Natural variation and differential diagnosis of skeletal changes in tuberculosis

Twenty-six documented cases (17 blacks, 9 whites) of skeletal tuberculosis from the Hamann-Todd Osteological Collection, Cleveland Museum of Natural History, were analyzed for lesion variability and patterns of multiple site involvement. In addition, several documented cases of pathologic conditions (osteomyelitis, vertebral fractures, and malignant bone tumors) that resemble skeletal tuberculosis were photographed and described for use in differential diagnosis. The range of variation of tuberculous lesions was found to be considerable. Thirty-eight percent (10/26) of the cases display skeletal lesions in two or more regions concomitantly. The average number of vertebrae affected, as well as the incidence of multiple bone involvement, were found to be higher in blacks. Certain combinations of skeletal lesions (e. g., spine-rib, spine-rib-sternum, and spine-hip) may be useful in the diagnosis of tuberculosis in dry bone material.     

Spinal arthritis and physical stress at Bronze Age Harappa

This study examines joint changes in the vertebral skeleton in human remains excavated in 1987 and 1988 at Bronze Age Harappa, an urban center of the Indus Valley civilization. The sample consists of 23 complete skeletons from primary burial context, the partial remains of more than 69 other individuals, and hundreds of skeletal elements from secondary context, totalling 3,084 vertebral joint margins and articular surfaces. Marginal bone proliferation, pitting of articular surfaces, eburnation, and ankylosis were scored macroscopically for vertebral body margins and surfaces and posterior apophyseal facet joints. Marginal lipping is far more prevalent on the vertebral bodies than on the apophyseal facets and surface pitting is also more frequent on vertebral bodies although its expression is relatively low overall. Cervical vertebrae in this sample exhibit the same amount of marginal new bone and much more surface pitting of the vertebral bodies than do either thoracic or lumbar vertebrae; the cervical segment also exhibits the most severe expressions of both types of lesions. In addition, although the frequencies of cervical and lumbar posterior facet involvement are similar, the cervical facets exhibit much more severe lipping as well as the only cases of eburnation and ankylosis. Pitting of the posterior facets is most common in the lumbar segment, but the cervical examples are the only severe cases. It is proposed that the severe joint changes in the cervical spine result from trauma, perhaps accumulated microtrauma from activity stresses. There are no age or sex associated patterns in the frequency of arthritis although this result may be influenced by the small proportions of the total sample for which age and sex could be determined. © 1994 Wiley-Liss, Inc.     

Skeletal evidence of tuberculosis in a modern identified human skeletal collection (Certosa cemetery,Bologna, Italy)

The diagnosis of tuberculosis (TB) in osteoarcheological series relies on the identification of osseous lesions caused by the disease. The study of identified skeletal collections provides the opportunity to investigate the distribution of skeletal lesions in relation to this disease. The aim of this study was to examine the skeletal evidence for TB in late adolescent and adult individuals from the identified human collection of the Certosa cemetery of Bologna (Italy, 19th–20th c.). The sample group consists of 244 individuals (138 males, 106 females) ranging from 17 to 88 years of age. The sample was divided into three groups on the basis of the recorded cause of death: TB (N = 64), pulmonary non‐TB (N = 29), and other diseases (N = 151). Skeletal lesions reported to be related to TB were analyzed. The vertebral lesions were classified into three types: enlarged foramina (EnF, vascular foramina with diameter of 3–5 mm), erosions (ER), and other foramina (OtF, cavities of various shapes > 3 mm). A CT scan analysis was also performed on vertebral bodies. Some lesions were seldom present in our sample (e.g., tuberculous arthritis). OtF (23.7%) and subperiosteal new bone formation on ribs (54.2%) are significantly more frequent in the TB group with respect to the other groups. The CT scan analysis showed that the vertebrae of individuals who have died of TB may have internal cavities in the absence of external lesions. These traits represent useful elements in the paleopathological diagnosis of TB. Am J Phys Anthropol 157:389–401, 2015. © 2015 Wiley Periodicals, Inc.     

Embryonic development of the skeleton of Amphisbaena darwini heterozonata (Squamata: Amphisbaenidae)

An assemblage of amphisbaenian embryos has allowed us to characterize the external morphology of the developing embryos as well as the chondrification and ossification sequences of their skeletal elements. The external characterization of embryos serves as an incomplete developmental table. In contrast to the condition in other squamates, the premaxilla seems to arise azygously from the beginning or to represent very early fusion during embryogenesis. The tabulosphenoid forms from two cartilages to which are added extensive membranous ossifications. The two parietals engage in medial fusion at the midline, where the anterior process of the synotic tectum ossifies and forms the sagittal crest. The lateral element‐X does not ossify until very late in embryogenesis and is interpreted as an epiphysial ossification. The compound mandibular bone arises from the ossification of the posterior part of Meckel's cartilage and the fusion of at least two dermal centers, interpreted as surangular and splenial. The vertebral column shows an antero‐posterior gradient of vertebral differentiation. The number of vertebrae is fixed from the beginning of their differentiation. The remnants of pectoral and pelvic girdles are represented by cartilaginous rods. Some reproductive data obtained during the collection of data could be compared with those from the literature. J. Morphol. 239:1–25, 1999. © 1999 Wiley‐Liss, Inc.     

Paleopathological Description and Diagnosis of Metastatic Carcinoma in an Early Bronze Age (4588+34 Cal. BP) Forager from the Cis-Baikal Region of Eastern Siberia

Extensive osteolytic and osteoblastic lesions were observed on the skeletal remains of an adult male excavated from an Early Bronze Age cemetery dated to 4556+32 years BP, located in the Cis-Baikal region of Siberia (Russian Federation). Lytic lesions ranged in size from several mm to over 60 mm in diameter and had irregular, moth-eaten borders. Many of these lesions destroyed trabecular bone, though a hollowed shell of cortical bone often remained observable. Radiographic analysis revealed numerous lytic lesions within trabecular bone that had not yet affected the cortex. Blastic lesions were identified as spiculated lines, bands, or nodules of mostly immature (woven) bone formed at irregular intervals. Anatomical elements with the greatest involvement included those of the axial skeleton (skull, vertebrae, sacrum, ribs, and sternum) as well as proximal appendicular elements (ossa coxae, proximal femora, clavicles, scapulae, and proximal humeri). Osteocoalescence of destructive foci was observed on the ilium and frontal bone, with the largest lesion found on the right ilium. Differential diagnoses include metastatic carcinoma, mycotic infections, tuberculosis, Langerhan''s cell histiocytosis, and multiple myeloma. Based on lesion appearance and distribution, age and sex of the individual, as well as pathogen endemism, the most likely diagnostic option for this set of lesions is metastatic carcinoma. The age and sex of this individual and appearance of the lesions may reflect carcinoma of the lung or, possibly, prostate. This represents one of the earliest cases of metastatic carcinoma worldwide and the oldest case documented thus far from Northeast Asia.     

Development of the Synarcual in the Elephant Sharks (Holocephali; Chondrichthyes): Implications for Vertebral Formation and Fusion

The synarcual is a structure incorporating multiple elements of two or more anterior vertebrae of the axial skeleton, forming immediately posterior to the cranium. It has been convergently acquired in the fossil group ‘Placodermi’, in Chondrichthyes (Holocephali, Batoidea), within the teleost group Syngnathiformes, and to varying degrees in a range of mammalian taxa. In addition, cervical vertebral fusion presents as an abnormal pathology in a variety of human disorders. Vertebrae develop from axially arranged somites, so that fusion could result from a failure of somite segmentation early in development, or from later heterotopic development of intervertebral bone or cartilage. Examination of early developmental stages indicates that in the Batoidea and the ‘Placodermi’, individual vertebrae developed normally and only later become incorporated into the synarcual, implying regular somite segmentation and vertebral development. Here we show that in the holocephalan Callorhinchus milii, uniform and regular vertebral segmentation also occurs, with anterior individual vertebra developing separately with subsequent fusion into a synarcual. Vertebral elements forming directly behind the synarcual continue to be incorporated into the synarcual through growth. This appears to be a common pattern through the Vertebrata. Research into human disorders, presenting as cervical fusion at birth, focuses on gene misexpression studies in humans and other mammals such as the mouse. However, in chondrichthyans, vertebral fusion represents the normal morphology, moreover, taxa such Leucoraja (Batoidea) and Callorhinchus (Holocephali) are increasingly used as laboratory animals, and the Callorhinchus genome has been sequenced and is available for study. Our observations on synarcual development in three major groups of early jawed vertebrates indicate that fusion involves heterotopic cartilage and perichondral bone/mineralised cartilage developing outside the regular skeleton. We suggest that chondrichthyans have potential as ideal extant models for identifying the genes involved in these processes, for application to human skeletal heterotopic disorders.     

Osteological and molecular identification of Brucellosis in ancient Butrint, Albania

Ancient skeletal remains can harbor unique information about past civilizations at both the morphological and molecular levels. For instance, a number of diseases manifest in bone, some of which have been confirmed through DNA analysis, verifying their presence in ancient populations. In this study, anthropological analysis of skeletal remains from the ancient Albanian city of Butrint identified individuals with severe circular lytic lesions on their thoracic and lumbar vertebrae. Differential diagnosis suggested that the lesions resulted from pathologies known to affect these skeletal regions, such as tuberculosis (TB) or brucellosis. Relevant bones of two adolescent males from the 10th to 13th century AD that displayed the lesions, along with unaffected individuals, were collected in the field. Genetic screening of the skeletal samples for TB was repeatedly negative, thus additional testing for Brucella spp.-bacteria of livestock and the causative agent of brucellosis in humans-was conducted. Two Brucella DNA markers, the IS6501 insertion element and Bcsp31 gene, amplified from the affected vertebrae and/or ribs, whereas all unaffected individuals and control samples were negative. Subsequent DNA sequencing confirmed the presence of the brucellar IS6501 insertion element. On the basis of the skeletal lesions, negative tests for TB, and positive Brucella findings, we report a confirmed occurrence of brucellosis in archaeologically recovered human bone. These findings suggest that brucellosis has been endemic to the area since at least the Middle Ages.     

椎弓根螺钉用于植骨融合术治疗胸腰椎结核的临床研究

目的:探讨椎弓根内固定联合植骨融合术治疗胸腰椎结核的临床效果。方法:回顾性分析2013年5月至2014年5月在我院接受治疗的50例胸腰椎结核患者的临床资料,结合影像资料评价患者手术前后的红细胞沉降率、后凸畸形矫正情况、Frankel分级及术后并发症的发生情况等。结果:所有患者术后病理均证实为脊柱结核,术中27例植入大块自体髂骨,23例植入自体肋骨捆绑植骨。24例采用椎体侧前方钉棒内固定,26例采用后路椎弓根螺钉系统内固定。术中未出现脊髓、神经、血管损伤及血气胸等并发症。患者术后红细胞沉降率获得改善,差异具有统计学意义(P0.05)。术后Cobb角明显获得矫正,差异具有统计学意义(P0.05)。患者术后脊柱损伤程度明显改善,差异具有统计学意义(P0.05)。结论:椎弓根内固定联合椎体间植骨融合术治疗胸腰椎结核具有良好的临床效果,不仅可以改善红细胞沉降率,而且可以矫正患者脊柱后凸畸形,值得临床推广应用。     

Molecular evidence for different stages of tuberculosis in ancient bone samples from Hungary

This paleomicrobiologic study was conducted on osseous tissue specimens from ancient Hungarian skeletal samples from the 7-8th and the 17th centuries AD with typical macromorphologic evidence of osseous tuberculosis (n = 3), morphologic alterations probably due to tuberculosis (n = 6), or with nontypical osseous changes of vertebral bodies suggestive of inflammatory reaction (n = 5). From these bone samples, DNA was extracted and amplified by polymerase chain reaction (PCR) by using various primer pairs recognizing DNA segments of different mycobacterial species. To confirm specificity of the analysis, the amplification products of several samples were subjected to restriction enzyme digestion and/or direct sequencing. Of the analyzed 14 cases, 8 were unambiguously positive for mycobacterial DNA of the Mycobacterium tuberculosis complex, as shown by the amplification of the IS6110 sequence. In 13 cases we found a PCR product with primers specific for the 65-kDa antigen gene, including 2 cases without genomic DNA. We conclude that the application of other mycobacterial DNA primers may reveal contamination of bones with atypical saprophytic mycobacteria. A positive result for typical mycobacteria was seen in 2 of 3 cases with typical morphologic signs of tuberculosis and amplifiable DNA, in 3 of 6 probable cases, but also in 3 of 6 cases with nontypical bone changes. This indicates that minor osseous reactions of the surface of vertebral bodies may be due-at least in several cases-to infections with bacteria of the M. tuberculosis complex. In these cases the disease may have proceeded rapidly, and the morphologic osseous changes may represent "early" stages of tuberculous infection of the vertebrae.     

Spondylitic changes in long-finned pilot whales (Globicephala melas) stranded on Cape Cod, Massachusetts, USA, between 1982 and 2000

The primary bone pathology diagnoses recognized in cetacea are osteomyelitis and spondylosis deformans. In this study, we determined the prevalence, type, and severity of vertebral pathology in 52 pilot whales, a mass stranding species that stranded on Cape Cod, Massachusetts, between 1982 and 2000. Eleven whales (21%) had hyperostosis and ossification of tendon insertion points on and between vertebrae, chevron bones, and costovertebral joints, with multiple fused blocks of vertebrae. These lesions are typical of a group of interrelated diseases described in humans as spondyloarthropathies, specifically ankylosing spondylitis, which has not been fully described in cetacea. In severe cases, ankylosing spondylitis in humans can inhibit mobility. If the lesions described here negatively affect the overall health of the whale, these lesions may be a contributing factor in stranding of this highly sociable species.     

A quantitative study of morphological and histological changes in the skeleton of Salmo salar during its anadromous migration

A quantitative study of morphological and histological changes in the skeleton (cranial bones and vertebrae) of adult Atlantic salmon Salmo salar during its anadromous migration was performed in order to specify various aspects of its skeletal biology in relationship to this migration. At the beginning of the ascent, there was no morphological difference in the cranial bones between males and females. As the spawning season approached, males showed marked secondary sexual characters particularly allometric breeding growth of some bones of the skull. The histological analysis of the vertebral bone tissue along the vertebral axis showed that bone compacity and number of trabeculae vary depending on their localization on the vertebral axis. Moreover, bone compacity decreased significantly with the sexual maturation of the fish whereas the number of trabeculae grew in both sexes. Thus, the vertebrae (like scales) represent an important source of calcium and other elements during anadromous migration in Atlantic salmon.     

椎体加椎间植骨融合术在腰椎爆裂性骨折患者中的应用效果与安全性探究

目的:探讨椎体加椎间植骨融合术在治疗腰椎爆裂性骨折患者中的临床效果及安全性。方法:选取2016年12月～2017年10月我院骨科收治的腰椎爆裂性骨折患者90例,按照手术方式将患者分成研究组和对照组,每组45例。研究组给予后路内固定术联合椎体加椎间植骨术治疗,对照组给予后路内固定术联合后外侧植骨术治疗。比较两组患者的手术时间、手术出血量以及术后3个月和12个月的椎体Cobb角、患者术后骨折愈合情况、内固定有效情况。结果:研究组手术时间、术中出血量、术后3个月和12个月椎体Cobb角明显短于或低于对照组,但骨折愈合率、内固定有效率显著高于对照组,组间差异均有统计学意义(P0.05)。结论:椎体加椎间植骨融合术治疗腰椎爆裂性骨折的临床综合效果显著优于后路内固定术联合后外侧植骨术治疗,且安全性较好。     

Anatomy of a serial killer: differential diagnosis of tuberculosis based on rib lesions of adult individuals from the Coimbra Identified Skeletal Collection, Portugal

The role of new bone formation on visceral surfaces of ribs in the diagnosis of tuberculosis (TB) in past human populations has been explored by many researchers, using both skeletal remains with known causes of death and archaeological samples. This study focuses, firstly, on adult skeletons from the Coimbra Identified Skeletal Collection in Portugal and investigates the skeletal manifestations of individuals known to have died from TB; secondly, this study focuses on the role of rib lesions in the diagnostic criteria for TB. One hundred and fifty-seven males and 106 females aged between 22-87 years were examined; causes of death were assigned as pulmonary TB, extrapulmonary TB, and pulmonary non-TB; a control group, extrapulmonary non-TB, was selected from the remaining individuals. Of individuals with rib lesions, 85.7% (69/81) had pulmonary or extrapulmonary TB as an assigned cause of death, while 17.8% (16/90) of individuals with rib lesions had a non-TB cause of death. Rib lesions were significantly more common in individuals who had died from TB, although the lesions cannot be considered pathognomonic for TB. In individuals dying from pulmonary TB, ribs in the central part of the rib cage were most affected, at their vertebral ends. The lower part of the rib cage may be a marker for peritoneal TB, and "coral-like" new bone formation on ribs may be an indicator of neoplastic disease. Further work on rib involvement in TB in clinical contexts, and the study of further documented skeletal collections, are recommended.     

Vertebral pathology in the afar australopithecines

Ten vertebral elements from the AL-288 partial hominid skeleton and 11 elements from the AL-333 collection are described. The AL-288 column presents a marked kyphosis at the level of thoracic vertebrae 6 through 10, with pronounced new bone formation on the ventral surfaces of these vertebrae. These features, associated with narrowed disc space and minor osteophytosis, resemble Scheuermann disease in the human. Even though this diagnosis is consistent with a basically human, bipedal locomotor repertoire, the presence of Scheuermann disease suggests that lifting, climbing, or acrobatic activities may have been important in early hominids.     

The Developmental and Morphological Studies on the Neural and Skeletal Abnormalities in the T/btm Tailless Mice

The crosses, T /+ or T/t ^w2× btm/btm , give rise to 50% incidence of the tailless mice, development of which was investigated. No difference was seen in external appearance of the embryos at 9 days of gestation. However, some embryos showed fusion of the notochord and the neural tube at the posterior part of the body on the histological examination. The prospective tailless individuals were distinguishable from the normal littermates by the constriction of the root of the tail at 10 days of gestation. Thereafter, they showed several abnormalities such as the poor growth of the posterior part of the body, thinning of the tail and a blood blister at the tail tip or in the lumbosacral region. The abnormal embryos of 11–12 days showed severer abnormalities in the medio-dorsal area, i.e., the notochord was branched or degenerated at several places and the neural tube was distorted, duplicated or fused with the mesenchyme. All the tailless newborn young had blood blisters or red scars on the dorsal skin at the middle of the lumbosacral region.
Histologically, the spinal cord posterior to the lumbosacral level was revealed to be severely distorted or duplicated and completely devoid of the bony vertebrae, and the dorsal blood blister was found to be the meningomyelocele derived from the abnormal development of the spinal cord. Skeletal abnormalities of the tailless young were as follows. The sacral and caudal vertebrae were absent. The cervical vertebrae were mostly normal, but the thoracic and lumbar vertebrae showed several abnormalities such as fusion of the ribs, lack of the vertebral body and vertebral arch.     

Conditional ablation of osteoblasts in medaka

Different from tetrapods, teleost vertebral centra form without prior establishment of a cartilaginous scaffold, in two steps: First, mineralization of the notochord sheath establishes the vertebral centra. Second, sclerotome derived mesenchymal cells migrate around the notochord sheath. These cells differentiate into osteoblasts and deposit bone onto the mineralized notochord sheath in a process of intramembranous bone formation. In contrast, most skeletal elements of the cranial skeleton arise by chondral bone formation, with remarkably similar mechanisms in fish and tetrapods. To further investigate the role of osteoblasts during formation of the cranial and axial skeleton, we generated a transgenic osx:CFP-NTR medaka line which enables conditional ablation of osterix expressing osteoblasts. By expressing a bacterial nitroreductase (NTR) fused to Cyan Fluorescent Protein (CFP) under control of the osterix promoter these cells become sensitive towards Metronidazole (Mtz). Mtz treatment of stable osx:CFP-NTR transgenic medaka for several consecutive days led to significant loss of osteoblasts by apoptosis. Live staining of mineralized bone matrix revealed reduced ossification in head skeletal elements such as cleithrum and operculum, as well as in the vertebral arches. Interestingly in Mtz treated larvae, intervertebral spaces were missing and the notochord sheath was often continuously mineralized resulting in the fusion of centra. We therefore propose a dual role for osx-positive osteoblasts in fish. Besides a role in bone deposition, we suggest an additional border function during mineralization of the chordal centra. After termination of Mtz treatment, osteoblasts gradually reappeared, indicating regenerative properties in this cell lineage. Taken together, the osx:CFP-NTR medaka line represents a valuable tool to study osteoblast function and regeneration at different stages of development in whole vertebrate specimens in vivo.     

Characterization of the Skeletal Fusion with Sterility (sks) Mouse Showing Axial Skeleton Abnormalities Caused by Defects of Embryonic Skeletal Development

The development of the axial skeleton is a complex process, consisting of segmentation and differentiation of somites and ossification of the vertebrae. The autosomal recessive skeletal fusion with sterility (sks) mutation of the mouse causes skeletal malformations due to fusion of the vertebrae and ribs, but the underlying defects of vertebral formation during embryonic development have not yet been elucidated. For the present study, we examined the skeletal phenotypes of sks/sks mice during embryonic development and the chromosomal localization of the sks locus. Multiple defects of the axial skeleton, including fusion of vertebrae and fusion and bifurcation of ribs, were observed in adult and neonatal sks/sks mice. In addition, we also found polydactyly and delayed skull ossification in the sks/sks mice. Morphological defects, including disorganized vertebral arches and fusions and bifurcations of the axial skeletal elements, were observed during embryonic development at embryonic day 12.5 (E12.5) and E14.5. However, no morphological abnormality was observed at E11.5, indicating that defects of the axial skeleton are caused by malformation of the cartilaginous vertebra and ribs at an early developmental stage after formation and segmentation of the somites. By linkage analysis, the sks locus was mapped to an 8-Mb region of chromosome 4 between D4Mit331 and D4Mit199. Since no gene has already been identified as a cause of malformation of the vertebra and ribs in this region, the gene responsible for sks is suggested to be a novel gene essential for the cartilaginous vertebra and ribs.     

Vertebral lesions in a titanosaurian dinosaur from the Lower-Upper Cretaceous of Brazil

In this paper we describe macroscopically two types of bone lesions on a caudal vertebra of an indeterminate titanosaur recovered from the Lower-Upper Cretaceous (Albian-Cenomanian) Açu Formation in the Potiguar Basin, Brazil. The first type of lesion corresponds to cystic lesions on cranial and caudal joint surfaces of the vertebral body, which are identified as subchondral cysts. The second type of lesion corresponds to an irregular bone overgrowth located on longitudinal ligament insertion points. This ossification can be associated with an axial spondyloarthropathy or diffuse idiopathic skeletal hyperostosis (DISH). Bone overgrowth on vertebrae is well documented in the dinosaur fossil record, whereas this is only the second case recorded of subchondral cysts.     

Physical maturity in common bottlenose dolphins (Tursiops truncatus) from Sarasota Bay,Florida

Cetacean physical maturity is defined by growth cessation and complete fusion of epiphyses to vertebral bodies indicated by invisible sutures. Many studies have shown epiphyseal fusion is highly variable among individuals. In-depth examinations into fusion variability are lacking. We analyzed vertebrae of 37 (n = 21 female, n = 16 male) stranded common bottlenose dolphins (Tursiops truncatus) from the well-studied Gulf of Mexico, Sarasota Bay community. For each specimen, vertebrae were examined by vertebral region for degree of fusion anteriorly and posteriorly of each centrum and categorized from unfused to fused in five degrees. An ordinal logistic regression was used to estimate degree of fusion probability for each epiphysis. The model had fixed effects for age, number of offspring, sex, sexual maturity, and a random effect for epiphysis. Results show that age/reproductive status significantly explains an individual's degree of fusion. Adult females with fewer calves had more fusion than those with more reproductive experience across multiple ages. Access to long-term observational and sample data on the dolphins residing in the area served by Mote Marine Laboratory's Stranding Investigations Program offers a unique opportunity to examine the relationship between energetic demands of reproduction (calcium production/reproductive output) versus preconceived definitions of physical maturity (skeletal fusion) more closely.