Legg-Calvé-Perthes disease in the UK: geographic and temporal trends in incidence reflecting differences in degree of deprivation in childhood.

OBJECTIVE: Little is known about Legg-Calvé-Perthes disease, a common childhood precursor to osteoarthritis of the hip. This study was undertaken to analyze the incidence of Legg-Calvé-Perthes disease in the UK, with respect to geographic and temporal trends over a 19-year period. METHODS: The General Practice Research database was analyzed to identify incident cases between 1990 and 2008 in children ages 0-14 years. Incidence rates were calculated by year and by region (National Health Service Strategic Health Authority regions in England, and Scotland, Wales, and Northern Ireland), and the association with regional markers of deprivation examined. RESULTS: Over the 19-year period there was a dramatic decline in Legg-Calvé-Perthes disease incidence, with annual rates among children 0-14 years old declining from 12.2 per 100,000 to 5.7 per 100,000 (P < 0.001). There was also marked geographic variation, with incidence rates in Scotland more than twice those in London (10.39 [95% confidence interval 8.05-13.2] versus 4.6 [95% confidence interval 3.4-6.1] per 100,000 0-14-year-olds). A more rapid decline in incidence was apparent in the Northern regions compared to Southern regions. The quintile with the highest degree of deprivation had the highest disease incidence (rate ratio 1.49 [95% confidence interval 1.10-2.04]) and, with the exception of London, regional incidence showed a strong linear relationship with regional deprivation score (P < 0.01). CONCLUSION: The incidence of Legg-Calvé-Perthes disease in the UK has a strong North-South divide, with a greater disease incidence within the Northern regions of the UK. There was a marked decline in incidence over the study period, which was more marked in Northern areas. The declining incidence, along with the geographic variation, suggests that a major etiologic determinant in Legg-Calvé-Perthes disease is environmental and closely linked to childhood deprivation.

Hyperactivity and the psychological burden of Perthes disease: a case-control study.

BACKGROUND: Legg-Calve-Perthes Disease (LCPD) is a childhood precursor to hip osteoarthritis, for which the etiology is unknown. There is a widespread belief that affected individuals are "hyperactive," propagating a theory that such children may have sustained an epiphyseal injury that precipitated the onset of LCPD. This study seeks to quantify the association with hyperactivity, and the wider psychological burden of the disease. METHODS: A case-control study was conducted among 146 cases of LCPD and 142 hospital controls, frequency matched by age and sex. Psychological domains were measured using the Strength and Difficulties Questionnaire. Adjustment was made for age, sex, and socioeconomic deprivation. Results were stratified by the time elapsed since LCPD was diagnosed. RESULTS: Significant associations (P<0.05) existed with the majority of the psychological domains captured by the Strength and Difficulties Questionnaire [odds ratio (OR) for "high" level of difficulties-Emotion OR 3.2, Conduct OR 2.1, Inattention-Hyperactivity OR 2.7, Prosocial Behavior OR 1.9]. Hyperactivity was especially marked among individuals within 2 years of diagnosis (OR 8.6; P<0.001), but not so among individuals over 4 years from diagnosis. Emotional symptoms persisted long after resolution of the active phase of disease. CONCLUSIONS: There was a marked psychological burden among individuals with LCPD, which was most marked amongst individuals with a recent diagnosis. The breadth and inferred temporality of these disturbances may be a function of the disease process, through restriction of activities and disability, or may be a fundamental disease characteristic related directly to disease or to its etiological determinant.

Racial and geographic factors in the incidence of Legg-Calvé-Perthes' disease: a systematic review.

Legg-Calvé-Perthes' disease (Perthes' disease) is a childhood osteonecrosis of the hip for which the disease determinants are poorly understood. In this review, the authors identify studies of Perthes' disease incidence published up to December 2010 and make denominator populations comparable in order to allow meaningful between-study evaluation. Incidence rates and confidence intervals were determined, and, where appropriate, denominator populations were obtained from national statistical offices. Poisson regression was used to determine the influence of race and geography. The review included 21 studies that described 27 populations in 16 countries, with 124 million person-years of observation. The annual incidence among children under age 15 years ranged from 0.2 per 100,000 to 19.1 per 100,000. Race was a key determinant, with East Asians being least affected and whites most affected, though data were insufficient to consider incidence among blacks (for South Asians vs. East Asians, incidence rate ratio = 2.9, 95% confidence interval (CI): 2.4, 3.5; for whites vs. East Asians, incidence rate ratio = 8.8, 95% CI: 8.2, 9.6). Latitude was a strong predictor of disease, even after adjustment for race. Each 10° increase in latitude was associated with an incidence increase of 1.44 (95% CI: 1.30, 1.58) times. While much of the international variation appears to be a function of race, latitude demonstrates a strong association. This observation may offer new epidemiologic insights into the determinants of Perthes' disease.

Whither the etiopathogenesis (and scoliogeny) of adolescent idiopathic scoliosis?

Although considerable progress had been made in the past two decades in understanding the etiopathogenesis of adolescent idiopathic scoliosis (AIS), it still lacks an agreed theory of etiopathogenesis. One problem may be that AIS results not from one cause, but several that interact with various genetic predisposing factors. There is a view there are two other pathogenic processes for idiopathic scoliosis namely, initiating (or inducing), and those that cause curve progression. Twin studies and observations of family aggregation have revealed significant genetic contributions to idiopathic scoliosis, that place AIS among other common disease or complex traits with a high heritability interpreted by the genetic variant hypothesis of disease. We summarize etiopathogenetic knowledge of AIS as theories of pathogenesis including recent multiple concepts, and blood tests for AIS based on predictive biomarkers and genetic variants that signify disease risk. There is increasing evidence for the possibility of an underlying neurological disorder for AIS, research which holds promise. Like brain research, most AIS workers focus on their own corner and there is a need for greater integration of research effort. Epigenetics, a relatively recent field, evaluates factors concerned with gene expression in relation to environment, disease, normal development and aging, with a complex regulation across the genome during the first decade of life. Research on the role of environmental factors, epigenetics and chronic non-communicable diseases (NCDs) including adiposity, after a slow start, has exploded in the last decade. Not so for AIS research and the environment where, except for monozygotic twin studies, there are only sporadic reports to suggest that environmental factors are at work in etiology. Here, we examine epigenetic concepts as they may relate to human development, normal life history phases and AIS pathogenesis. Although AIS is not regarded as an NCD, like them, it is associated with whole organism metabolic phenomena, including lower body mass index, lower circulating leptin levels and other systemic disorders. Some epigenetic research applied to Silver-Russell syndrome and adiposity is examined, from which suggestions are made for consideration of AIS epigenetic research, cross-sectional and longitudinal. The word scoliogeny is suggested to include etiology, pathogenesis and pathomechanism.

Upper arm length model suggests transient bilateral asymmetry is associated with right thoracic adolescent idiopathic scoliosis (RT-AIS) with implications for pathogenesis and estimation of linear skeletal overgrowth.

INTRODUCTION: In girls with adolescent idiopathic scoliosis (AIS) the finding of abnormal extra-spinal bilateral skeletal length asymmetries in upper limbs, periapical ribs, and ilia begs the question whether these bilateral asymmetries are connected in some way with pathogenesis. MATERIAL AND METHODS: We investigated upper arm length (UAL) asymmetries in two groups of right-handed girls aged 11-18 years with right thoracic adolescent idiopathic scoliosis (RT-AIS, n=95) from preoperative and screening referrals (mean Cobb angle 46°) and healthy controls (n=240). Right and left UAL were measured with a Harpenden anthropometer of the Holtain equipment, Asymmetry was calculated as UAL difference, right minus left, in mm. Repeatability of the measurements was assessed as technical error of the measurement and coefficient of reliability. RESULTS: In girls with RT-AIS, UAL asymmetry was greater than in healthy girls, regressed negatively with age and correlated significantly with Cobb angle and apical vertebral rotation. In healthy girls, UAL asymmetry was unrelated to age. Plotted against years after estimated menarcheal age, UAL asymmetry decreased significantly for girls with RT-AIS but not for healthy girls. DISCUSSION AND CONCLUSIONS: The apparent transience of the abnormal UAL asymmetry suggests it is not secondary to spinal deformity but pathogenetically associated with it. We suggest two hypotheses to account for these changes: (1) a transient asymmetry process with growth velocity; and (2) in the light of subsequent research, early skeletal overgrowth with catch-down growth affecting right but not left upper arm. The relation of the upper arm length asymmetry to the increased length of periapical left ribs reported for RT-AIS is unknown. Right upper arm length may provide a more simple model than arm span, for estimating linear skeletal overgrowth of girls with RT-AIS.

Developing professionalism through the use of wikis: A study with first-year undergraduate medical students.

AIM: Learning about professionalism occurs through collaboration, with peer groups being important sources of support for students [Sandars J, Homer M, Pell G, Croker T. 2008. Web 2.0 and social software: The medical student way of e-learning. Med Teach 14:1-5. Accessed 2008 February 14]. This study aimed to discover whether the use of wikis (collaborative websites) could enhance medical students' development of professionalism. METHODS: An online wiki was made available to four problem-based learning (PBL) groups, involving 32 students. Data collection comprised a small-scale student survey and four focus groups eliciting their views about wiki use, triangulated with facilitator interviews and wiki usage statistics. RESULTS: Several factors affected individual student and group engagement with wikis, such as positive group dynamics. Students shared web links, helping clarify PBL discussions and increase their confidence. CONCLUSIONS: Two main benefits of using wikis for the development of professionalism with medical students were revealed. First, wikis acted as a shared knowledge base for hard-to-find resources on professionalism. Second, it was precisely when students reflected on the difference between interacting in wikis and their online social spaces, or when they considered whether or not to post a resource that their sense of professionalism emerged.

The impact of COVID-19 on Medical education and Medical Students. How and when can they return to placements?

This article was migrated. The article was marked as recommended. The defining feature of 2020 will be the early and mid-stages of the covid-19 pandemic, declared by the World Health Organisation on 11 th March. Rapid worldwide exponential spread continues and by 15 April, more than 1 900 000 cases and 123 000 deaths had been reported worldwide (WHO, 2020). Health services have coped to varying degrees. One common feature has been the withdrawal of routine care (Iacobucci, 2020a) and 'non-essential' staff including learners, although many have returned to undertake care roles. As the likely timeframe for stabilisation of health services becomes clearer, certainly in the United Kingdom (UK) (Iacobucci, 2020b), medical educators need to rapidly get the teaching of the next generation of health care workers back on track if they are to enter health services as confident and competent practitioners in 2020 and 2021. Although a 'whole world' experience, the effects of covid-19 sit in national contexts. We detail the issues for the UK in re-starting and re-inventing medical education, noting that the principles, if not necessarily the detail, will be common across the world.

Concepts on the pathogenesis of adolescent idiopathic scoliosis. Bone growth and mass, vertebral column, spinal cord, brain, skull, extra-spinal left-right skeletal length asymmetries, disproportions and molecular pathogenesis.

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). Encouraging advances thought to be related to AIS pathogenesis have recently been made in several fields including anthropometry of bone growth, bone mass, spinal growth modulation, extra-spinal left-right skeletal length asymmetries and disproportions, magnetic resonance imaging of vertebral column, spinal cord, brain, skull, and molecular pathogenesis. These advances are leading to the evaluation of new treatments including attempts at minimally invasive surgery on the spine and peri-apical ribs. Several concepts of AIS are outlined indicating their clinical applications but not their research potential. The concepts, by derivation morphological, molecular and mathematical, are addressed in 15 sections: 1) initiating and progressive factors; 2) relative anterior spinal overgrowth; 3) dorsal shear forces that create axial rotational instability; 4) rotational preconstraint; 5) uncoupled, or asynchronous, spinal neuro-osseous growth; 6) brain, nervous system and skull; 7) a novel neuro-osseous escalator concept based on a putative abnormality of two normal polarized processes namely, a) increasing skeletal dimensions, and b) the CNS body schema - both contained within a neuro-osseous timing of maturation (NOTOM) concept; 8) transverse plane pelvic rotation, skeletal asymmetries and developmental theory; 9) thoraco-spinal concept; 10) origin in contracture at the hips; 11) osteopenia; 12) melatonin deficiency; 13) systemic melatonin-signaling pathway dysfunction; 14) platelet calmodulin dysfunction; and 15) biomechanical spinal growth modulation. From these concepts, a collective model for AIS pathogenesis is formulated. The central concept of this model includes the body schema of the neural systems, widely-studied in adults, that control normal posture and coordinated movements with frames of reference in the posterior parietal cortex. The escalator concept has implications for the normal development of upright posture, and the evolution in humans of neural control, the trunk and unique bipedal gait.

Pathogenesis of progressive adolescent idiopathic scoliosis. Platelet activation and vascular biology in immature vertebrae: an alternative molecular hypothesis.

Altered paraspinal muscle activity was suggested by Lowe et al (2002) to explain a relationship between Cobb angle changes and platelet calmodulin level changes in adolescent idiopathic scoliosis (AIS). We formulate an alternative platelet-skeletal hypothesis which involves: (1) a small scoliosis curve; (2) axial loads transmitted directly from the intervertebral discs to vertebral body growth plates (endplate physes) as axial inward bulges that create mechanical micro-insults; (3) the latter cause dilatation of juxta-physeal vessels and, in deforming vertebrae, vascular damage with exposure of subendothelial collagen and other agonist proteins; (4) subject to predisposition, platelet activation with calmodulin changes occurs within dilated vessels of deforming vertebral bodies; (5) the activated platelets in juxta-physeal vessels release growth factors that, after extravasation, abet the hormone-driven growth of the already mechanically-compromised vertebral endplate physes to promote the relative anterior spinal overgrowth and curve progression of AIS. The hypothesis links several fields in each of which research within ethical restraints is suggested to refute it.

Can posture analysis point towards curve progression in scoliotic subjects?

Previous research employing biomechanical measurement has demonstrated asymmetries in kinematics and kinetics. Similar asymmetries have been reported from anthropometric studies. These findings suggest that asymmetry may play an important aetiological role in adolescent idiopathic scoliosis (AIS). The present study is a part of a wider comprehensive investigation aimed at identifying asymmetries in lower limb kinematics and pelvic and back movements during level walking in a sample of scoliotic subjects. Such asymmetries may be related to the spinal deformity. While previous studies indicate that force platform measurements provide a good estimation of the static balance of individuals, there remains a paucity of information on dynamic balance during walking. There is published evidence on the use of Centre of Pressure (CoP) and net joint moments in gait assessment. Although these investigations have assessed Centre of Mass (CoM)-CoP distance relationships in clinical conditions, there is a paucity of data relating to the moments about CoM. An objective of the present study was to assess and establish the asymmetry in the CoP pattern and moments about CoM during level walking and its relationship to spinal deformity. Results indicate differences across the subjects depending on the laterality of the major curve. Furthermore, the results indicate that the variables identified in this study could be applied to initial screening and surgical evaluation of scoliosis and other spinal deformities. Further studies are being undertaken to validate these findings.

Postural differences in the shoulder girdle during normal locomotion in treadmill vs. over ground walking.

In a clinical setting, most musculoskeletal assessment related to gait is undertaken using a treadmill which is additionally widely used during gait and neurological rehabilitation. Although previous studies have reported the range of motion of gait characteristics during running, there is a paucity of information on normative walking data applicable to clinical assessment. Movements and posture of the shoulder girdle is an important indication of back and upper extremity function. While studies indicate that shoulder girdle kinematics are changed during shoulder dysfunction there is little information on the postural relationship between the shoulder and pelvis. The present investigation aims to create a normative database for kinematics during treadmill walking by examining the differences between the treadmill and over ground walking patterns. Additionally, the research will also assess shoulder girdle posture and to establish its relationship with the pelvic complex which will contribute to further understanding scoliotic posture and movement. 14 normal subjects walked over ground at a self-selected speed followed by walking on the treadmill at a speed matched to each subject's respective average over-ground speed. Three-dimensional kinematic data was captured using a passive marker based motion analysis system (Vicon Peak, UK). Angular and temporal kinematic parameters were estimated. The results indicate differences in angular kinematics between over-ground and treadmill locomotion. These differences should be considered when treadmill kinematics are used for clinical evaluation as opposed to over ground ambulation is scoliosis and other conditions.

Adolescent idiopathic scoliosis (AIS): a multifactorial cascade concept for pathogenesis and embryonic origin.

This paper formulates a novel multifactorial Cascade Concept for the pathogenesis of adolescent idiopathic scoliosis (AIS). This Concept stems from the longitudinal findings of Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) who identified leptin body composition factors at 10 years of age associated with a scoliosis deformity found at 15 years. We interpret these findings in the light of some concepts for AIS pathogenesis. In particular, we speculate that the leptin body composition effect is linked to central nervous system development and the initiation of the asynchronous neuro-osseous growth mechanism that involves the creation of a neuraxis tether of relative anterior vertebral overgrowth. The latter mechanism in combination with age and gender-related anatomical variants of vertebral backward tilt (dorsal shear concept), human upright posture, adolescent growth factors, Hueter-Volkmann effect in vertebrae and vertebral bone mass abnormalities, lead to AIS, possibly both initiation and progression of scoliosis curvatures. Being multifactorial, while the Cascade Concept cannot be tested for all its components, some components should be testable by the method of numerical simulation. Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) also suggested the origin of scoliosis was in the embryonic stages of life from cell types, including adipocytes and osteoblasts, derived from the same progenitor cells, and myoblasts from mesodermal somites. The involvement of cell types from different developmental origins suggests a process acting in embryonic life at a similar time, probably environmental, as previously proposed from anthropometric studies. As a Complex disease, AIS will involve genetic, environmental and life style factors operating in development and growth; this possibility needs evaluating in epidemiological studies.

Examination of relative movement between the back and lower limb.

The importance of trunk movement in human gait has been established by many studies. However, these investigations have examined trunk/pelvis motion or the pelvic/thoracic motion in isolation to lower limb kinematics. Studies quantifying spinal deformities and the range of spinal and trunkal movement have concentrated on spinal/back movement, with the subject performing tasks, such as flexion, while maintaining a static position. There is also a paucity of data detailing the real relative motion between the back and lower limb during gait, an important consideration when testing the Nottingham 'flag-pole' hypothesis for spinal curvature generation. Research into the use of opto-electronic gait analysis systems to measure dynamic back movements has shown the capability of these systems in producing repeatable patterns of back movements. While using a motion analysis system, if a relationship between the spinal movement and lower limb kinematics could be established, such a relationship would provide a new opportunity for range of movement studies in conditions like scoliosis. Furthermore, establishing such a relationship would allow investigation into the influence of one segment over another during locomotion. This present study has examined the movement of markers placed on the back and pelvis, used in three-dimensional opto-electronic systems for gait studies, in relation to the markers placed on the lower limbs. The results of a pilot study have highlighted relative movements between various segments in simple tasks like flexion, lateral bending and negotiating steps, which have implications for spinal deformity generation. The findings also demonstrate the points to be considered in order to define dynamic trunk and spinal movement. Further ongoing studies are being undertaken to validate the findings.

Study of marker placements in the back for opto-electronic motion analysis.

Various investigations into anatomical landmarks that could be employed in spine and back surface measurement have highlighted the usefulness of the spinous processes of the vertebra and the posterior superior iliac spines of the pelvis. Earlier studies used an opto-electronic gait analysis system to examine the motion of skin markers and compared results with similar inter-vertebral movement recorded through radiographs. Consistent patterns of movement suggested a relationship between spinal and back surface motion. Further investigations into the use of opto-electronic gait analysis systems to measure dynamic back movements showed the capability of producing repeatable patterns of back movements. However, these studies, mainly measuring the range of movement (ROM) of spine, have not examined the effects of marker placements. While most ROM studies concentrate on stationary repetitive flexion/extension and bending movements, spinal ROM during walking and in scoliosis has not been widely reported. Spinal range of motion is an important indicator of spinal function and is used in the determination of disability and compensation. The present study has evaluated the placement of markers on the back and pelvis, used in three-dimensional opto-electronic systems for gait and movement studies. Various marker configurations have been compared and reported. The findings highlight the drawbacks of previously reported techniques, and particularly indicate that skin movement can adversely affect findings. However, the results confirm the feasibility of application of this technique to investigate dynamic trunk and spinal movement in both normal and deformed spines.

Rotation of the atlantico-axial joint, investigated using CT and MRI.

The vertebral column is composed of a series of joints, each capable of a specific range of movement. To investigate these movements, a study into the physiological range of rotation at the atlanto-axial joint has been undertaken. The movements and their interpretation under imaging conditions are crucial if any underlying spinal deformity or the consequences of trauma are present in an individual. 28 healthy volunteers were examined using dynamic Magnetic Resonance Imaging with maximum head rotation to the right and left sides in turn. An anatomical specimen of the atlanto-occipital joint was imaged using Computed Tomography with the specimen fixed in varying degrees of rotation. The results indicate that there is a significant but incomplete loss of contact between the articular surfaces of C1 (atlas) and C2 (axis). The range of motion to the right was between 20 and 48.5 degrees (mean 32.4 degrees) and to the left was between 13 and 52.75 degrees (mean 3.2 degrees). Statistical significance between left and right movement was not demonstrated. The instantaneous axis of rotation was examined for the joint and was found to be located within the odontoid peg (dens). These findings indicated that a wide range of movement occurs within the atlanto-axial joint in normal subjects. Furthermore, the appearances under imaging could be misinterpreted as a pathological subluxation. This has implications if the subject with a spinal deformity also has a dysplasia associated with a potential subluxation. The siting of the instantaneous axis of rotation within the odontoid is also important in furthering the understanding of the movement of this joint.

Movement analysis of scoliotic subjects using Fastrak.

An attempt has been made to simplify the measurement of composite movement involving abnormal rotation in scoliosis, which is considered to have an important role in the diagnosis and treatment of the condition. Analysis of three-dimensional movement provides pertinent information concerning the morphological description of scoliotic deformities. The description of this movement is of clinical interest for aiding diagnosis and/or prognosis of spinal deformity evolution. Previous studies have indicated that idiopathic scoliosis is a three-dimensional deformity accompanied by a generalised torsion phenomenon and attempts have been made to associate the geometric torsion index with the curvi-linear shape of idiopathic scoliosis. Although previous investigations have documented the three-dimensional reconstruction of scoliotic spine, most methods either expose the subject to a high level of radiation, as in stereo-radiographs, or demand a high degree of technical input and time, as in video based gait analysis systems. This study employs an electro magnetic field capturing system (FASTRAK) to estimate the spinal movements. This simple system is inexpensive and highly portable. Furthermore, it can give instant graphic and numerical values of the composite movement. The results of this study indicate the usefulness this system in the diagnosis of scoliosis and highlights the possibility of its uses in screening school children and other surveys.

Kinematic differences in lower limb gait analysis of scoliotic subjects.

Although various factors have been attributed to the etiology of idiopathic scoliosis, studies have indicated that the kinematic differences in the spine, pelvis and lower limb may contribute to the causation and progression of idiopathic scoliosis. The aim of this investigation was to identify asymmetries in lower limb kinematics and pelvic and back movements during level walking in scoliotic subjects that can be related to the spinal deformity. The study has employed a movement analysis system to estimate various joint angles in the lower extremities and other kinematic parameters in the pelvis and back. The results of a pilot study have highlighted the potential usefulness of a range of parameters in the indication of asymmetries and their implications for spinal deformity generation. While demonstrating the value that movement analysis systems may have in investigating pathogenesis and aetiology, these preliminary findings indicate that the identified variables can also used in the kinematic analysis of spinal deformities such as scoliosis. Further studies are being undertaken to validate these findings.

Body mass index in relation to truncal asymmetry of healthy adolescents, a physiopathogenetic concept in common with idiopathic scoliosis: summary of an electronic focus group debate of the IBSE.

There is no generally accepted scientific theory for the cause of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE).introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr TB Grivas. It is based on published research from Athens, Greece evaluating schoolchildren age 11-17 years for the relation of body mass index (BMI) to each of truncal asymmetry (TA) and menarcheal status. Girls with relatively lower BMI were found to have a significant excess of severe TAs and significantly later menarche confirming the well-known relation of BMI to menarche. Together with other evidence linking nutritional status to skeletal growth, the observations suggest energy balance via the hypothalamus is related to trunk asymmetry. As with a recent speculative hypothesis for the pathogenesis of AIS in girls, Grivas et al. suggest that the severe TAs involve a genetically-determined selectively increased sensitivity (up-regulation) of the hypothalamus to circulating leptin with asymmetry as an adverse response to stress (hormesis). The TA is expressed bilaterally via the sympathetic nervous system to produce left-right asymmetry in ribs and/or vertebrae leading to severe TAs when beyond the capacity of postural mechanisms of the somatic nervous system to control the shape distortion in the trunk. This EFG discusses the findings and interpretations of the paper by Grivas and colleagues as research at the borderland between the genesis of TA (physiogenesis) and AIS (pathogenesis). It is suggested that TAs, here regarded in common with AIS, result from the combination of secondary sexual development affecting body composition, adolescent skeletal growth velocity, and an asymmetry process. The possible involvement of epigenetic factors is not considered.

Whither the etiopathogenesis (and scoliogeny) of adolescent idiopathic scoliosis? Incorporating presentations on scoliogeny at the 2012 IRSSD and SRS meetings.

This paper aims to integrate into current understanding of AIS causation, etiopathogenetic information presented at two Meetings during 2012 namely, the International Research Society of Spinal Deformities (IRSSD) and the Scoliosis Research Society (SRS). The ultimate hope is to prevent the occurrence or progression of the spinal deformity of AIS with non-invasive treatment, possibly medical. This might be attained by personalised polymechanistic preventive therapy targeting the appropriate etiology and/or etiopathogenetic pathways, to avoid fusion and maintain spinal mobility. Although considerable progress had been made in the past two decades in understanding the etiopathogenesis of adolescent idiopathic scoliosis (AIS), it still lacks an agreed theory of etiopathogenesis. One problem may be that AIS results not from one cause, but several that interact with various genetic predisposing factors. There is a view there are two other pathogenic processes for idiopathic scoliosis namely, initiating (or inducing), and those that cause curve progression. Twin studies and observations of family aggregation have revealed significant genetic contributions to idiopathic scoliosis, that place AIS among other common disease or complex traits with a high heritability interpreted by the genetic variant hypothesis of disease. We summarize etiopathogenetic knowledge of AIS as theories of pathogenesis including recent multiple concepts, and blood tests for AIS based on predictive biomarkers and genetic variants that signify disease risk. There is increasing evidence for the possibility of an underlying neurological disorder for AIS, research which holds promise. Like brain research, most AIS workers focus on their own corner and there is a need for greater integration of research effort. Epigenetics, a relatively recent field, evaluates factors concerned with gene expression in relation to environment, disease, normal development and aging, with a complex regulation across the genome during the first decade of life. Research on the role of environmental factors, epigenetics and chronic non-communicable diseases (NCDs) including adiposity, after a slow start, has exploded in the last decade. Not so for AIS research and the environment where, except for monozygotic twin studies, there are only sporadic reports to suggest that environmental factors are at work in etiology. Here, we examine epigenetic concepts as they may relate to human development, normal life history phases and AIS pathogenesis. Although AIS is not regarded as an NCD, like them, it is associated with whole organism metabolic phenomena, including lower body mass index, lower circulating leptin levels and other systemic disorders. Some epigenetic research applied to Silver-Russell syndrome and adiposity is examined, from which suggestions are made for consideration of AIS epigenetic research, cross-sectional and longitudinal. The word scoliogeny is suggested to include etiology, pathogenesis and pathomechanism.

Abnormalities of vascular structure and function in children with Perthes disease.

BACKGROUND AND OBJECTIVES: Perthes disease is a childhood precipitant to osteoarthritis of the hip, for which the etiology and mechanism are unknown. There is mounting evidence to suggest a vascular insult is responsible for disease, and it is suggested that this may have long-term implications for the vascular health of affected individuals. This study sought to use ultrasound measures to investigate vascular structure and function in children affected by Perthes disease. METHODS: This case control study encompassed 149 cases and 146 controls, frequency matched for age and gender. Endothelial function was measured by using the technique of flow-mediated dilation of the brachial artery, and alterations in arterial flow were recorded in response to an ischemic stimulus. RESULTS: There was a significant structural alteration in the vasculature among individuals with Perthes disease (resting brachial artery diameter (cases 2.97 mm versus controls 3.11 mm; P = .01), which remained even after adjusting for height. In addition, there was a notable reduction in blood velocity (cases 33.84 cm/s versus controls 37.83 cm/s; P = .01) and blood flow (cases 149.82 mL/min versus controls 184.67 mL/min; P = .001), which was independent of baseline arterial size. There was no evidence to suggest that flow-mediated dilation of the brachial artery was impaired among affected individuals (P = .71). CONCLUSIONS: Children with Perthes disease exhibit small artery caliber and reduced function, which is independent of body composition. These data imply that that Perthes disease may reflect a wider vascular phenomenon that could have long-term implications for the vascular health of affected individuals.