http://informahealthcare.com/ijf ISSN: 0963-7486 (print), 1465-3478 (electronic) Int J Food Sci Nutr, 2014; 65(2): 172–176 ! 2014 Informa UK Ltd. DOI: 10.3109/09637486.2013.854741
FOOD AND NUTRITION SURVEYS
Bone porosity and longevity in early medieval Southern Croatia Kristijan Becˇic´1, Darija Jandric´ Becˇic´1, Marija Definis-Gojanovic´1,2, Sandra Zekic´ Tomasˇ3, Ivana Anteric´4, and Zˇeljana Basˇic´4 School of Medicine, University of Split, Split, Croatia, 2Clinical Department for Forensic Pathology, Clinical Hospital Center Split, Split, Croatia, Clinical Department for Pathology, Clinical Hospital Center Split, Split, Croatia, and 4University Center for Forensic Sciences, University of Split, Split, Croatia
3
Abstract
Keywords
Porosity of the skull and skeletal remains, especially of the orbital roof, are one of the most frequent pathological findings on ancient human skeletal remains. There are several presumed causes of this condition and anthropologists consider skull porosities as a marker of physical and nutritional stress. A total of 115 graves were discovered at the early-medieval graveyard near Zadar (Croatia) that contained 128 partially preserved skeletons. Average estimated age at death was 37.2 12.6 years for men, 31.9 13.9 for women, and 5.3 3.6 years for subadults. Pathological bone porosity was analysed. Cribra orbitalia was observed on 21 skulls (28.7%), signs of temporal porosity were noticed on six skulls and signs of subperiosteal bleeding on three skulls. Nineteen skulls had bone porosities in other areas. There was a significant difference (p ¼ 0.039) in achieved age of adults with and without cribra orbitalia as those with cribra orbitalia lived on average 8.1 years longer. The bone porosity was probably caused by malnutrition that might have had a beneficial effect on longevity of adults, similar to effects of restricted food intake on extending lifespan through epigenetic signatures influencing gene expression.
Anemia, cribra orbitalia, porotic hyperostosis, rickets, scurvy
Introduction The study of skeletal remains, age at death, signs of infectious diseases and archaeological information are pieces of the puzzle of reconstructing the lives of ancestors. Signs of trauma, osteoarthritis and Schmorl’s defects (protrusions of the intervertebral disc though the vertebral body) are markers of physical stress. Bone porosities and deformities, as well as subperiosteal hematomas are markers of nutrition quality (Novak & Sˇlaus, 2010; Sˇlaus, 2006). Besides determining basic demographic data of human skeletal remains excavated in southern Croatia, this article focuses on pathological bone porosity and discusses possible causes. The analysed sample is dated from the seventh to ninth century and represents the first Croatian population that inhabited mid-Dalmatia. Porotic hyperostosis is one of the most common pathological finding on archaeological skeletal remains, usually described as areas of cranial pitting on the outer skull surface (Novak & Sˇlaus, 2010; Sˇlaus, 2006; Walker et al., 2009). Type of porotic hyperostosis found on orbital roofs is called cribra orbitalia. Since different pathological conditions are considered as cause of porotic hyperostosis in adults and subadults, in order to establish the etiology it is important to evaluate the distribution of porosity on whole skeleton. It is often accepted that porotic hyperostosis is caused by bone marrow hypertrophy due to the iron deficiency anemia. Such conclusion is based on the findings of a several epidemiological studies of modern clinical cases, where radiograph images showed porotic hyperostosis-similar patterns on the Correspondence: Kristijan Becˇic´, School of Medicine, University of Split, Sˇoltanska 2, 21000 Split, Croatia. Tel: +385 98 910 9740. E-mail: [email protected]
History Received 18 March 2013 Revised 6 October 2013 Accepted 9 October 2013 Published online 12 November 2013
skull (Novak & Sˇlaus, 2010; Sˇlaus, 2006; Walker et al., 2009). Porosity of the growth plate and specific pattern of lesions in subadults indicate rickets (Aufderheide & Rodriguez-Martin, 1998; Sˇlaus, 2006). Megaloblastic and hemolytic anemia (more severe forms, like thalassemia major and sickle-cell disease) have also been reported as possible causes of porotic hyperostosis (Hershkovitz et al., 1997; Ortner, 2003; Walker et al., 2009). It was hypothesised that several other diseases, like parasitism, periostitis, rickets and scurvy, might cause porotic hyperostosis without bone marrow hypertrophy (Aufderheide & RodriguezMartin, 1998; Brickley & Ives, 2006; Hershkovitz et al., 1997; Ortner & Mays, 1998; Walker et al., 2009). The exact cause of porotic hyperostosis might not be determined with certainty in every case, however, by analysing porosity distribution, archeological findings and population customs, it might be easier to accept or decline the existing theories.
20 14
Int J Food Sci Nutr Downloaded from informahealthcare.com by The University of Manchester on 10/15/14 For personal use only.
1
Materials and methods Skeletal remains from graveyard Ostrovica-Greblje (Figure 1) were excavated by archaeologists of the Museum of Croatian Archaeological Monuments (Split, Croatia). The osteological material was cleaned and, where possible, anatomically reconstructed. Anthropological analysis of bones and teeth was preformed following the ‘‘Standards for data collection from human skeletal remains’’ (Buikstra & Ubelaker, 1994). Sex, age and pathological changes were analysed according to criteria and recommendations on diagnosing pathological porosity (Aufderheide & Rodriguez-Martin, 1998). All available bones were macroscopically examined for the presence of bone hypertrophy, new bone formation, increased vascular
Malnutrition in early medieval Croatia
Int J Food Sci Nutr Downloaded from informahealthcare.com by The University of Manchester on 10/15/14 For personal use only.
DOI: 10.3109/09637486.2013.854741
173
Figure 1. Location of the Ostrovica-Greblje graveyard.
response, swellings and their patterns on the skeleton. The age of adults was determined by analysing the pubic symphysis morphology and cranial suture closing, while sex was determined by analysing pelvic and skull morphology (Phenice, 1969; Sˇlaus, 2006). All individuals under the age of 16 were classified as subadults, according to Baker et al. (2005). The age of subadult remains was determined by bone ossification, teeth eruption and long bones diaphysis length (Liversidge et al., 1998; Lysell et al., 1962; Sˇlaus, 2006). As determining the sex of the skeleton mostly relies on secondary sex characteristics, sex of subadults was not determined (Bass, 1981; Sˇlaus, 2006). The prevalence of cribra orbitalia was studied in sample grouped according to the age and sex (men, women and subadults). The normality of distribution was tested with Shapiro–Wilk test. Differences between the groups with normal distribution were tested using t-test for independent samples and one-way ANOVA test. Groups without normal distribution were compared with Kruskal–Wallis and Mann– Whitney test. Correlation, 2 and Fischer’s test were used to investigate the relationships among variables. Level of significance was accepted for p50.05.
Results According to the characteristic jewelry and tools, the graveyard was dated to the 7th–9th century. Excavations recovered 128 individuals within 115 graves, and 10 graves contained no skeletal remains. Graves were simple, surrounded by rectangular stone plates, with pieces of wood found in some graves, implying that some of inhumations were in a wooden coffin. Social differentiation based on grave findings and burial forms could not be performed, so it was assumed that all individuals belonged to the single social category.
Sex was determined with certainty for 84 skeletons: 49 male (47 with the age determined), 33 females (30 with the age determined) and 29 skeletons of subadults. In total, age was determined for 108 skeletons, with average age of 28.9 16.6 years at the time of death. The age at death for adults was 36.2 11.4 years (median of 37.5 years), with 37.2 12.6 years for males and 31.9 13.9 years for females, without difference in achieved age among sexes (p ¼ 0.064). Average age at death for subadults was 5.3 3.6 years (median 4.9 years). The majority of pathological findings of the bones were signs of aging and malnutrition (like osteoarthritis, cribra orbitalia, deformities of the long bones and Schmorl’s nodes). Teeth with caries and surface abrasion were often found, and alveolar resorption of more than 2 mm was found on 30 skulls. Signs of age and traumas were not further discussed in this study. A total of 73 skulls (one skull is shown in Figure 2) with at least one orbit preserved were found and cribra orbitalia (in an active form or in a sanation) was established on 21 skulls (28.8%). Prevalence of cribra orbitalia was 15.8% among women (3/19), 21.8% (7/32) among men (without significant difference between sexes (p ¼ 0. 725)), and 61.1% (11/18) among subadults. The difference in prevalence of cribra orbitalia between adults and subadults was significant (p ¼ 0.004), as well as prevalence of cribra orbitalia among the subadults (p ¼ 0.005). Only eight skulls had cribra orbitalia as only pathological finding, two had only temporal porosity, and 19 had more than one pathological finding. Temporal porosity was found in six and other cranial porosity in 19 skeletons. Four skeletons besides temporal porosity had other forms of cranial porosity (cribra orbitalia or subperiostal hematoma). Association between cribra orbitalia and temporal porosity was border significant (p ¼ 0.053). Periostitis and other types of skull porosities were associated (p ¼ 0.036). Porosity of the bone growth plate was found in three
174
K. Becˇic´et al.
Int J Food Sci Nutr, 2014; 65(2): 172–176
Int J Food Sci Nutr Downloaded from informahealthcare.com by The University of Manchester on 10/15/14 For personal use only.
Figure 2. Skull from woman from early medieval time with severe porotic hyperostosis (seventh to ninth century; graveyard Ostrovica-Greblje near Zadar, Croatia).
subadult skeletons, but due to poor preservation, no conclusions could be made with certainty. There was no significant difference in achieved age between subadults with and without cribra orbitalia (p ¼ 0.950). In adults, those with cribra orbitalia lived 8.1 years longer than those without these signs, as men with signs of cribra orbitalia (average age 44.9 13.2) lived longer (p ¼ 0.039) than males without signs of cribra orbitalia (35.2 10.3), but without significant difference in achieved age between females with (40.8 7.6) and without (35.2 10.9 years) signs of cribra orbitalia (p ¼ 0.359). However, in the entire sample, individuals without signs of cribra orbitalia lived 7.6 years longer than those with these signs (p ¼ 0.201).
Discussion The life was harsh in early medieval time in Croatia; population was exposed to low life standard, nutritional and physical stressors. The average achieved age was short, especially among women and subadults (mainly due to increased mortality during pregnancy, and due to diseases and malnutrition, respectively). Findings of periostitis and other types of skull porosities on same skeletons indicate that subadults and females had increased risk for malnutrition and/or infectious diseases. The most of the authors agree that porotic hyperostosis and cribra orbitalia are probably caused by iron-deficiency anemia associated with hypertrophy of the diploe¨, thinning of the cortical bone and formation of new spongy bone. It is accepted as an important indicator of inadequate nutrition (Martin et al., 1985; Novak & Sˇlaus, 2010; Sˇlaus, 2006; Walker et al., 2009). One method for estimating the diet of ancient populations is an analysis of the content of heavy metals in the bones (Schutkowski et al., 1999). In bone and soil samples from locality OstrovicaGreblje (Stipisˇic´, 2011) iron content was higher than in the modern bone samples (Sˇcˇancˇar et al., 2000) and some skeletons from Ostrovica-Greblje had several times higher iron content. Results from Ostrovica-Greblje are in line with the results of analysis of metal content of bone samples from medieval graveyard distanced 110 km (Sutlovic´ et al., 2010). Low zinc– calcium ratio was established in samples from these both medieval localities (Stipisˇic´, 2011; Sutlovic´ et al., 2010), what is considered as indication of very low intake of food of animal origin. If metal concentrations in the bones are accepted as valid, a diet of our sample population mainly consisted of different vegetables with considerable amount of iron (Sutlovic´ et al., 2010). Iron content analysis of bone samples from OstrovicaGreblje indicate that iron deficiency is not probable single cause of porotic hyperostosis or cribra orbitalia.
Other possible causes of porotic hyperostosis; infectious and chronic diseases and various metabolic conditions come down to one of two denominators – anemia and/or malnutrition. Some studies showed over 60% prevalence of cribra orbitalia among subadults (Rajic´ & Ujcˇic´, 2003). Scurvy was also suggested as cause of bone porosity; due to an impaired iron uptake in the gastrointestinal tract, or malnutrition. Bone porosity occurs because of easily rupturing vessels and formation of subperiostal hematomas (Aufderheide & Rodriguez-Martin, 1998; Brickley & Ives, 2006). Rickets is another proposed cause of bone porosity, evident through the formation of small spiculated patterns on the orbits and on the ectocranial surface (Ortner & Mays, 1998). Scurvy and rickets are less probable causes of cribra orbitalia in our sample (prevalence of 28.8%), since the population in mildclimate region of Dalmatia should have had enough sun and adequate intake of vegetables as a source of vitamin C. Prevalence of cribra orbitalia on skeletons on other localities across continental and Mediterranean Europe (comparable sample size and similar time period or geographical proximity) varied from 9.1% to 66.6% (Table 1). In our sample, finding of cribra orbitalia on the skeletal remains was associated with achieved age. Although in the entire analysed sample those that had signs of cribra orbitalia lived 7.6 years shorter, when only skeletal remains of adult individuals were observed, individuals that had signs of cribra orbitalia lived 8.1 years longer. This was primarily due to higher achieved age in males with signs of cribra orbitalia (9.6 years), since females with signs of cribra orbitalia achieved higher age (5.7 years), but the difference was not statistically significant. The most of cribra orbitalia found in adults were inactive forms, indicating that these individuals had adequate nutrition after a period of malnutrition. An observation that adult with cribra orbitalia lived longer than members of the same population without cribra orbitalia, has not been reported previously and is yet to be explained. The main limitation of this study is a small sample size due to a limited number of adequate skeletal remains found in the graveyard Ostrovica-Greblje. Since presented study is a crosssectional study, it is impossible to establish causal relationships. It is also very ungrateful to discuss about longevity in a sample where, from the present-day point of view, the average achieved age was short. Nevertheless, if the most favoured iron deficiency theory about cribra orbitalia etiology is assumed (and high iron concentrations in the sample are explained by diagenesis – any chemical, physical, or biological change undergone by sediment after its initial deposition), finding of association of cribra orbitalia and longevity would be in line with the theory that iron is the single most important factor in the control of aging. Also, several studies point that lower iron levels at some point or to
Malnutrition in early medieval Croatia
DOI: 10.3109/09637486.2013.854741
175
Table 1. Prevalence of cribra orbitalia on skeletal remains found in localities in Continental and Mediterranean Europe dating from a similar time period and/or geographical proximity.
Iron age Antique
Coastal Continental
Coastal
Int J Food Sci Nutr Downloaded from informahealthcare.com by The University of Manchester on 10/15/14 For personal use only.
Medieval
Coastal Continental
Coastal
Nadin (Croatia) Vinkovci (Croatia) Zmajevac (Croatia) Sˇtrbinci (Croatia) Continental (Late antique – Croatia)a Privlaka (Croatia) Zadar (Croatia) Adriatic (Late antique – Croatia)a Dorset (Scotland) Rimini (Italy) Ravena (Italy) Adriatic (Early medieval – Croatia)a Continental (Early medieval – Croatia)a Nova Racˇa (Croatia) Ostro´w Lednicki (Poland) Stara Torina (Serbia) Mursa (Croatia) Novigrad (Croatia) Ostrovica-Greblje (Croatia)
Cribra orbitalia (%)
Total sample size
Authors
40.0 33.3 21.7 18.7 21.6 27.0 20.1 20.0 38.5 52.6 60.0 32.5 19.7 39.7 30.2 43.1 9.1 66.6 28.8
37 25 28 17 232 181 255 244 364 76 104 286 218 104 494 81 21 8 128
Rajic´, 2006 Sˇlaus, 2002b Sˇlaus, 2002b Sˇlaus, 2002b Sˇlaus, 2008 Sˇlaus, 1996 Novak & Sˇlaus, 2010 Sˇlaus, 2008 Lewis, 2010 Facchini et al., 2004 Facchini et al., 2004 Sˇlaus, 2008 Sˇlaus, 2008 Sˇlaus, 2000 Lubocka, 2000 Djuric´ et al., 2010 Sˇlaus, 2002 Rajic´ & Ujcˇic´, 2003 This study
a
Multiple locations.
some extent have lower cardiovascular risk (endothelial dysfunction, atherosclerosis, cardiac myofibril damage) (Fontana et al., 2004; Ma de la Cruz et al., 2011; Sullivan, 1981, 1999), although it is difficult to say whether cardiovascular diseases were important morbidity of Medieval population. Another alluring explanation of association of cribra orbitalia and longevity is the long-term influence of nutritional status on extending the lifespan through the epigenetic signatures influencing gene expression (Ford et al., 2011; Niculescu & Lupu, 2011; Tammen et al., 2013). It is well known that majority of medieval population was in constant famine, what to some extent can be considered as dietary restriction. Restricted food intake without severe nutritional deprivation was shown as a robust dietary intervention that can extend lifespan in different model organisms, including primates (Coleman et al., 2009; Ford et al., 2011; Niculescu & Lupu, 2011; Tammen et al., 2013). The lack of significance in association of higher achieved age in females might be explained by increased mortality during pregnancy and delivery, so long-term beneficial effects of dietary restriction and/or low iron intake decreased would be less apparent.
Conclusion Causes of the pathological findings on ancient bones are various and etiology can be assumed only in the light of other geographical, historical, anthropological and archaeological data. Analysis of early medieval bone samples found in Croatian coast showed that common pathological finding was porotic hyperostosis. The etiology was probably malnutrition that might have had a beneficial effect on longevity of adults.
Acknowledgements The authors would like to thank Rebecca Skaglin from the University of New Haven for her help with translation and proofreading this article, Dr Goran C´uric´ and Dr Zvonimir Vrselja from the University of Osijek for their valuable advices and help with data analysis.
Declaration of interest This study was financially supported by the Ministry of Science, Education and Sports of the Republic of Croatia and was conducted
under the project ‘‘Anthropological analysis of early medieval skeletons from southern Croatia’’ (project number 216-2160800-0799). The authors declare no conflicts of interests. The authors alone are responsible for the content and writing of this article.
References Aufderheide AC, Rodriguez-Martin C. 1998. The Cambridge encyclopedia of human paleopathology. Cambridge: Cambridge University Press. Baker BJ, Dupras TL, Tocheri MW. 2005. The osteology of infants and children. College station (TX): Texas A&M University Press. Bass WM. 1981. Human osteology. Missouri: Missouri Arhaeological Society. Brickley M, Ives R. 2006. Skeletal manifestations of infantile scurvy. Am J Phys Anthropol 129:163–172. Buikstra J, Ubelaker D. 1994. Standards for data collection from human skeletal remains. Proceedings of a seminar at the Field Museum of Natural History. Arkansas Archaeological Survey research series 44. Fayeteville: Arkansas Archaeological survey. Coleman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, et al. 2009. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325:201–204. Djuric´ M, Aleksa J, Petar M, Ksenija D, Milenkovic´ P, Draskovic´ M, Roksandic´ M. 2010. Adolescent health in medieval Serbia: signs of infectious diseases and risk of trauma. Homo 61:130–149. Facchini F, Elisa R, Brasili P. 2004. Cribra orbitalia and cribra cranii in Roman skeletal remains from the Ravenna Area and Rimini. Int J Osteoarchaeol 14:126–136. Fontana L, Meyer TE, Klein S, Holloszycˇ JO. 2004. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. PNAS 101:6659–6663. Ford D, Ions LJ, Alatawi F, Wakeling LA. 2011. The potential role of epigenetic responses to diet in ageing. P Nutr Soc 70:374–384. Hershkovitz I, Rothschild BM, Latimer B, Dutour O, Leonetti G, Greenwald CM, Rothschild C, et al. 1997. Recognition of sickle cell anemia in skeletal remains of children. Am J Phys Anthropol 104: 213–226. Lewis EM. 2010. Life and death in a civitas capital: metabolic disease and trauma in the children from late Roman Dorchester, Dorset. Am J Phys Anthropol 142:405–416. Liversidge HM, Herdeg B, Rosing FW. 1998. Dental age estimation of non-adults. A review of methods and principles. In: Alt KW, Rosing FW, Terschler-Nicola M, editors. Dental anthropology, fundamentals, limits and prospects. Vienna: Springer. p 419–442. Lubocka Z. 2000. Cribra orbitalia in early medieval population from Ostro´w Lednicki (Poland). Acta U Carol Med 41:93–98. Lysell L, Magnusson B, Thilander B. 1962. Time and order of eruption of the primary teeth: a longitudinal study. Odontologisk Revy 13:217–234.
Int J Food Sci Nutr Downloaded from informahealthcare.com by The University of Manchester on 10/15/14 For personal use only.
176
K. Becˇic´et al.
Ma de la Cruz R-J, Guizar-Mendoza JM, Amador-Licona N, GutierrezNavarro MJ, Hernandez-Gonzales MA, Dubey-Ortega LA, SolorioMeza SE, et al. 2011. Iron overload as cardiovascular risk factor in children and adolescents with renal disease. Nephrol Dial Transpl 26: 3268–3273. Martin DL, Goodman AH, Armelagos GJ. 1985. Skeletal pathologies as indicators of quality and quantity of diet. In: Gilbert RI, Mielke JH, editors. The analysis of prehistoric diets. Orlando (FL): Academic Press. p 227–279. Niculescu MD, Lupu DS. 2011. Nutritional influence on epigenetics and effects on longevity. Curr Opin Clin Nutr 14:35–40. Novak M, Sˇlaus M. 2010. Health and disease in a Roman walled city: an example of Colonia Iulia Iader. J Anthropol Sci 88:189–206. Ortner D. 2003. Identification of pathological conditions in human skeletal remains. San Diego (CA): Academic Press. Ortner D, Mays S. 1998. Dry bone manifestations of rickets in infancy and early childhood. Int J Osteoarchaeol 8:45–55. Phenice TW. 1969. A newly developed visual method of sexing os pubis. Am J Phys Anthropol 8:679–685. Rajic´ P. 2006. Analysis of human skeletal remains from Nadin iron age burial mound. Collegium Antropol 30:795–799. Rajic´ P, Ujcˇic´ Zˇ. 2003. Anthropological analysis of the late Roman/early Medieval Cemetery of Novigrad (Istria). Collegium Anthropol 27: 803–808. Schutkowski H, Bernd H, Felicitas W, Herve B, Gisela G. 1999. Diet, status and decomposition at Weingarten: trace element and isotope analyses on early mediaeval skeletal material. J Archaeol Sci 26: 675–685. Stipisˇic´ A. 2011. Koncentracije metala u arheolosˇkim kostima i zˇivotne navike starohrvatske populacije. Ph.D dissertation, University of Split, Croatia. p 1–141.
Int J Food Sci Nutr, 2014; 65(2): 172–176
Sullivan JL. 1981. Iron and the sex difference in heart disease risk. Lancet 317:1293–1294. Sullivan JL. 1999. Iron and the genetics of cardiovascular disease. Circulation 100:1260–1263. Sutlovic´ D, Stipisˇic´ A, Marusˇic´ J, Pavlov J, Versˇic´ M, Definis-Gojanovic´ M, Gugic´ D, Anðelinovic´ S. 2010. Elemental status in individuals from Naklice burial site (Southern Croatia): medieval diet reconstruction. Croat Chem Acta 83:217–221. Sˇcˇancˇar J, Milacˇic´ R, Benedik M, Bukovec P. 2000. Determination of trace elements and calcium in bone of the human iliac crest by atomic absorption spectometry. Clin Chem Acta 293:187–197. Sˇlaus M. 1996. Demography and disease in the early medieval site of Privlaka. Opvs Archaeol 20:141–149. Sˇlaus M. 2000. Biocultural analysis of sex differences in mortality profiles and stress levels in the late medieval population from Nova racˇa, Croatia. Am J Phys Anthropol 111:193–209. Sˇlaus M. 2002a. Temporal trends in demographic profiles and stress levels in medieval (6th–13th century) population samples from continental Croatia. Croat Med J 45:598–605. Sˇlaus M. 2002b. The bioarchaeology of continental Croatia: an analysis of human skeletal remains from the Prehistoric to post-Medieval periods. Oxford: BAR International Series 1021. Sˇlaus M. 2006. Bioarheo.logija. Zagreb: Sˇkolska knjiga. Sˇlaus M. 2008. Osteological and dental markers of health in the transition from the Late Antique to the Early Medieval period in Croatia. Am J Phys Anthropol 136:455–469. Tammen SA, Simonetta F, Sang-Woon C. 2013. Epigenetics: the link between nature and nurture. Mol Aspects Med 34:753–764. Walker PL, Bathurst RB, Richman R, Gjerdum T, Andrushko VA. 2009. The causes of porotic hyperostosis and cribra orbitalia: a reappraisal of the iron-deficiency-anaemia hypothesis. Am J Phys Anthropol 139: 109–125.
FOOD AND NUTRITION SURVEYS
Bone porosity and longevity in early medieval Southern Croatia Kristijan Becˇic´1, Darija Jandric´ Becˇic´1, Marija Definis-Gojanovic´1,2, Sandra Zekic´ Tomasˇ3, Ivana Anteric´4, and Zˇeljana Basˇic´4 School of Medicine, University of Split, Split, Croatia, 2Clinical Department for Forensic Pathology, Clinical Hospital Center Split, Split, Croatia, Clinical Department for Pathology, Clinical Hospital Center Split, Split, Croatia, and 4University Center for Forensic Sciences, University of Split, Split, Croatia
3
Abstract
Keywords
Porosity of the skull and skeletal remains, especially of the orbital roof, are one of the most frequent pathological findings on ancient human skeletal remains. There are several presumed causes of this condition and anthropologists consider skull porosities as a marker of physical and nutritional stress. A total of 115 graves were discovered at the early-medieval graveyard near Zadar (Croatia) that contained 128 partially preserved skeletons. Average estimated age at death was 37.2 12.6 years for men, 31.9 13.9 for women, and 5.3 3.6 years for subadults. Pathological bone porosity was analysed. Cribra orbitalia was observed on 21 skulls (28.7%), signs of temporal porosity were noticed on six skulls and signs of subperiosteal bleeding on three skulls. Nineteen skulls had bone porosities in other areas. There was a significant difference (p ¼ 0.039) in achieved age of adults with and without cribra orbitalia as those with cribra orbitalia lived on average 8.1 years longer. The bone porosity was probably caused by malnutrition that might have had a beneficial effect on longevity of adults, similar to effects of restricted food intake on extending lifespan through epigenetic signatures influencing gene expression.
Anemia, cribra orbitalia, porotic hyperostosis, rickets, scurvy
Introduction The study of skeletal remains, age at death, signs of infectious diseases and archaeological information are pieces of the puzzle of reconstructing the lives of ancestors. Signs of trauma, osteoarthritis and Schmorl’s defects (protrusions of the intervertebral disc though the vertebral body) are markers of physical stress. Bone porosities and deformities, as well as subperiosteal hematomas are markers of nutrition quality (Novak & Sˇlaus, 2010; Sˇlaus, 2006). Besides determining basic demographic data of human skeletal remains excavated in southern Croatia, this article focuses on pathological bone porosity and discusses possible causes. The analysed sample is dated from the seventh to ninth century and represents the first Croatian population that inhabited mid-Dalmatia. Porotic hyperostosis is one of the most common pathological finding on archaeological skeletal remains, usually described as areas of cranial pitting on the outer skull surface (Novak & Sˇlaus, 2010; Sˇlaus, 2006; Walker et al., 2009). Type of porotic hyperostosis found on orbital roofs is called cribra orbitalia. Since different pathological conditions are considered as cause of porotic hyperostosis in adults and subadults, in order to establish the etiology it is important to evaluate the distribution of porosity on whole skeleton. It is often accepted that porotic hyperostosis is caused by bone marrow hypertrophy due to the iron deficiency anemia. Such conclusion is based on the findings of a several epidemiological studies of modern clinical cases, where radiograph images showed porotic hyperostosis-similar patterns on the Correspondence: Kristijan Becˇic´, School of Medicine, University of Split, Sˇoltanska 2, 21000 Split, Croatia. Tel: +385 98 910 9740. E-mail: [email protected]
History Received 18 March 2013 Revised 6 October 2013 Accepted 9 October 2013 Published online 12 November 2013
skull (Novak & Sˇlaus, 2010; Sˇlaus, 2006; Walker et al., 2009). Porosity of the growth plate and specific pattern of lesions in subadults indicate rickets (Aufderheide & Rodriguez-Martin, 1998; Sˇlaus, 2006). Megaloblastic and hemolytic anemia (more severe forms, like thalassemia major and sickle-cell disease) have also been reported as possible causes of porotic hyperostosis (Hershkovitz et al., 1997; Ortner, 2003; Walker et al., 2009). It was hypothesised that several other diseases, like parasitism, periostitis, rickets and scurvy, might cause porotic hyperostosis without bone marrow hypertrophy (Aufderheide & RodriguezMartin, 1998; Brickley & Ives, 2006; Hershkovitz et al., 1997; Ortner & Mays, 1998; Walker et al., 2009). The exact cause of porotic hyperostosis might not be determined with certainty in every case, however, by analysing porosity distribution, archeological findings and population customs, it might be easier to accept or decline the existing theories.
20 14
Int J Food Sci Nutr Downloaded from informahealthcare.com by The University of Manchester on 10/15/14 For personal use only.
1
Materials and methods Skeletal remains from graveyard Ostrovica-Greblje (Figure 1) were excavated by archaeologists of the Museum of Croatian Archaeological Monuments (Split, Croatia). The osteological material was cleaned and, where possible, anatomically reconstructed. Anthropological analysis of bones and teeth was preformed following the ‘‘Standards for data collection from human skeletal remains’’ (Buikstra & Ubelaker, 1994). Sex, age and pathological changes were analysed according to criteria and recommendations on diagnosing pathological porosity (Aufderheide & Rodriguez-Martin, 1998). All available bones were macroscopically examined for the presence of bone hypertrophy, new bone formation, increased vascular
Malnutrition in early medieval Croatia
Int J Food Sci Nutr Downloaded from informahealthcare.com by The University of Manchester on 10/15/14 For personal use only.
DOI: 10.3109/09637486.2013.854741
173
Figure 1. Location of the Ostrovica-Greblje graveyard.
response, swellings and their patterns on the skeleton. The age of adults was determined by analysing the pubic symphysis morphology and cranial suture closing, while sex was determined by analysing pelvic and skull morphology (Phenice, 1969; Sˇlaus, 2006). All individuals under the age of 16 were classified as subadults, according to Baker et al. (2005). The age of subadult remains was determined by bone ossification, teeth eruption and long bones diaphysis length (Liversidge et al., 1998; Lysell et al., 1962; Sˇlaus, 2006). As determining the sex of the skeleton mostly relies on secondary sex characteristics, sex of subadults was not determined (Bass, 1981; Sˇlaus, 2006). The prevalence of cribra orbitalia was studied in sample grouped according to the age and sex (men, women and subadults). The normality of distribution was tested with Shapiro–Wilk test. Differences between the groups with normal distribution were tested using t-test for independent samples and one-way ANOVA test. Groups without normal distribution were compared with Kruskal–Wallis and Mann– Whitney test. Correlation, 2 and Fischer’s test were used to investigate the relationships among variables. Level of significance was accepted for p50.05.
Results According to the characteristic jewelry and tools, the graveyard was dated to the 7th–9th century. Excavations recovered 128 individuals within 115 graves, and 10 graves contained no skeletal remains. Graves were simple, surrounded by rectangular stone plates, with pieces of wood found in some graves, implying that some of inhumations were in a wooden coffin. Social differentiation based on grave findings and burial forms could not be performed, so it was assumed that all individuals belonged to the single social category.
Sex was determined with certainty for 84 skeletons: 49 male (47 with the age determined), 33 females (30 with the age determined) and 29 skeletons of subadults. In total, age was determined for 108 skeletons, with average age of 28.9 16.6 years at the time of death. The age at death for adults was 36.2 11.4 years (median of 37.5 years), with 37.2 12.6 years for males and 31.9 13.9 years for females, without difference in achieved age among sexes (p ¼ 0.064). Average age at death for subadults was 5.3 3.6 years (median 4.9 years). The majority of pathological findings of the bones were signs of aging and malnutrition (like osteoarthritis, cribra orbitalia, deformities of the long bones and Schmorl’s nodes). Teeth with caries and surface abrasion were often found, and alveolar resorption of more than 2 mm was found on 30 skulls. Signs of age and traumas were not further discussed in this study. A total of 73 skulls (one skull is shown in Figure 2) with at least one orbit preserved were found and cribra orbitalia (in an active form or in a sanation) was established on 21 skulls (28.8%). Prevalence of cribra orbitalia was 15.8% among women (3/19), 21.8% (7/32) among men (without significant difference between sexes (p ¼ 0. 725)), and 61.1% (11/18) among subadults. The difference in prevalence of cribra orbitalia between adults and subadults was significant (p ¼ 0.004), as well as prevalence of cribra orbitalia among the subadults (p ¼ 0.005). Only eight skulls had cribra orbitalia as only pathological finding, two had only temporal porosity, and 19 had more than one pathological finding. Temporal porosity was found in six and other cranial porosity in 19 skeletons. Four skeletons besides temporal porosity had other forms of cranial porosity (cribra orbitalia or subperiostal hematoma). Association between cribra orbitalia and temporal porosity was border significant (p ¼ 0.053). Periostitis and other types of skull porosities were associated (p ¼ 0.036). Porosity of the bone growth plate was found in three
174
K. Becˇic´et al.
Int J Food Sci Nutr, 2014; 65(2): 172–176
Int J Food Sci Nutr Downloaded from informahealthcare.com by The University of Manchester on 10/15/14 For personal use only.
Figure 2. Skull from woman from early medieval time with severe porotic hyperostosis (seventh to ninth century; graveyard Ostrovica-Greblje near Zadar, Croatia).
subadult skeletons, but due to poor preservation, no conclusions could be made with certainty. There was no significant difference in achieved age between subadults with and without cribra orbitalia (p ¼ 0.950). In adults, those with cribra orbitalia lived 8.1 years longer than those without these signs, as men with signs of cribra orbitalia (average age 44.9 13.2) lived longer (p ¼ 0.039) than males without signs of cribra orbitalia (35.2 10.3), but without significant difference in achieved age between females with (40.8 7.6) and without (35.2 10.9 years) signs of cribra orbitalia (p ¼ 0.359). However, in the entire sample, individuals without signs of cribra orbitalia lived 7.6 years longer than those with these signs (p ¼ 0.201).
Discussion The life was harsh in early medieval time in Croatia; population was exposed to low life standard, nutritional and physical stressors. The average achieved age was short, especially among women and subadults (mainly due to increased mortality during pregnancy, and due to diseases and malnutrition, respectively). Findings of periostitis and other types of skull porosities on same skeletons indicate that subadults and females had increased risk for malnutrition and/or infectious diseases. The most of the authors agree that porotic hyperostosis and cribra orbitalia are probably caused by iron-deficiency anemia associated with hypertrophy of the diploe¨, thinning of the cortical bone and formation of new spongy bone. It is accepted as an important indicator of inadequate nutrition (Martin et al., 1985; Novak & Sˇlaus, 2010; Sˇlaus, 2006; Walker et al., 2009). One method for estimating the diet of ancient populations is an analysis of the content of heavy metals in the bones (Schutkowski et al., 1999). In bone and soil samples from locality OstrovicaGreblje (Stipisˇic´, 2011) iron content was higher than in the modern bone samples (Sˇcˇancˇar et al., 2000) and some skeletons from Ostrovica-Greblje had several times higher iron content. Results from Ostrovica-Greblje are in line with the results of analysis of metal content of bone samples from medieval graveyard distanced 110 km (Sutlovic´ et al., 2010). Low zinc– calcium ratio was established in samples from these both medieval localities (Stipisˇic´, 2011; Sutlovic´ et al., 2010), what is considered as indication of very low intake of food of animal origin. If metal concentrations in the bones are accepted as valid, a diet of our sample population mainly consisted of different vegetables with considerable amount of iron (Sutlovic´ et al., 2010). Iron content analysis of bone samples from OstrovicaGreblje indicate that iron deficiency is not probable single cause of porotic hyperostosis or cribra orbitalia.
Other possible causes of porotic hyperostosis; infectious and chronic diseases and various metabolic conditions come down to one of two denominators – anemia and/or malnutrition. Some studies showed over 60% prevalence of cribra orbitalia among subadults (Rajic´ & Ujcˇic´, 2003). Scurvy was also suggested as cause of bone porosity; due to an impaired iron uptake in the gastrointestinal tract, or malnutrition. Bone porosity occurs because of easily rupturing vessels and formation of subperiostal hematomas (Aufderheide & Rodriguez-Martin, 1998; Brickley & Ives, 2006). Rickets is another proposed cause of bone porosity, evident through the formation of small spiculated patterns on the orbits and on the ectocranial surface (Ortner & Mays, 1998). Scurvy and rickets are less probable causes of cribra orbitalia in our sample (prevalence of 28.8%), since the population in mildclimate region of Dalmatia should have had enough sun and adequate intake of vegetables as a source of vitamin C. Prevalence of cribra orbitalia on skeletons on other localities across continental and Mediterranean Europe (comparable sample size and similar time period or geographical proximity) varied from 9.1% to 66.6% (Table 1). In our sample, finding of cribra orbitalia on the skeletal remains was associated with achieved age. Although in the entire analysed sample those that had signs of cribra orbitalia lived 7.6 years shorter, when only skeletal remains of adult individuals were observed, individuals that had signs of cribra orbitalia lived 8.1 years longer. This was primarily due to higher achieved age in males with signs of cribra orbitalia (9.6 years), since females with signs of cribra orbitalia achieved higher age (5.7 years), but the difference was not statistically significant. The most of cribra orbitalia found in adults were inactive forms, indicating that these individuals had adequate nutrition after a period of malnutrition. An observation that adult with cribra orbitalia lived longer than members of the same population without cribra orbitalia, has not been reported previously and is yet to be explained. The main limitation of this study is a small sample size due to a limited number of adequate skeletal remains found in the graveyard Ostrovica-Greblje. Since presented study is a crosssectional study, it is impossible to establish causal relationships. It is also very ungrateful to discuss about longevity in a sample where, from the present-day point of view, the average achieved age was short. Nevertheless, if the most favoured iron deficiency theory about cribra orbitalia etiology is assumed (and high iron concentrations in the sample are explained by diagenesis – any chemical, physical, or biological change undergone by sediment after its initial deposition), finding of association of cribra orbitalia and longevity would be in line with the theory that iron is the single most important factor in the control of aging. Also, several studies point that lower iron levels at some point or to
Malnutrition in early medieval Croatia
DOI: 10.3109/09637486.2013.854741
175
Table 1. Prevalence of cribra orbitalia on skeletal remains found in localities in Continental and Mediterranean Europe dating from a similar time period and/or geographical proximity.
Iron age Antique
Coastal Continental
Coastal
Int J Food Sci Nutr Downloaded from informahealthcare.com by The University of Manchester on 10/15/14 For personal use only.
Medieval
Coastal Continental
Coastal
Nadin (Croatia) Vinkovci (Croatia) Zmajevac (Croatia) Sˇtrbinci (Croatia) Continental (Late antique – Croatia)a Privlaka (Croatia) Zadar (Croatia) Adriatic (Late antique – Croatia)a Dorset (Scotland) Rimini (Italy) Ravena (Italy) Adriatic (Early medieval – Croatia)a Continental (Early medieval – Croatia)a Nova Racˇa (Croatia) Ostro´w Lednicki (Poland) Stara Torina (Serbia) Mursa (Croatia) Novigrad (Croatia) Ostrovica-Greblje (Croatia)
Cribra orbitalia (%)
Total sample size
Authors
40.0 33.3 21.7 18.7 21.6 27.0 20.1 20.0 38.5 52.6 60.0 32.5 19.7 39.7 30.2 43.1 9.1 66.6 28.8
37 25 28 17 232 181 255 244 364 76 104 286 218 104 494 81 21 8 128
Rajic´, 2006 Sˇlaus, 2002b Sˇlaus, 2002b Sˇlaus, 2002b Sˇlaus, 2008 Sˇlaus, 1996 Novak & Sˇlaus, 2010 Sˇlaus, 2008 Lewis, 2010 Facchini et al., 2004 Facchini et al., 2004 Sˇlaus, 2008 Sˇlaus, 2008 Sˇlaus, 2000 Lubocka, 2000 Djuric´ et al., 2010 Sˇlaus, 2002 Rajic´ & Ujcˇic´, 2003 This study
a
Multiple locations.
some extent have lower cardiovascular risk (endothelial dysfunction, atherosclerosis, cardiac myofibril damage) (Fontana et al., 2004; Ma de la Cruz et al., 2011; Sullivan, 1981, 1999), although it is difficult to say whether cardiovascular diseases were important morbidity of Medieval population. Another alluring explanation of association of cribra orbitalia and longevity is the long-term influence of nutritional status on extending the lifespan through the epigenetic signatures influencing gene expression (Ford et al., 2011; Niculescu & Lupu, 2011; Tammen et al., 2013). It is well known that majority of medieval population was in constant famine, what to some extent can be considered as dietary restriction. Restricted food intake without severe nutritional deprivation was shown as a robust dietary intervention that can extend lifespan in different model organisms, including primates (Coleman et al., 2009; Ford et al., 2011; Niculescu & Lupu, 2011; Tammen et al., 2013). The lack of significance in association of higher achieved age in females might be explained by increased mortality during pregnancy and delivery, so long-term beneficial effects of dietary restriction and/or low iron intake decreased would be less apparent.
Conclusion Causes of the pathological findings on ancient bones are various and etiology can be assumed only in the light of other geographical, historical, anthropological and archaeological data. Analysis of early medieval bone samples found in Croatian coast showed that common pathological finding was porotic hyperostosis. The etiology was probably malnutrition that might have had a beneficial effect on longevity of adults.
Acknowledgements The authors would like to thank Rebecca Skaglin from the University of New Haven for her help with translation and proofreading this article, Dr Goran C´uric´ and Dr Zvonimir Vrselja from the University of Osijek for their valuable advices and help with data analysis.
Declaration of interest This study was financially supported by the Ministry of Science, Education and Sports of the Republic of Croatia and was conducted
under the project ‘‘Anthropological analysis of early medieval skeletons from southern Croatia’’ (project number 216-2160800-0799). The authors declare no conflicts of interests. The authors alone are responsible for the content and writing of this article.
References Aufderheide AC, Rodriguez-Martin C. 1998. The Cambridge encyclopedia of human paleopathology. Cambridge: Cambridge University Press. Baker BJ, Dupras TL, Tocheri MW. 2005. The osteology of infants and children. College station (TX): Texas A&M University Press. Bass WM. 1981. Human osteology. Missouri: Missouri Arhaeological Society. Brickley M, Ives R. 2006. Skeletal manifestations of infantile scurvy. Am J Phys Anthropol 129:163–172. Buikstra J, Ubelaker D. 1994. Standards for data collection from human skeletal remains. Proceedings of a seminar at the Field Museum of Natural History. Arkansas Archaeological Survey research series 44. Fayeteville: Arkansas Archaeological survey. Coleman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, et al. 2009. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325:201–204. Djuric´ M, Aleksa J, Petar M, Ksenija D, Milenkovic´ P, Draskovic´ M, Roksandic´ M. 2010. Adolescent health in medieval Serbia: signs of infectious diseases and risk of trauma. Homo 61:130–149. Facchini F, Elisa R, Brasili P. 2004. Cribra orbitalia and cribra cranii in Roman skeletal remains from the Ravenna Area and Rimini. Int J Osteoarchaeol 14:126–136. Fontana L, Meyer TE, Klein S, Holloszycˇ JO. 2004. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. PNAS 101:6659–6663. Ford D, Ions LJ, Alatawi F, Wakeling LA. 2011. The potential role of epigenetic responses to diet in ageing. P Nutr Soc 70:374–384. Hershkovitz I, Rothschild BM, Latimer B, Dutour O, Leonetti G, Greenwald CM, Rothschild C, et al. 1997. Recognition of sickle cell anemia in skeletal remains of children. Am J Phys Anthropol 104: 213–226. Lewis EM. 2010. Life and death in a civitas capital: metabolic disease and trauma in the children from late Roman Dorchester, Dorset. Am J Phys Anthropol 142:405–416. Liversidge HM, Herdeg B, Rosing FW. 1998. Dental age estimation of non-adults. A review of methods and principles. In: Alt KW, Rosing FW, Terschler-Nicola M, editors. Dental anthropology, fundamentals, limits and prospects. Vienna: Springer. p 419–442. Lubocka Z. 2000. Cribra orbitalia in early medieval population from Ostro´w Lednicki (Poland). Acta U Carol Med 41:93–98. Lysell L, Magnusson B, Thilander B. 1962. Time and order of eruption of the primary teeth: a longitudinal study. Odontologisk Revy 13:217–234.
Int J Food Sci Nutr Downloaded from informahealthcare.com by The University of Manchester on 10/15/14 For personal use only.
176
K. Becˇic´et al.
Ma de la Cruz R-J, Guizar-Mendoza JM, Amador-Licona N, GutierrezNavarro MJ, Hernandez-Gonzales MA, Dubey-Ortega LA, SolorioMeza SE, et al. 2011. Iron overload as cardiovascular risk factor in children and adolescents with renal disease. Nephrol Dial Transpl 26: 3268–3273. Martin DL, Goodman AH, Armelagos GJ. 1985. Skeletal pathologies as indicators of quality and quantity of diet. In: Gilbert RI, Mielke JH, editors. The analysis of prehistoric diets. Orlando (FL): Academic Press. p 227–279. Niculescu MD, Lupu DS. 2011. Nutritional influence on epigenetics and effects on longevity. Curr Opin Clin Nutr 14:35–40. Novak M, Sˇlaus M. 2010. Health and disease in a Roman walled city: an example of Colonia Iulia Iader. J Anthropol Sci 88:189–206. Ortner D. 2003. Identification of pathological conditions in human skeletal remains. San Diego (CA): Academic Press. Ortner D, Mays S. 1998. Dry bone manifestations of rickets in infancy and early childhood. Int J Osteoarchaeol 8:45–55. Phenice TW. 1969. A newly developed visual method of sexing os pubis. Am J Phys Anthropol 8:679–685. Rajic´ P. 2006. Analysis of human skeletal remains from Nadin iron age burial mound. Collegium Antropol 30:795–799. Rajic´ P, Ujcˇic´ Zˇ. 2003. Anthropological analysis of the late Roman/early Medieval Cemetery of Novigrad (Istria). Collegium Anthropol 27: 803–808. Schutkowski H, Bernd H, Felicitas W, Herve B, Gisela G. 1999. Diet, status and decomposition at Weingarten: trace element and isotope analyses on early mediaeval skeletal material. J Archaeol Sci 26: 675–685. Stipisˇic´ A. 2011. Koncentracije metala u arheolosˇkim kostima i zˇivotne navike starohrvatske populacije. Ph.D dissertation, University of Split, Croatia. p 1–141.
Int J Food Sci Nutr, 2014; 65(2): 172–176
Sullivan JL. 1981. Iron and the sex difference in heart disease risk. Lancet 317:1293–1294. Sullivan JL. 1999. Iron and the genetics of cardiovascular disease. Circulation 100:1260–1263. Sutlovic´ D, Stipisˇic´ A, Marusˇic´ J, Pavlov J, Versˇic´ M, Definis-Gojanovic´ M, Gugic´ D, Anðelinovic´ S. 2010. Elemental status in individuals from Naklice burial site (Southern Croatia): medieval diet reconstruction. Croat Chem Acta 83:217–221. Sˇcˇancˇar J, Milacˇic´ R, Benedik M, Bukovec P. 2000. Determination of trace elements and calcium in bone of the human iliac crest by atomic absorption spectometry. Clin Chem Acta 293:187–197. Sˇlaus M. 1996. Demography and disease in the early medieval site of Privlaka. Opvs Archaeol 20:141–149. Sˇlaus M. 2000. Biocultural analysis of sex differences in mortality profiles and stress levels in the late medieval population from Nova racˇa, Croatia. Am J Phys Anthropol 111:193–209. Sˇlaus M. 2002a. Temporal trends in demographic profiles and stress levels in medieval (6th–13th century) population samples from continental Croatia. Croat Med J 45:598–605. Sˇlaus M. 2002b. The bioarchaeology of continental Croatia: an analysis of human skeletal remains from the Prehistoric to post-Medieval periods. Oxford: BAR International Series 1021. Sˇlaus M. 2006. Bioarheo.logija. Zagreb: Sˇkolska knjiga. Sˇlaus M. 2008. Osteological and dental markers of health in the transition from the Late Antique to the Early Medieval period in Croatia. Am J Phys Anthropol 136:455–469. Tammen SA, Simonetta F, Sang-Woon C. 2013. Epigenetics: the link between nature and nurture. Mol Aspects Med 34:753–764. Walker PL, Bathurst RB, Richman R, Gjerdum T, Andrushko VA. 2009. The causes of porotic hyperostosis and cribra orbitalia: a reappraisal of the iron-deficiency-anaemia hypothesis. Am J Phys Anthropol 139: 109–125.
