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OBJECTS: Joint morphology is a risk factor for hip osteoarthritis (HOA) and could explain ethnic differences in HOA prevalence. Therefore, we aimed to compare the prevalence of radiographic HOA (rHOA) and hip morphology between the predominantly White UK Biobank (UKB) and exclusively Chinese Shanghai Changfeng (SC) cohorts. METHODS: Left hip iDXA scans were used to quantify rHOA, from a combination of osteophytes (grade ≥1) and joint space narrowing (grade ≥1), and hip morphology. Using an 85-point Statistical Shape Model (SSM) we evaluated cam (alpha angle ≥60°) and pincer (lateral centre-edge angle (LCEA) ≥45°) morphology and acetabular dysplasia (LCEA <25°). Diameter of femoral head (DFH), femoral neck width (FNW), and hip axis length (HAL) were also obtained from these points. Results were adjusted for differences in age, height, and weight and stratified by sex. RESULTS: Complete data were available for 5924 SC and 39,020 White UKB participants with mean ages of 63.4 and 63.7 years old. rHOA prevalence was considerably lower in female (2.2% versus 13.1%) and male (12.0% and 25.1%) SC compared to UKB participants. Cam morphology, rarely seen in females, was less common in SC compared with UKB males (6.3% versus 16.5%). Composite SSM modes, scaled to the same overall size, revealed SC participants to have a wider femoral head compared to UKB participants. FNW and HAL were smaller in SC compared to UKB, whereas DFH/FNW ratio was higher in SC. CONCLUSIONS: rHOA prevalence is lower in Chinese compared with White individuals. Several differences in hip shape were observed, including frequency of cam morphology, FNW, and DFH/FNW ratio. These characteristics have previously been identified as risk factors for HOA and may contribute to observed ethnic differences in HOA prevalence.
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Muscle bulk in adult healthy humans is highly variable even after height, age, and sex are accounted for. Low muscle mass, due to fewer and/or smaller constituent muscle fibers, would exacerbate the impact of muscle loss occurring in aging or disease. Genetic variability substantially influences muscle mass differences, but causative genes remain largely unknown. In a genome-wide association study (GWAS) on appendicular lean mass (ALM) in a population of 85,750 middle-aged (aged 38-49 years) individuals from the UK Biobank (UKB), we found 182 loci associated with ALM (p < 5 × 10-8). We replicated associations for 78% of these loci (p < 5 × 10-8) with ALM in a population of 181,862 elderly (aged 60-74 years) individuals from UKB. We also conducted a GWAS on hindlimb skeletal muscle mass of 1,867 mice from an advanced intercross between two inbred strains (LG/J and SM/J); this GWAS identified 23 quantitative trait loci. Thirty-eight positional candidates distributed across five loci overlapped between the two species. In vitro studies of positional candidates confirmed CPNE1 and STC2 as modifiers of myogenesis. Collectively, these findings shed light on the genetics of muscle mass variability in humans and identify targets for the development of interventions for treatment of muscle loss. The overlapping results between humans and the mouse model GWAS point to shared genetic mechanisms across species.
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Composição Corporal/genética , Proteínas de Ligação ao Cálcio/genética , Estudo de Associação Genômica Ampla , Glicoproteínas/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Desenvolvimento Muscular/genética , Músculo Esquelético/citologia , Magreza/genética , Adulto , Idoso , Envelhecimento , Animais , Peso Corporal , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Locos de Características QuantitativasRESUMO
OBJECTIVE: Conventional scoring methods for radiographic hip OA (rHOA) are subjective and show inconsistent relationships with clinical outcomes. To provide a more objective rHOA scoring method, we aimed to develop a semi-automated classifier based on DXA images and confirm its relationships with clinical outcomes. METHODS: Hip DXAs in UK Biobank (UKB) were marked up for osteophyte area from which acetabular, superior and inferior femoral head osteophyte grades were derived. Joint space narrowing (JSN) grade was obtained automatically from minimum joint space width (mJSW) measures. Clinical outcomes related to rHOA comprised hip pain, hospital diagnosed OA (HES OA) and total hip replacement. Logistic regression and Cox proportional hazard modelling were used to examine associations between overall rHOA grade (0-4; derived from combining osteophyte and JSN grades) and the clinical outcomes. RESULTS: A toal of 40 340 individuals were included in the study (mean age 63.7), of whom 81.2% had no evidence of rHOA, while 18.8% had grade ≥1 rHOA. Grade ≥1 osteophytes at each location and JSN were associated with hip pain, HES OA and total hip replacement. Associations with all three clinical outcomes increased progressively according to rHOA grade, with grade 4 rHOA and total hip replacement showing the strongest association [57.70 (38.08-87.44)]. CONCLUSIONS: Our novel semi-automated tool provides a useful means for classifying rHOA on hip DXAs, given its strong and progressive relationships with clinical outcomes. These findings suggest DXA scanning can be used to classify rHOA in large DXA-based cohort studies supporting further research, with the future potential for population-based screening.
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Osteoartrite do Quadril , Osteófito , Artralgia , Bancos de Espécimes Biológicos , Articulação do Quadril/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Osteófito/diagnóstico por imagem , Dor , Radiografia , Reino UnidoRESUMO
OBJECTIVES: Responsive biomarkers are needed to assess the progression of OA and their lack has hampered previous clinical trials. Statistical shape modelling (SSM) from radiographic images identifies those at greatest risk of fast-progression or joint replacement, but its sensitivity to change has not previously been measured. This study evaluates the responsiveness of SSM in knee OA in a 12-month observational study. METHODS: A total of 109 people were recruited who had undergone knee radiographs in the previous 12 months, and were grouped based on severity of radiographic OA (Kellgren-Lawrence grading). An SSM was built from three dual-energy X-ray absorptiometry scans at 6-month intervals. Change-over-time and OA were assessed using generalized estimating equations, standardized response means (SRM) and reliable change indices. RESULTS: Mode 1 showed typical features of radiographic OA and had a strong link with Kellgren-Lawrence grading but did not change significantly during the study. Mode 3 showed asymmetrical changes consistent with medial cartilage loss, osteophytes and joint malalignment, and was responsive to change, with a 12-month SRM of 0.63. The greatest change was observed in the moderate radiographic OA group (SRM 0.92) compared with the controls (SRM 0.21), and the reliable change index identified 14% of this group whose progression was clinically significant. CONCLUSION: Shape changes linked the progression of osteophytosis with increasing malalignment within the joint. Modelling of the whole joint enabled quantification of change beyond the point where bone-to-bone contact has been made. The knee SSM is, therefore, a responsive biomarker for radiographic change in knees over 12 months.
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Modelos Estatísticos , Osteoartrite do Joelho/diagnóstico por imagem , Radiografia/estatística & dados numéricos , Avaliação de Sintomas/estatística & dados numéricos , Fatores de Tempo , Adulto , Idoso , Biomarcadores/análise , Cartilagem Articular/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteófito/diagnóstico por imagem , Osteófito/etiologia , Estudos Prospectivos , Radiografia/métodos , Avaliação de Sintomas/métodosRESUMO
OBJECTIVES: Hip development is influenced by mechanical loading, but associations between prenatal loading and hip shape in later life remain unexplored. METHODS: We examined associations between prenatal loading indicators (gestation length, oligohydramnios (OH) and breech) obtained from obstetric records and hip shape modes (HSMs) generated using dual-energy X-ray absorptiometry images taken at age 14- and 18-years in participants from the UK Avon Longitudinal Study of Parents and Children (ALSPAC). These associations were examined in 2453 (30 OH, 105 breech) and 2330 (27 OH, 95 breech) participants with complete data at age 14- and 18-years respectively using confounder-adjusted models. RESULTS: At 14 years HSM2 was 0.59SD lower in OH males, and HSM5 (-0.31SD) and HSM9 (-0.32SD) were lower in OH in both sexes. At 18 years HSM1 (-0.44SD) and HSM2 (-0.71SD) were lower and HSM6 (0.61SD) and HSM8 (1.06SD) were higher in OH males, whilst HSM5 was lower in OH in both sexes. OH appeared to be associated with a wider femoral neck and head, and larger lesser/greater trochanters. Only weak associations were observed between gestation length/breech and HSMs. CONCLUSIONS: These results suggest that prenatal skeletal loading, in particular oligohydramnios, may influence adolescent joint shape with associations generally stronger in males.
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Fenômenos Biomecânicos/fisiologia , Fêmur/crescimento & desenvolvimento , Complicações na Gravidez , Adolescente , Feminino , Feto , Humanos , Estudos Longitudinais , Masculino , GravidezRESUMO
BACKGROUND: Lumbar disc degeneration (LDD) is a condition associated with recurrent low back pain (LBP). Knowledge regarding effective management is limited. As a step towards the identification of risk, prognostic or potentially modifiable factors in LDD patients, the aim of this study was to explore the hypothesis that intrinsic lumbar spine shape is associated with LDD and clinical outcomes in symptomatic adults. METHODS: 3 T MRI was used to acquire T2-weighted sagittal images (L1-S1) from 70 healthy controls and LDD patients (mean age 49 years, SD 11, range 31-71 years). Statistical Shape Modelling (SSM) was used to describe lumbar spine shape. SSM identified variations in lumbar shape as 'modes' of variation and quantified deviation from the mean. Intrinsic shape differences were determined between LDD groups using analysis of variance with post-hoc comparisons. The relationship between intrinsic shape and self-reported function, mental health and quality of life were also examined. RESULTS: The first 7 modes of variation explained 91% of variance in lumbar shape. Higher LDD sum scores correlated with a larger lumbar lordosis (Mode 1 (55% variance), P = 0.02), even lumbar curve distribution (Mode 2 (12% variance), P = 0.05), larger anterior-posterior (A-P) vertebral diameter (Mode 3 (10% variance), P = 0.007) and smaller L4-S1 disc spaces (Mode 7 (2% variance), P ≤ 0.001). In the presence of recurrent LBP, LDD was associated with a larger A-P vertebral diameter (Mode 3) and a more even lumbar curvature with smaller L5/S1 disc spaces (Mode 4), which was significantly associated with patient quality of life (P = 0.002-0.04, rp = 0.43-0.61)). CONCLUSIONS: This exploratory study provides new evidence that intrinsic shape phenotypes are associated with LDD and quality of life in patients. Longitudinal studies are required to establish the potential role of these risk or prognostic shape phenotypes.
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Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/patologia , Lordose/patologia , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Adulto , Idoso , Feminino , Humanos , Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/complicações , Lordose/diagnóstico por imagem , Dor Lombar/etiologia , Dor Lombar/patologia , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Qualidade de VidaRESUMO
The anatomical shape of bones and joints is important for their proper function but quantifying this, and detecting pathological variations, is difficult to do. Numerical descriptions would also enable correlations between joint shapes to be explored. Statistical shape modelling (SSM) is a method of image analysis employing pattern recognition statistics to describe and quantify such shapes from images; it uses principal components analysis to generate modes of variation describing each image in terms of a set of numerical scores after removing global size variation. We used SSM to quantify the shapes of the hip and the lumbar spine in dual-energy x-ray absorptiometry (DXA) images from 1511 individuals in the MRC National Survey of Health and Development at ages 60-64 years. We compared shapes of both joints in men and women and hypothesised that hip and spine shape would be strongly correlated. We also investigated associations with height, weight, body mass index (BMI) and local (hip or lumber spine) bone mineral density. In the hip, all except one of the first 10 modes differed between men and women. Men had a wider femoral neck, smaller neck-shaft angle, increased presence of osteophytes and a loss of the femoral head/neck curvature compared with women. Women presented with a flattening of the femoral head and greater acetabular coverage of the femoral head. Greater weight was associated with a shorter, wider femoral neck and larger greater and lesser trochanters. Taller height was accompanied by a flattening of the curve between superior head and neck and a larger lesser trochanter. Four of the first eight modes describing lumbar spine shape differed between men and women. Women tended to have a more lordotic spine than men with relatively smaller but caudally increasing anterior-posterior (a-p) vertebral diameters. Men were more likely to have a straighter spine with larger vertebral a-p diameters relative to vertebral height than women, increasing cranially. A weak correlation was found between body weight and a-p vertebral diameter. No correlations were found between shape modes and height in men, whereas in women there was a weak positive correlation between height and evenness of spinal curvature. Linear relationships between hip and spine shapes were weak and inconsistent in both sexes, thereby offering little support for our hypothesis. In conclusion, men and women entering their seventh decade have small but statistically significant differences in the shapes of their hips and their spines. Associations with height, weight, BMI and BMD are small and correspond to subtle variations whose anatomical significance is not yet clear. Correlations between hip and spine shapes are small.
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Articulação do Quadril/anatomia & histologia , Vértebras Lombares/anatomia & histologia , Absorciometria de Fóton , Densidade Óssea , Estudos de Coortes , Feminino , Articulação do Quadril/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Inquéritos e QuestionáriosRESUMO
PURPOSE: To characterize the distribution of bone marrow fat in hip osteoarthritis (OA) using magnetic resonance imaging (MRI) and to assess its use as a potential biomarker. MATERIALS AND METHODS: In all, 67 subjects (39 female, 28 male) with either total hip replacement (THA) or different severities of radiographic OA, assessed by Kellgren-Lawrence grading (KLG), underwent 3T MRI of the pelvis using the IDEAL sequence to separate fat and water signals. Six regions of interest (ROIs) were identified within the proximal femur. Within each ROI the fractional-fat distribution, represented by pixel intensities, was described by its mean, standard deviation, skewness, kurtosis, and entropy. RESULTS: Hips were graded: 12 as severe symptomatic (THA), 33 had KLG0 or 1, 9 were KLG2, 11 with KLG3, and 2 with KLG4 were analyzed together. The fractional-fat content in the whole proximal femur did not vary with severity in males (mean (SD) 91.2 (6.0)%) but reduced with severity in females from 89.1 (6.7)% (KLG0,1), 91.5 (2.9)% (KLG2), 85.8 (16.7)% (KLG3,4) to 77.5 (11.9)% (THA) (analysis of variance [ANOVA] P = 0.029). These differences were most pronounced in the femoral head, where mean values fell with OA severity in both sexes from 97.9% (2.5%) (KLG0,1) to 73.0% (25.9%) (THA, P < 0.001) with the largest difference at the final stage. The standard deviation and the entropy of the distribution both increased (P < 0.001). CONCLUSION: Descriptors of the fractional fat distribution varied little with the severity of OA until the most severe stage, when changes appeared mainly in the femoral head, and have, therefore, limited value as biomarkers. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:42-50.
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Tecido Adiposo/diagnóstico por imagem , Adiposidade , Medula Óssea/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Quadril/diagnóstico por imagem , Tecido Adiposo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Medula Óssea/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/patologia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Advances in image quality from modern dual-energy X-ray absorptiometry (DXA) scanners now allow near radiograph-like quality images at a low radiation dose. This opens potential new applications for the use of DXA scanners to study other musculoskeletal conditions, such as osteoarthritis, which is often investigated by visual assessment of radiographs. Together, osteoporosis and osteoarthritis are the 2 most common musculoskeletal conditions, both of which primarily affect older people. The aim of this study was to determine whether Kellgren-Lawrence grading of DXA images can be used to grade hip osteoarthritis as effectively as radiographs. People who had attended for recent pelvic radiographs underwent DXA of hips (50 hips from 25 people) using a GE Healthcare iDXA scanner. Three observers assigned Kellgren-Lawrence grades to each image, and grading was repeated at least 1 week apart. Intraobserver and interobserver reliability for radiographs and DXA images were calculated using quadratic-weighted kappa (QWK). People were recalled 12 months later, and the tests were repeated with both the radiograph and DXA scans taken within 2 weeks of each other. Hip DXA intraobserver reproducibility achieved a QWK range of 0.88-0.95 and interobserver reproducibility of 0.85-0.88, similar to QWK from hip radiographs. Intraobserver reliability between subject-matched radiograph and iDXA images revealed QWK ranging between 0.80 and 0.88. Reproducibility of hip osteoarthritis grading using DXA was comparable with that of radiographs in this study and similar to repeatability scores previously published in literature. Given the lower radiation dose and the opportunity to simultaneously investigate osteoporosis, DXA presents an attractive imaging option for osteoarthritis.
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Absorciometria de Fóton , Articulação do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/diagnóstico por imagem , Índice de Gravidade de Doença , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: We sought to examine associations between height gain across childhood and adolescence with hip shape in individuals aged 60-64 years from the Medical Research Council National Survey of Health and Development, a nationally representative British birth cohort. METHODS: Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at age 20 years. 10 modes of variation in hip shape (HM1-10), described by statistical shape models, were previously ascertained from DXA images taken at ages 60-64 years. Associations between (1) height at each age; (2) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity; and (3) height gain during specific periods of childhood and adolescence, and HM1-10 were tested. RESULTS: Faster growth velocity was associated with a wider, flatter femoral head and neck, as described by positive scores for HM6 (regression coefficient 0.014; 95% CI 0.08 to 0.019; p<0.001) and HM7 (regression coefficient 0.07; 95% CI 0.002 to 0.013; p=0.009), and negative scores for HM10 (regression coefficient -0.006; 95% CI -0.011 to 0.00, p=0.04) and HM2 (males only, regression coefficient -0.017; 95% CI -0.026 to -0.09; p<0.001). Similar associations were observed with greater height size and later height tempo. Examination of height gains during specific periods of childhood and adolescence identified those during the adolescence period as being most consistently associated. CONCLUSION: Our analyses suggest that individual growth patterns, particularly in the adolescent period, are associated with modest variations in hip shape at 60-64 years, which are consistent with features seen in osteoarthritis.
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Quadril , Acontecimentos que Mudam a Vida , Humanos , Masculino , Quadril/anatomia & histologia , Quadril/crescimento & desenvolvimento , Pessoa de Meia-IdadeRESUMO
Objective: We aimed to create an imaging biomarker for knee shape using knee dual-energy x-ray absorptiometry (DXA) scans and investigate its potential association with subsequent total knee replacement (TKR), independently of radiographic features of knee osteoarthritis and established risk factors. Methods: Using a 129-point statistical shape model, knee shape (expressed as a B-score) and minimum joint space width (mJSW) of the medial joint compartment (binarized as above or below the first quartile) were derived. Osteophytes were manually graded in a subset of images and an overall score was assigned. Cox proportional hazards models were used to examine the associations of B-score, mJSW and osteophyte score with TKR risk, adjusting for age, sex, height and weight. Results: The analysis included 37,843 individuals (mean age 63.7 years). In adjusted models, B-score was associated with TKR: each unit increase in B-score, reflecting one standard deviation from the mean healthy shape, corresponded to a hazard ratio (HR) of 2.25 (2.08, 2.43), while a lower mJSW had a HR of 2.28 (1.88, 2.77). Among the 6719 images scored for osteophytes, mJSW was replaced by osteophyte score in the most strongly predictive model for TKR. In ROC analyses, a model combining B-score, osteophyte score, and demographics outperformed a model including demographics alone (AUC â= â0.87 vs 0.73). Conclusions: Using statistical shape modelling, we derived a DXA-based imaging biomarker for knee shape that was associated with kOA progression. When combined with osteophytes and demographic data, this biomarker may help identify individuals at high risk of TKR, facilitating targeted interventions.
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OBJECTIVE: To examine the genetic architecture of cam morphology using alpha angle (AA) as a proxy measure and conduct an AA genome-wide association study (GWAS) followed by Mendelian randomization (MR) to evaluate its causal relationship with hip osteoarthritis (OA). METHODS: Observational analyses examined associations between AA measurements derived from hip dual x-ray absorptiometry (DXA) scans from the UK Biobank study and radiographic hip OA outcomes and subsequent total hip replacement. Following these analyses, an AA GWAS meta-analysis was performed (N = 44,214) using AA measurements previously derived in the Rotterdam Study. Linkage disequilibrium score regression assessed the genetic correlation between AA and hip OA. Genetic associations considered significant (P < 5 × 10-8 ) were used as AA genetic instrument for 2-sample MR analysis. RESULTS: DXA-derived AA showed expected associations between AA and radiographic hip OA (adjusted odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.58, 1.67]) and between AA and total hip replacement (adjusted hazard ratio 1.45 [95% CI 1.33, 1.59]) in the UK Biobank study cohort. The heritability of AA was 10%, and AA had a moderate genetic correlation with hip OA (rg = 0.26 [95% CI 0.10, 0.43]). Eight independent genetic signals were associated with AA. Two-sample MR provided weak evidence of causal effects of AA on hip OA risk (inverse variance weighted OR 1.84 [95% CI 1.14, 2.96], P = 0.01). In contrast, genetic predisposition for hip OA had stronger evidence of a causal effect on increased AA (inverse variance weighted ß = 0.09 [95% CI 0.04, 0.13], P = 4.58 × 10-5 ). CONCLUSION: Expected observational associations between AA and related clinical outcomes provided face validity for the DXA-derived AA measurements. Evidence of bidirectional associations between AA and hip OA, particularly for risk of hip OA on AA, suggests that hip shape modeling secondary to a genetic predisposition to hip OA contributes to the well-established relationship between hip OA and cam morphology in older adults.
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Artroplastia de Quadril , Osteoartrite do Quadril , Humanos , Idoso , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/genética , Osteoartrite do Quadril/cirurgia , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Causalidade , Polimorfismo de Nucleotídeo Único , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: Hip minimum joint space width (mJSW) provides a proxy for cartilage thickness. This study aimed to conduct a genome-wide association study (GWAS) of mJSW to (i) identify new genetic determinants of mJSW and (ii) identify which mJSW loci convey hip osteoarthritis (HOA) risk and would therefore be of therapeutic interest. METHODS: GWAS meta-analysis of hip mJSW derived from plain X-rays and DXA was performed, stratified by sex and adjusted for age and ancestry principal components. Mendelian randomisation (MR) and cluster analyses were used to examine causal effect of mJSW on HOA. FINDINGS: 50,745 individuals were included in the meta-analysis. 42 SNPs, which mapped to 39 loci, were identified. Mendelian randomisation (MR) revealed little evidence of a causal effect of mJSW on HOA (ORIVW 0.98 [95% CI 0.82-1.18]). However, MR-Clust analysis suggested the null MR estimates reflected the net effect of two distinct causal mechanisms cancelling each other out, one of which was protective, whereas the other increased HOA susceptibility. For the latter mechanism, all loci were positively associated with height, suggesting mechanisms leading to greater height and mJSW increase the risk of HOA in later life. INTERPRETATIONS: One group of mJSW loci reduce HOA risk via increased mJSW, suggesting possible utility as targets for chondroprotective therapies. The second group of mJSW loci increased HOA risk, despite increasing mJSW, but were also positively related to height, suggesting they contribute to HOA risk via a growth-related mechanism. FUNDING: Primarily funded by the Medical Research Council and Wellcome Trust.
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Estudo de Associação Genômica Ampla , Osteoartrite do Quadril , Humanos , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/genética , Articulações , Análise por Conglomerados , Análise da Randomização MendelianaRESUMO
OBJECTIVE: Previously, active shape modelling (ASM) of the proximal femur was shown to identify those individuals at highest risk of developing radiographic OA. Here we determine whether ASM predicts the need for total hip replacement (THR) independent of Kellgren-Lawrence grade (KLG) and other known risk factors. METHODS: A retrospective cohort study of 141 subjects consulting primary care with new hip pain was conducted. Pelvic radiographs taken on recruitment were assessed for KLG, centre-edge angle, acetabular depth and femoral head migration. Clinical factors (duration of pain, use of a stick and physical function) were collected by self-completed questionnaires. ASM differences between shape mode scores at baseline for individuals who underwent THR during the 5-year follow-up (n = 27) and those whose OA did not progress radiographically (n = 75) were compared. RESULTS: A 1 s.d. reduction in baseline ASM mode 2 score was associated with an 81% reduction in odds of THR (OR = 0.19, 95% CI 0.52, 0.70) after adjustment for KLG, radiographic and clinical factors. A similar reduction in odds of THR was associated with a 1 s.d. reduction in mode 3 (OR = 0.45, 95% CI 0.28, 0.71) and a 1 s.d. increase in mode 4 score (OR = 2.8, 95% CI 1.7, 4.7), although these associations were no longer significant after adjustment for KLG and clinical factors. CONCLUSION: ASM of the hip joint is a reliable early biomarker of radiographic OA severity, which can improve the ability to identify patients at higher risk of rapid progression and poor outcome even when KLG and clinical risk factors are taken into account.
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Acetábulo/patologia , Artroplastia de Quadril , Progressão da Doença , Cabeça do Fêmur/patologia , Osteoartrite do Quadril/fisiopatologia , Acetábulo/diagnóstico por imagem , Idoso , Artralgia , Biomarcadores , Estudos de Coortes , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Seguimentos , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos Anatômicos , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/cirurgia , Valor Preditivo dos Testes , Radiografia , Estudos Retrospectivos , Fatores de Risco , Estatísticas não Paramétricas , Inquéritos e QuestionáriosRESUMO
The contribution of shape changes to hip osteoarthritis (HOA) remains unclear, as is the extent to which these vary according to HOA severity. In the present study, we used statistical shape modeling (SSM) to evaluate relationships between hip shape and HOA of different severities using UK Biobank DXA images. We performed a cross-sectional study in individuals with left hip dual-energy X-ray absorptiometry (DXA) scans. Statistical shape modeling (SSM) was used to quantify hip shape. Radiographic HOA (rHOA) was classified using osteophyte size and number and joint space narrowing. HOA outcomes ranged in severity from moderate (grade 2) to severe (grade ≥3) rHOA, hospital-diagnosed HOA, and subsequent total hip replacement (THR). Confounder-adjusted logistic regression between the top 10 hip shape modes (HSMs) and OA outcomes was performed. Further models adjusted for alpha angle (AA) and lateral center-edge angle (LCEA), reflecting acetabular dysplasia and cam morphology, respectively. Composite HSM figures were produced combining HSMs associated with separate OA outcomes. A total of 40,311 individuals were included (mean 63.7 years, 47.8% male), of whom 5.7% had grade 2 rHOA, 1.7% grade ≥3 rHOA, 1.3% hospital-diagnosed HOA, and 0.6% underwent THR. Composite HSM figures for grade 2 rHOA revealed femoral neck widening, increased acetabular coverage, and enlarged lesser and greater trochanters. In contrast, grade ≥3 rHOA, hospital-diagnosed HOA, and THR were suggestive of cam morphology and reduced acetabular coverage. Associations between HSMs depicting cam morphology and reduced acetabular coverage and more severe HOA were attenuated by AA and LCEA adjustment, respectively. Relationships between hip shape and HOA differed according to severity. Notably, cam morphology and acetabular dysplasia were features of severe HOA, but unrelated to moderate disease, suggesting possible prognostic utility. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Osteoartrite do Quadril , Feminino , Humanos , Masculino , Bancos de Espécimes Biológicos , Estudos Transversais , Articulação do Quadril , Aprendizado de Máquina , Osteoartrite do Quadril/diagnóstico por imagem , Reino UnidoRESUMO
The growing burden from osteoporosis and fragility fractures highlights a need to improve osteoporosis management across healthcare systems. Sub-optimal management of osteoporosis is an area suitable for digital health interventions. While fracture liaison services (FLSs) are proven to greatly improve care for people with osteoporosis, such services might benefit from technologies that enhance automation. The term 'Digital Health' covers a variety of different tools including clinical decision support systems, electronic medical record tools, patient decision aids, patient apps, education tools, and novel artificial intelligence (AI) algorithms. Within the scope of this review are AI solutions that use algorithms within health system registries to target interventions. Clinician-targeted, patient-targeted, or system-targeted digital health interventions could be used to improve management and prevent fragility fractures. This review was commissioned by The Royal Osteoporosis Society and Bone Research Academy during the production of the 2020 Research Roadmap (https://theros.org.uk), with the intention of identifying gaps where targeted research funding could lead to improved patient health. We explore potential uses of digital technology in the general management of osteoporosis. Evidence suggests that digital technologies can support multidisciplinary teams to provide the best possible patient care based on current evidence and to support patients in self-management. However, robust randomised controlled studies are still needed to assess the effectiveness and cost-effectiveness of these technologies.
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OBJECTIVE: It remains unclear how the different features of radiographic hip osteoarthritis (rHOA) contribute to hip pain. We examined the relationship between rHOA, including its individual components, and hip pain using a novel dual-energy x-ray absorptiometry (DXA)-based method. METHODS: Hip DXAs were obtained from UK Biobank. A novel automated method obtained minimum joint space width (mJSW) from points placed around the femoral head and acetabulum. Osteophyte areas at the lateral acetabulum, superior and inferior femoral head were derived manually. Semi-quantitative measures of osteophytes and joint space narrowing (JSN) were combined to define rHOA. Logistic regression was used to examine the relationships between these variables and hip pain, obtained via questionnaires. RESULTS: 6807 hip DXAs were examined. rHOA was present in 353 (5.2%) individuals and was associated with hip pain [OR 2.42 (1.78-3.29)] and hospital diagnosed OA [6.01 (2.98-12.16)]. Total osteophyte area but not mJSW was associated with hip pain in mutually adjusted models [1.31 (1.23-1.39), 0.95 (0.87-1.04) respectively]. On the other hand, JSN as a categorical variable showed weak associations between grade ≥ 1 and grade ≥ 2 JSN with hip pain [1.30 (1.06-1.60), 1.80 (1.34-2.42) respectively]. Acetabular, superior and inferior femoral osteophyte areas were all independently associated with hip pain [1.13 (1.06-1.20), 1.13 (1.05-1.24), 1.10 (1.03-1.17) respectively]. CONCLUSION: In this cohort, the relationship between rHOA and prevalent hip pain was explained by 2-dimensional osteophyte area, but not by the apparent mJSW. Osteophytes at different locations showed important, potentially independent, associations with hip pain, possibly reflecting the contribution of distinct biomechanical pathways.
Assuntos
Osteoartrite do Quadril , Osteófito , Absorciometria de Fóton , Bancos de Espécimes Biológicos , Estudos Transversais , Humanos , Osteoartrite do Quadril/diagnóstico por imagem , Osteófito/diagnóstico por imagem , Dor , Radiografia , Reino Unido/epidemiologiaRESUMO
Osteoporosis causes bones to become weak, porous and fracture more easily. While a vertebral fracture is the archetypal fracture of osteoporosis, it is also the most difficult to diagnose clinically. Patients often suffer further spine or other fractures, deformity, height loss and pain before diagnosis. There were an estimated 520,000 fragility fractures in the United Kingdom (UK) in 2017 (costing £4.5 billion), a figure set to increase 30% by 2030. One way to improve both vertebral fracture identification and the diagnosis of osteoporosis is to assess a patient's spine or hips during routine computed tomography (CT) scans. Patients attend routine CT for diagnosis and monitoring of various medical conditions, but the skeleton can be overlooked as radiologists concentrate on the primary reason for scanning. More than half a million CT scans done each year in the National Health Service (NHS) could potentially be screened for osteoporosis (increasing 5% annually). If CT-based screening became embedded in practice, then the technique could have a positive clinical impact in the identification of fragility fracture and/or low bone density. Several companies have developed software methods to diagnose osteoporosis/fragile bone strength and/or identify vertebral fractures in CT datasets, using various methods that include image processing, computational modelling, artificial intelligence and biomechanical engineering concepts. Technology to evaluate Hounsfield units is used to calculate bone density, but not necessarily bone strength. In this rapid evidence review, we summarise the current literature underpinning approved technologies for opportunistic screening of routine CT images to identify fractures, bone density or strength information. We highlight how other new software technologies have become embedded in NHS clinical practice (having overcome barriers to implementation) and highlight how the novel osteoporosis technologies could follow suit. We define the key unanswered questions where further research is needed to enable the adoption of these technologies for maximal patient benefit.
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OBJECTIVE: To examine the relationship between pubertal timing (using measures of height tempo) and proximal femur shape in a large adolescent cohort. METHODS: Hip DXA scans were obtained in offspring from the Avon Longitudinal Study of Parents and Children. To quantify hip morphology, the images were analyzed using Shape software based on a 53-point statistical shape model and independent modes of variation (hip shape mode (HSM) scores) for each image were generated. Height tempo (which corresponds to age at peak height velocity (aPHV)) was estimated from serial height measurements collected between age 5-20 years. Multivariable linear regression was used to examine cross-sectional associations between height tempo and the top ten HSMs at age 14 and 18, adjusting for sex and fat mass index (FMI). RESULTS: Complete outcome and covariate data were available from 3827 and 3507 participants at age 14 and 18 years, respectively. Mean aPHV was 13.5 and 11.8 years for males and females, respectively. At age 14, height tempo was associated with a majority of modes, except for HSM4 and there was strong evidence of interaction by sex. In males, all modes showed evidence of an association with tempo, independent of FMI, with the strongest observed for HSM8 (adjusted ß 0.38 (0.33, 0.43) p = 4.1 × 10-50). Compared with males, the associations were generally weaker in females, with the strongest effect observed for HSM8 (adjusted ß 0.10 (0.05, 0.14) p = 1.6 × 10-5). The overall effect of later pubertal timing on proximal femur shape in males was a narrower femoral neck and larger superolateral head, whereas in females these changes were hard to discern. When assessed at age 18, there was little relationship between tempo and proximal femur shape in either sex. CONCLUSION: Our results indicate that significant changes in hip shape occur during puberty, including aspects of shape which may be related to future risk of hip OA and/or fracture. However, puberty timing per se does not appear to exert long lasting effects on proximal femur shape.