Bone abnormalities in the middle Anisian marine sauropsids from Winterswijk.

While the occurrence of skeletal pathologies in Middle Triassic marine reptiles has been poorly documented until now, massive accumulations of bone remains from the Germanic Basin provide the opportunities for documentation. Herein, we describe skeletal abnormalities in the Middle Triassic bone material from the Vossenveld Formation of Winterswijk, the Netherlands. The aim of the study is to distinguish in the studied bones pathologies resulting from malady or trauma and taphonomic alterations. Furthermore, an attempt was made to assess on how the pathologies also represent paleoecological data. Our survey led to the identification of one broken and healed bone, one case of abnormal coossification, and one case of posttraumatic fibro-osseous dysplasia. While the latter two pathologies give little insight into the ecology and function of the affected animals, the fractured dentary is attributed to Nothosaurus marchicus, a common sauropterygian macropredator. It proves that the individual survived long enough to heal, despite the injury hampering its hunting potential. One abnormally shaped humerus is interpreted as postmortem taphonomic deformation, emphasizing the necessity of utilization of detailed diagnostics to distinguish actual paleopathologies from nonbiological distortion.

Metastatic cancer and multiple myeloma: One ancient, the other a disease of modernity?

Background: Diagnostic caveats have often been incorporated in publications suggesting possible multiple myeloma in archeological sites, noting difficulty distinguishing it from metastatic cancer. It seems appropriate to assess whether suggested cases in the archeological record differ from what modern medicine recognizes/diagnoses. Methods: The published literature and archives were surveyed for reports of multiple myeloma in archeological sites. Descriptions were examined for fulfilment of diagnostic anatomic criteria (sharply defined, spherical defects, expansion without regard for the density of surrounding bone in the absence of bone reaction or residual internal structures and contained structures). Lytic areas were examined for shape homogeneity, sharp or graded edges, relative expansion through adjacent trabecular and cortical bone and for presence of new bone formation either bordering the lesion or as periosteal reaction. Results: None of the 49 reported accessible cases described/illustrated individuals had appearances consistent with what today is recognized as multiple myeloma. The mean age of reported cases of 44 was significantly less than that of 69 in clinically diagnosed cases (t test 4.62123, p = 0.00028). Descriptions of bone lesions in many actually were often at variance with that recognized on review of their images. The significance of subtle peri-lesional density variation was often overlooked and oval lesions were often mischaracterized as "punched out." Most cases likely represent metastatic cancer. A previously unreported alteration, rosette formation, was noted in a female subgroup. Discussion: Macroscopic, radiologic and epidemiologic comparison of clinically-diagnosed cases with purported archeologic cases evidences that they represent very different diseases. Since multiple myeloma has yet to be confidently diagnosed/recognized in the archeologic record, the possibility must considered is that it is a disease of the modern epoch. A further observation is that the newly recognized finding of peri-lesional rosettes might be a marker for the breast cancer origination of observed metastases.

Unusual lesions seen in the caudals of the hadrosaur, Edmontosaurus annectens.

The study of pathologies in the fossil record allows for unique insights into the physiology, immunology, biomechanics, and daily life history of extinct organisms. This is especially important in organisms that have body structures dissimilar to those of extant organisms as well as transitional groups whose extant relatives may have very dissimilar physiologies. Comparisons between modern groups and their fossil ancestors are further complicated by the fact that fossil groups may have experienced unique biomechanical stresses as well as possessing a mixture of anatomical features seen in their related extant groups. In this study, we present lesions in the caudal vertebrae of the hadrosaur, Edmontosaurus annectens from the Ruth Mason Dinosaur Quarry of South Dakota, which exhibit unique morphologies. X-ray microtomography was performed on the most extreme example of this morphology to allow for both a detailed and more accurate diagnosis of the pathologic condition as well as virtual conservation of the specimen. Based on the location, the overall morphology of the lesion, and the relative "normal" appearance of the internal microstructure, the most probable cause is postulated as long-term biomechanical stresses exerted on this section of the tail by both lateral and dorsoventral motions of the tail. This deduction was based on a process of elimination for a variety of known osteological conditions; however, future work is needed to determine the nature of the stresses and why this condition has not been recorded in more hadrosaurian specimens.

An insight into cancer palaeobiology: does the Mesozoic neoplasm support tissue organization field theory of tumorigenesis?

BACKGROUND: Neoplasms are common across the animal kingdom and seem to be a feature plesiomorphic for metazoans, related with an increase in somatic complexity. The fossil record of cancer complements our knowledge of the origin of neoplasms and vulnerability of various vertebrate taxa. Here, we document the first undoubted record of primary malignant bone tumour in a Mesozoic non-amniote. The diagnosed osteosarcoma developed in the vertebral intercentrum of a temnospondyl amphibian, Metoposaurus krasiejowensis from the Krasiejów locality, southern Poland. RESULTS: A wide array of data collected from gross anatomy, histology, and microstructure of the affected intercentrum reveals the tumour growth dynamics and pathophysiological aspects of the neoplasm formation on the histological level. The pathological process almost exclusively pertains to the periosteal part of the bone composed from a highly vascularised tissue with lamellar matrix. The unorganised arrangement of osteocyte lacunae observed in the tissue is characteristic for bone tissue types connected with static osteogenesis, and not for lamellar bone. The neoplastic bone mimics on the structural level the fast growing fibrolamellar bone, but on the histological level develops through a novel ossification type. The physiological process of bone remodelling inside the endochondral domain continued uninterrupted across the pathology of the periosteal part. CONCLUSIONS: Based on the results, we discuss our case study's consistence with the Tissue Organization Field Theory of tumorigenesis, which locates the causes of neoplastic transformations in disorders of tissue architecture.

Beyond transcortical channels, a supraparietal vascular plexus: A newly recognized anatomical feature.

Survey of transcortical channels across mammalian phylogeny exposes a previously unrecognized phenomena, localized to the most caudal third of a Sus scrofa parietal. The current study is performed to assess the nature, ontogeny and phylogenetic distribution of this phenomenon. Dissection of a fresh S. scrofa is performed to characterize the nature of these structures and assess the relationship of the phenomenon to overlying tissues. The external surface of the parietal region of the skulls of recent Artiodactyla, Perissodactyla, Lagomorpha, and Rodentia and Pleistocene Platygonus compressus are systematically examined by surface microscopy. Dissection of the parietal region of a S. scrofa head revealed a structure localized to the most caudal third of the parietal bone. It is composed of anastomosing blood vessels interposed between the dermis and bone. The phenomenon is present among Artiodactyla in all examined Suidae and Tayassuidae, but limited among Cervidae to Odocoileus and apparently limited among Perissodactyla to Tapiridae, both extant and extinct and independent of sex and age. A previously undescribed anatomic structure is observed during survey of transcortical parietal circulation. There is connection between the structure and parietal diploic vessels. Interpreted as a vascular plexus, the possibility of a countercurrent system for brain thermoregulation is considered.

Demographics and significance of porotic hyperostosis as assessed by surface microscopy.

BACKGROUND: Examination of parietal surface anatomy has been limited because standard techniques have insufficient resolution to identify and characterize the structures of interest. Perspectives derived thereof have not clarified their nature. Surface microscopy is pursued as a nondestructive technique to assess the character and implications of porotic pores (referred to as porotic hyperostosis), which have been subject of much speculation. METHODS: The external surface of the skulls, selected on the basis of age and gender, from the Hamann-Todd human collection are examined by epi-illumination microscopy for surface pores and to assess correlation with age, ethnicity, gender, anemia, infection, cancer, hypertrophic bone disorders, renal disease, and fractures. RESULTS: Pore-like surface defects are present in 2.7%-5% of individuals in the third-fifth decades of life; 7%, in the sixth-eighth; and 25%, in the ninth-11th, but absent in the second decade of life. They are gender and birthdate independent, but slightly more common in African Americans. Fractures are more common among individuals with parietal pores, while tuberculosis, cancer, and hypertrophic bone diseases and anemia are less common. DISCUSSION: This is the first study to actually examine the prevalence of parietal pores as a function of known age, race, and sex and provides a baseline for comparison with populations in which those variables are not clearly identifiable. While some porotic pores may be related to marrow hyperplasia, transcortical circulation may explain the majority.

An apparently phylogeny-independent method for identification of skeletal (longitudinal) growth cessation (skeletal maturity) in birds.

Identification of skeletal maturity is of interest as a measure of species longevity and for identifying its maximal achievable size/mass. Measurement of age on the basis of growth arrest/accentuation lines and external fundamental system evidences cessation or at least extreme slowing of circumferential bone growth. Such intramembranous (periosteal)-derived growth is distinct from the endochondral ossification responsible for longitudinal growth and therefore achievable organismal size/mass. As subchondral transcortical channels are required for nourishment, their loss should identify cessation of longitudinal growth. Predicated on phylogenetic bracketing/relationship and shared anatomical structures with and without growth plates, birds represent an appropriate model for the study of dinosaur ontogeny. Persistence of transcortical subchondral channels in the long bones of birds are examined at ×100-200 magnification and correlated with bone length. Transcortical channels are present in subchondral articular surfaces, but disappear when terminal longitudinal growth is achieved. Articular vascular channels perforating articular surfaces from within the bone are detected. Loss of penetrating channels is interpreted as evidence of skeletal growth cessation, identifying the longitudinal bone length at which skeletal growth cessation has been achieved. The current study provides evidence that maximal bone length does correlate with endochondral cessation growth. Failure of circumferential growth reduction/cessation to correlate with bone length may be related to lack of synchronicity of periosteal-based circumferential growth with the endochondral process responsible for bone lengthening. Loss/closure of articular vascular channels may be the most reliable measure of a bird's achievement of maximal growth (indicating cessation of appendicular element lengthening).

Cribra orbitalia is correlated with the meningo-orbital foramen and is vascular and developmental in nature.

Cribra orbitalia is a phenomenon with interdisciplinary interest. However, the etiology of cribra orbitalia remains unclear. Recently, the appearance of cribra orbitalia was identified as vascular in nature. This study assessed the relationship between anatomical variation of vasculature, as determined by the presence of meningo-orbital foramina, and the presence of cribra orbitalia in 178 orbits. Cribra orbitalia was identified in 27.5% (49:178) of orbits (22.7%, 35:154 adult orbits and 58.3%, 14:24 subadult orbits) and meningo-orbital foramina were identified in 65.8% (100:152) of orbits. Among the 150 total intact adult orbits (i.e., orbital roof and posterior orbits both intact), cribra orbitalia was found in 35 (23.3%). Of these 35 occurrences of cribra orbitalia, 32 (91.4%) had the concurrent finding of a meningo-orbital foramen. However, in the absence of the meningo-orbital foramen, cribra orbitalia was only found in three sides out of the total sample of intact orbits (3:150; 2.0%). Fisher's exact test revealed that the presence of cribra orbitalia and the meningo-orbital foramen were statistically dependent variables (p = .0002). Visual evidence corroborated statistical findings-vascular impressions joined cribra orbitalia to meningo-orbital foramina. This study identifies that individuals who possess a meningo-orbital foramen are anatomically predisposed to developing cribra orbitalia. Conversely, cribra orbitalia is unlikely to occur in an individual who does not possess a meningo-orbital foramen. Thus, the antecedent of cribra orbitalia is both vascular and developmental in nature. This report represents an important advancement in the understanding of cribra orbitalia-there is an anatomical predisposition to the development of cribra orbitalia.

Osteophytes: The product of convergent evolution.

The very reasonable suggestion, that diarthrodial joint and juxta-discal (vertebral centra-marginal) bony overgrowths (referred to as osteophytes) have different etiologies, has eluded previous confirmation. The prevailing perspective is that diarthrodial osteophytes represent the product of compressive forces and that those on the margins of vertebral centra result from traction and therefore are enthesial in derivation. If diarthrodial joint osteophytes result from intrinsic pressures, any surface responses would require transcortical nutritional support, easily recognized by en face microscopic examination. This contrasts with enthesially derived growth, the surface of which is characterized by Sharpey's fiber insertions. These are recognized as inverted cones with a central protrusion on examination of related bone surfaces. We hypothesize that diarthrodial and disc-adjacent osteophytes have a different pathophysiology, distinguishable on the basis of microscopic surface appearance. We pursued microscopic examination of the surfaces of osteophytes present on diarthrodial joints (hip, knee, elbow, costovertebral) and vertebrae (cervical, thoracic, and lumbar) from the CAL Milano Cemetery Skeletal Collection for presence of transcortical channels and the inverted cones of Sharpey's fiber insertions. Examination of 22 diarthrodial joint osteophytes reveals the presence solely of transcortical channels, while examination of 35 vertebral centra marginal osteophytes reveals the presence only of inverted cones. Findings are independent of age, gender, joint affected, position in the spinal column and osteophyte "severity." It is now evidenced that all osteophytes are not created equal. Diarthrodial joint osteophytes are endochondrally derived; vertebral centra osteophytes, enthesial in derivation. Different pathophysiology at least partially explain the clinical character of these processes.

Survival of an Indian Ocean humpback dolphin Sousa plumbea in the wild despite chronic osteologic pathologies.

Skeletal examination of a female adult Indian Ocean humpback dolphin Sousa plumbea from South Africa suggested a chronic disease process. It manifested as erosions and pitting of the atlanto-occipital articulation as well as circumferential hyperostosis and ankylosis of some of the caudal vertebrae, findings rarely recorded together in the same animal. The character of the erosive process and vertebral fusion appeared chronic, and further findings of underdevelopment of the fluke, sternum and left humerus with remodeling of the periarticular region of the left scapula may support initiation of the process early in life. Because such chronic pathology would have affected the individual's locomotion and foraging abilities, we also postulate how this individual survived until its demise in a human-derived environmental hazard. Ecological and socio-behavioral aspects observed in S. plumbea, including habitat preference for inshore and shallow waters, small social group aggregations and feeding cooperation, may have contributed to its ability to survive.

Possible vertebral brucellosis infection in a Neanderthal.

The La Chapelle-aux-Saints 1 skeleton of an old (>60-year-old) male Neanderthal is renowned for the advanced osteoarthritis of its spinal column and hip joint, and their implications for posture and lifestyle in these Mid- to Late Pleistocene humans. Reassessment of the pathologic lesions reveals erosions at multiple non-contiguous vertebrae and reactive bone formation extending far beyond the left hip joint, which suggests the additional diagnosis of brucellosis. This implies the earliest secure evidence of this zoonotic disease in hominin evolution. Brucellosis might have been transmitted via butchering or eating raw meat and is well compatible with the range of prey animals documented for Neanderthals. The associated infertility could have represented an important aspect of health in these late archaic humans.

Dinosaur senescence: a hadrosauroid with age-related diseases brings a new perspective of "old" dinosaurs.

Senile vertebrates are extremely rare in the fossil record, making their recognition difficult. Here we present the largest known representative of the Late Cretaceous hadrosauriform Gobihadros mongoliensis showing features of cessation of growth indicating attainment of the terminal size. Moreover, this is the first non-avian dinosaur with an age-related pathology recognized as primary calcium pyrophosphate deposition disease indicating its advanced age. Because senile dinosaurs are so rare and thus "senescence" in dinosaurs is unclear, we also propose a new unified definition of a senile dinosaur: an individual which achieved the terminal size as revealed by the presence of the external fundamental system and closed transcortical channels, has completely secondary remodeled weight-bearing bones and possesses non-traumatic, non-contagious bone pathologies correlated with advanced age.

Survey of Post-Cranial Skeletal Pathology in Snakes.

Previous reports on skeletal pathology in captive snakes did not clarify the relationship of lesions to captive or free-ranging status. In this study, post-cranial skeletons from 7,950 captive and free-ranging snakes in nine of the major North American collections were examined macroscopically, microscopically and radiologically for the presence of pathology. Micro-computerized tomography was performed on two skeletons on which surface microscopy failed to provide a definitive diagnosis. Osteomyelitis was identified in the vertebrae of 24 snakes and spondyloarthropathy in one snake. Neoplasia or congenital anomalies were not found. Osteomyelitis was four times as common in Viperidae than in Colubridae and twice as common as in Boidae, independent of captive or free-ranging status. A lytic lesion in the vertebrae of one snake was suggestive of fungal disease. The progression of bone lesions was greater in captive snakes, but the prevalence was independent of captive or free-ranging status. The results of this study indicate that bone alterations, previously proposed as neoplastic disease, in archival snake skeletons were most likely of infectious aetiology, and establish macroscopic examination as a useful technique for characterizing skeletal pathology in snakes.

Distinguishing between congenital phenomena and traumatic experiences: Osteochondrosis versus osteochondritis.

The current study is to distinguish between osteochondrosis and osteochondritis, utilizing surface microscopy of individuals with documented pathology. Osteochondrosis is associated with smooth borders and gradient from edge to defect base, while osteochondritis and subchondral impaction fractures are associated with subsidence of the affected area of articular surface with irregular edges. The base of osteochondrosis is penetrated by multiple channels, smoothly perforate its surface, indistinguishable from unfused epiphyses, confirming their vascular nature. This study provides a technique for distinguishing osteochondrosis and osteochondritis and further documents of the value of epi-illumination microscopy in expanding our understanding of bone and joint disease.

The character of parietal and orbital alterations in the superfamily Hominoidea (families Hominidae [exclusive of Homo] and Hylobotidae).

Parietal external surface disruption routinely referred to as porotic hyperostosis, and orbital alterations (cribra orbitalia), have been attributed to anemia-related bone marrow hyperplasia in humans. A recent study in humans identified that they were actually vascular in nature. Skeletons were examined and epi-illumination surface microscopy was performed on the parietal region and orbit of 156 Hominidae and 123 Hylobotidae to assess if these phenomena were trans-phylogenetic. Trans-cortical channels were recognized on the basis of visualized ectocranial surface defects penetrating the parietal; cribra orbitalia, by alteration of the normally smooth orbital roof appearance. Trans-cortical parietal channels, ranging in size from 20 to 100 µm, are rare in Gorilla and Pan troglodytes and absent in Pan paniscus. They are universally present in adult Pongo abeli and in Hylobatidae, independent of species. Cribra orbitalia was common in Hylobotidae, Pongo pygmaeus and P. abelii, less prevalent in adult P. troglodytes, and not recognized in any Gorilla gorilla or P. paniscus examined. The proliferative form predominated, with the exception of Hylobates concolor and muelleri, in which uncalcified vascular grooves predominated. No correlation was observed between the presence of either trans-cortical channels or cribra orbitalia and fractures, osteoarthritis, or inflammatory arthritis. Parietal alterations observed in apes are trans-cortical channels, analogous to those observed in humans, and do not represent porosity. Similarly, cribra orbitalia in apes is confirmed as vascular in nature. The proliferative form apparently represents calcification of blood vessel walls, indistinguishable from observations in humans. Predominant presence in adults rather than in juveniles suggests that both forms are acquired rather than developmental in derivation. Sex and bone alteration/disease-independence suggests that mechanical, endocrine, and inflammatory phenomena do not contribute to the development of either. Further, independent occurrence of trans-cortical channels and cribra orbitalia suggests that they do not have a shared etiology.

Cribra orbitalia is a vascular phenomenon unrelated to marrow hyperplasia or anemia: Paradigm shift for cribra orbitalia.

The orbital phenomenon, cribra orbitalia, has long been a source of controversy, especially with regard to its nature, derivation, and relationship to anemia. Therefore, the external surfaces of orbital roofs were systematically examined microscopically in human skulls from historical collections. Superior orbital surfaces of 278 individual crania within the Hamann-Todd collection were assessed at various magnifications using epi-illumination microscopy to identify the presence of cribra orbitalia and characterize its nature. Also, 12 additional individuals with diagnosed anemia in the Hamann-Todd collection were evaluated. Orbital roof alterations, present in one-third of examined crania, had two discrete appearances: Vascular grooves (45%) and application of new bone in a vascular branching pattern on the orbit surface (55%). Porosity of the orbit was not observed. Evaluation of the orbits of 12 individuals with diagnosed anemia revealed one with a single deep defect, suggesting a space-occupying phenomenon, but no evidence of bone accretion, vascular grooves, or porosity. Cribra orbitalia has often been lumped indiscriminately as an indicator of organismal stress, rather than identified as a indicating a specific etiology. Neither that perspective nor porosity are supported by high resolution examination of orbital roof changes. Recognition of the blood vessel imprint pattern falsifies previous speculations and provides a new paradigm. The actual character of cribra orbitalia is documented and new hypotheses generated. While population prevalence of cribra orbitalia seems excessive for explanation on the basis of these hypotheses, the imprints are clearly vascular in origin.