American Journal of Biological Anthropology

AbstractThe rules and structure of human culture impact health and disease as much as genetics or the natural environment. To study the origin and evolution of these patterns, we take a multidisciplinary approach combining ancient DNA, skeletal metrics, paleopathology, and stable isotopes. Our analysis focuses on cultural, environmental, and genetic contributions to variation in stature in four populations of Early Neolithic Europe. In Central Europe, low female stature is likely due to male preference in resource allocation under conditions of stress. In contrast, shorter male stature in Mediterranean populations may reflect a lack of preference. Our analysis suggests that biological consequences of sex-specific inequities can be linked to culture as early as 7000 years before present. Understanding these patterns is key to interpreting the evolution of genetic and socio-cultural determinants of health, and our results show that culture, more than environment or genetics, drove height disparities in Early Neolithic Europe.

The timing and causes of brain size reduction in domestic dogs remain uncertain. Using endocasts volume as a proxy for brain size, this study provides a first insight into long-term brain size evolution in the wolf-dog lineage. We compared endocranial volumes of 185 modern and 22 prehistoric wolves and dogs ranging from Western Europe to Australia, and spanning the Pleniglacial (35 Ky BP) to the Late Neolithic (5 Ky BP). Our results reveal that Pleistocene so called "protodogs" show no brain size reduction compared to coeval Pleistocene wolves. Instead, we observed a slightly larger relative endocranial volume in the 35,000-year-old protodog from Goyet, which could suggest increased behavioural flexibility in the presence of humans. This hypothesis needs to be tested further. In contrast, Late Neolithic dogs show a drastic 46% brain size reduction with an endocranial volumes comparable to modern small terrier and toy breeds. The anxious and wary temperaments of these Late Neolithic dogs, induced by the brain tissue reorganization associated with such a size reduction, could have served an alerting purpose, among the many other potential roles dogs could have played within this Late Neolithic socio-ecosystems.

Describing and interpreting spatiotemporal patterns in human culture has been a central focus of anthropology and archaeology for over a century. Recent ethnographic studies have highlighted the complexity of the processes generating these patterns, including isolation-by-distance, homophily, and common descent. However, investigating these processes in prehistoric archaeology remains challenging. Here we make use of a new interdisciplinary database and a combined dataset of ancient DNA (aDNA) genomic sequences to analyse the relationship between spatiotemporal patterns in cultural and genomic variation, by testing whether broadly defined clusters of genomic affinities correspond to spatiotemporal changes in burial rites, while controlling for other factors, using a Gaussian process model. We use data from the Big Interdisciplinary Archaeological Database (BIAD), linking mortuary information from [~]4,200 individuals with genetic ancestry and mobility data inferred from over 1,300 human genomes, from Western Eurasia [~]10,000-2000 BP. By integrating and modelling these diverse datasets, we aim to provide a detailed understanding of how genomic history intersects with cultural evolution, offering new insights into the dynamics behind these complex processes, and the extent to which genes and culture are transmitted in parallel. In the case of burial orientation, we found that cultural affiliation was the main factor accounting for variation with little to no role for ancestry, while for body position the picture was more mixed but cultural affiliation also played an important role.

The Roman period saw the empire expand across Europe and the Mediterranean, including much of what is today the United Kingdom. While there is written evidence of high mobility into and out of Britain for administrators, traders and the military, the impact of imperialism on local population structure is invisible in the textual record. The extent of genetic change that occurred in Britain before the Early Medieval Period and how closely linked by genetic kinship the local populations were, remains underexplored. Here, using genome-wide data from 52 ancient individuals from Cambridgeshire, we show low levels of genetic ancestry differentiation between Romano-British sites and lower levels of runs of homozygosity over 4 centimorgans (cM than in the Bronze Age and Neolithic. We find fourteen cases of genetic relatedness within and one between sites without evidence of patrilineal dominance and one case of temporary mobility within a family unit during the Late Romano-British period. We also show that the modern patterns of genetic ancestry composition in Modern Britain emerged after the Roman period.

ObjectivesThe intricate trabecular architecture of long-bone epiphyses underpins functional adaptations for diverse mammalian locomotion. Despite extensive study in other mammals, tamarin trabecular structure and fine-grained differences among leaping taxa remain poorly characterized. Materials and MethodsWe examined humeral and tibial trabecular networks in four tamarin species representing short- and long-distance leapers using {micro}CT-scans and a whole-epiphysis approach. We quantified network complexity with topological indices (node density, tortuosity, trabecular length, fractal dimension) alongside traditional metrics (degree of anisotropy [DA], bone volume fraction [BV/TV]) to capture both geometric and topological features. ResultsLong leapers exhibit significantly higher node density in both humeral and tibial epiphyses and increased trabecular tortuosity in the distal humerus. Elevated node density localizes beneath the humero-scapular joint, within the proximal humerus, and in variable regions across other epiphyses. Other parameters (DA, BV/TV, trabecular length, fractal dimension) showed no leaping-related differences, instead correlating with sex and captivity. DiscussionIncreased mechanical strain during longer leaps likely drives higher node density and, to a lesser extent, tortuosity in humeral and tibial epiphyses, with node density showing the strongest functional signal. While sex and captivity influence other trabecular traits, patterns in these key metrics support locomotor adaptation. Integrating whole-epiphysis analyses with novel topological indices enhances detection of subtle functional signals and complements VOI-based and traditional frameworks in comparative trabecular bone studies.

Domestic dogs (Canis familiaris) display more morphological variation than any other mammal. Cranial morphology has been extensively studied, as have the relationships with function, development, genetics, veterinary medicine, and breed welfare. Postcrania remain comparatively understudied, despite well-documented breed-specific predispositions to musculoskeletal disease. Here, we apply three-dimensional landmark-free morphometrics to quantify the shape of 743 elements from 213 dogs, including the scapula, humerus, radius, ulna, pelvic girdle, femur, tibia, and fibula. We assess integration among limb elements and investigate drivers of shape variation within and between breeds. Across most breeds, limb bone shape is strikingly similar. Dachshunds, however, exhibit distinct morphology across all elements and one to two orders of magnitude greater variation than any other breed. Despite this disparity, integration remains high between all element pairs. Remarkably, we find no significant relationship between bone shape and body mass, age, or pathology, but comparison with historic specimens reveals marked changes in dachshund long bone shape over the past [~]150 years. These extreme differences are not shared by other sampled chondrodysplastic breeds, underscoring the need to understand morphological diversity beyond simple categorisation. These findings provide a quantitative framework for linking postcranial morphology with function, disease risk, and evidence-based improvements to canine welfare.

Cities are characterized by elevated temperatures, increased pollution, and high-density human populations which often are accompanied by changes in available resources, like food. These shifts have the potential to drive phenotypic divergence in urban wildlife. Functional morphological traits, like body size, can mediate interactions between wildlife and habitat and are closely tied to life history and fitness. While examples of functional morphological variation associated with urbanization are increasing, variation in such traits as a response to urbanization remains unexplored for most taxa. Here, we investigated morphological divergence between urban and rural populations of house mice (Mus musculus domesticus). House mice are globally distributed in diverse habitats and are a model system with a wealth of phenotypic data, making them useful for the study of the impacts of urbanization on morphology. Using a paired replicate design, we sampled urban and rural populations in three distinct metropolitan regions in the eastern United States. We found that body size was smaller in urban populations. Using 3D geometric morphometrics, we also analyzed variation in cranial shape across habitats. Differences in cranial shape were largely allometric, that is, driven by differences in body size. However, we also uncovered evidence of cranial shape variation between habitats not explained by size. In contrast, we did not find evidence for habitat-driven differences in cranial capacity independent of size. Overall, our results suggest a key role for body size in mediating morphological responses to urbanization and highlight the potential of house mice as a globally-distributed model for urbanization.

Ethnonyms such as "Goth" in Late Antique sources capture political and cultural affiliations that may not map cleanly onto biological descent. Here we report genome - wide ancient DNA from 38 individuals associated with Gothic - period mortuary contexts at two sites in present - day Bulgaria: the Aquae Calidae necropolis ([~]320 - 375 CE) and the Aul of Khan Omurtag necropolis ([~]350 - 489 CE). Using PCA, f - statistics, qpAdm, uniparental markers, and IBD/kinship analyses, we find: (i) strong within - site heterogeneity, rejecting a single "Gothic" genetic profile; (ii) a reproducible north - south genetic contrast, with Aquae Calidae individuals shifted toward a Balkan/Anatolian - related ancestry axis and AKO individuals enriched in northern European - related ancestry consistent with Wielbark/Chernyakhiv proxies; and (iii) admixture dating with DATES placing the mixing between northern and southern ancestry poles at [~]11 - 13 generations before burial (point estimates in the 1st century CE, depending on target grouping), based on 23 individuals with sufficient coverage. Together, these results support models in which Gothic material culture in the Balkans was practiced by multi - ethnic communities and illustrate how cultural "Gothic" identity could persist despite substantial genetic diversity. Full f3/qpAdm/DATES outputs, f4 validation, and kinship/IBD summaries are provided in Supplementary Tables S1-S6, Supplementary Notes S2-S4, and the Supplementary IBD Workbook.

Studies of climate variation commonly rely on chemical and isotopic changes recorded in sequentially-produced growth layers, such as in corals, shells and tree rings, as well as in accretionary deposits--ice and sediment cores, and speleothems. Oxygen isotopic compositions ({delta}18O) of tooth enamel are a direct method of reconstructing environmental variation experienced by an individual animal. Here we utilize long-forming orangutan dentitions (Pongo spp.) to probe recent and ancient rainfall trends on a weekly basis over [~] 3-11 years per individual. We first demonstrate the lack of any consistent isotopic enrichment effect during exclusive nursing, supporting the use of primate first molar teeth as environmental proxies. Comparisons of {delta}18O values (n = 2016) in twelve molars from six modern Bornean and Sumatran orangutans reveal a high degree of overlap, with more consistent annual and bimodal rainfall patterns in the Sumatran individuals. Comparisons with fossil orangutan {delta}18O values (n = 955 measurements from six molars) reveal similarities between modern and late Pleistocene fossil Sumatran individuals, but differences between modern and late Pleistocene/early Holocene Bornean orangutans. These suggest drier and more open environments with reduced monsoon intensity during this earlier period in northern Borneo, consistent with other Niah Caves studies and long-term speleothem {delta}18O records in the broader region. This approach can be extended to test hypotheses about the paleoenvironments that early humans encountered in southeast Asia.

The Medieval Ottonian dynasty had a lasting impact on European history. We obtained ancient genomic DNA from the purported remains of Otto I (912-973) and Heinrich (Henry) II (973-1024), the first and last emperors of this dynasty, preserved in the cathedrals of Magdeburg and Bamberg, respectively. Historical records attest that they were related as a great-uncle and a grandnephew via the paternal line. Whole-genome sequencing confirms such a relationship between the two individuals, as we identify a third-degree genetic relationship based on shared DNA segments and infer matching Y haplogroups. This genetic relatedness effectively identifies the remains of the two emperors. The authentication yields a valuable resource for refining and calibrating bio-archaeological methods. Because historical records provide the precise lifespans and dates of death of these individuals, their remains can serve as a "ground-truth" for methods such as radiocarbon dating and age-at-death estimates. They can provide calibration data to improve our understanding of the radiocarbon reservoir effects of Medieval elites. As the Ottonian lineage was closely linked to the mating networks of elites across Europe, the genomes of the two emperors are valuable resources for identifying other potential elite burials.

The colonial-period arrival of Europeans in southern Africa is associated with strong sex-biased migration by which male settlers displaced indigenous Khoekhoe and San men. Simultaneously, the importation of South Asian, Indonesian and Eastern African slaves may have contributed female-biased migration to Cape Town and surrounding areas. We examine the spatial and temporal spread of sex-biased migration from the Cape northward into Namaqualand and the southern Kalahari using genetic data from more than 1,400 individuals. In all regions, admixture patterns were sex-biased, with evidence of a greater male contribution of European ancestry and greater female contribution of Khoe-San ancestry. While admixture among Khoe-San, European, equatorial African, and Asian groups has likely been continuous from the founding of Cape Town to present-day, we find that Khoe-San groups further north experienced a single pulse of European admixture 6-8 generations ago. European admixture was followed by additional Khoe-San gene flow, potentially reflecting an aggregation of indigenous groups due to disruption by colonial interlopers. Male migration into the northern frontier territories was not a homogenous group of expanding Afrikaners and slaves. The Nama show evidence of distinct founder effects and derive 15% of their male lineages from Asian men, a pattern absent in the =Khomani San. Khoe-San ancestry from the paternal line is greatly diminished in populations from Cape Town, the Cederberg Mountains and Upington, but remains more frequent in self-identified ethnically indigenous groups. Strikingly, we estimate that Khoe-San Y-chromosomes were experiencing unprecedented population growth at the time of European arrival. Our findings shed light on the patterns of admixture and the population history of South Africa as the colonial frontier expanded.

Because brain tissues rarely fossilize, pinpointing when and how modern human cerebral traits emerged in the hominin lineage is particularly challenging. The fragmentary nature of the fossil material, coupled with the difficulty of characterizing such a complex organ, have been the source of long-standing debates. Prominent among them is the uncertainties around the derived or primitive state of the brain organization in the earliest representatives of the genus Homo, more particularly in key areas such as the Brocas area. By revisiting a particularly well-preserved fossil endocast from the Turkana basin (Kenya) attributed to early Homo, here we confirm that humans in Africa had a primitive organization of the Brocas area ca. 1.9 million years ago. Additionally, our description of KNM-ER 3732 adds further information about the variation pattern of the inferior frontal gyrus in fossil hominins, with implications for early Homo taxic diversity (i.e., one or two Homo species at Koobi Fora) and the nature of the mechanisms involved in the emergence of derived cerebral traits.

We present the first radiographic ageing framework for common dolphins (Delphinus delphis), based on ossification and epiphyseal fusion patterns in the pectoral flipper, demonstrating higher reliability for chronological age estimation than currently available epigenetic approaches for this species. Using individuals of known dental age, we calibrated two modelling approaches to predict dental age from radiographic bone scores: 1) a univariate polynomial regression using a total bone score (sum of 16 scores across all assessed flipper bones), and 2) a multivariate canonical analysis of principal coordinates (CAP) incorporating 16 individual bone-score variables. Both approaches successfully predicted dental age from skeletal ossification patterns. For an age range of 0 to 24 years, polynomial regression demonstrated high predictive accuracy with median absolute errors (MAEs) of 1.25 years in females (Spearmans {rho} = 0.93, R{superscript 2} = 0.90) and 1.08 years in males ({rho} = 0.95, R{superscript 2} = 0.86). The CAP model yielded MAEs of 1.35 years in females ({rho} = 0.90, R{superscript 2} = 0.85) and 1.80 years in males ({rho} = 0.94, R{superscript 2} = 0.84). Notably, both radiographic bone ageing models achieved equal or lower median absolute errors and higher coefficients of determination than a recently developed epigenetic clock for common dolphins derived from the same population (MAE = 1.80, Pearsons correlation (r) = 0.91, R{superscript 2} = 0.82). When applying the bone ageing models to individuals of unknown dental age, both models produced age estimates consistent with expected life-history stages (foetus, neonate, juvenile, subadult, adult), although accuracy declined in dolphins above 20 years, likely as a consequence of subtle age-related variation in skeletal changes in this species. Radiographic ageing provides an accurate non-invasive tool for demographic assessment to support conservation management of common dolphins.

Selective funerary practices can inform about social relationships in prehistoric societies but are often difficult to discern. Here we present evidence for an age-specific practice at the Neolithic site of Catalhoyuk in Anatolia, dating to the 7th millennium BCE. Among ancient DNA libraries produced from 362 petrous bone samples, those of subadults contained three times higher average human DNA than those of adults. This difference in organic preservation was also confirmed by FTIR analysis. Studying similar datasets from seven prehistoric and historical sites, we found a similar age-related difference in only one cemetery. We propose that the organic preservation difference with age was caused by the special treatment of chosen corpses before interment, such as defleshing or drying, which was more frequently applied to Catalhoyuk adults and promoted organic decay.

Proboscideans, including mammoths, played a crucial role in past herbivore communities, where resource partitioning helped reduce competition and promote coexistence. Stable carbon isotopes are frequently employed to differentiate between the consumption of C3 and C4 plants in the fossil record. However, as geographic variability influences {delta}13C values, dental microwear texture analysis (DMTA) is often used in tandem to infer dietary preferences among extinct taxa (e.g., the consumption of grass vs. browse). Interpreting the dietary ecology of proboscideans, like mammoths, rests on our ability to compare fossil specimens to modern taxa with known diets. Here, we established a modern reference for interpreting mammoth DMTA by analyzing teeth from 11 African bush elephants (Loxodonta africana) culled in 1993 from Kruger National Park (KNP), South Africa (CITES permit certificate no. 780873). These specimens, housed at the Illinois State Museum, originated from the arid bushveld of northern KNP and were collected during the beginning of the dry season. Previous studies indicate that modern elephants in this region consume a mixed diet, consisting of [~]40% grass in the dry season and 50% grass in the wet season. The well-documented dietary and environmental context of these individuals provides an opportunity to assess dental microwear patterns in a modern analog and compare individuals with known diets to extinct mammoths. Specifically, we compared newly acquired modern African bush elephants DMTA to published DMTA data from fossil specimens of Columbian mammoths (Mammuthus columbi). Comparisons with fossil assemblages reveal few statistically significant differences in microwear between mammoth and KNP elephants, with the exception of mammoths from Leisey Shell Pit 1A having significantly lower complexity values than modern African bush elephants--indicative of some mammoth populations eating softer foods and/or less woody browse. Variation and breadth of DMTA from mammoths are similar to the temporally and geographically constrained population of L. africana. Despite potential time averaging in fossil assemblages, the variation in mammoth DMTA aligns with that of a geographically and temporally constrained modern population, indicating that microwear variability in fossil taxa is not necessarily greater than that observed in extant species and is consistent with the highly varied diets of modern African elephants.

The early evolutionary history of modern domestic horses (Equus caballus/E. ferus caballus), known as the DOM2 lineage, is well documented due to numerous archaeological and ancient DNA (aDNA) studies. Although many uncertainties remain in the domestication timeline, current evidence suggests that the domestication of modern horses began in the Pontic-Caspian steppe at least [~]2700 BCE (before common era), or even earlier. However, it is not known how long remnant wild horse populations survived or when domestic horses were introduced into Northern Europe. In this study, we review the current knowledge of horse domestication, focusing on Northern Europe. We analysed prehistoric horses from western Russia to assess the body sizes of wild horses from the Ivanovskaya site (5900-3800 BCE) in the Pontic-Caspian steppe, and the body weight of one Lithuanian wild horse (4000-3800 BCE). Additionally, we analysed body sizes of Late Bronze Age-Early Roman Age horses (1100 BCE-300 CE; common era) and re-analysed body sizes and estimated rider weights of historic domestic horses from Lithuania (100-1400 CE). We searched for pathological changes and signs of bit wear indicative of bridling. Furthermore, we investigated maternal genetic diversity by sequencing ancient mitochondrial DNA. We found that wild horses from Ivanovskaya were intermediate in body size between earlier and more recent horses of the Eurasian Steppe, and that the Lithuanian wild horse weighed only [~]270 kg and Late Bronze Age-Early Roman Age horses 200-300 kg. Lithuanian domestic horses were pony-sized (< 130 cm on average). Bit wear was confirmed on one tooth, the oldest domestic horse in Lithuania (799-570 cal BCE). Another tooth showed signs of the Equine Odontoclastic Tooth Resorption and Hypercementosis (EOTRH) condition. Mitochondrial DNA was successfully amplified from one Ivanovskaya wild horse along with 25 other ancient samples, including Lithuanias oldest domestic horse. mtDNA diversity was high, revealing several maternal lineages.

The Southern Cone represents the southernmost region of South America to be colonized by humans. Although ancient genomes have been sequenced from southern Patagonia, genomic data from the central Southern Cone remain temporally and spatially sparse. The archaeological record of this region documents major cultural transformations during the Middle and Late Holocene, yet their relationship to demographic processes has long been debated. Here, we present genome-wide data from 52 individuals spanning the past 5,000 years, originating from four regions of the central Southern Cone in present-day Argentina and Uruguay: the central and southern Pampas, Northwest Patagonia, the Parana River Delta and Lower Uruguay River, and the eastern lowlands of Uruguay. Genomic evidence from the Pampas reveals the presence of at least three distinct ancestries during the Middle Holocene. While genetic contacts with southern Patagonian groups were sporadic, we identify the expansion of an ancestry of unknown geographic origin by 4,800 years ago, which increased substantially during the Late Holocene. This same ancestry arrived in Northwest Patagonia by at least 600 years ago, and it co-existed with individuals carrying a southern Andean genetic profile until colonial times. Genetic structure differentiates populations along the Parana River Delta and the Lower Uruguay River by approximately 1,600 years ago. In contrast, individuals from the eastern lowlands of Uruguay show genetic links with Sambaqui-associated populations from the southern coast of Brazil, suggesting the role of human dispersals in connecting tropical lowland cultural traditions. Overall, our work documents the diffusion of genetically distinct groups across all regions studied and provides compelling evidence that large-scale human movements contributed to the remarkable cultural diversity of central Southern Cone populations during the Middle and Late Holocene.

Adrenarche, the pre-pubertal rise in adrenal androgens, particularly dehydroepiandrosterone (DHEA) and its sulfated form DHEAS, is a critical driver of middle childhood cognitive and social development in modern humans. Compared to other apes, modern human adrenarche is more prolonged, with higher DHEAS levels. Whether this uniquely prolonged human adrenarche is a derived trait of Homo sapiens or has deeper hominin roots remains unresolved. Here, we examine the Neanderthal genetic variation in five key DHEAS biosynthesis genes (HSD3B2, CYP17A1, POR, CYB5A, SULT2A1). We also examine archaic introgression in these genes by comparing high-coverage Neanderthal genomes with globally diverse modern human sequences from the 1000 Genomes Project. We identify 29 Neanderthal-derived single nucleotide variants across these genes. Key steroidogenic genes in the biosynthesis pathway show no evidence of introgression, consistent with selection on pleiotropic regulators of steroidogenesis. In contrast, accessory genes carried introgressed Neanderthal haplotypes at moderate frequencies in non-African human populations, indicating Neanderthal variants are compatible with the human DHEAS synthesis pathway. All Neanderthal-specific variants were in non-coding regions, with three variants associated with reduced enzyme efficiency or DHEAS production in adults. Additionally, for all 29 positions, the modern human major allele is ancestral, and there is no evidence for a suite of novel adrenarche-extending variants. We conclude that the genetic foundation for extended adrenarche is shared between Homo sapiens and Neanderthals, and may have deeper hominin roots. Any phenotypic variation in adrenarche between modern humans and Neanderthals is more likely attributable to differential gene expression than to divergence in protein-coding sequences.

While early Neolithic populations in Europe were largely descended from early Aegean farmers, there is also evidence of episodic gene flow from local Mesolithic hunter-gatherers into early Neolithic communities. Exactly how and where this occurred is still unknown. Here we report direct evidence for admixture between the two groups at the Danube Gorges in Serbia. Analysis of palaeogenomes recovered from skeletons revealed that second-generation mixed individuals were buried amidst individuals whose ancestry was either exclusively Aegean Neolithic or exclusively local Mesolithic. The mixed ancestry is also reflected in a corresponding mosaic of grave goods. With its deep sequence of occupation and its unique dwellings that suggest at least semi-sedentary occupation since the late Mesolithic, the area of the Danube Gorges has been at the center of the debate about the contribution of Mesolithic societies to the Neolithisation of Europe. As suggested by our data, which were processed exclusively with uncertainty-aware bioinformatic tools, it may have been precisely in such contexts that close interactions between these societies were established, and Mesolithic ancestry and cultural elements were assimilated.

The ontogeny of Neanderthal (Homo neanderthalensis) perinates is poorly understood due to the paucity of juvenile skeletal remains. Here we reconstruct fetal bone growth, and explore deciduous tooth structures, in three Neanderthal juveniles (Sesselfelsgrotte, 1, 2 and 3) (90,000-50,000 years ago) from southeastern Germany using non-destructive microcomputed tomography. Sesselfelsgrotte 1 exhibited bone tissue consistent with modern human perinatal plexiform-like structures and primary osteons. Long bones showed regions of advanced growth compared to the mandible and frontal bone, which can be explained through different processes of ossification and potentially localized faster development in Neanderthals compared to modern humans. Bone microstructure resembles that of the late third trimester of modern humans, agreeing with previous estimates based on macroscopic data. Sesselfelsgrotte 2 and 3 deciduous teeth retain hypodensities deep within the crown dentine consistent with interglobular dentine. We conclude that the fetal bone patterning is similar to modern humans with areas of advanced growth, indicating that the growth trajectory for this Neanderthal perinate was broadly equivalent to that of modern humans. The abnormal dentine mineralization points toward a possible systemic disorder.