D), recrudesced shortly before death. The arm bones show lit- radii, and ulnae. Radiographically, there was osteopenia, tle deformity, but there is abnormal angulation of the loss of normal corticomedullary distinction and coarsen- mandibular condyles (Fig. 15.28) and abnormal curvature

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright ing and thinning of cancellous bone structure (Fig. 15.25). of ribs and femora (Fig. 15.29). The latter show marked Scanning electron microscopy of a section taken from localized anterior angulation in the subtrochanteric area. the distal radial metaphysis showed poor levels of The tibiae are rather damaged and difficult to assess for

FIGURE 15.29 Wharram Percy, UK, burial SA070. There is abnormal anterior curvature of the femur shaft, most pronounced in the subtrochanteric area (arrowed).

FIGURE 15.27 Wharram Percy, UK, burial V57. Left radius showing abnormal angulation toward its distal end.

FIGURE 15.30 A femur from a 19th-century adult from St Martin’s Birmingham, UK (disarticulated bone D3). The bending deformity suggests that this person suffered from rickets as a child.

diaphyseal bowing, but the deformation of the femora suggests active disease after the child had begun walking, which normally occurs at about 12 months (Størvold FIGURE 15.28 Wharram Percy, UK, burial SA070. Posterior view of Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright the right mandibular ramus; there is abnormal angulation of the mandib- et al., 2013). Similar femoral deformity, persisting into ular condyle (arrowed). On the left is a normal individual for adult life, is illustrated by another case from St Martin’s, comparison. Birmingham (Fig. 15.30).

OSTEOMALACIA development of osteopenia, and in adults profound bone loss has been reported in those with vitamin D deficiency Pathological changes to the skeleton in cases of osteoma- (Reid and Bolland, 2014). Bone loss is, however, a non- lacia are reliant on bone turnover and so require a longer- specific skeletal change linked to advancing age and a standing deficiency to manifest, and in most cases will be variety of pathological conditions that can cooccur, so is far less marked than skeletal changes in subadults. In of limited value in suggesting the diagnosis of a specific investigations where deficiency has been considered in condition in paleopathology (Ortner, 2012). both adults and subadults, cases of skeletal pathology are Skeletal changes include deformation due to the accu- much higher in subadults who are undergoing bone mulation of osteoid (Jaffe, 1972; Mankin, 1974) and path- growth and development (Mays et al., 2006; Brickley ological fractures at sites of osteoid accumulation et al., 2007). The development of osteomalacia due to an (Mankin, 1974; Albright et al., 1946; Hodkinson, 1971; underlying pathological condition is possible in adults Lips et al., 2013). Common sites for changes are listed in from past communities, but would be relatively rare. Table 15.4. The most marked changes occur in bones In many cases muscle weakness and bone pain would with a high remodeling rate due to considerable trabecular have been the main symptom of osteomalacia, with some bone content. Buildup of osteoid can eventually result in individuals having limited mobility (Stapleton, 1925). The bones literally folding; affected vertebral bodies can severe bony deformity and extensive pathological frac- resemble a crumpled tin can. Both deformity and fractures tures that have been collected in European pathology commonly occur in the thorax, with ribs, sterna, and ver- museums (Brickley et al., 2005) would only have tebrae often affected. The systemic nature of the condi- occurred in the most extreme cases. Descriptions of osteo- tion, however, means long bones can also develop malacia in historical sources are limited (see brief review pathological changes, with those of the leg more fre- in Maxwell, 1947), but due to the desperate consequences, quently affected than arm bones (Hess, 1930; Jaffe, deformity to the pelvis (Fig. 15.31) causing complications 1972). The weight of the body or simple daily activities of childbirth has received quite a bit of attention. Severe can be sufficient to produce these changes (Figs. 15.32 pelvic deformities have been reported from a number of and 15.33). Pseudofractures are a key feature of osteoma- regions including Europe, India, and China (Hess, 1930: lacia, occurring due to a build-up of osteoid. Clinically 317 20). pseudofractures appear on radiographs as zones of high In both adults and subadults the failure of newly radiolucency (Steinbach et al., 1954; Mankin, 1974; Pitt, formed bone matrix to mineralize can lead to the 1988: 2096). Frequently, fractures develop at these sites

FIGURE 15.31 Active osteomalacia. Pelvis and lumbar spine that show maximal malacic deformity of the cardboard- like bones and delayed fusion of the growth plates. This individual, an 18-year-old male (DPUS 7664c and 7664d, 1896), displayed changes across the skeleton with bending deformi-

TABLE 15.4 Typical Sites for Bone Deformation and Pseudofractures in Osteomalacia

Lesion Location Comments Postcranial 1. Ribs Deformation can be hard to identify in fragmented bone Pseudofractures, often multiple. Particularly common where corsets were worn, but also noted in noncorset- wearing communities 2. Scapulae Deformation of blade, exaggerated posterior curvature Pseudofractures noted at spinous process and lateral boarder 3. Iliac crest Deformation Pseudofractures 4. Pubic bone Deformation Pseudofractures 5. Spine Compression fractures of vertebral body Pseudofractures noted on transverse processes 6. Long bones Deformation From macroscopic assessment it can be difficult to establish when the deformity occurred. Deformity more common in cases of rickets Pseudofractures Any bone can be affected, but more commonly noted locations include the femoral neck 7. Sternum Deformation 8. Sacrum Deformation Cranial 1. Extensive porosity and “cardboard-like” texture reported in pathology museum collections. Not observed in archeological bone to date 2. Invagination of foramen magnum. Not observed in archeological bone to date

Sources: Brickley et al. (2005), Brickley and Ives (2008), Ives and Brickley (2014).

and, observed on dry bone, slight raised areas of spicu- Analysis of evidence for systematic mineralization lated bone will often be present at the margins and in defects in dentin (defects have been termed interglobular fractured ends as a result of often long-standing impaired dentin) offers the potential to identify individuals who attempts at repair. Unless very extensive it is unlikely experienced past deficiency. Interglobular dentin pseudofractures (Stapleton, 1925) or deformity would (Fig. 15.34) is formed when some of the calcospherites, have been noticed by affected individuals. Maxwell groups of crystals that compose dentin, fail to fuse, result- (1930) states that the extent to which bending deformity ing in hypomineralized (poorly mineralized) areas that and fracture are present in cases of osteomalacia is very have a marbled appearance when thin sections are viewed variable. It is likely that expression and distribution of microscopically using polarized light (D’Ortenzio et al., these features will depend on the length and severity of 2016). deficiency experienced coupled with habitual activities undertaken. In considering activities all things from the

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright wearing of a corset to lifting and carrying heavy objects Paleopathology and the customary mode of sitting or standing should be Vitamin D deficiency can occur at any stage of life, and considered. it is likely that individuals who are affected once will

FIGURE 15.32 Osteomalacia skeleton with severe pelvic and thoracic deformity. Notable rib deformities are present from the weight of the arms. Other features present are angulated protruding sacrum and the folded iliac wings. (Adult female; died after seventh pregnancy; PMES 1 QAM(1).)

have a high probability of being affected multiple 2007; Mensforth, 2002; Schamall et al., 2003a,b). The times (Brickley et al., 2014). This adds a certain level skeletal changes associated with osteomalacia are easily of complexity to examination of pathological features, overlooked and it is likely that many cases have not been but consideration of this point increases the potential con- spotted because the observers were not specifically look- tributions paleopathological investigations can ing for the condition. A large-scale study of pathological make regarding the experiences of individuals in past changes found in archeological skeletons undertaken communities. using UK sites (c. AD 17001855) revealed examples of

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright The number of paleopathological investigations under- pathological fractures in many areas of the skeleton (Ives taken to date is relatively small (Brickley et al., 2005, and Brickley, 2014). Ribs, which have been noted to be

frequently affected by deformity and fractures (Jaffe, 1972; Pettifor and Daniels, 1997), were the bones most often affected. The prevalence of rib fractures in the study by Ives and Brickley (2014) was probably influenced by corset wearing amongst females, but individuals with numerous fractured ribs and multiple fractures in a single rib have been reported by clinicians working with noncorset-wearing communities (Jaffe, 1972). Deformity can be viewed by macroscopic examination of bone in paleopathology, as can many pseudofractures. Features of pseudofractures such as disorganized and poorly formed bone callus (spiculated bone) produced by individuals with vitamin D deficiency are discussed by Brickley and Ives (2008, pp. 118119). Recent work in the Roman site (1st2nd century AD) of Velia, Italy, identified a case of osteomalacia in an older adult female (VEL94). Pathological fractures were identified across the thoracic skeleton, scapulae, ilium (Fig. 15.35), ribs (Fig. 15.36), and a lumbar vertebra. A clear pseudofracture was present in the left scapula (Fig. 15.37). On the right scapula an area of spiculated new bone formation was located on the spinous FIGURE 15.33 Severe osteomalacia with angular kinking of sacrum through a segment (arrow) from sitting. (43-year-old female; FPAM process, a classic site at which pseudofractures have 5676.) been recorded in other archeological skeletons (Ives

FIGURE 15.34 Histological image of interglobular dentin observed in a thin section of a first maxillary molar from an adult with past deficiency. The circle marks an area of extensive mineralization defects (grade 3 interglobular severity, D’Ortenzio et al., 2016) from St. Matthew, Quebec City, Canada (AD 17711860). This figure was kindly supplied by Dr.

FIGURE 15.35 (M3) Pseudofracture on left ilium, immediately lateral to the superior portion of the sacroiliac joint. There is a slight raised area of spiculated new bone formation around the margins of the fracture (V94, Velia Italy).

FIGURE 15.36 (M4) Pseudofracture of a right rib. (A) The two sides of the pseudofracture. (B) End-on view of the left side of the rib fracture with clear build-up of spiculated bone that will have formed as the body attempted to heal the fracture (V94, Velia, Italy).

and Brickley, 2014). Radiological examination would have helped determine whether a pseudofracture was present on the right scapula, but was not possible in this case. The location of the lesions was not symmet- rical between the left and right sides. A probable pseudofracture, that was not quite as clear as the others, was present at the inferior articular process of a lumbar vertebra (Fig. 15.38); if this was the only fracture present there is a strong possibility it would have been overlooked. Careful examination of the margins revealed spiculated bone, and in light of the other fractures present in this individual and previously reported FIGURE 15.37 Pseudofracture of the left scapula located immediately cases of fractures in the transverse processes of verte- inferior to the spinous process. A raised area of poorly formed fracture brae (Ives and Brickley, 2014) the fracture is taken as callus (outlined with white oval) with a small curvilinear fracture line Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright a pseudofracture. running across part of the area is present (V94, Velia, Italy).

CO-OCCURRENCE OF RICKETS AND SCURVY Situations that leave individuals open to poor health often facilitate the development of multiple pathological conditions. The term co-occurrence is used where multiple conditions occur simultaneously; it may also be possible to suggest the occurrence of multiple conditions at different stages of the life of an individual. Rickets and scurvy, which were frequently noted to cooccur in past clinical work, have now been identified from a number of archeological sites (see review in Schattmann et al., 2016). Features of both conditions as set out in Tables 15.1 and 15.3 need to be present to suggest a case of co- occurrence. A number of the lesions that can develop in rickets and scurvy are similar; in archeological bone it may be impossible to determine the cause of these lesions. Interaction of the two conditions, order of initia- tion, and severity will all influence lesion appearance. Consideration of disease stage is an important aspect of evaluation of c-ooccurrence. In scurvy there will be impaired osteoid formation, thus limiting the development of bone deformity in rickets. Rickets will be far more visible if it occurs first and bone deformity due to an accu- FIGURE 15.38 Location of the probable pseudofracture marked with mulation of osteoid has time to develop. In contrast, an arrow on the right inferior articular process of a lumbar vertebra hemorrhage, a key feature of scurvy, will not be disrupted (V94, Velia, Italy). by the presence of rickets (see Fig. 15.39); these issues

FIGURE 15.39 Individuals from Saint-Ame´ collegiate church in Douai, France (AD1500 and AD 1776). (A) Cranial changes in co-occurrence case, porosity on the sphenoid greater wing, S56. (B) Ribs showing pathological features of rickets and scurvy co-occurrence. Clear porosity and flaring of the sternal ends, S264. Comparison of long bone deformity in the left humerus. (C) Cases of co-occurrence of rickets and scurvy. Left hand bone, S221 has no bending and slight abnormal curvature is present in S208 (right). (D) More marked deformity in case

are discussed more fully by Schattmann et al. (2016). bone mass. In rheumatoid arthritis, activation of osteo- Those authors found use of macroscopic, radiological clasts near joints affected by the disease leads to localized assessment of rickets and scurvy, and histological assess- osteoporosis (Sommer et al., 2005). Conditions that inter- ment of rickets facilitated identification and interpretation fere with collagen formation (e.g., vitamin C deficiency), of pathological lesions observed. or that prevent adequate absorption of calcium from the gut (e.g., vitamin D deficiency or inflammatory bowel disease) may lead to systemic loss of bone mass, as may a OSTEOPOROSIS variety of other types of conditions (Mirza and Canalis, When there is sustained alteration of the normal balance 2015). However, in paleopathology, most attention has between bone formation and bone resorption in favor of focused upon the progressive, systemic loss of bone mass the latter there is loss of bone mass (osteoporosis). that occurs with advancing age. This reflects the impor- Osteoporosis may occur secondary to some diseases or to tance of age-related osteoporosis in modern populations. injury or immobility, and may be either localized or sys- Osteoporosis weakens the skeleton and leads to a propen- temic. In addition, systemic loss of bone mass is an sity to fracture, often consequent upon only minor trauma, accompaniment of the aging process in the adult. so that it presents a major health threat to the elderly Localized reduction of biomechanical forces, such as today. may occur to a limb that is injured or paralyzed leads to Bone mass is built up during the growth period, and localized osteoporosis in the affected area (Fig. 15.40). peaks in early adult life, but from middle age onward, Systemic loss of bone mass may occur in those with spi- bone resorption generally outstrips bone formation so that nal cord injury or in individuals who are bed-ridden there is progressive loss of skeletal mass. In osteoporosis,

(Sieva¨nen, 2010). Some diseases lead to localized loss of bone resorption occurs from the endosteal envelope Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright FIGURE 15.40 Anteroposterior radiograph of long bones from the lower limbs of a male adult burial (6th century AD, Austria). This individual had suffered an amputation of the left foot. The left leg bones (to the right in the radiographs) show thinned cortical bone and rarified spongiosa, consistent with osteoporosis due to reduced weight bearing on the affected leg. (Fig. 15.12 from Binder et al., 2016.)

FIGURE 15.41 Anteroposterior radiographs of three second metacarpals from (from left to right) young adult, middle aged, and elderly females excavated from St Bride’s Lower Churchyard, London, UK (post-medieval), to illustrate progressive thinning of cortical bone with age. (Brickley and Ives, 2008, Fig. 6.2.)

(Parfitt, 2003; Szulc and Seeman, 2009). There is rarifica- bone mass, osteoporosis is less severe in men (Khosla tion of trabecular bone. The normal slow apposition of and Riggs, 2005). cortical bone continues subperiosteally (Lazenby, 1990), Osteoporosis is clinically silent until fracture occurs. but this is not enough to compensate for loss at the endos- Fractures may affect any skeletal element, but sites rich teal surface so that there is progressive thinning of corti- in trabecular bone are most vulnerable. Characteristic cal bone. There is also increased intracortical porosity. fracture sites are the hip, wrist, and spine. Hip fracture Because of its greater metabolic activity, there is earlier (Brunner and Eshillian-Oates, 2003) occurs in the proxi- and greater loss of trabecular bone (Riggs and Melton, mal femur, most often in the region of the neck 1986) and losses here lead to alterations in bone micro- (Figs. 15.43 and 15.44). Due to the nature of the blood structure, an aspect of “bone quality” that, in addition to supply at the proximal femur, fracture union is often bone mass, influences resistance to fracture (Grynpas, problematic and hip fractures may lead to significant dis- 2003). Perforations occur in the trabecular structure, inter- ability and increased risk of mortality (Brunner and rupting its continuity, so that mechanical strength is com- Eshillian-Oates, 2003). Osteoporotic fracture due to a fall promised to a greater extent than simple loss of mass on an outstretched hand may lead to fracture of the distal would predict. Some age-related changes in cortical thick- radial metaphysis, with dorsal angulation of the distal ness and trabecular bone microarchitecture are illustrated fragment—Colles’ fracture (de Brujn, 1987). Vertebral in Figs. 15.41 and 15.42. compression fractures, which may result in forward angu- The amount of bone mass retained into old age is lation of the spine or in biconcave “cod-fish” deformity dependent both on peak bone mass attained in early adult- of the vertebrae, may occur during normal activities such hood and on the amount lost during the aging process. as lifting. They mainly occur in the lumbar spine and in A multiplicity of environmental, lifestyle, and genetic thoracic segments below T3 (Griffith et al., 2013). factors influence these parameters, but sex hormones play a pivotal role (Carnevale et al., 2010; Clarke and Khosla, 2010). In females, there is a phase of rapid bone Methods in the Study of Osteoporosis in loss following menopause, with a slower rate of loss Paleopathology

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright thereafter. Males also lose bone with age, but because Paleopathological studies of hip fracture (e.g., Curate they lack the early phase of accelerated loss seen in et al., 2011; Ives et al., 2017), Colles’ fracture (e.g., women, and because they normally attain higher peak Mays, 2006a), and vertebral compression fracture (e.g.,

FIGURE 15.43 Basic fracture types in the region of the femoral neck.

FIGURE 15.44 Right femur from an elderly adult male from medieval St Mary Spital, London. There is a healed fracture of the femoral neck, with inferior displacement of the head. Comparison with Fig. 15.43 iden- FIGURE 15.42 Vertical section of fourth lumbar vertebral bodies from tifies this as a subcapital fracture. (Walker, 2012, Fig. 208.) female adults from medieval Wharram Percy: (A) aged 1830 years, (B) aged 3050 years, (C) aged 50 1 years, to demonstrate age changes in trabecular bone structure. (A) Three-zonal arrangement of cancellous bone, characteristic of a young adult. Superior and inferior zones of Curate et al., 2016) have been undertaken. However, frac- dense cancellous bone surround a central band of more open trabecular structure. (B) Thinning of trabecular structure, especially by loss/thin- tures at these locations may occur due to trauma in indivi- ning of horizontal trabeculae, is evident. (C) Further rarification of can- duals showing no reduction in bone mass, so the presence cellous bone is apparent. Some very long, slender trabeculae are evident, of these types of fracture is insufficient to diagnose osteo- and the loss of many horizontally orientated trabecular elements means porosis. The dominant approach to studying osteoporosis that the course of some vertically orientated struts can be traced through in past populations has been to identify patterns of loss of most of the height of the vertebral body.

FIGURE 15.45 Dual-energy X-ray absorptiometry (DXA) scan of the proximal femur of a 58-year-old woman from the Coimbra identified skeletal collection (early 20th century, Portugal). The rectangular box drawn across the femur neck defines the area scanned for bone mineral density (BMD) measurement at the neck. The smaller box within this defines Ward’s triangle, an area of low bone density where the greatest age-related loss of BMD generally occurs. The scanner calculates BMD at these and other sites in the proximal femur and tabulates the results. (Curate, 2014, Fig. 6.)

Measurement of Bone Quantity However, these are arbitrary diagnostic thresholds In clinical practice, and in biomedical research, the “gold imposed upon what is a continuous process of BMD loss. standard” for assessment of bone status in osteoporosis is Rather than using BMD to classify individuals as osteopo- measurement of bone mineral density (BMD) using dual- rotic or not, most paleopathological work has taken a energy X-ray absorptiometry (DXA). This uses an X-ray more exploratory approach, investigating age patterning source that emits beams at two different energy levels. in BMD. Radiographic or other imaging, microscopy, and This allows attenuation specifically due to bone to be iso- chemical analyses can be used to check for diagenetic lated and used to calculate BMD. Scanned sites are gener- alterations that might alter BMD readings in ancient ally those that are most vulnerable to fracture: the hip bones (Mays, 2008a,b). (Fig. 15.45), spine, and wrist. This produces a measure- Cortical bone may be quantified by taking measurement of areal density (i.e., g.cm2) rather than a true (volu- ments of cortical thickness from radiographs—a method metric) density (Lees et al., 1998), so results are not fully termed radiogrammetry. In clinical practice, measurement normalized for bone size. Because archeological bones is normally taken at the metacarpals. The method predicts lack marrow and soft tissue, absolute BMD, measured bone density and fracture risk at the hip, spine, and wrist, using DXA, is not directly comparable with data from liv- and is a rapid, low-cost way of screening patients for ing subjects. Therefore peak BMD cannot be compared osteoporosis (Ka¨lvesten et al., 2016). Clinicians use an between skeletal and living populations. However, pro- automated method which involves measurements at meta- vided significant diagenetic alteration in BMD can be carpals 2 4. This has not been applied to archeological excluded, patterns of age-related loss of BMD can be material, due in part to the requirement for three intact compared between living and ancient populations. The metacarpals limiting sample size in the fragmentary and World Health Organization defines osteoporosis as a incomplete remains typical of the archeological record. BMD, measured using DXA, .2.5 standard deviations Paleopathologists typically use an older method in which

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright below the young adult mean for individuals of the same measurements are taken at the second metacarpal alone, sex; a value of between 1.0 and 2.5 standard deviations either with calipers from hard-copy radiographs (Ives and below the mean is termed osteopenia (WHO, 1994). Brickley, 2004), or digitally using image analysis. Results

radiography in the last decade of the 19th century it was impossible to evaluate bone mass in living patients. Therefore, to investigate osteoporosis in the past we are reliant on paleopathological studies. These have focused on investigating patterns of bone loss with age in the past and on assessing the health impact of the disease through study of osteoporotic fracture. Because the study of osteoporosis in the past is based on measuring bone status in individuals of different ages, rather than identification of lesions, its study has demanded a population-based FIGURE 15.46 Schematic diagram of a second metacarpal showing the method for measuring total bone width (T) and medullary width (M) approach rather than one focused on case studies of iso- from anteroposterior radiographs. Measurements are taken at the mid- lated skeletons. A key avenue of investigation has been shaft, and cortical index is calculated as 100 3 (TM)/T. the extent to which patterns of age-related loss of bone in the past resemble or differ from that seen today (reviews in Mays, 2008a; Curate, 2014). are usually expressed in terms of cortical index, a mea- One skeletal collection in which osteoporosis has sure of thickness of cortical bone standardized by bone been extensively studied is that from medieval width (Fig. 15.46). In dry bone studies, the metacarpal Wharram Percy, England (summarized in Mays, 2007). can be positioned for radiography in an orientation that Among the variety of techniques that have been used to closely mimics that used in radiographic work on living assess bone status in this group is DXA of the femoral subjects. This means that, provided that bones showing neck. Studies were done to assess whether readings soil erosion or other damage are excluded, results on skel- might be affected by soil ingress or by postdepositional etal remains are closely comparable with older clinical chemical alteration of bone. Femora were radiographed and and biomedical studies, which used second metacarpal any that showed soil intrusion were excluded from study. radiogrammetric measurements. Unlike BMD, both peak Microscopic analysis showed little evidence for minor soil cortical bone thickness and patterns of loss can be directly ingress that might have escaped detection on radiography; compared between living and skeletal populations. chemical and microscopic analyses suggested no great changes to bulk mineral content or composition (Turner- Measurement of Bone Quality Walker and Syversen, 2002; Mays, 2003). This seemed to support the validity of using DXA to assess osteoporosis Bone quality comprises various structural parameters of in this population. bone that affect fragility, including bone microarchitec- The results for the Wharram Percy women, together ture, mineralization, and material properties (Grynpas, with some modern comparative data, are shown in 2003). An aspect of bone quality that can be fairly readily Fig. 15.47. Recalling that absolute BMD measured using assessed in paleopathology is microarchitecture. Bones DXA cannot be directly compared between living subjects may be physically sectioned, and microstructural features and dry bone studies, comparisons were restricted to age- captured photographically or microscopically (Agarwal related patterning. Given the shortcomings in currently et al., 2004). High-resolution computed tomography pro- available methods of estimating age from skeletal vides an alternative, noninvasive method of capturing remains, individuals were assigned to the broad age at three-dimensional images of trabecular structure (Macho death classes. It seems likely that menopause generally et al., 2005), and potentially facilitates comparisons began in the late 40s in the past, as it does today (Pavelka between archeological skeletal remains and modern data and Fedigan, 1991). Comparing BMD in 3049 and gathered on living individuals. In trabecular bone, various 50 1 age groups suggests a similar postmenopausal loss microstructural parameters may be measured using image to today. A problem with this comparison is that if the analysis, including trabecular number, thickness, and con- age composition of the 50 1 age group differed between nectivity (Agarwal et al., 2004). Aspects of cortical the Wharram Percy group and the modern reference sam- microarchitecture, such as intracortical porosity, may also ple then this could prejudice comparisons. In an attempt be quantified (Agnew and Stout, 2012). to deal with this problem, the age composition of the 50 1 group at Wharram Percy was modeled using medieval demographic data from historical sources. This sug- Paleopathology gested that if anything the women in the 50 1 group at

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright As long ago as the 18th century, physicians began to note Wharram Percy were likely to have been younger than that bones in elderly people were more vulnerable to frac- those in the same group in the modern reference popula- ture (Brickley, 2002), but prior to the advent of tion used for the comparative data in Fig. 15.47. This

suggests that postmenopausal bone loss in the Wharram Percy women was likely no less than in modern subjects, although it leaves open the possibility that it was greater. Unlike the modern population, the medieval women showed evidence of significant reduction on BMD in the 3049 age group compared with the 1829 group. This suggests significant premenopausal loss of BMD. Reasons for this are unclear but one factor may be losses of BMD due to prolonged lactation combined with poor nutrition, and/or hormonal changes consequent upon poor energy balance due to high levels of physical activity coupled with inadequate nutrition (Mays, 2010). Some vertebral compression fractures were identified in the Wharram Percy women (Fig. 15.48). Despite the age-related loss of BMD demonstrated at the hip, no hip fractures were found. One reason might be that too few women survived into the advanced old age groups at which hip fractures typically tend to occur. However, additional studies of the Wharram Percy bones suggested other possible explanations. Study of trabecular bone quality (Agarwal et al., 2004) suggested trabecular microstructural integrity was conserved into old age, perhaps helping to offset the effects of loss of BMD on bone strength. In addition, the relative length of the femur neck was less at Wharram FIGURE 15.47 Bone mineral density at the femoral neck in women from Percy than in a modern reference group (Chumley et al., Wharram Percy, UK (N 5 54), compared with results from a living reference 2004). Shorter femoral necks tend to be less vulnerable to population (Lunar Corporation, 1993). Although absolute BMD figures from fracture (Cummings et al., 1994). dry bones cannot be directly compared with reference data from living popu- Successful study of BMD in trabecular bone-rich loca- lations, valid comparisons of age-related patterns can be made. tions in the skeleton demands well-preserved remains. At

FIGURE 15.48 Healed compression fractures of the bodies of the twelfth thoracic and first lumbar vertebrae from an elderly female from Wharram Percy, UK. This individual had a femur neck BMD approximately four standard deviations

another British cemetery site, Ancaster (3rd4th century AD), many of the femora and vertebrae were damaged or showed soil ingress, precluding use of DXA. Instead, radiogrammetry of the second metacarpal was used (Mays, 2006b). Plain-film radiographs were taken, and total width and medullary width were measured using calipers, and cortical index calculated (Fig. 15.46). The results are shown in Fig. 15.49. Mean peak cortical index, taken as the value in women in the 1829-year group, was less than the modern group. This was also a finding for Wharram Percy (Fig. 15.49) and appears to be a general pattern in past populations (Mays, 2008a). Reasons for this are unclear, but one factor may be poorer nutrition in the growth period—this is known to lead to deficient apposition of cortical bone (Himes et al., 1975). At both Ancaster and Wharram Percy, there was evidence for premenopausal loss of bone. Comparison of cortical index in 3049 and 50 1 age groups suggested postmenopausal bone loss was greater at Ancaster than in modern women (Fig. 15.49), a pattern that demographic modeling using Roman written sources suggested was unlikely to be due to discrepancies in the age composition of the 50 1 age group. A total of six Ancaster females showed eight oste- FIGURE 15.49 Metacarpal cortical index in women from Ancaster, UK (N 5 39). Data from women from Wharram Percy, UK (N 5 67) and oporotic fractures—one hip, four Colles’ fractures (Mays, a modern female reference population (Virtama and Helela¨, 1969) are 2006a)(Fig. 15.50), and three vertebral compression frac- also included. tures. Unlike other fractures, these injuries were only seen

FIGURE 15.50 Medial view of radii from an elderly female burial from Ancaster, UK. The right radius shows a Colles’ fracture (arrowed) through its distal metaphysis. The fracture is firmly healed and shows the dorsal angulation of the distal fragment (“dinner fork deformity”) char-

in the 50 1 age group. The frequency of these types of magnesium), renal function, and possibly genetic factors fractures was greater than at Wharram Percy, presumably all play a role in the pathological consequences of exposure reflecting the lower cortical index in the Ancaster women. to high levels of fluoride (DenBesten and Li, 2011). Why the Ancaster females should have suffered osteopo- Dental fluorosis will reflect exposure to fluoride dur- rosis more severely than their modern or medieval coun- ing enamel development and in most cases the permanent terparts was unclear. dentition, which forms during childhood, is affected (Jarvis et al., 2013). Disrupted mineralization of enamel is the primary pathological change associated with raised Conclusion fluoride intake. Changes include subsurface porosity, G The study of osteoporosis in the past demands a hyper- and hypomineralized areas, and marked pitting population-based rather than case study-based approach. (hypoplastic defects) in severe cases. Dentin formation G Ideally, several different methods of assessing bone can also be affected, but these changes are less well status (quantity, quality) should be brought to bear so understood (DenBesten and Li, 2011). The system of clas- that a fuller picture of age-related patterns in the group sifying and recording dental fluorosis developed by Dean under study can be obtained. (1942), the dental fluorosis index, which allows enamel G Study of fractures should be integrated within this changes to be recorded for each tooth is still considered approach. the “gold standard” for clinical recording (DenBesten and G Attention should be paid to possible diagenetic effects Li, 2011). on DXA BMD studies. Skeletal fluorosis develops in cases of prolonged G Attention should be paid to the potential effects of exposure to high levels of fluoride (Perumal et al., 2013). imprecision in currently available age estimation tech- In adults, levels of skeletal fluorosis have been noted niques for adults when interpreting results. to increase with age (Shruthi et al., 2016), but skeletal fluorosis can also occur in subadults, most often following rapid bone growth in adolescence (Jarvis et al., 2013). Skeletal changes include an increase in density (osteo- FLUOROSIS sclerosis) and ossification of skeletal attachment sites of Fluoride is essential for normal development and mainte- ligaments and tendons (Gupta et al., 2016). Bone formed nance of bones and teeth (Perumal et al., 2013) and is is of poor quality and pathological fractures can occur. added to drinking water in many areas of the world to There is considerable subperiosteal and endosteal bony increase the ability of dental enamel to resist caries accretion, often accompanied by increased resorption in (WHO, 2011). Naturally high fluoride concentrations in the old cortex on long bones (Fig. 15.51) (see Aggarwal, water are found in many regions of the world, but have 1973). Skeletal fluorosis in subadults can result in defor- been noted to be unusually high in some areas (e.g., areas mity of weight-bearing bones (Jarvis et al., 2013). of the United States, with the highest levels recorded in Idaho, parts of India, China, South America, and Iran). Many foodstuffs, particularly those derived from vegeta- Paleopathology tion, also contain at least traces of fluoride (DenBesten Fluorosis has not been widely studied and this is probably and Li, 2011). Exposure to fluoride can also occur though a reflection of relative levels of paleopathological inhalation of fluoride dust from burning fluoride-rich research undertaken in areas of the world where fluoride coal, although in homes where such coal is used most in the water supply has been present at toxic levels. The fluoride is probably ingested from foods contaminated earliest cases of fluorosis were reported from the site of during cooking and drying (Qin et al., 2009). Mehrgarh in Baluchistan (Lukacs et al., 1985). Dental Levels of fluoride added to water for therapeutic pur- pathology associated with fluorosis was found in nine poses usually result in water with between 0.5 and 1 part skeletons from two levels dating between 7000 and 4000 per million (ppm) (DenBesten and Li, 2011; units con- BC. The abnormalities are limited to staining and pitting verted using unit conversion.org). Fluoride of ,2 ppm of the enamel of adult teeth and no lesions were found in can cause dental fluorosis with mottled enamel develop- the bones. ment (Shomar et al., 2004) and levels of .3 ppm can Both dental and severe skeletal fluorosis were present lead to the development of skeletal fluorosis (Jha et al., in the skeleton of an adult male (aged 45 1 ) from a site 2013). Research has demonstrated that the type of expo- in Bahrain dated to about 2100 BC (Frohlich et al., sure (chronic exposure to low levels vs acute exposure to 19871988). Brown staining and pitting were present on

Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright high levels), type of intake (ingested vs inhaled), age when the enamel, lesions characteristic of skeletal fluorosis exposure occurs (which will affect type and speed of tissue were present in the spine, and fusion of ligaments that formation), nutrition (e.g., availability of calcium and connect the vertebrae can be seen in Figs. 15.52 and 15.53.

FIGURE 15.51 Severe fluorosis. Radiograph of a cross-section of a femur that shows massive subperiosteal bone deposition and some intracortical resorption. (Adult Asian Indian male. Courtesy of Dr. Niranjan Das Aggarwal, Rajendra Hospital and Medical College, Patiala, India.)

FIGURE 15.53 Skeletal evidence of fluorosis in a burial from an archeological site in Bahrain dated to about 2100 BC (shown in Fig. 15.52). (A) T9T12 vertebrae fused into a single block of bone. The fused vertebrae were broken postmortem. (B) Mineralized connective tissue partially filling the neural canal, and there is partial minerali-

zation of the intervertebral disk on the inferior vertebral body. Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright FIGURE 15.52 Skeletal evidence of fluorosis in a burial from an archeological site in Bahrain dated to about 2100 BC. Right lateral view of the completely fused spine.

Bone formation in the neurological canal (Fig. 15.53)could have been associated with some neurological problems. Bone also formed in the interosseous ligaments of the forearm (Fig. 15.54). Littleton and colleagues also identified individuals with both dental (Fig. 15.55)and skeletal changes indicative of fluorosis from historic Bahrain (Littleton and Frolich, 1989; Littleton, 1999). More recently, cases of fluorosis have been recognized from a number of geographical contexts with individuals with both skeletal and dental evidence for fluorosis reported from the Ray Site (Middle Woodland, 50 BC to AD 400) in west-central Illinois (n 5 8/117) (Nelson et al., 2016).

HYPEROSTOSIS FRONTALIS INTERNA Hyperostosis frontalis interna (HFI) is a condition in which the endocranial surface, principally on the frontal bone, displays marked thickening through deposits of bone. Only the cranial bones are involved. Hershkovitz and coworkers (1999) report that the condition was first described by Morgagni in 1769, and it is frequently observed during modern autopsies (Bracanovic et al., 2016). There is a strong relationship between age and sex and the presence of HFI. Females are more likely to have the condition than males, and both prevalence and severity have been noted to increase with age, with the highest FIGURE 15.54 Skeletal evidence of fluorosis in a burial from an archeological site in Bahrain dated to about 2100 BC. Mineralization of levels seen in postmenopausal women (Bracanovic et al., the interosseous ligament between the radius and ulna on both sides. 2016). Links with sex and age are sufficiently strong that HFI has been investigated as a way of establishing probable sex and age at death in forensic examinations (May et al., 2011). No significant differences in occurrence linked to ancestry have been reported (Hershkovitz et al., 1999; May et al., 2011). The most common location of the lesion is the frontal bone, but cases that involve the temporal, parietal, and very rarely, the sphenoid bones have been noted (Nguyen et al., 2015). The thickening occurs as a result of expan- sion of the diploe¨, with increased porosity noted in the endocranial bone (Bracanovic et al., 2016). Although various symptoms have been reported as a consequence of HFI (Bracanovic et al., 2016), HFI does not usually cause significant clinical disease and is often an incidental finding (She and Szakacs, 2004). HFI was originally thought to be a feature of one of the syndromes that affect multiple organs, but is now known to occur independently (Raikos et al., 2011). Hormonal factors are now believed to be the most likely cause with strong consideration of the possible role of the sex hormones; at present there are FIGURE 15.55 Mottled and pitted enamel on the labial surfaces of the insufficient data to make firm statements on the pathogen- maxillary central incisors of an adult diagnosed with fluorosis from an esis (Bracanovic et al., 2016).

early Dilmun period tomb Bahrain c.22001800 BC. The irregular non- Copyright © 2019. Elsevier Science & Technology. All rights reserved. rights All Technology. & Science Elsevier 2019. © Copyright chronological pitting near the crown with staining is characteristic of There has been some discussion of the possibility that fluorosis teeth beyond the whitening seen with modern fluoridated water there has been a rise in prevalence of HFI, potentially supplies. Picture courtesy of Dr. Judith Littleton. linked to changes in parity, breastfeeding, and increases

known individuals, the study by Western and Bekvalac (2016) study recorded HFI to clinical standards to investigate the effects of industrialization, age, and parity on the condition. Age was found to be the primary factor in the development of HFI, but at 15.9% the prevalence was lower than that reported for more recent and current groups. This research provides a good overview of considerations pertinent to paleopathological work and current ideas on the condition (Western and Bekvalac, 2016).

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