Vertebral Size Research Articles

Mensuração do tamanho cardíaco pelo método VHS (vertebral heart size) em cães sadios da raça American pit bull terrier

Vários métodos surgiram com a finalidade de aumentar a acurácia e diminuir a subjetividade na avaliação das radiografias. O melhor aceito é o VHS (vertebral heart size), ou tamanho do coração em relação à unidade de vértebra torácica. O objetivo deste trabalho foi aplicar o método de mensuração pelo VHS em cães da raça American pit bull terrier clinicamente sadios, com a finalidade de se estabelecer o valor médio de VHS para esta raça. Realizaram-se radiografias de tórax, na projeção lateral direita, que foram avaliadas empiricamente e realizadas as medidas necessárias para obtenção do VHS, além da obtenção da relação profundidade/largura (P/L) torácica. Nenhum animal apresentou alteração através da análise empírica. Os valores de VHS obtidos apresentaram distribuição normal, assim como a relação P/L, com média de 10,9±0,4 vértebras para o VHS e 0,80±0,07 para a relação P/L. O valor do VHS apresentou diferença significativa (P>0,05) em comparação com os resultados obtidos por BUCHANAN & BÜCHELER (1995). Porém, o valor de VHS deste estudo é semelhante ao descrito por diversos autores nos estudo de raças específicas, confirmando a necessidade de se estabelecer valores de VHS específicos para cada raça.

Therapeutic Changes of Plasma N-Terminal Pro-Brain Natriuretic Peptide Concentrations in 9 Dogs with Patent Ductus Arteriosus

The plasma N-terminal proBNP (NT-proBNP) concentration is measured for determining the diagnosis and severity of heart failure in dogs. However, it is still unclear whether measurements of circulating NT-proBNP levels provide clinical utility as an indicator of therapeutic efficacy. Thus, we investigated the surgical correction-related changes of plasma NT-proBNP concentrations in 9 dogs with patent ductus arteriosus (PDA). Physical examination, thoracic radiography and echocardiography were conducted both before and after surgery. Similarly, the plasma NT-proBNP concentrations were determined using an enzyme immunoassay for canine pro-BNP. The International Small Animal Cardiac Health Council (ISACHC) class and murmur grade were significantly improved after surgery compared with before surgery. Vertebral heart size (VHS) and cardiothoracic ratio (CTR) were significantly decreased after surgery. Fractional shortening was significantly decreased and relative wall thickness (RWT) was significantly increased after surgery. Furthermore, the plasma NT-proBNP concentrations were significantly decreased by surgical correction. The plasma NT-proBNP concentration showed significant positive correlation with the ISACHC class, murmur grade, VHS and CTR and significant negative correlation with the RWT. Therefore, measurement of plasma NT-proBNP levels can be used to monitor the effectiveness of therapies such as surgical correction of PDA.

Bone density and size in ambulatory children with cerebral palsy

To examine the relation of axial and appendicular bone properties in ambulatory children with cerebral palsy (CP) to functional (Gross Motor Function Classification System [GMFCS]) level. Quantitative computed tomography measurements were compared among 37 children with CP (12 children in GMFCS level I, five in level II, 18 in level III, two in level IV; five with hemiplegia, 23 with diplegia, two with triplegia, seven with quadriplegia; mean age 9y 4mo, SD 1y 6mo; 18 males, 19 females) and 37 children in a comparison group (same age and sex distributions). Linear regression was used to evaluate differences in volumetric cancellous bone density (vBMD) and geometric properties of the L3 vertebra and tibia, adjusting for height, weight, and sex as covariates. The comparison group had larger vertebrae than the children with CP (p = 0.02) owing to smaller vertebral size in GMFCS levels III and IV, but there was no difference in vertebral vBMD (p = 0.49). In the tibia, bone volumetric density (p = 0.09) and size (p = 0.02) decreased with increasing GMFCS level. GMFCS level had a greater effect on bone size in females than in males (p<0.07). Children with CP of all levels may have less bone in their tibias, whereas spine deficits differentially affect more involved children. Because even small bone deficits may manifest as osteoporosis later in life, it is important to study bone acquisition in all children with CP.

Genetic analysis of vertebral trabecular bone density and cross-sectional area in older men

We investigated 383 bone candidate genes for associations between single nucleotide polymorphisms and vertebral trabecular volumetric bone mineral density (vBMD) and cross-sectional area (CSA) in 2,018 Caucasian men aged ≥ 65 years. SNPs in TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE were associated with vBMD and SNPs in CYP11B1, DVL2, DLX5, WNT4, and PAX7 were associated with CSA in independent study samples (p < 0.005). Vertebral bone mineral density and cross-sectional area are important determinants of vertebral bone strength. Little is known about the specific genetic variants that influence these phenotypes in humans. We investigated the potential genetic variants associated with vertebral trabecular volumetric BMD and CSA measured by quantitative computed tomography. We initially tested for association between these phenotypes and 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes in 862 community-dwelling Caucasian men aged ≥ 65 years in the Osteoporotic Fractures in Men Study. SNP associations were then validated by genotyping an additional 1,156 randomly sampled men from the same cohort. We identified 11 SNPs in 10 genes (TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE) that were consistently associated with trabecular vBMD and five SNPs in five genes (CYP11B1, DVL2, DLX5, WNT4, and PAX7) that were consistently associated with CSA in both samples (p < 0.005). None of the SNPs associated with trabecular vBMD were associated with CSA. Our findings raise the possibility that at least some of the loci for vertebral trabecular BMD and bone size may be distinct.

Signs of left heart volume overload in severely anaemic cats.

Anaemia induces haemodynamic compensatory mechanisms resulting in volume overload and increased left heart dimensions in humans and dogs. Theaims of this retrospective study were to investigate the effects of anaemia onechocardiographic left heart dimensions, vertebral heart size (VHS) and radiographic evidence of congestive heart failure (CHF) in cats. Fifteen cats fulfilled the inclusion criteria and were classified as mildly anaemic (haematocrit (Hct)>18-24%) or severely anaemic (Hct≤18%). Eight out of eight severely anaemic cats had left atrial enlargement compared with 1/6 mildly anaemic cats (P<0.005) and severely anaemic cats also had a larger median left ventricular end-diastolic diameter (1.80cm versus 1.27cm, respectively; P<0.05). No difference was found between the groups in VHS or frequency of radiographic signs of CHF. Despite the small sample size, these preliminary findings suggest that severely anaemic cats are more likely to have enlarged left heart dimensions than mildly anaemic cats.

Recent spatial and temporal changes in body size of terrestrial vertebrates: probable causes and pitfalls

Geographical and temporal variations in body size are common phenomena among organisms and may evolve within a few years. We argue that body size acts much like a barometer, fluctuating in parallel with changes in the relevant key predictor(s), and that geographical and temporal changes in body size are actually manifestations of the same drivers. Frequently, the principal predictors of body size are food availability during the period of growth and ambient temperature, which often affects food availability. Food availability depends on net primary productivity that, in turn, is determined by climate and weather (mainly temperature and precipitation), and these depend mainly on solar radiation and other solar activities. When the above predictors are related to latitude the changes have often been interpreted as conforming to Bergmann's rule, but in many cases such interpretations should be viewed with caution due to the interrelationships among various environmental predictors. Recent temporal changes in body size have often been related to global warming. However, in many cases the above key predictors are not related to either latitude and/or year, and it is the task of the researcher to determine which particular environmental predictor is the one that determines food availability and, in turn, body size. The chance of discerning a significant change in body size depends to a large extent on sample size (specimens/year). The most recent changes in body size are probably phenotypic, but there are some cases in which they are partly genetic.

Comparison of the Immature Sheep Spine and the Growing Human Spine

A comparative study on growth of the sheep and human spine. To validate the immature sheep spine as model for the growing human spine and to yield a database for planning and interpretation of future animal experiments. With the current change of paradigm to nonfusion strategies for pediatric spine deformities, experimental surgery on spines of growing goats, sheep, and pigs has gained importance as preclinical proof-of-concept test. However, despite the proceeding use of animals, there is a lack of knowledge regarding the growth of the sheep spine and the relation to the human spine. Thoracic and lumbar cadaver spines were harvested from 50 Swiss alpine sheep. Specimens were obtained from newborn, 1, 3, 6, 9 and 12, 15 and 18 months old female sheep. Direct spondylometry yielded vertebral body heights, widths, and depths and spinal canal size, which were compared to pooled data on human spine growth retrieved from the literature. Sheep spine growth ceases at age 15 to 18 months, which corresponds to a time-lapse model of human growth. Main growth occurs within the first 3 to 6 months of life, as opposed to human spines with maximal growth during the first 4 years and puberty. The relation between sheep and human vertebral shape is continuously changing with growth: at birth, sheep vertebrae are twice as tall, but equally wide and deep. At skeletal maturity, height is 15% to 25% bigger in sheep, but width 15% to 30% and depth 30% to 50% are smaller. The immature sheep spine offers fast effects if growth-modulating interventions are performed within the first 3 to 6 months of age. The differences in vertebral shapes and further distinctions between human and sheep spines such as biomechanics, facet anatomy, and rib cage morphology have to be considered when interpreting results after experimental surgery.

Reduced predator species richness drives the body gigantism of a frog species on the Zhoushan Archipelago in China

1. Shifts in the body size of insular vertebrates have been an interesting theme in ecological and evolutionary studies. Four primary factors, including predation pressures, resource availability, inter-species competition and immigrant selection, have been proposed to explain the trend in insular body size. Life-history theory predicts that body size, average age, the proportion of old-aged members and the density of insular populations are negatively correlated with predator species richness, and that body size and population density are positively related to resource availability. The niche expansion hypothesis argues that a positive relationship is expected to exist between insular body size and prey size, which varies in response to extinction due to small or large competitors. The immigrant hypothesis predicts that insular body size is positively correlated with distance to the mainland. 2. We tested these hypotheses by using populations of rice frogs Rana limnocharis on 20 islands in the Zhoushan Archipelago and two sites of nearby mainland China. 3. The body size (snout-vent length) of rice frogs on half of the islands was larger before and after the variable of age was controlled for; rice frog density and prey availability was higher and prey size was larger on most of the islands as compared to the two mainland sites. On the islands, the body size and other features [e.g. average age, the proportion of old-aged frogs (ages 3 and 4) and density] of the rice frogs were negatively associated with predator species richness; female body size and other features were positively associated with prey availability. The inference of multivariate linear models based on corrected Akaike Information Criterion (AIC(c) ) showed that the relative importance of predator species richness on body size and each of the other features was larger than that of prey availability, prey size and distance to the mainland. In addition, the parameters for predator species richness were all negative. 4. The results provided strong support for the life-history theory of predation pressures, but weak evidence for the life-history theory of prey availability, the niche expansion or the immigrant hypothesis. The reduced predator species richness was a dominant factor contributing to the body gigantism of rice frogs on the islands.

Bone size and density measurements in prepubertal children with Turner syndrome prior to growth hormone therapy

Using computed tomography (CT), we found the decreases in bone size of vertebrae and femur, cortical bone area (CBA) of femur and bone density (BD) of vertebrae in prepubertal female with Turner syndrome (TS) compared to those of controls. Bone mineral density results from previous studies utilizing single-photon absorptiometry (SPA) or dual-energy X-ray absorptiometry (DXA) in children with TS are controversial. The present study used CT to assess the differences in cancellous and cortical bone size and BD between prepubertal TS patients prior to growth hormone therapy and historical age and ethnicity-matched female controls. Anthropometrics and CT bone measurements including cross-sectional area (CSA) and BD of lumbar vertebrae and femur and CBA of femur in prepubertal TS females were reviewed and compared with those in controls. Twenty-two prepubertal TS patients had delayed bone age, were shorter and lighter than controls (Ps < 0.001). After adjusting for weight, height and skeletal age, vertebral BD and CBA of the femur were lower in patients than in controls (P < 0.001 and P = 0.021, respectively). However, after additional adjusting for puberty, results were not different from controls. While a positive correlation between vertebral BD and age was noted in controls (r = 0.367, P = 0.092), a significant negative correlation was noted in patients (r = -0.615, P = 0.002). While the decrease in vertebrae and femur sizes of patients with TS appeared to be secondary to their small body size, the decreased BD of vertebrae and CBA of femur were likely secondary to estrogen deficiency.

Reappraisal of the South American Miocene Snakes of the GenusColombophis, with Description of a New Species

A redescription of the extinct snake genus Colombophis is presented, on the basis of new specimens from the late Miocene of southwestern Brazilian Amazonia, and those previously reported for the middle Miocene of Colombia and Venezuela. The reappraisal of Colombophis allows the recognition of a new species, C. spinosus sp. nov. The revised diagnosis of the genus is based on the midtrunk vertebrae, distinct from those of other snakes mainly in the features of the neural arch, position and shape of the neural spine, inclination of the zygapophyses, shape of the centrum, and development of the haemal keel. The affinities of Colombophis with “Anilioidea” are still unresolved; it is distinguished from all known extinct and extant “anilioids” due to its great vertebral size and the frequent presence of paracotylar foramina. The posterior paired apophyses of the haemal keel in some vertebrae, and the high neural spine of C. spinosus also contrast significantly with the “anilioid” genera, making the allocation of the genus into this probably paraphyletic group not well supported. Here, we recognized Colombophis as a basal alethinophidian of uncertain relationships.

Ecogeographical variation of body size in the newt Triturus carnifex: comparing the hypotheses using an information‐theoretic approach

ABSTRACTAim Ecogeographical variation of body size in vertebrates (e.g. Bergmann's rule) has long been recognized. However, the patterns and causes of intra‐specific ecogeographical variation of body size in ectotherms, and in amphibians in particular, are strongly debated. We identified the relationship between bioclimatic variables and body size predicted a priori by alternative hypotheses (heat balance, endurance, seasonality, starvation resistance, water availability, primary productivity, parental investment) proposed to explain ecogeographical patterns of body size in ectotherms, and we evaluated the relative support of these hypotheses in explaining variation in body size of the Italian crested newt, Triturus carnifex.Location Twenty‐three populations covering the whole range of T. carnifex (Austria, Croatia, Italy and Slovenia).Methods We obtained data on body size (snout–vent length, SVL) of 2639 adult newts from direct measurements and the literature; we obtained high‐resolution environmental data for the sampled localities. We used an information‐theoretic approach to evaluate the support of the data for the different hypotheses. We also integrated information on population genetics in our models.Results We observed strong geographical variation of body size. The best Akaike information criterion (AIC) models showed that populations with larger body size are associated with cold climates and secondarily with high primary productivity. Furthermore, sexual dimorphism increases in cold climates, as the increase in body size was stronger for females. When taking into account population genetics, we did not find support for relationships with the other variables.Main conclusion Our results are consistent with three hypotheses proposed to explain ecogeographical variation in amphibians: heat balance, increased parental investment of females and productivity. Information theory provides the framework for comparing hypotheses rather than looking for patterns. We suggest that evaluating the support for mechanisms can provide better insights than simply assessing whether ecogeographical variation is in agreement with some ‘rule’.

Ligamentum Flavum Thickness in Normal and Stenotic Lumbar Spines

A descriptive computed tomography (CT) study of the ligamentum flavum (LF) thickness in individuals with normal and stenotic lumbar spines. To establish standards for normal and pathologic range of LF thickness and its asymmetry as indicated in CT images and to examine its association with vertebral body size, age, and gender. LF lines a considerable part of the posterior and lateral walls of the spinal canal and is a major role contributor to spinal canal stenosis. Due to methodologic deficiencies (e.g., small sample size, lack of control for vertebral body size, gender, and age), the normal range of LF thickness is still controversial. Furthermore, data on important aspect of LF thickness such as left-right differences are missing. Two groups of individuals were studied. The first group included 65 individuals with lumbar spinal stenosis (LSS) (mean age: 66 +/- 9.7 years) and the second, 150 individuals (mean age: 52 +/- 19 years) without LSS-related symptoms. LF thickness was measured on CT images (Philips Brilliance 64), obtained from axial plane scan at the intervertebral disc level. Measurements were performed at the levels of L3-L4, L4-L5, and L5-S1. Analysis of variance and t test were carried out to evaluate the association between LF thickness and demographic factors. Absolute and relative LF thickness were significantly greater in the LSS group at the levels of L3-L4 and L4-L5 on both sides, compared to control group (P < 0.05). LF thickness was independent of gender (absolute and relative thickness). Even though LF thickness at all levels significantly increases with age, significant changes after the age of 60 occurred only at L3-L4. Significant asymmetry in LF thickness was found at L3-L4 (2.9 +/- 0.90 mm on the right vs. 2.76 +/- 0.90 mm on the left) and L5-S1 (3.42 +/- 1.1 mm on the right vs. 3.22 +/- 1.22 mm on the left) (P < 0.05). LF thickness is an age-dependent and gender-independent phenomenon. LF is significantly thicker on the right side. The borderline between normal and pathologic LF thickness should not be set at 4 mm.

Effect of sex, age, and anthropometric parameters on the size and shape of vertebrae in densitometric morphometry. Results of the EPOLOS study

Morphometric densitometry (morphometric X-ray absorptiometry - MXA) allows to identify vertebral fractures, based on the objective measurement of vertebral dimensions. The aim of the study was to assess the effect of sex, age, height, and body mass index (BMI) on selected parameters of vertebral size and shape measured by MXA. A random study sample comprised 829 patients (520 women and 309 men) aged 20 to 79 years, none of whom had been previously treated for osteoporosis. Lateral densitometric scans of the thoracic-lumbar spine (T4-L4) were performed using a fan-beam densitometer. Anterior (Ha), central (Hc), and posterior (Hp) vertebral heights were determined. The analysis included 9632 vertebrae. Higher values of Ha, Hc, and Hp were observed in men (P <0.001). The Ha/Hp ratio from T7 to L3 was lower in men compared with women (P <0.05). The Hc/Hp ratio was lower in T12 to L3 vertebrae in men (P <0.05). Wedging was significantly greater in men in thoracic vertebrae, and significantly lower in L3 and L4 (P <0.05). Concavity was similar in men and women in thoracic vertebrae from T5 to T10. We observed weak and moderate negative correlations between age and vertebral heights, Ha/Hp and Hc/Hp (P <0.001), and a moderate positive correlation between body height and vertebral heights (P <0.001). There were no statistically significant correlations between the body mass index and the remaining variables. Morphometric parameters of vertebrae vary depending on sex and age, which has to be considered when choosing reference groups. Knowledge about the differences in vertebral size and shape may prevent diagnostic errors and bias.

Influence of physical activity on vertebral size

Dear Editors, The role of vertebral cross-sectional area (CSA) is widely recognised as an essential factor for vertebral strength [1], and the knowledge about the factors behind vertebral size could be vital for the further prevention of vertebral fractures. Physical activity and mechanical loadings have major effects on bone structure and cross-sectional geometry [2]. To clarify the role of loading induced adaptations on vertebral size, we utilised Northern Finland Birth Cohort 1986 (NFBC 1986) population. The present analyses include 380 members who answered the question concerning physical activity both at 16 and 19 years and participated in lumbar spine MRI at a mean age of 21 years. The research protocol was reviewed by the Ethics Committee of the University Hospital of Oulu. MRI scans were obtained with a 1.5-T unit (Sigma, General Electric, Milwaukee, WI, USA) with a Phased Array CTL Spine Coil (USA Instruments, Aurora, OH, USA). We measured mediolateral and anteroposterior dimensions from the fourth lumbar vertebra (L4) to estimate vertebral size and to calculate the CSA of the vertebral body. Physical activity was evaluated with a question about participation in moderate-to-vigorous physical activity (MVPA), causing at least some sweating and shortness of breath. Subjects were classified into three physical activity

Increase in vertebral body size in postmenopausal women with osteoporosis

Bone geometry plays a prominent role in bone strength. Cross-sectional studies have shown that advancing age is associated with increasing diameter of long bones, related to both periostal apposition and endosteal resorption. However, there are few data provided by prospective studies, especially concerning the changes in vertebral body dimensions. The objective of this prospective study was to measure the changes occurring in the vertebral body size of women with postmenopausal osteoporosis. Three-year data from placebo groups of the SOTI and TROPOS trials, performed in women with postmenopausal osteoporosis, were used for this study. In these trials, patients underwent lateral radiographs of the thoracic and lumbar spine at baseline and annually over 3 years, according to standardized procedures. Six-point digitization method was used: the four corner points of the vertebral body from T4 to L4 are marked, as well as an additional point in the middle of the upper and lower endplates. From these 6 points, the vertebral body perimeter, area and depth were measured at baseline and at 3 years. The analysis excluded all vertebrae with prevalent or incident fracture. A total of 2017 postmenopausal women (mean age 73.4 ± 6.1 years) with a mean lumbar spine T score of – 3.1 ± 1.5, and a mean femoral neck T score of – 3.0 ± 0.7 are included in the analysis. Vertebral body dimensions increased over 3 years, by 2.1 ± 5.5% (mean depth ± SD), by 1.7 ± 8.3% (mean area ± SD) and by 1.5 ± 4.9% (mean perimeter ± SD) at the thoracic level (T4 to T12). At the lumbar level (L1 to L4), these dimensions increased as well: 1.4 ± 3.6% (mean depth ± SD), 1.4 ± 5.7% (mean area ± SD), 0.7 ± 2.9% (mean perimeter ± SD). A significant increase in vertebral body size was observed for each vertebral level from T5 to L4 for each of these parameters ( p < 0.01). These prospective results demonstrate that vertebral body dimensions increase over 3 years in women with postmenopausal osteoporosis.

Radiographic Analysis of Newly Developed Degenerative Spondylolisthesis in a Mean Twelve-Year Prospective Study

Prospective study of community-based female volunteers. To investigate the incidence of newly developed degenerative spondylolisthesis (DS) among those without baseline deformity, and to clarify radiographic characteristics and predictors of DS. There has been limited number of prospective studies of DS. Our on-going cohort study of healthy volunteers enabled long-term observation of highly susceptible perimenopause female subjects. A final total of 142 female subjects without spondylolisthesis at baseline radiographs were included and followed up for more than 8 years. Standardized serial entire spine radiographs were used to measure spinopelvic alignment, including pelvic incidence (PI), vertebral inclination angle, disc height, vertebral size, and facet orientation. The incidence of newly developed DS was 12.7%. Comparison between DS and non-DS subjects demonstrated that DS subjects had significantly greater baseline lumbar lordosis, PI, vertebral inclination angle, and smaller vertebral size. Exaggerated lumbopelvic alignment was more prominent in L3-DS than in L4-DS, and L4-DS was associated with the decrease in L4/5 disc height. Multivariate analysis revealed that PI, L4 vertebral inclination, adjusted vertebral size, and facet sagittalization were independent predictors of the development of DS. This was the first study to confirm the relationship of PI and the development of DS in a long-term prospective observation. Proposed pathogenetic differences might explain the fact that L4-DS is far more prevalent than L3-DS. The development of DS could be predicted by baseline lumbopelvic morphology among the highly susceptible perimenopause women.

Analysis of ESTs for alternatively spliced 3′ and 5′ splice sites reveals optimal exon size in vertebrates

In vertebrates most exons are small surrounded by much larger introns. Due to this architecture, splice sites are initially recognized across the exon in what is known as exon definition. Here we examine the relative usage of 3,000 pairs of alternative 3′ splice sites and 2,000 pairs of alternative 5′ splice sites in the human genome. We find that within an optimal exon length window &gt;50 &lt;250 nts, there is a positive correlation between splice site strength and splice site usage. However, when one splice site is located inside of this exon length and the other is not, the splice site inside of the optimal exon length is preferred regardless of splice site strength. Our analysis reveals that splice sites within an optimal exon size are preferentially used when compared to splice sites outside of this optimal size. We conclude that a constraint of exon size is a fundamental parameter that dictates splice site usage. Because the spliceosome eventually forms across the intron, it is believed that intron definition is the predominant mode of splice site recognition for introns smaller than 250 nucleotides in length. However, in a subset of our alternative splice sites, in which one splice site is exon defined and the other is intron defined, the exon defined splice site is preferentially used, suggesting that exon recognition is the default mode of splice site recognition in vertebrates.NIH

Atmospheric hypoxia increases bone robusticity in the American alligator

During vertebrate evolution, atmospheric oxygen (O2) level may have varied from as low as 12% to as high as 30%, but no studies to date have considered the effect of ambient O2 on skeletal plasticity. We incubated eggs and subsequently grew alligator hatchlings under chronic hypoxia (12% O2), normoxia (21% O2) and hyperoxia (30% O2). Animals received monthly injections of fluorescent dyes to determine bone deposition rates. After three months, animals were sacrificed and their femora either sectioned at mid‐diaphysis, or ashed. We found femora of hypoxic alligators to have significantly greater mass‐specific cross‐sectional area (+15%), second moment of area (+20%) and polar moment of inertia (+23%) than those of either normoxic or hyperoxic hatchlings. Mineral content was also significantly higher (+6%) in bones of hypoxic animals. This suggests that exposure to chronic hypoxia, but not hyperoxia, resulted in increased resistance to compressive, bending and torsional stresses on the skeleton. Furthermore, the relationship between body mass growth and periosteal deposition rate was different between treatments groups, with hypoxic animals accruing more bone per unit body mass. We suggest that prevalent atmospheric O2 level need be considered when reconstructing size and growth curves of extinct vertebrates. Funded by the NSF IOB 04445680 and IOS 0922756 to JWH.

Mechanisms of heart development in the Japanese lamprey, Lethenteron japonicum

Vertebrate hearts have evolved from undivided tubular hearts of chordate ancestors. One of the most intriguing issues in heart evolution is the abrupt appearance of multichambered hearts in the agnathan vertebrates. To explore the developmental mechanisms behind the drastic morphological changes that led to complex vertebrate hearts, we examined the developmental patterning of the agnathan lamprey Lethenteron japonicum. We isolated lamprey orthologs of genes thought to be essential for heart development in chicken and mouse embryos, including genes responsible for differentiation and proliferation of the myocardium (LjTbx20, LjTbx4/5, and LjIsl1/2A), establishment of left-right heart asymmetry (LjPitxA), and partitioning of the heart tube (LjTbx2/3A), and studied their expression patterns during lamprey cardiogenesis. We confirmed the presence of the cardiac progenitors expressing LjIsl1/2A in the pharyngeal and splanchnic mesoderm and the heart tube of the lamprey. The presence of LjIsl1/2A-positive cardiac progenitor cells in cardiogenesis may have permitted an increase of myocardial size in vertebrates. We also observed LjPitxA expression in the left side of lamprey cardiac mesoderm, suggesting that asymmetric expression of Pitx in the heart has been acquired in the vertebrate lineage. Additionally, we observed LjTbx2/3A expression in the nonchambered myocardium, supporting the view that acquisition of Tbx2/3 expression may have allowed primitive tubular hearts to partition, giving rise to multichambered hearts.

Evolving Role of Imaging in the Evaluation of Bone Structure

A top priority in osteoporosis research is the identification of the structural parameters that contribute to variations in the strength of bone and the risk of fragility fractures. For the past two decades, DXA has been used to diagnose osteoporosis based on measurements of BMC and areal BMD. Whereas DXA has become the most commonly used technique worldwide to predict fracture risk and assess response to therapy, it is based on a 2D interpretation of the 3D skeleton and provides limited information on the structural properties of bone. Other imaging modalities such as CT and MR offer considerably greater characterization of bone architecture, but their cost and inaccessibility have precluded them from becoming widely adopted clinically. Recent advances, however, have led to the introduction of more manageable CT and MR techniques that provide 3D assessments of the appendicular skeleton. In this issue of the Journal, two studies by Wang et al. and Walker et al. highlight how progress in analyzing variations in bone structure among humans comes from the use of these techniques in comparative studies to identify the skeletal differences between persons who are susceptible to fractures and those who are not. Using high-resolution peripheral QCT (HR-pQCT), Wang et al. and Walker et al. examined the differences in macroand microarchitecture of the peripheral skeleton between young white and Chinese women. Available data indicate that Asian women have a lower incidence of hip and forearm fractures despite consistently being reported to have lower areal BMD values as measured by DXA compared with white women and other racial groups. With the detailed analysis of cancellous and cortical bone in the distal radius and tibia that HR-pQCT provides, these two studies arrived at strikingly similar explanations for this paradox. Both Wang et al. and Walker et al. found Asian women to have significantly greater cortical thickness and density, as well as greater trabecular thickness at both sites. Trabecular number was also greater in the distal tibia but not in the radius in both studies. The authors reasonably suggest that these anatomical differences are likely contributors to the lower risk for fractures in the appendicular skeleton of Chinese women. In contrast, the study by Walker et al. found the areal BMD by DXA of the axial and appendicular skeleton did not differ between races. It is remarkable that such comparable results were obtained in both studies with relatively small cohorts of white and Chinese women from two different continents with different environmental conditions. This consistency underscores the power of 3D techniques and the generalizability of the results. It is also likely a reflection of the young age of the participants in both studies, because the magnitude of the genetic effect on bone mass and bone architecture is higher in young premenopausal women. As indicated by these two studies, advances in our understanding of the great variations in bone structure in the appendicular skeleton among humans will likely come from improved 3D imaging technology, much like prior studies using CT had done for our knowledge of the axial skeleton. Conventional CT advanced our understanding of the relationships between vertebral size and fracture risk beyond the knowledge that could be provided by using DXA. The use of CT indicated that men have larger vertebrae than women, even after adjusting for differences in body size, and that the lower vertebral mass of women compared with men resulted from early sex differences in the size of bone rather than differences in bone densities. 3D techniques also helped establish vertebral size as an important determinant of vertebral fracture risk. Additionally, the ability of 3D techniques to assess BMD without soft tissue errors was key to establishing that peak BMD in the axial skeleton, a major contributor to osteoporosis in the elderly, is achieved soon after sexual maturity and not in the third, fourth, or fifth decades as indicated by DXA. CT and pQCT have the advantages of allowing for the segmentation of trabecular and cortical bone, as well as for measurements of bone geometry, cortical density, and the apparent density of trabecular bone. Further advances, as reported by Wang et al. and Walker et al., came from the introduction of HR-pQCT equipment with the ability to