Vertebral Shape Research Articles

Application of statistical shape analysis for the estimation of bone and forensic age using the shapes of the 2nd, 3rd, and 4th cervical vertebrae in a young Japanese population

ObjectiveFrom computed tomographic images, the dentocentral synchondrosis can be identified in the second cervical vertebra. This can demarcate the border between the odontoid process and the body of the 2nd cervical vertebra and serve as a good model for the prediction of bone and forensic age. Nevertheless, until now, there has been no application of the 2nd cervical vertebra based on the dentocentral synchondrosis. MethodsIn this study, statistical shape analysis was used to build bone and forensic age estimation regression models. Following the principles of statistical shape analysis and principal components analysis, we used cone-beam computed tomography (CBCT) to evaluate a Japanese population (35 males and 45 females, from 5 to 19 years old). ResultsThe narrowest prediction intervals among the multivariate regression models were 19.63 for bone age and 2.99 for forensic age. There was no significant difference between form space and shape space in the bone and forensic age estimation models. However, for gender comparison, the bone and forensic age estimation models for males had the higher explanatory power. ConclusionThis study derived an improved objective and quantitative method for bone and forensic age estimation based on only the 2nd, 3rd and 4th cervical vertebral shapes.

Vertebral Scheuermann's disease in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8% in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8% with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.

Treatment of childhood osteoporosis – current and future perspectives

Bisphosphonates are the mainstay of medical therapy in the fracturing child with osteoporosis. The majority of the data in children pertains to intravenous pamidronate use in children and adolescents with osteogenesis imperfecta (OI), where pamidronate has been associated with improvements in bone mineral density, cortical thickness, vertebral shape, pain, mobility and height [1]. Side-effects of pamidronate including acute phase response to the initial dose and retardation of bone healing have also become apparent. To date, there have been no reports of osteonecrosis of the jaw. The best functional outcomes occur when bisphosphonates are given as part of a multidisciplinary approach to treatment. More recently, bisphosphonates have been used to treat other primary and secondary osteoporotic disorders e.g. immobility and glucocorticoid. Zoledronate is a third generation bisphosphonate with a potency 100-200 times that of pamidronate. Even though both pamidronate and zoledronate have a similar mechanism of action, zoledronate has potential advantages over pamidronate in the management of paediatric bone disorders due to its shorter infusion time and longer duration of action. Zoledronate has been shown to be effective in the management of osteogenesis imperfecta [2] and secondary osteoporosis [3]. The optimal regimen for intravenous bisphosphonate use in both the acute and maintenance phase of treatment remains to be developed. Oral bisphosphonates do not appear to be as beneficial as intravenous bisphosphonates in children. Although they result in increased bone density, they do not improve bone pain or alter bone histomorphometry [4]. Larger studies await publication. Further the use of bisphosphonates in primary fracture prevention in children is yet to be investigated. Biological agents hold promise for the future. Denosumab (RANKL inhibitor) use in children has been reported but it would appear unlikely it will be used widely. Anti-sclerostin antibodies and Dickkopf-1 (DKK1), two Wnt pathway inhibitors, however are potential treatments for primary and secondary osteoporosis with their potent effects on periosteal bone formation [5]. In summary, bisphosphonates have improved the life of children with significant bone fragility. Their use in primary fracture prevention and the utility of new agents such as anti-sclerostin antibodies and DKK1 require further investigation.

The ancestral shape hypothesis: an evolutionary explanation for the occurrence of intervertebral disc herniation in humans.

BackgroundRecent studies suggest there is a relationship between intervertebral disc herniation and vertebral shape. The nature of this relationship is unclear, however. Humans are more commonly afflicted with spinal disease than are non-human primates and one suggested explanation for this is the stress placed on the spine by bipedalism. With this in mind, we carried out a study of human, chimpanzee, and orangutan vertebrae to examine the links between vertebral shape, locomotion, and Schmorl’s nodes, which are bony indicators of vertical intervertebral disc herniation. We tested the hypothesis that vertical disc herniation preferentially affects individuals with vertebrae that are towards the ancestral end of the range of shape variation within Homo sapiens and therefore are less well adapted for bipedalism.ResultsThe study employed geometric morphometric techniques. Two-dimensional landmarks were used to capture the shapes of the superior aspect of the body and posterior elements of the last thoracic and first lumbar vertebrae of chimpanzees, orangutans, and humans with and without Schmorl’s nodes. These data were subjected to multivariate statistical analyses.Canonical Variates Analysis indicated that the last thoracic and first lumbar vertebrae of healthy humans, chimpanzees, and orangutans can be distinguished from each other (p<0.028), but vertebrae of pathological humans and chimpanzees cannot (p>0.4590). The Procrustes distance between pathological humans and chimpanzees was found to be smaller than the one between pathological and healthy humans. This was the case for both vertebrae. Pair-wise MANOVAs of Principal Component scores for both the thoracic and lumbar vertebrae found significant differences between all pairs of taxa (p<0.029), except pathological humans vs chimpanzees (p>0.367). Together, these results suggest that human vertebrae with Schmorl’s nodes are closer in shape to chimpanzee vertebrae than are healthy human vertebrae.ConclusionsThe results support the hypothesis that intervertebral disc herniation preferentially affects individuals with vertebrae that are towards the ancestral end of the range of shape variation within H. sapiens and therefore are less well adapted for bipedalism. This finding not only has clinical implications but also illustrates the benefits of bringing the tools of evolutionary biology to bear on problems in medicine and public health.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0336-y) contains supplementary material, which is available to authorized users.

The T Protein: Vertebrae Fit to a T

Congenital vertebral malformations (CVMs) comprise a group of spinal abnormalities that include alterations in vertebral shape or number. Evidence suggests CVMs have a genetic link, possibly resulting from mutations in multiple genes. One candidate gene is T. T protein, a transcription factor found in a variety of animals including humans, is essential for correct embryonic development and guides the development of bone and cartilage from embryonic mesodermal tissue. T protein accumulates in the nuclei of notochord cells, interacts with DNA at specific genes, and acts as a genetic switch to activate the genes. T protein binds to the major and minor grooves of DNA as a dimer. Mutations in T (turning “off” the T protein switch) are hypothesized to result in defects in spinal development. The Cedarburg SMART (Students Modeling A Research Topic) Team has designed a partial model of T protein using 3D printing technology to investigate its structure‐function relationship, focusing primarily on the residues important for dimerization of T (Pro125, Asp126, and Pro128) and for binding DNA (Arg67). A 3D model could indicate how the location of the mutations may impact the function of T. T could consequently be a potential target for the development of treatment or prevention options. Program supported by a grant from NIH‐CTSA.

Does the correlation between Schmorl's nodes and vertebral morphology extend into the lumbar spine?

Schmorl's nodes are depressions on vertebrae due to herniation of the nucleus pulposus of the intervertebral disc into the vertebral body. This study provides an extension of our previous study which analyzed the shape of the lower thoracic spine and found that vertebral morphology was associated with the presence of Schmorl's nodes. Ninety adult individuals from the late Medieval site of Fishergate House, York, and the Post-Medieval site of Coach Lane, North Shields, Tyne and Wear, England, were analysed using 2D geometric morphometrics to identify possible relationships between vertebral morphology and Schmorl's nodes at the thoraco-lumbar junction and in the lumbar spine. A significant correlation was found between vertebral shape and the presence of Schmorl's nodes in the twelfth thoracic vertebrae and the first to third lumbar vertebrae. The findings corroborate previous studies and suggest that vertebral shape may be an important factor in spinal health. It is hypothesized that the pedicle shape of affected vertebrae may not provide adequate structural support for the vertebral bodies, resulting in vertical disc herniation.

Functional morphology of the primate head and neck.

The vertebral column plays a key role in maintaining posture, locomotion, and transmitting loads between body components. Cervical vertebrae act as a bridge between the torso and head and play a crucial role in the maintenance of head position and the visual field. Despite its importance in positional behaviors, the functional morphology of the cervical region remains poorly understood, particularly in comparison to the thoracic and lumbar sections of the spinal column. This study tests whether morphological variation in the primate cervical vertebrae correlates with differences in postural behavior. Phylogenetic generalized least-squares analyses were performed on a taxonomically broad sample of 26 extant primate taxa to test the link between vertebral morphology and posture. Kinematic data on primate head and neck postures were used instead of behavioral categories in an effort to provide a more direct analysis of our functional hypothesis. Results provide evidence for a function-form link between cervical vertebral shape and postural behaviors. Specifically, taxa with more pronograde heads and necks and less kyphotic orbits exhibit cervical vertebrae with longer spinous processes, indicating increased mechanical advantage for deep nuchal musculature, and craniocaudally longer vertebral bodies and more coronally oriented zygapophyseal articular facets, suggesting an emphasis on curve formation and maintenance within the cervical lordosis, coupled with a greater resistance to translation and ventral displacement. These results not only document support for functional relationships in cervical vertebrae features across a wide range of primate taxa, but highlight the utility of quantitative behavioral data in functional investigations.

Performance of statistical models of shape and appearance for semiautomatic segmentations of spinal vertebrae T4–L4 on digitized vertebral fracture assessment images

Background contextDespite its clinical importance, accurate identification of vertebral fractures is problematic and time-consuming. There is a recognized need to improve the detection of vertebral fractures so that appropriate high-risk patients can be selected to initiate clinically beneficial therapeutic interventions. PurposeTo develop and evaluate semiautomatic algorithms for detailed annotation of vertebral bodies from T4 to L4 in digitized lateral spinal dual-energy X-ray absorptiometry (DXA) vertebral fracture assessment (VFA) images. Study designUsing lateral spinal DXA VFA images from subjects imaged at University Hospital fracture liaison service, image algorithms were developed for semiautomatic detailed annotation of vertebral bodies from T4 to L4. Patient sampleTwo hundred one women aged 50 years or older with nonvertebral fractures. Outcome measuresAlgorithm accuracy and precision. MethodsStatistical models of vertebral shape and appearance from T4 to L4 were constructed using VFA images from 130 subjects. The resulting models form a part of an algorithm for performing semiautomatic detailed annotation of vertebral bodies from T4 to L4. Algorithm accuracy and precision were evaluated on a test-set of 71 independent images. ResultsOverall accuracy was 0.72 mm (3.00% of vertebral height) and overall precision was 0.26 mm (1.11%) for point-to-line distance. Accuracy and precision were best on normal vertebrae (0.65 mm [2.67%] and 0.21 mm [0.90%], respectively) and mild fractures (0.78 mm [3.18%] and 0.32 mm [1.39%], respectively), but accuracy and precision errors were higher for moderate (1.07 mm [4.66%] and 0.48 mm [2.15%], respectively) and severe fractures (2.07 mm [9.65%] and 1.10 mm [5.09%], respectively). Accuracy and precision results for the algorithm were comparable with other reported results in the literature. ConclusionsThis semiautomatic image analysis had high overall accuracy and precision on normal vertebrae and mild fractures, but performed less well in moderate and severe fractures. It is, therefore, a useful tool to identify normality of vertebral shape and to identify mild fractures.

The skeletal maturation status estimated by statistical shape analysis: axial images of Japanese cervical vertebra.

To evaluate axial cervical vertebral (ACV) shape quantitatively and to build a prediction model for skeletal maturation level using statistical shape analysis for Japanese individuals. The sample included 24 female and 19 male patients with hand-wrist radiographs and CBCT images. Through generalized Procrustes analysis and principal components (PCs) analysis, the meaningful PCs were extracted from each ACV shape and analysed for the estimation regression model. Each ACV shape had meaningful PCs, except for the second axial cervical vertebra. Based on these models, the smallest prediction intervals (PIs) were from the combination of the shape space PCs, age and gender. Overall, the PIs of the male group were smaller than those of the female group. There was no significant correlation between centroid size as a size factor and skeletal maturation level. Our findings suggest that the ACV maturation method, which was applied by statistical shape analysis, could confirm information about skeletal maturation in Japanese individuals as an available quantifier of skeletal maturation and could be as useful a quantitative method as the skeletal maturation index.

Evolution of neck vertebral shape and neck retraction at the transition to modern turtles: an integrated geometric morphometric approach.

The unique ability of modern turtles to retract their head and neck into the shell through a side-necked (pleurodiran) or hidden-necked (cryptodiran) motion is thought to have evolved independently in crown turtles. The anatomical changes that led to the vertebral shapes of modern turtles, however, are still poorly understood. Here we present comprehensive geometric morphometric analyses that trace turtle vertebral evolution and reconstruct disparity across phylogeny. Disparity of vertebral shape was high at the dawn of turtle evolution and decreased after the modern groups evolved, reflecting a stabilization of morphotypes that correspond to the two retraction modes. Stem turtles, which had a very simple mode of retraction, the lateral head tuck, show increasing flexibility of the neck through evolution towards a pleurodiran-like morphotype. The latter was the precondition for evolving pleurodiran and cryptodiran vertebrae. There is no correlation between the construction of formed articulations in the cervical centra and neck mobility. An increasing mobility between vertebrae, associated with changes in vertebral shape, resulted in a more advanced ability to retract the neck. In this regard, we hypothesize that the lateral tucking retraction of stem turtles was not only the precondition for pleurodiran but also of cryptodiran retraction. For the former, a kink in the middle third of the neck needed to be acquired, whereas for the latter modification was necessary between the eighth cervical vertebra and first thoracic vertebra. Our paper highlights the utility of 3D shape data, analyzed in a phylogenetic framework, to examine the magnitude and mode of evolutionary modifications to vertebral morphology. By reconstructing and visualizing ancestral anatomical shapes, we provide insight into the anatomical features underlying neck retraction mode, which is a salient component of extant turtle classification.

Two years' experience with denosumab for children with osteogenesis imperfecta type VI.

BackgroundOsteogenesis imperfecta (OI) is a hereditary disease causing reduced bone mass, increased fracture rate, long bone deformities and vertebral compressions. Additional non skeletal findings are caused by impaired collagen function and include hyperlaxity of joints and blue sclera. Most OI cases are caused by dominant mutations in COL1A1/2 affecting bone formation. During the last years, recessive forms of OI have been identified, mostly affecting posttranslational modification of collagen. In 2011, mutations in SERPINF1 were identified as the molecular cause of OI type VI, and thereby a novel pathophysiology of the disease was elucidated. The subgroup of patients with OI type VI are affected by an increased bone resorption, leading to the same symptoms as observed in patients with an impaired bone formation. Severely affected children are currently treated with intravenous bisphosphonates regardless of the underlying mutation and pathophysiology. Patients with OI type VI are known to have a poor response to such a bisphosphonate treatment.MethodDeciphering the genetic cause of OI type VI in our 4 patients (three children and one adolescent) led to an immediate translational approach in the form of a treatment with the monoclonal RANKL antibody Denosumab (1 mg/kg body weight every 12 weeks).ResultsShort-term biochemical response to this treatment was reported previously. We now present the results after 2 years of treatment and demonstrate a long term benefit as well as an increase of bone mineral density, a normalization of vertebral shape, an increase of mobility, and a reduced fracture rate.ConclusionThis report presents the first two-year data of denosumab treatment in patients with Osteogenesis imperfecta type VI and in Osteogenesis imperfecta in general as an effective and apparently safe treatment option.

Is vertebroplasty a risk factor for subsequent vertebral fracture, meta-analysis of published evidence?

In our paper, we systemically retrieved the eligible study evaluating whether increased incidence of subsequent vertebral fracture is associated with vertebroplasty. Main effect sizes were vertebral fracture rates reported in terms of hazard ratio (HR) for time-to-event data or relative risk (RR) for dichotomous outcome. Our results do not support the hypothesis that vertebroplasty contributes to increased risk of subsequent vertebral fracture, neither adjacent nor total vertebral fracture. Vertebroplasty has been implicated in significant changes in vertebral strength, vertebral shape, and consequently increased risk for subsequent vertebral fracture, especially the adjacent level. Here, we further tested the hypothesis whether new-onset vertebral fracture is a natural result of osteoporosis or consequence of cement augmentation. Relevant literatures were retrieved using PubMed, Web of Knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL), supplemented by a hand-search of the reference lists of selected articles. Eligible studies assessed whether increased morbidity of subsequent vertebral fracture is associated with vertebroplasty. Main effect sizes were vertebral fracture rates reported in terms of hazard ratio (HR) for time-to-event data or relative risk (RR) for dichotomous outcome. Random-effects model was used to account for clinical or methodological heterogeneity across studies. Thirteen studies with a number of 2,551 individuals (1,631 in vertebroplasty group and 920 in control group) were suitable for this meta-analysis. In trials that reported adjacent vertebral fracture as time-to-event data (two trials, n = 328), we found a similar incidence of vertebral fracture in percutaneous vertebroplasty (PVP) group compared to conservative therapy (HR 0.60, 95% confidence interval 0.29 to 1.26; P = 0.18). In trials that reported overall vertebral fracture as time-to-event data (three trials, n = 704), vertebroplasty was associated with a slightly increased but non-significant risk for vertebral fracture (HR 1.14, 95% confidence interval 0.65 to 2.00; P = 0.65). The outcome was further confirmed in the secondary meta-analysis of studies that reported vertebral fracture as dichotomous data. Subgroup analysis according to study design revealed no difference either. Our results do not support the hypothesis that vertebroplasty contributes to increased risk of subsequent vertebral fracture, neither adjacent nor total vertebral fracture. However, adequately designed randomized controlled trials are warranted to confirm the present findings.

Revisiting scoliosis in the KNM-WT 15000 Homo erectus skeleton

Owing to its completeness, the 1.5 million year old Nariokotome boy skeleton KNM-WT 15000 is central for understanding the skeletal biology of Homo erectus. Nevertheless, since the reported asymmetries and distortions of Nariokotome boy's axial skeleton suggest adolescent idiopathic scoliosis, possibly associated with congenital skeletal dysplasia, it is questionable whether it still can be used as a reference for H. erectus. Recently, however, the presence of skeletal dysplasia has been refuted. Here, we present a morphological and morphometric reanalysis of the assertion of idiopathic scoliosis. We demonstrate that unarticulated vertebral columns of non-scoliotic and scoliotic individuals can be distinguished based on the lateral deviation of the spinous process, lateral and sagittal wedging, vertebral body torsion, pedicle thickness asymmetry, and asymmetry of superior and inferior articular facet areas. A principal component analysis of the overall asymmetry of all seven vertebral shape variables groups KNM-WT 15000 within non-scoliotic modern humans. There is, however, an anomaly of vertebrae T1–T2 that is compatible with a short left convex curve at the uppermost thoracic region, possibly due to injury or local growth dysbalance. Asymmetries of the facet joints L3–L5 suggest a local right convex curve in the lower lumbar region that probably resulted from juvenile traumatic disc herniation. This pattern is incompatible with adolescent idiopathic scoliosis or other types of scoliosis, including congenital, neuromuscular or syndromic scoliosis. It is, however, consistent with a recent reanalysis of the rib cage that did not reveal any asymmetry. Except for these possibly trauma-related anomalies, the Nariokotome boy fossil therefore seems to belong to a normal H. erectus youth without evidence for adolescent idiopathic scoliosis or other severe pathologies of the axial skeleton.

Spinal imaging features in Japanese patients with Marfan syndrome: a case-control study

The purpose of our study was to evaluate the morphology of the lumbosacral spine, i.e. the dura and vertebral body shape, of Japanese patients with Marfan syndrome (MFS) by comparing it with sex- and age-matched controls. Spinal MR or CT images of 32 MFS patients and 32 controls were retrospectively reviewed. The anteroposterior dural sac diameter (DSD), anteroposterior vertebral body diameter (VBD), and vertebral body height (VBH) were measured from L1 to S1 levels and the dural sac ratio [DSR = (DSD/VBD)] and vertebral body aspect ratio [VAR = (VBH/VBD)] were calculated. At each level, mean DSD and DSR were significantly higher in MFS patients; VBD was not. The cutoff values for DSR to differentiate between MFS patients and the controls were 0.59, 0.46, 0.42, 0.45, 0.47, and 0.47 from the level of L1 to S1. At a sensitivity of 93.8 % and a specificity of 84.4 % the cutoff value at S1 was most diagnostic. In MFS patients VAR was significantly higher at L3 and L4. Our cutoff value for DSR >0.47 at S1 may help to identify MFS in the Japanese population. A square-like appearance of the L3 and L4 vertebral bodies is a supplementary finding in MFS patients.

Six monthly intravenous zoledronic acid in childhood osteoporosis

Childhood osteoporosis can be treated with intravenous bisphosphonates in order to improve bone mass and density. The aims of this study were to evaluatethe safety and efficacy of six-monthly zoledronic acid (ZA) in children with osteoporosis. A retrospective cohort study of 27 patients (16 males and 11 females) weretreated with six-monthly ZA (0.05mg/kg/dose) for a minimum of one year.17 patients were immobile, 4 had steroid-induced osteoporosis, 2 had osteogenesis imperfecta and 4 had other diagnoses. 16/27 (59%) had long bone fractures and 12/27 (44.4%) had vertebral wedging at baseline. Mineral homeostasis, bone mineral density by DXA and vertebral morphometry were evaluated at baseline and 1year. The median age at commencement of treatment was 12.3 years (range 8-15.8). Following the first infusion, 2/27 (7%) and 1/27 (4%) developed asymptomatic hypocalcemia at 48 hours and 72 hours, respectively.A fever above 38°C developed in 14/27 (52%), generalised aches/pains in 13/27 (48%) and nausea in 6/27 (22%).At 1year there was a significant reduction in bone turnover and improvement in bone mineral density (BMD) (see Table ​Table1).1). Patients with vertebral wedging at baseline showed significant improvement in anterior, middle and posterior vertebral height ratios at 1year. Only one patient fractured after starting ZA. There was normal growth. Table 1 Mineral homeostasis and DXA data at baseline and 1 year Six monthly ZA was associated with an acute phase reaction to the first dose and improvement in BMD, reduction in bone turnover and improved vertebral shape at 1 year.

Intravenous Zoledronic Acid Given Every 6 Months in Childhood Osteoporosis

Aim: To evaluate the safety and efficacy of 12 months of zoledronic acid (ZA) administered every 6 months to children with osteoporosis. Methods: Retrospective cohort study of 27 patients (16 male, 11 female) treated with ZA (0.05 mg/kg/dose) every 6 months for 1 year. 20 were immobile, 4 steroid-induced osteoporosis, 2 idiopathic osteoporosis and 1 neurofibromatosis type 1. 16 had long bone fractures and 12 had vertebral wedging at baseline. Mineral homeostasis, bone mineral density (BMD) and vertebral morphometry were evaluated at baseline and 12 months. Results were compared to published data on 3-monthly ZA treatment. Results: Median age at ZA start was 10.5 years (range 6.2-13.3). Following the first infusion, 2 developed asymptomatic hypocalcemic, 14 developed temperature >38°C, 13 aches/pain and 6 nausea. At 12 months, there was reduction in bone turnover and improvement in BMD and vertebral shape. No patient fractured after starting ZA. Growth was normal. Outcomes were similar to 3-monthly ZA. Conclusion: ZA administered 6-monthly was associated with acute phase reaction to the first dose and improvement in BMD, reduction in bone turnover and improved vertebral shape at 12 months.

Intravenous Pamidronate Treatment in Children with Moderate-to-Severe Osteogenesis Imperfecta Started under Three Years of Age

Objective: Evaluate clinical outcome of early cyclic intravenous pamidronate treatment in children with moderate-to-severe osteogenesis imperfecta (OI), commenced before three years of age. Methods: A retrospective review of 17 patients with moderate-to-severe OI. Development, anthropometry, fracture history, bone mineral density (BMD) and biochemistry were collected at baseline, 12 and 24 months. Results: Four had OI type I, eleven had type III, one OI-FKBP10 type and one OI type V. Mean age at start of pamidronate was 14 ± 11 months. Pamidronate ranged from 6 to 12 mg/kg/year. No adverse reaction apart from fever and vomiting was noted. Long bone fracture decreased from a mean of 10.4/year to 1.2/year after 12 months and 1.4/year after 24 months (p = 0.02). Lumbar spine age- and height-matched BMD Z-scores increased (p < 0.005). Sixteen with vertebral compression fractures at baseline all showed improved vertebral shape (p < 0.001). Concavity index, likewise, improved (p < 0.005). Motor milestones compared to historical data show earlier attainment in rolling over, crawling, pulling to stand and walking independently but not sitting. Conclusion: Cyclic intravenous pamidronate, started under 3 years of age in children with moderate-to-severe OI, was well tolerated and associated with an increase in lumbar spine BMD, reduced fracture frequency, vertebral remodelling and attainment of motor milestones at an earlier age.

3D reconstruction of the lumbar vertebrae from anteroposterior and lateral dual-energy X-ray absorptiometry

Current vertebral fracture prevention measures use Dual-energy X-ray Absorptiometry (DXA) to quantify the density of the vertebrae and subsequently determine the risk of fracture. This modality however only provides information about the projected Bone Mineral Density (BMD) while the shape and spatial distribution of the bone determines the strength of the vertebrae. Quantitative Computed Tomography (QCT) allows for the measurement of the vertebral dimensions and volumetric densities, which have been shown to be able to determine the fracture risk more reliably than DXA. However, for the high cost and high radiation dose, QCT is not used in clinical routine for fracture risk assessment. In this work, we therefore propose a method to reconstruct the 3D shape and density volume of lumbar vertebrae from an anteroposterior (AP) and lateral DXA image used in clinical routine. The method is evaluated for the L2, L3 and L4 vertebra. Of these vertebrae a statistical model of the vertebral shape and density distribution is first constructed from a large dataset of QCT scans. All three models are then simultaneously registered onto both AP and lateral DXA image. The shape and volumetric BMD at several regions of the reconstructed vertebrae is then evaluated with respect to the ground truth QCT volumes. For the L2, L3 and L4 vertebrae respectively the shape was reconstructed with a mean (2RMS) point-to-surface distance of 1.00 (2.64) mm, 0.93(2.52) mm and 1.34(3.72) mm and a strong correlation (r > 0.82) was found between the trabecular volumetric BMD extracted from the reconstructions and from the same subject QCT scans. These results indicate that the proposed method is able to accurately reconstruct the 3D shape and density volume of the lumbar vertebrae from AP and lateral DXA, which can potentially improve the fracture risk estimation accuracy with respect to the currently used DXA derived areal BMD measurements.

Vertebral morphology influences the development of Schmorl's nodes in the lower thoracic vertebrae

Schmorl's nodes are the result of herniations of the nucleus pulposus into the adjacent vertebral body and are commonly identified in both clinical and archaeological contexts. The current study aims to identify aspects of vertebral shape that correlate with Schmorl's nodes. Two-dimensional statistical shape analysis was performed on digital images of the lower thoracic spine (T10-T12) of adult skeletons from the late medieval skeletal assemblages from Fishergate House, York, St. Mary Graces and East Smithfield Black Death cemeteries, London, and postmedieval Chelsea Old Church, London. Schmorl's nodes were scored on the basis of their location, depth, and size. Results indicate that there is a correlation between the shape of the posterior margin of the vertebral body and pedicles and the presence of Schmorl's nodes in the lower thoracic spine. The size of the vertebral body in males was also found to correlate with the lesions. Vertebral shape differences associated with the macroscopic characteristics of Schmorl's nodes, indicating severity of the lesion, were also analyzed. The shape of the pedicles and the posterior margin of the vertebral body, along with a larger vertebral body size in males, have a strong association with both the presence and severity of Schmorl's nodes. This suggests that shape and/or size of these vertebral components are predisposing to, or resulting in, vertically directed disc herniation.

Quantitative vertebral morphometry based on parametric modeling of vertebral bodies in 3D

Quantitative vertebral morphometry (QVM) was performed by parametric modeling of vertebral bodies in three dimensions (3D). Identification of vertebral fractures in two dimensions is a challenging task due to the projective nature of radiographic images and variability in the vertebral shape. By generating detailed 3D anatomical images, computed tomography (CT) enables accurate measurement of vertebral deformations and fractures. A detailed 3D representation of the vertebral body shape is obtained by automatically aligning a parametric 3D model to vertebral bodies in CT images. The parameters of the 3D model describe clinically meaningful morphometric vertebral body features, and QVM in 3D is performed by comparing the parameters to their statistical values. Thresholds and parameters that best discriminate between normal and fractured vertebral bodies are determined by applying statistical classification analysis. The proposed QVM in 3D was applied to 454 normal and 228 fractured vertebral bodies, yielding classification sensitivity of 92.5% at 7.5% specificity, with corresponding accuracy of 92.5% and precision of 86.1%. The 3D shape parameters that provided the best separation between normal and fractured vertebral bodies were the vertebral body height and the inclination and concavity of both vertebral endplates. The described QVM in 3D is able to efficiently and objectively discriminate between normal and fractured vertebral bodies and identify morphological cases (wedge, (bi)concavity, or crush) and grades (1, 2, or 3) of vertebral body fractures. It may be therefore valuable for diagnosing and predicting vertebral fractures in patients who are at risk of osteoporosis.