Prevalence and risk factors of radiographic vertebral fracture in Brazilian community-dwelling elderly

The prevalence and risk factors of radiographic vertebral fracture were determined among Brazilian community-dwelling elderly. Vertebral fractures were a common condition in this elderly population, and lower hip bone mineral density was a significant risk factor for vertebral fractures in both genders. The aim of the study was to estimate the prevalence of radiographic vertebral fracture and investigate factors associated with this condition in Brazilian community-dwelling elderly. This cross-sectional study included 943 elderly subjects (561 women and 382 men) living in So Paulo, Brazil. Thoracic and lumbar spine radiographs were obtained, and vertebral fractures were evaluated using Genant`s semiquantitative method. Bone mineral density (BMD) was measured by dual X-ray absorptiometry, and bone biochemical markers were also evaluated. Female and male subjects were analyzed independently, and each gender was divided into two groups based on whether vertebral fractures were present. The prevalence of vertebral fracture was 27.5% (95% CI 23.8-31.1) in women and 31.8% in men (95% CI 27.1-36.5) (P = 0.116). Cox regression analyses using variables that were significant in the univariate analysis showed that age (prevalence ratio = 1.03, 95% CI 1.01-1.06; p = 0.019) and total femur BMD (PR = 0.27, 95% CI 0.08-0.98; p = 0.048) were independent factors in predicting vertebral fracture for the female group. In the male group, Cox regression analyses demonstrated that femoral neck BMD (PR = 0.26, 95% CI 0.07-0.98; p = 0.046) was an independent parameter in predicting vertebral fractures. Our results suggest that radiographic vertebral fractures are common in Brazilian community-dwelling elderly and that a low hip BMD was an important risk factor for this condition in both genders. Age was also significantly correlated with the presence of vertebral fractures in women.

Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p<5×10-8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6×10-8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98-1.14; p=0.17), displaying high degree of heterogeneity (I2=57%; Qhet p=0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (p=0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.

Prediction of adjacent vertebral fracture risk associated with vertebroplasty : a computer-based simulation study

Vertebrplasty involved injecting cement into a fractured vertebra to provide stabilisation. There is clinical evidence to suggest however that vertebroplasty may be assocated with a higher risk of adjacent vertebral fracture; which may be due to the change in material properties of the post-procedure vertebra modifying the transmission of mechanical stresses to adjacent vertebrae.

The effect of osteoporotic vertebral fracture of predicted spinal loads in vivo

he aetiology of osteoporotic vertebral fractures is multi-factorial, and cannot be explained solely by low bone mass. After sustaining an initial vertebral fracture, the risk of subsequent fracture increases greatly. Examination of physiologic loads imposed on vertebral bodies may help to explain a mechanism underlying this fracture cascade. This study tested the hypothesis that model-derived segmental vertebral loading is greater in individuals who have sustained an osteoporotic vertebral fracture compared to those with osteoporosis and no history of fracture. Flexion moments, and compression and shear loads were calculated from T2 to L5 in 12 participants with fractures (66.4 ± 6.4 years, 162.2 ± 5.1 cm, 69.1 ± 11.2 kg) and 19 without fractures (62.9 ± 7.9 years, 158.3 ± 4.4 cm, 59.3 ± 8.9 kg) while standing. Static analysis was used to solve gravitational loads while muscle-derived forces were calculated using a detailed trunk muscle model driven by optimization with a cost function set to minimise muscle fatigue. Least squares regression was used to derive polynomial functions to describe normalised load profiles. Regression co-efficients were compared between groups to examine differences in loading profiles. Loading at the fractured level, and at one level above and below, were also compared between groups. The fracture group had significantly greater normalised compression (p = 0.0008) and shear force (p < 0.0001) profiles and a trend for a greater flexion moment profile. At the level of fracture, a significantly greater flexion moment (p = 0.001) and shear force (p < 0.001) was observed in the fracture group. A greater flexion moment (p = 0.003) and compression force (p = 0.007) one level below the fracture, and a greater flexion moment (p = 0.002) and shear force (p = 0.002) one level above the fracture was observed in the fracture group. The differences observed in multi-level spinal loading between the groups may explain a mechanism for increased risk of subsequent vertebral fractures. Interventions aimed at restoring vertebral morphology or reduce thoracic curvature may assist in normalising spine load profiles.

Hormone therapy and risk of non-vertebral fracture : Geelong Osteoporosis Study

In this population-based study, we evaluated the association between exposure to hormone therapy (HT), bone mineral density (BMD) and the prevalence of non-vertebral fractures. The study was set in a region located in southeastern Australia where complete fracture ascertainment was determined from radiological reports. Current HT use for at least 6 months was ascertained in women with non-vertebral fractures [median age 70.9 years; inter-quartile range (IQR) 66.5–75.9 years] and randomly selected controls (median age 70.8 years; IQR 65.2–75.0 years). Current HT use was documented in 20 of 262 cases and 49 of 364 controls. The odds ratio (OR) for non-vertebral fracture associated with HT use was 0.53 (95% CI 0.31–0.92). HT use was associated with 2.6–7.5% higher BMD at axial and appendicular sites. HT use is associated with a halving of risk for non-vertebral fractures and higher BMD.

High resolution quantitative computed tomography-based assessment of trabecular microstructure and strength estimates by finite-element analysis of the spine, but not DXA, reflects vertebral fracture status in men with glucocorticoid-induced osteoporosis

High-resolution quantitative computed tomography (HRQCT)-based analysis of spinal bone density and microstructure, finite element analysis (FEA), and DXA were used to investigate the vertebral bone status of men with glucocorticoid-induced osteoporosis (GIO). DXA of L1–L3 and total hip, QCT of L1–L3, and HRQCT of T12 were available for 73 men (54.6±14.0years) with GIO. Prevalent vertebral fracture status was evaluated on radiographs using a semi-quantitative (SQ) score (normal=0 to severe fracture=3), and the spinal deformity index (SDI) score (sum of SQ scores of T4 to L4 vertebrae). Thirty-one (42.4%) subjects had prevalent vertebral fractures. Cortical BMD (Ct.BMD) and thickness (Ct.Th), trabecular BMD (Tb.BMD), apparent trabecular bone volume fraction (app.BV/TV), and apparent trabecular separation (app.Tb.Sp) were analyzed by HRQCT. Stiffness and strength of T12 were computed by HRQCT-based nonlinear FEA for axial compression, anterior bending and axial torsion. In logistic regressions adjusted for age, glucocorticoid dose and osteoporosis treatment, Tb.BMD was most closely associated with vertebral fracture status (standardized odds ratio [sOR]: Tb.BMD T12: 4.05 [95% CI: 1.8–9.0], Tb.BMD L1–L3: 3.95 [1.8–8.9]). Strength divided by cross-sectional area for axial compression showed the most significant association with spine fracture status among FEA variables (2.56 [1.29–5.07]). SDI was best predicted by a microstructural model using Ct.Th and app.Tb.Sp (r2=0.57, p<0.001). Spinal or hip DXA measurements did not show significant associations with fracture status or severity. In this cross-sectional study of males with GIO, QCT, HRQCT-based measurements and FEA variables were superior to DXA in discriminating between patients of differing prevalent vertebral fracture status. A microstructural model combining aspects of cortical and trabecular bone reflected fracture severity most accurately.

Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance

International audience

A model of osteoporosis impact in Switzerland 2000-2020

The aim of our study was to develop a modeling framework suitable to quantify the incidence, absolute number and economic impact of osteoporosis-attributable hip, vertebral and distal forearm fractures, with a particular focus on change over time, and with application to the situation in Switzerland from 2000 to 2020. A Markov process model was developed and analyzed by Monte Carlo simulation. A demographic scenario provided by the Swiss Federal Statistical Office and various Swiss and international data sources were used as model inputs. Demographic and epidemiologic input parameters were reproduced correctly, confirming the internal validity of the model. The proportion of the Swiss population aged 50 years or over will rise from 33.3% in 2000 to 41.3% in 2020. At the total population level, osteoporosis-attributable incidence will rise from 1.16 to 1.54 per 1,000 person-years in the case of hip fracture, from 3.28 to 4.18 per 1,000 person-years in the case of radiographic vertebral fracture, and from 0.59 to 0.70 per 1,000 person-years in the case of distal forearm fracture. Osteoporosis-attributable hip fracture numbers will rise from 8,375 to 11,353, vertebral fracture numbers will rise from 23,584 to 30,883, and distal forearm fracture numbers will rise from 4,209 to 5,186. Population-level osteoporosis-related direct medical inpatient costs per year will rise from 713.4 million Swiss francs (CHF) to CHF946.2 million. These figures correspond to 1.6% and 2.2% of Swiss health care expenditures in 2000. The modeling framework described can be applied to a wide variety of settings. It can be used to assess the impact of new prevention, diagnostic and treatment strategies. In Switzerland incidences of osteoporotic hip, vertebral and distal forearm fracture will rise by 33%, 27%, and 19%, respectively, between 2000 and 2020, if current prevention and treatment patterns are maintained. Corresponding absolute fracture numbers will rise by 36%, 31%, and 23%. Related direct medical inpatient costs are predicted to increase by 33%; however, this estimate is subject to uncertainty due to limited availability of input data.

Efficacy and safety of vertebroplasty for treatment of painful osteoporotic vertebral fractures: a randomised controlled trial [ACTRN012605000079640]

Background: Vertebroplasty is a promising but as yet unproven treatment for painful osteoporotic vertebral fractures. It involves radiographic-guided injection of various types of bone cement directly into the vertebral fracture site. Uncontrolled studies and two controlled quasi-experimental before-after studies comparing volunteers who were offered treatment to those who refused it, have suggested an early benefit including rapid pain relief and improved function. Conversely, several uncontrolled studies and one of the controlled before-after studies have also suggested that vertebroplasty may increase the risk of subsequent vertebral fractures, particularly in vertebrae adjacent to treated levels or if cement leakage into the adjacent disc has occurred. As yet, there are no completed randomised controlled trials of vertebroplasty for osteoporotic vertebral fractures. The aims of this participant and outcome assessor-blinded randomised placebo-controlled trial are to i) determine the short-term efficacy and safety (3 months) of vertebroplasty for alleviating pain and improving function for painful osteoporotic vertebral fractures; and ii) determine its medium to longer-term efficacy and safety, particularly the risk of further fracture over 2 years.

Design: A double-blind randomised controlled trial of 200 participants with one or two recent painful osteoporotic vertebral fractures. Participants will be stratified by duration of symptoms (< and ≥ 6 weeks), gender and treating radiologist and randomly allocated to either the treatment or placebo. Outcomes will be assessed at baseline, 1 week, 1, 3, 6, 12 and 24 months. Outcome measures include overall, night and rest pain on 10 cm visual analogue scales, quality of life measured by the Assessment of Quality of Life, Osteoporosis Quality of Life and EQ-5D questionnaires; participant perceived recovery on a 7-point ordinal scale ranging from 'a great deal worse' to 'a great deal better'; disability measured by the Roland-Morris Disability Questionnaire; timed 'Up and Go' test; and adverse effects. The presence of new fractures will be assessed by radiographs of the thoracic and lumbar spine performed at 12 and 24 months.

Discussion: The results of this trial will be of major international importance and findings will be immediately translatable into clinical practice.

Trial registration: Australian Clinical Trial Register # [ACTRN012605000079640]

Image-based biomechanical assessment of vertebral body and intervertebral disc in the human lumbar spine

Life expectancy continuously increases but our society faces age-related conditions. Among musculoskeletal diseases, osteoporosis associated with risk of vertebral fracture and degenerative intervertebral disc (IVD) are painful pathologies responsible for tremendous healthcare costs. Hence, reliable diagnostic tools are necessary to plan a treatment or follow up its efficacy. Yet, radiographic and MRI techniques, respectively clinical standards for evaluation of bone strength and IVD degeneration, are unspecific and not objective. Increasingly used in biomedical engineering, CT-based finite element (FE) models constitute the state-of-art for vertebral strength prediction. However, as non-invasive biomechanical evaluation and personalised FE models of the IVD are not available, rigid boundary conditions (BCs) are applied on the FE models to avoid uncertainties of disc degeneration that might bias the predictions. Moreover, considering the impact of low back pain, the biomechanical status of the IVD is needed as a criterion for early disc degeneration. Thus, the first FE study focuses on two rigid BCs applied on the vertebral bodies during compression test of cadaver vertebral bodies, vertebral sections and PMMA embedding. The second FE study highlights the large influence of the intervertebral disc’s compliance on the vertebral strength, damage distribution and its initiation. The third study introduces a new protocol for normalisation of the IVD stiffness in compression, torsion and bending using MRI-based data to account for its morphology. In the last study, a new criterion (Otsu threshold) for disc degeneration based on quantitative MRI data (axial T2 map) is proposed. The results show that vertebral strength and damage distribution computed with rigid BCs are identical. Yet, large discrepancies in strength and damage localisation were observed when the vertebral bodies were loaded via IVDs. The normalisation protocol attenuated the effect of geometry on the IVD stiffnesses without complete suppression. Finally, the Otsu threshold computed in the posterior part of annulus fibrosus was related to the disc biomechanics and meet objectivity and simplicity required for a clinical application. In conclusion, the stiffness normalisation protocol necessary for consistent IVD comparisons and the relation found between degeneration, mechanical response of the IVD and Otsu threshold lead the way for non-invasive evaluation biomechanical status of the IVD. As the FE prediction of vertebral strength is largely influenced by the IVD conditions, this data could also improve the future FE models of osteoporotic vertebra.

Non-hip and non-vertebral fractures : the neglected fracture sites

Summary: Non-hip, non-vertebral fractures (NHNVF) were compared with hip, vertebral and controls. NHNVF were younger and heavier than controls and hip/vertebral fractures in both men and women, respectively. Falls and prior fractures were less common in NHNVF than hip fractures. Glucocorticoid use was lower in NHNVF compared to vertebral fracture (VF) in men. Introduction: Although hip fracture (HF) and vertebral fractures (VF) receive the most attention in the literature and are the targeted sites for fracture prevention, non-hip, non-vertebral fracture (NHNVF) sites account for a greater proportion of fractures than the hip or vertebrae. This study aimed to assess risk factors for NHNVF and compare them with those for HF, VF and controls. Methods: Incident fractures during 2005–2007 for men and 1994–1996 for women were identified using computerised keyword searches of radiological reports, and controls were selected at random from electoral rolls for participation in the Geelong Osteoporosis Study. Participants aged 60+ years were included in this study. Results: Compared to controls, men and women with NHNVF were younger (ORs, 0.90, 95 % CI 0.86–0.94; and 0.96, 0.93–0.98, respectively) and had a lower femoral neck bone mineral density (BMD) T-score (age-adjusted; difference [men] 0.383, P = 0.002; [women] 0.287, P = 0.001). Compared to HF, men and women with NHNVF were heavier (difference [men] 9.0 kg, P = 0.01; [women] 7.6 kg, P < 0.001). Heavier weight was also a risk factor for women with NHNVF compared to VF (1.03, 1.01–1.06). In men with NHNVF, falls (0.37, 0.14–0.97) and prior fractures (0.38, 0.15–0.98) were less common compared to HF; and glucocorticoid use was less common for NHNVF (0.30, 0.11–0.85) compared to VF. Conclusions: Given the high numbers of NHNVF sustained by men and women in this study, fracture prevention strategies should focus on individuals with high risk of sustaining these types of fractures, as well as on individuals who are more likely to sustain a HF or VF.

Consequences of Vertebral Fractures

Vertebral fractures occur due to forces applied to spinal structures. When the bone tissue is weakened, vertebral fractures can result from a minor trauma. Adult vertebral fractures are commonly considered to be an indication for osteoporosis. In children osteoporosis is a rare condition, and pediatric vertebral fractures are usually clearly trauma-related. The aims of this dissertation are to produce knowledge of the epidemiology of osteoporotic vertebral fractures and to analyse their association with total and cause-specific mortality, to find indicators with which to identify individuals who are at great risk of subsequent fractures, to study the incidence of pediatric vertebral fractures and need for their operative treatment and hospital care. The Mobile-Clinic and Mini-Finland Health surveys of the adult population were used as materials in this research. Record linkages to the Finnish Hospital Discharge Register and the Official Cause of Death register were used to study mortality and hospitalization in the same population group. These registers were also used to evaluate epidemiology, mortality, hospitalization and the need for operative management of pediatric vertebral fracture patients. The main findings and conclusions of the present dissertation are: 1. The presence of a thoracic vertebral fracture in adults is a significant predictor of cancer and respiratory mortality. In women, but not in men, vertebral fractures strongly predict mortality due to injuries. Most of these deaths in the study group were hip fracture related. 2. Severe thoracic vertebral fracture in adults was a strong predictor of a subsequent hip fracture, whereas mild or moderate fractures and the number of compressed vertebrae were much weaker predictors, 3. Pediatric spinal fractures were rare: The incidence was 66 per one million children per year. In younger children cervical spine was most often affected, whereas in older children fractures of the thoracic and lumbar spine were more common. Maturation of spinal structures seems to play a major role in the typical injury patterns in children. Thirty per cent of pediatric spinal fractures required surgical treatment. The current study focuses on consequences of vertebral fractures in general, without evaluating further the causation of the studied phenomena. Further studies are needed to clarify the mechanisms of association between vertebral fractures and specific causes of mortality. A severe vertebral fracture appears to indicate a substantial risk of a subsequent hip fracture. If such a fracture is identified from a chest radiograph, urgent clinical evaluation, treatment of osteoporosis and protective measures against falls are recommended.

Morphometric vertebral fractures of the lower thoracic and lumbar spine, physical function and quality of life in men

The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly documented. We found that MVFs of the lower thoracic and lumbar spine were associated with poor quality of life and impaired physical function in men. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry.