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Objectives: To assess the prevalences across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal BMD (aBMD) and change in aBMD with time., Methods: In the population-based European Prospective Osteoporosis Study, 27 age-stratified samples of men and women from across the continent aged 50+ years had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature., Results: Images from 10 132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD., Conclusion: KL grades 3 and 4 are often used clinically to categorize radiological DDD. Highly variable European prevalences of radiologically defined DDD grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Vertebral deformities are prevalent in chronic obstructive pulmonary disease (COPD) patients and may cause excessive loss of height. As height is used for calculating reference values for pulmonary function tests, larger than normal height reduction could cause overestimation of lung function. In this cross-sectional study of 465 COPD patients and 462 controls, we explored how often lung function is misinterpreted due to height reduction in COPD patients, and whether the number or severity of vertebral deformities correlate with height reduction. Measured height was compared to recalled tallest height (RTH) and height calculated from arm span (ASH) to assess height reduction. Vertebral deformities were assessed from radiographs and pulmonary function was assessed using standard formulae. Height reduction was frequent in both the study and control groups, and increased with the number and severity of vertebral deformities. When using current measured height, lung function was overestimated in a significant proportion of COPD patients at relatively modest height reductions. The effects were smallest for forced expiratory volume in 1 s and forced vital capacity, and most pronounced for total lung capacity and residual volume. Therefore, we propose that in COPD patients with excessive height reduction, one might use RTH or ASH in calculating predicted values. Furthermore, such patients should be evaluated for co-existing vertebral deformities and osteoporosis.

Objective: To investigate basic assumptions of prediction models for future vertebral fractures., Methods: Lateral radiographs of the spine were obtained from 314 Portuguese individuals aged 60 years or older (205 women and 109 men) with bone mineral density (BMD) measurements at several sites. Associations between BMD at various sites, participant characteristics, and vertebral fractures were investigated. For men and women separately, logistic regression analyses and analyses of areas under the receiver-operating characteristic (ROC) curves were performed to determine the accuracy of BMD measurement at predicting the presence of vertebral deformities., Results: BMD measurements at all sites significantly predicted the presence of osteoporotic vertebral deformities in women but not in men. Similarly, in analyses of areas under ROC curves, BMD assessments were statistically significantly related to vertebral deformities in women but not in men. In multivariate analyses, BMD measurements of the lumbar spine and of the forearm, adjusted for gender, age, and body mass index, significantly predicted the presence of vertebral deformity, but BMD of the hip sites did not., Conclusion: Prediction of fractures is specific for gender and site of BMD measurement. This challenges the use of similar algorithms for men and women as well as the use of hip BMD data to accurately estimate future vertebral fracture risk.

The International Society for Clinical Densitometry (ISCD) has developed Official Positions for the clinical use of dual-energy X-ray absorptiometry (DXA) and non-DXA technologies. While only DXA can be used for diagnostic classification according to criteria established by the World Health Organization, DXA and some other technologies may predict fracture risk and be used to monitor skeletal changes over time. ISCD task forces reviewed the evidence for clinical applications of non-DXA techniques and presented reports with recommendations at the 2007 ISCD Position Development Conference. Here we present the ISCD Official Positions for quantitative computed tomography (QCT) and peripheral QCT (pQCT), with supporting medical evidence, rationale, controversy, and suggestions for further study. QCT is available for bone mineral density measurements at the spine, hip, forearm, and tibia. The ISCD Official Positions presented here focus on QCT of the spine and pQCT of the forearm. Measurements at the hip may have clinical relevance, as this is an important fracture site; however, due to limited medical evidence, definitive advice on its use in clinical practice cannot be provided until more data emerge.

Introduction: Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5-20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age., Methods: Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models., Results: In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010)., Conclusion: We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.

Unlabelled: Vertebral fractures are common but usually remain unrecognized in primary care. Data from 2908 women and 2653 men in the EPOS study were used to derive algorithms to indicate the need for a spine X-ray to identify a fracture using easily elicited determinants. At a sensitivity of 50% for identifying cases, the specificity was increased from 50% to 78% in women and from 50% to 72% in men compared with a random allocation of X-rays. Use of X-rays can be optimized by selecting patients at high risk using a short screening procedure., Introduction: Previous osteoporotic fracture is an independent risk factor for further fractures and an indication for treatment. Vertebral fractures are the most common osteoporotic fractures before age 75, accounting for 48% of all fractures in men and 39% in women over 50. They usually remain unrecognized, so many patients requiring treatment are denied it, doubling their risk of a further fracture. Our objective was to develop an efficient algorithm indicating the need for an X-ray., Materials and Methods: Data from 2908 women and 2653 men >or=50 years of age in the European Prospective Osteoporosis Study (EPOS) were analyzed. Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. Prevalent fractures were qualitatively diagnosed by an experienced radiologist. Fracture risk was modeled as a function of age, statural height loss since age 25, gender, and fracture history including limb fractures in the last 3 years using negative binomial regression. Receiver operating characteristic (ROC) curves were used to summarize a model's predictive ability, and a prediction algorithm was devised to identify those most likely to have a fracture., Results: In a multivariate model for women, the risk of prevalent vertebral fracture significantly increased with age (RR, 1.67 [95% CI, 1.46, 1.93] per decade), statural height loss (1.06, [1.03, 1.10] per centimeter decrease), self-reported history of spine fracture (7.52 [5.52, 10.23]), and history of other major fracture (1.83 [1.46, 2.28]). Higher body weight reduced risk (0.86 [0.79, 0.95] per 10-kg increase). In men, the respective RR estimates were as follows: age (1.32 [1.18, 1.49]); height loss (1.06 [1.04, 1.09]); self-reported spine fracture (5.05 [3.69, 6.90]); other major fracture (1.42 [1.12, 1.81]); and weight (0.86 [0.79, 0.94]). Using algorithms based on these easily elicited determinants, specificity was increased from 50% to 78% in women and from 50% to 72% in men at a sensitivity of 50% compared with a random allocation of X-rays. At a sensitivity of 75%, the specificity was 50% in women and 40% in men. Inclusion of hip BMD (femoral neck or trochanter), measured in 1360 women and 1046 men, significantly improved the area under the ROC curves by 4% in women (p < 0.002) but not in men (p > 0.350). Spine BMD, measured in 982 women and 847 men, produced a significant 5% AUC improvement in women (p = 0.007) but not in men (p = 0.554)., Conclusion: A woman 65 years of age with one vertebral fracture has a one in four chance of another fracture over 5 years, which can be reduced to one in eight by treatment. Positive treatment decisions are often contingent on identifying a vertebral fracture. Selective use of lateral vertebral X-rays can be optimized using a 2-minute screening procedure administered by a nurse.

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Background and Aims: Osteopenia and osteoporosis are frequent in Crohn's disease. However, there are few data on related vertebral fractures. Therefore, we evaluated prospectively the prevalence of osteoporotic vertebral fractures in these patients., Methods: A total of 293 patients were screened with dual energy x ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur. In 156 patients with lumbar osteopenia or osteoporosis (T score <-1), x ray examinations of the thoracic and lumbar spine were performed. Assessment of fractures included visual reading of x rays and quantitative morphometry of the vertebral bodies (T4-L4), analogous to the criteria of the European Vertebral Osteoporosis Study., Results: In 34 (21.8%; 18 female) of 156 Crohn's disease patients with reduced bone mineral density, 63 osteoporotic vertebral fractures (50 fx. (osteoporotic fracture with visible fracture line running into the vertebral body and/or change of outer shape) and 13 fxd. (osteoporotic fracture with change of outer shape but without visible fracture line)) were found, 50 fx. in 25 (16%, 15 female) patients and 13 fxd. in nine (5.8%, three female) patients. In four patients the fractures were clinically evident and associated with severe back pain. Approximately one third of patients with fractures were younger than 30 years. Lumbar bone mineral density was significantly reduced in patients with fractures compared with those without (T score -2.50 (0.88) v -2.07 (0.66); p<0.025) but not at the hip (-2.0 (1.1) v -1.81 (0.87); p=0.38). In subgroups analyses, no significant differences were observed., Conclusions: In patients with Crohn's disease and reduced bone mineral density, the prevalence of vertebral fractures-that is, manifest osteoporosis-was strikingly high at 22%, even in those aged less than 30 years, a problem deserving further clinical attention.

Vertebral fracture is one of the major adverse clinical consequences of osteoporosis; however, there are few data concerning the incidence of vertebral fracture in population samples of men and women. The aim of this study was to determine the incidence of vertebral fracture in European men and women. A total of 14,011 men and women aged 50 years and over were recruited from population-based registers in 29 European centers and had an interviewer-administered questionnaire and lateral spinal radiographs performed. The response rate for participation in the study was approximately 50%. Repeat spinal radiographs were performed a mean of 3.8 years following the baseline film. All films were evaluated morphometrically. The definition of a morphometric fracture was a vertebra in which there was evidence of a 20% (+4 mm) or more reduction in anterior, middle, or posterior vertebral height between films--plus the additional requirement that a vertebra satisfy criteria for a prevalent deformity (using the McCloskey-Kanis method) in the follow-up film. There were 3174 men, mean age 63.1 years, and 3,614 women, mean age 62.2 years, with paired duplicate spinal radiographs (48% of those originally recruited to the baseline survey). The age standardized incidence of morphometric fracture was 10.7/1,000 person years (pyr) in women and 5.7/1,000 pyr in men. The age-standardized incidence of vertebral fracture as assessed qualitatively by the radiologist was broadly similar-12.1/1,000 pyr and 6.8/1,000 pyr, respectively. The incidence increased markedly with age in both men and women. There was some evidence of geographic variation in fracture occurrence; rates were higher in Sweden than elsewhere in Europe. This is the first large population-based study to ascertain the incidence of vertebral fracture in men and women over 50 years of age across Europe. The data confirm the frequent occurrence of the disorder in men as well as in women and the rise in incidence with age.

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mineral density and increased fracture risk. Although the genetic basis of osteoporosis is incompletely understood, previous studies have identified a polymorphism affecting an Sp1 binding site in the COLIA1 gene that predicts bone mineral density and osteoporotic fractures in several populations. Here we investigated the role of COLIA1 genotyping and bone densitometry in the prediction of osteoporotic fractures in a prospective, population-based study of men (n = 156) and women (n = 185) who were followed up for a mean (+/- SEM) of 4.88+/-0.03 years. There was no significant difference in bone density, rate of bone loss, body weight, height, or years since menopause between the genotype groups but women with the 'ss' genotype were significantly older than the other genotype groups (p = 0.03). Thirty-nine individuals sustained 54 fractures during follow-up and these predominantly occurred in women (45 fractures in 30 individuals). Fractures were significantly more common in females who carried the COLIA1 's' allele (p = 0.001), although there was no significant association between COLIA1 genotype and the occurrence of fractures in men. Logistic regression analysis showed that carriage of the COLIA1 's' allele was an independent predictor of fracture in women with an odds ratio (OR) [95% CI] of 2.59 [1.23-5.45], along with spine bone mineral density (OR = 1.57 [1.04-2.37] per Z-score unit) and body weight (OR = 1.05 [1.01-1.10] per kilogram). Moreover, bone densitometry and COLIA1 genotyping interacted significantly to enhance fracture prediction in women (p = 0.01), such that the incidence of fractures was 45 times higher in those with low BMD who carried the 's' allele (24.3 fractures/100 patient-years) compared with those with high BMD who were 'SS' homozygotes (0.54 fracture/100 patient-years). We conclude that in our population, COLIA1 genotyping predicts fractures independently of bone mass and interacts with bone densitometry to help identify women who are at high and low risk of sustaining osteoporotic fractures.

Several algorithms are currently in use for evaluating vertebral deformities from plain lateral radiographs of the lumbar and thoracic spine. However, the effects of measurement imprecision as well as uncertainties over image magnification on the correct identification of prevalent and incident vertebral deformities with these algorithms has been little studied. In a pilot study for the European Prospective Osteoporosis Study (EPOS), plain radiographs were submitted to a single central evaluating centre for measurement of vertebral height from T4 to L4. The thoracic and lumbar spines were imaged on separate films, and we have assessed the precision of measurement of vertebral heights and height ratios. The standard deviation of the differences between films of each of three height measurements ranged from 1.1 to 1.2 mm. A two-stage strategy for identifying incident deformities was devised. This required that the vertebra be a prevalent deformity at the time of the second radiograph and also that at least one of the vertebral ratios should have changed significantly since the first radiograph. The second stage removed all but two of the 18 vertebrae flagged positive in the first stage but not considered to be certain incident fractures by clinical reading of the radiographs.

Background: The prevalence of radiographically defined vertebral deformities, as a marker of vertebral osteoporosis, was calculated in a population based cross-sectional survey in Germany., Method: Lateral spine X-rays were taken according to a standardized protocol and evaluated centrally. Three thousand nine hundred and eighty subjects (2064 male and 1916 female) aged 50 to 79 years, have been examined in 8 German centers., Results: Based on McCloskey's method of deformity definition the age-standardized mean prevalence of vertebral deformities in Germany was 10.2% for males and 10.5% for females. Based on the definition by Melton/Eastell a significant higher prevalence was calculated (males 17.8%, females 18.7%). The prevalence increased with age in both sexes with a steeper increase in females. There was no difference in East and West German populations. There were substantial variations between the centers regarding the prevalence of deformities in females and males.

The European Vertebral Osteoporosis Study (EVOS) is one of the largest studies to investigate the prevalence of osteoporosis related vertebral fractures in a population based cross-sectional study. One of the main tasks was to create standards and logistics to obtain uniform and comparable radiographs in all 36 European centers. Furthermore the central reading of the X-rays and the morphometry of the vertebral bodies were 2 important challenges. This paper describes the standardized patient positioning and making of the radiographs as well as their morphometry, reading, and evaluation.

Abstract: Introduction and hypothesis: : Diagnosis of prevalent osteoporotic vertebral fracture is complicated by normal or developmental variation in vertebral shape or size and non-osteoporotic deformities that appear to have ‘reduced’ height. Using our visual approach, the algorithm-based qualitative method (ABQ) a vertebra with apparent “reduced” height without evidence of osteoporotic endplate depression is classified as non-osteoporotic short vertebral height (SVH). We aimed to determine whether ABQ classification of SVH represents true or false negative diagnosis of osteoporotic vertebral fracture, by testing the associations with clinical outcomes of osteoporosis or vertebral fracture. Methods: : The ABQ method was used to assess spinal radiographs acquired at baseline for a subset of 904 postmenopausal women participating in the Osteoporosis and Ultrasound Study (OPUS). The sample was enriched with vertebral fracture cases. Subjects were categorized by ABQ diagnosis as (i) normal, (ii) non-osteoporotic short vertebral height (SVH) or (iii) osteoporotic vertebral fracture. Results: : Women were classified by ABQ as follows: osteoporotic vertebral fracture, n =231; SVH, n =376 and normal, n =297. Women with vertebral fracture were older, with lower height, weight and height loss than those classified as SVH or normal. Women with SVH were heavier and older, with greater historical height loss than normal women. Age-adjusted SD units (z-scores) for BMD were lower than expected among women with osteoporotic vertebral fracture, but not among those with SVH. There was a significant association between diagnosis of osteoporotic vertebral fracture and history of low-trauma non-vertebral and vertebral fracture (p <0.001, odds ratios=3.2 and 20.6, respectively). There was also an association between diagnosis of SVH and previous low-trauma non-vertebral fracture (p <0.05, odds ratio=1.7). Conclusions: : Short vertebral height without evidence of central endplate fracture in postmenopausal women is largely unrelated to osteoporosis. Quantitative morphometry should not be used alone for the assessment of vertebral fracture in clinical decision making: we recommend differential diagnosis of morphometric vertebral deformities by an expert reader to rule out non-osteoporotic deformities with short vertebral height. [Copyright &y& Elsevier]

Abstract: In a recent multinational, double-blind, placebo-controlled, randomized, phase III study (BONE: IBandronate Osteoporosis Vertebral Fracture trial in North America and Europe), oral daily ibandronate (2.5 mg) significantly and substantially reduced the risk of new vertebral fractures by 62% relative to placebo after 3 years of treatment. The objective of the present study was to retrospectively analyze data from the BONE study to examine the efficacy of oral ibandronate in preventing incident vertebral fractures of greater severity. This analysis was conducted on the placebo and oral daily ibandronate (2.5 mg) arms of the BONE study, comprising a total of 1964 women (aged 55–80 years, ≥5 years postmenopause) with osteoporosis. Vertebral fractures on annual lateral radiographs of the spine were graded as mild, moderate, or severe, using criteria derived from an established semiquantitative technique. The findings demonstrate that in addition to being effective in significantly reducing the risk of new vertebral fractures of all severities, oral daily ibandronate has a pronounced effect on the more severe, most clinically relevant, vertebral fractures: a significant and sustained reduction of 59% in the relative risk of combined new moderate and severe vertebral fractures was observed at years 1 (P = 0.0164), 2 (P = 0.0004), and 3 (P < 0.0001). [Copyright &y& Elsevier]