Burden Of Vertebral Fractures Research Articles

Vertebral Fractures in Ireland: A Sub-analysis of the DXA HIP Project

Osteoporosis is an important global health problem resulting in fragility fractures. The vertebrae are the commonest site of fracture resulting in extreme illness burden, and having the highest associated mortality. International studies show that vertebral fractures (VF) increase in prevalence with age, similarly in men and women, but differ across different regions of the world. Ireland has one of the highest rates of hip fracture in the world but data on vertebral fractures are limited. In this study we examined the prevalence of VF and associated major risk factors, using a sample of subjects who underwent vertebral fracture assessment (VFA) performed on 2 dual-energy X-ray absorptiometry (DXA) machines. A total of 1296 subjects aged 40 years and older had a valid VFA report and DXA information available, including 254 men and 1042 women. Subjects had a mean age of 70 years, 805 (62%) had prior fractures, mean spine T-score was − 1.4 and mean total hip T-scores was − 1.2, while mean FRAX scores were 15.4% and 4.8% for major osteoporotic fracture and hip fracture, respectively. Although 95 (7%) had a known VF prior to scanning, 283 (22%) patients had at least 1 VF on their scan: 161 had 1, 61 had 2, and 61 had 3 or more. The prevalence of VF increased with age from 11.5% in those aged 40–49 years to > 33% among those aged ≥ 80 years. Both men and women with VF had significantly lower BMD at each measured site, and significantly higher FRAX scores, P < 0.01. These data suggest VF are common in high risk populations, particularly older men and women with low BMD, previous fractures, and at high risk of fracture. Urgent attention is needed to examine effective ways to identify those at risk and to reduce the burden of VF.

The Influence of Restrictive Pulmonary Dysfunction on Osteoporotic Thoracic Vertebral Fractures.

Study DesignA cross-sectional study.PurposeTo examine the influence of restrictive pulmonary dysfunction on osteoporotic thoracic vertebral fractures.Overview of LiteratureOsteoporotic thoracic vertebral fractures generally result in an increased kyphotic angle, which in turn may lead to pulmonary function impairment. Impaired pulmonary function could be associated with vertebral fractures. However, an association between osteoporotic thoracic vertebral fractures and pulmonary function remains controversial.MethodsA total of 96 patients were enrolled in this study, 30 of whom had osteoporotic thoracic vertebral fractures (group 1), 30 with chronic back pain (group 2), and 36 with chronic pulmonary diseases (group 3). Radiologic study of prevalent vertebral fractures, thoracic kyphotic angle, bone mineral density, relaxed expiratory vital capacity, forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) in spirometry was investigated.ResultsThe mean FVC and FEV1 were 75.66%±20.23% and 79.93%±22.48%, respectively, in group 1; 84.50%±16.25% and 91.87%±21.65%, respectively, in group 2; and 91.64%±17.53% and 91.03%±23.71%, respectively, in group 3. Group 1 (patients with osteoporotic thoracic vertebral fracture) had the lowest FVC among the three groups (p=0.01). Group 1 revealed worse result of pulmonary dysfunction than group 3 (patients with chronic pulmonary diseases) (p=0.01). The average kyphosis angle of the thoracic spine was 26.95°±15.17°, 36.47°±20.08°, and 28.58°±10.58° in groups 1, 2, and 3, respectively. There was a negative correlation between thoracic kyphosis and FEV1 (r=−0.309, p=0.01).ConclusionsThe results suggest that osteoporotic thoracic vertebral fracture burden could be affected by restrictive pulmonary dysfunction.

Idiopathic pulmonary fibrosis a rare disease with severe bone fragility.

Idiopathic pulmonary fibrosis (IPF) is a rare form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. The aim of this cross-sectional study was to assess the prevalence of osteoporosis and fragility fracture in a population of adults with IPF and to identify whether any possible clinical and pulmonary function parameters may be associated with increased bone fragility. In 58 IPF patients (mean age 65.1±9.1years), we measured bone mineral density (BMD) of the lumbar spine, the femoral neck, and the entire hip. Moreover, the presence of vertebral fractures on a lateral chest X-ray study was evaluated, and a vertebral fracture burden was quantified using the spinal deformity index (SDI). As expected, osteoporosis was significantly more frequent in females with respect to males (57.9 vs 20.5%, respectively), whereas the fractures prevailed in males with respect to females (38.5 vs 26.3%, respectively). There were positive correlations between BMD at all skeletal sites and respiratory parameters; in particular for FVC % and DLCO % with BMD at femoral sub-regions. Moreover, we compared the average of DLCO (%) measure by values of SDI score that was higher in those patients with lower values of DLCO (%). The study shows a high prevalence of fragility with vertebral fractures in IPF patients, especially in males. Moreover, the vertebral fracture burden is associated with a worsening of FVC (%) and DLCO (%). Therefore, an evaluation of bone status is recommended, especially in those patients who are candidates for lung transplantation.

Relationship Between Vertebral Fracture Burden, Height Loss, and Pulmonary Function in Postmenopausal Women With Osteoporosis

The purpose of this analysis was to assess the association of osteoporosis-related vertebral fracture burden and pulmonary function. This study also examined the relationship between vertebral fracture burden and height loss, estimated by arm span − height. This was a single-site and single-visit study. Patients had a history of at least 1 moderate or severe vertebral fracture. Vertebral fracture burden was quantified using the spinal deformity index (SDI). Pulmonary function during inspiration was determined by spirometry. Forty-one women aged 70–91 completed the study. Vertebral fracture burden negatively correlated with forced inspiratory vital capacity and inspiratory time. For each unit increase in SDI, forced inspiratory vital capacity decreased by 1.62%, and inspiratory time decreased by 2.39%. There was no correlation between SDI and measures of inspiratory flow. For each unit increase in SDI, height decreased by about 0.5 cm. Vertebral fractures were associated with decreased lung volume and height loss.

Association of Chronic Obstructive Pulmonary Disease and Smoking Status With Bone Density and Vertebral Fractures in Male Lung Cancer Screening Participants

We studied the vertebral fracture prevalence on low-dose chest computed tomography (CT) in male lung cancer screening participants and the association of fractures and bone density with chronic obstructive pulmonary disease (COPD) and smoking. 1140 male current and former smokers with ≥ 16.5 packyears from the NELSON lung cancer screening trial were included. Age, body mass index, and smoking status were registered. CT scans and pulmonary function tests were obtained on the same day. On CT, vertebral fractures and bone density were measured. The cohort had a mean age of 62.5 years (standard deviation 5.2) old; 531 (46.6%) had quit smoking; and 437 (38.3%) had COPD. Of the group, 100 (8.8%) participants had a vertebral fracture. Fracture prevalence was higher in current compared to former smokers (11.3% versus 5.8%, p = 0.001), but similar in participants with COPD compared to those without (9.6% versus 8.3%, p = 0.430). The multivariable adjusted odds ratio for fracture presence was 1.79 (95% CI: 1.13-2.84) in current smokers and 1.08 (95% CI: 0.69-1.67) in COPD participants. Bone density was lower in current compared to former smokers (103.2 HU versus 108.7 HU, p = 0.006) and in participants with COPD compared to those without [100.7 Hounsfield Units (HU) versus 108.9 HU, p < 0.001]. In multivariate analysis, smoking status and COPD status were independently associated with bone density, corrected for age and body mass index. In conclusion, our study shows that lung cancer screening participants have a substantial vertebral fracture burden. Fractures are more common in current smokers, who also have lower bone density. We could not confirm that COPD is independently associated with vertebral fractures.

Hospital burden of vertebral fractures in France: influence of vertebroplasty

We described the whole population of patients hospitalized for vertebral fractures in France in 2009. Only 6.4 % of them were operated by vertebroplasty; these patients were younger and healthier than non-operated patients. This study aims to describe the burden of vertebral fractures from the 2009 French Hospital National Database in acute care in people aged 60 years and over, with or without vertebroplasty. All stays due to nonmalignant and nontraumatic vertebral fractures as primary cause were selected. Patients' characteristics were described and compared between patients with or without vertebroplasty. The in-patient mortality was compared to the one related to hip and upper humerus fracture in patients hospitalized during the same year. In 2009, 13,624 patients were hospitalized for vertebral fracture. Men accounted for 29.3 % of cases. Length of stay was 9.6 ± 8.2 days, higher in patients with at least one comorbidity than in patients without (11.2 ± 8.6 and 7.8 ± 7.2 days, respectively). The in-patient mortality was 0.9 %; it was 3.8 and 1.1 % for hip and upper humerus fractures, respectively. Vertebroplasty was performed in 6.4 % of them. Patients with vertebroplasty were younger (mean age of 75 ± 8 versus 79 ± 9 years), had a less duration of stay (7 ± 7.5 versus 9.8 ± 8.2 days), less comorbidities (at least one comorbidity, 45 versus 54 %), and less in-patient mortality (0.1 versus 0.9 %). Rehospitalization for vertebral fracture occurred in 9 and 6 % of the patient with and without vertebroplasty. This is the first French study assessing the national burden of vertebral fractures based on hospital data. In-hospital death rate is lower in patients with vertebroplasty, who are younger and have less comorbidities than the general population with vertebral fractures.

The assessment of vertebral fractures in elderly women with recent hip fractures: the BREAK Study

This study aimed to evaluate the prevalence of vertebral fractures in elderly women with a recent hip fracture. The burden of vertebral fractures expressed by the Spinal Deformity Index (SDI) is more strictly associated with the trochanteric than the cervical localization of hip fracture and may influence short-term functional outcomes. This study aimed to determine the prevalence and severity of vertebral fractures in elderly women with recent hip fracture and to assess whether the burden of vertebral fractures may be differently associated with trochanteric hip fractures with respect to cervical hip fractures. We studied 689 Italian women aged 60 years or over with a recent low trauma hip fracture and for whom an adequate X-ray evaluation of spine was available. All radiographs were examined centrally for the presence of any vertebral deformities and radiological morphometry was performed. The SDI, which integrates both the number and the severity of fractures, was also calculated. Prevalent vertebral fractures were present in 55.7% of subjects and 95 women (13.7%) had at least one severe fracture. The women with trochanteric hip fracture showed higher SDI and higher prevalence of diabetes with respect to those with cervical hip fracture, p=0.017 and p=0.001, respectively. SDI, surgical menopause, family history of fragility fracture, and type2 diabetes mellitus were independently associated with the risk of trochanteric hip fracture. Moreover, a higher SDI was associated with a higher percentage of post-surgery complications (p=0.05) and slower recovery (p<0.05). Our study suggests that the burden of prevalent vertebral fractures is more strictly associated with the trochanteric than the cervical localisation of hip fracture and that elevated values of SDI negatively influence short term functional outcomes in women with hip fracture.

The Burden of Prevalent Vertebral Fractures is Negatively Associated with Functional Outcome in Women with Hip Fracture

The aim of this study was to investigate the association between the burden of prevalent vertebral fractures and functional outcome in women with hip fracture. We investigated 164 of 180 women with hip fracture admitted consecutively to a rehabilitation hospital. Lateral radiographs of the spine were taken 20.0 ± 5.1 days (mean ± SD) after fracture occurrence. To obtain a summary measure of vertebral fracture burden, we calculated the spinal deformity index by summing the fracture grades of all vertebrae (T4 to L4), assessed using Genant's method. Functional outcome was assessed using Barthel index scores. In a Spearman rank test, we observed a significant negative correlation between spinal deformity index scores and Barthel index scores at discharge from rehabilitation (ρ = -0.23; P = 0.003). The association between spinal deformity index and Barthel index scores was confirmed (P = 0.039) after adjustment for eight potential confounders. Multiple regression also showed a significant negative association between spinal deformity index scores and increase in Barthel index scores during rehabilitation (P = 0.012). The panel of prognostic factors that we included in the multivariate analysis accounted for 62% of the variance in the Barthel index scores at discharge from rehabilitation and 43% of their increase during rehabilitation. The burden of prevalent vertebral fractures is negatively associated with functional outcome in women with hip fracture.

How geometry parameters may use to predict vertebral fractures

Credible inferences regarding the burden of vertebral fractures (VFs) cannot be made without a globally accepted quantitative definition of ‘fracture’. Currently, differences in anterior, middle, or posterior vertebral heights (VHs) within a vertebra, or between adjacent vertebrae, are used to define ‘fracture’. However, VH differences are essential for the construction of thoracolumbar curves, evolutionary adaptations that provide stability in bipedal stance and gait. As there is no reference standard to distinguish anatomical variation from fracture, approaches to defining a VF use a reference range of VH ratios derived in premenopausal women or derived by trimming, a method that iteratively removes the tails of a distribution of VH ratios to produce a normal distribution. From this, reference ranges of VH ratio means and standard deviations (SDs) are obtained and a nominal deviation of 15% or more, or 3 SD or more is regarded as a ‘fracture’.We measured VHs by quantitative vertebral morphometry (QVM) and bone mineral density (BMD) by dual energy X-ray absorptiometry in 697 Lebanese women (age 20–89 years) to compare the prevalence of VF ascertained by published methods and a new method that uses the premenopausal range (without trimming) and requires two VH abnormalities. VF prevalence using published methods reached 60% to 70% in pre- and post-menopausal women, and in women with normal or high BMD because VH ratios were not normally distributed and cut-offs used to define VF fracture fell within the observed distribution of the data. The new method resulted in a VF prevalence of 3.3% in younger and 14% in older women, 7% (high), 10% (middle), and 20% (low) BMD tertiles consistent with the notion that the method detected VF due to bone fragility. We suggest that using a fixed trimming method to define reference range and cut-offs or applying fixed cut-offs to identify VFs in populations, where these ratios are not normally distributed, may result in the capture of anatomical variation, not structural failure. Thus, group differences in the VF prevalence may reflect differences in methodology, not bone fragility. Improved criteria to define VF are needed before credible inferences can be made regarding the burden of VFs in women and men, and between sexes, races, countries, decades, and placebo arms of clinical trials.

Enhanced prediction of fracture risk combining vertebral fracture status and BMD

Prevalent vertebral fractures are associated with increased fracture risk, but the magnitude of this effect across a range of BMD T-scores has not been quantified. In this analysis, for any given BMD T-score, incident fracture risk varied up to twelve fold when information regarding prevalent radiographic vertebral fracture status was considered. Clinical fracture risk evaluation of older women usually includes assessment of bone mineral density (BMD) but often not vertebral fracture status. In this analysis, we quantified the impact of vertebral fracture burden on two year fracture risk across a range of BMD T-scores. Data were from 2,651 postmenopausal women who were assigned to the placebo groups of the Fracture Prevention Trial (median observation 21 months) and the Multiple Outcomes of Raloxifene Evaluation Trial (MORE; observation 2 years). Using the Genant visual semiquantitative criteria, we defined prevalent vertebral fracture status as: a) presence or absence of fracture; b) fracture number; c) maximum semi-quantitative (SQ) score (normal=0, mild fracture=1, moderate fracture=2, severe fracture=3); and d) spinal deformity index (SDI) score (sum of SQ scores of T4 to L4 vertebrae). Incident fractures over two years were identified via lateral spine radiographs and outside the spine by questioning of patients and review of radiographs or radiographic reports. Femoral neck BMD T-score provided significant information regarding fracture risk. Across the range of T-scores, vertebral fracture status provided additional prognostic information. The risk increased with increasing number and severity of prevalent vertebral fractures and SDI, a summary measure of spine fracture burden. Across a range of BMD values, prevalent spine fracture burden as assessed by SDI increased the risk of incident vertebral fractures by up to 12-fold, nonvertebral fractures by about twofold, and any fractures by up to sevenfold. These findings indicate that at any given BMD T-score, the risk of incident vertebral, non-vertebral, and any fracture depended heavily on prevalent radiographic vertebral fracture status. Assessment of vertebral fracture status, in addition to BMD, provides practical and relevant clinical information to aid in predicting fracture risk in postmenopausal women.

Effect of Teriparatide {rhPTH(1-34)} on BMD When Given to Postmenopausal Women Receiving Hormone Replacement Therapy

The effects of teriparatide when given in combination with HRT were studied in postmenopausal women with low bone mass or osteoporosis. The data provide evidence that the adverse event profile for combination therapy with teriparatide + HRT together is consistent with that expected for each treatment alone and that the BMD response is greater than for HRT alone. Teriparatide [rhPTH(1-34)], given as a once-daily injection, activates new bone formation in patients with osteoporosis. Hormone replacement therapy (HRT) prevents osteoporosis by reducing bone resorption and formation. Combination therapy with these two compounds, in small clinical trials, increased BMD and reduced vertebral fracture burden. The purpose of this study was to determine whether teriparatide provided additional effect on BMD when given in combination with HRT. A randomized, double-blind, placebo-controlled study was conducted in postmenopausal women with either low bone mass or osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n = 125) or teriparatide 40 microg/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median treatment exposure of 13.8 months. Approximately one-half of the patients in each group were pretreated with HRT for at least 12 months before randomization. Patients received 1000 mg calcium and 400-1200 IU of vitamin D daily as oral supplementation. BMD was measured by DXA. Compared with HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one-third distal radius was lower, in the combination therapy but not in the HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared with HRT. A similar profile of BMD and bone markers was evident in both randomized patients as well as in subgroups of patients not pretreated or pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg cramps were more frequently reported in the TPTD40 + HRT group. Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent, provides additional increases in BMD beyond that provided by HRT alone. The adverse effects of teriparatide when added to HRT were similar to the adverse effects described for teriparatide administered alone. Whether teriparatide was initiated at the same time as HRT or after at least 1 year on HRT, the incremental increases over HRT alone were similar.

Quality-of-life issues in osteoporosis

Osteoporosis is responsible for more than 1.5 million fractures per year in the United States including vertebral and nonvertebral fractures of the hip and wrist. Most of the impact of osteoporosis on quality of life relates to fracture. While the morbidity and mortality of hip fractures have long been recognized, only recently have we also recognized the significant burden of vertebral fractures. With the development of generic and disease targeted quality-of-life instruments we have now confirmed observational studies showing that clinical vertebral fractures have significant effects on quality of life. The economic burden of vertebral fractures, if we include direct and indirect costs, may be similar to hip fractures. The relative risk for mortality after clinical vertebral fracture is at least equivalent to that of hip fracture. The burden of vertebral fractures relates not only to pain but also to kyphosis. Because vertebral fractures are often under diagnosed and under treated, these findings are a call to action because the first vertebral fracture leads to significantly increased risk for subsequent vertebral and osteoporotic fracture with further loss of quality of life.

The varying distribution of intra- and inter-vertebral height ratios determines the prevalence of vertebral fractures

Credible inferences regarding the burden of vertebral fractures (VFs) cannot be made without a globally accepted quantitative definition of ‘fracture’. Currently, differences in anterior, middle, or posterior vertebral heights (VHs) within a vertebra, or between adjacent vertebrae, are used to define ‘fracture’. However, VH differences are essential for the construction of thoracolumbar curves, evolutionary adaptations that provide stability in bipedal stance and gait. As there is no reference standard to distinguish anatomical variation from fracture, approaches to defining a VF use a reference range of VH ratios derived in premenopausal women or derived by trimming, a method that iteratively removes the tails of a distribution of VH ratios to produce a normal distribution. From this, reference ranges of VH ratio means and standard deviations (SDs) are obtained and a nominal deviation of 15% or more, or 3 SD or more is regarded as a ‘fracture’. We measured VHs by quantitative vertebral morphometry (QVM) and bone mineral density (BMD) by dual energy X-ray absorptiometry in 697 Lebanese women (age 20–89 years) to compare the prevalence of VF ascertained by published methods and a new method that uses the premenopausal range (without trimming) and requires two VH abnormalities. VF prevalence using published methods reached 60% to 70% in pre- and post-menopausal women, and in women with normal or high BMD because VH ratios were not normally distributed and cut-offs used to define VF fracture fell within the observed distribution of the data. The new method resulted in a VF prevalence of 3.3% in younger and 14% in older women, 7% (high), 10% (middle), and 20% (low) BMD tertiles consistent with the notion that the method detected VF due to bone fragility. We suggest that using a fixed trimming method to define reference range and cut-offs or applying fixed cut-offs to identify VFs in populations, where these ratios are not normally distributed, may result in the capture of anatomical variation, not structural failure. Thus, group differences in the VF prevalence may reflect differences in methodology, not bone fragility. Improved criteria to define VF are needed before credible inferences can be made regarding the burden of VFs in women and men, and between sexes, races, countries, decades, and placebo arms of clinical trials.

The risk and burden of vertebral fractures in Sweden.

The aim of this study was to determine the risk and burden of vertebral fractures judged as those coming to clinical attention and as morphometric fractures. Incidence and utility loss were computed from data from Malmo, Sweden. Clinical fractures accounted for 23% of all vertebral deformities in women and for 42% in men. The average 10-year fracture probability for morphometric fractures increased with age in men from 2.9% at the age of 50 years (7.2% in women) to 8.4 at the age of 85 years (26.7% in women). As expected, probabilities increased with decreasing T-score for hip BMD. Cumulative utility loss from a clinical vertebral fracture was substantial and was 50-62% of that due to a hip fracture depending on age. When incidence of fractures in the population was weighted by disutility, all spine fractures accounted for more morbidity than hip fracture up to the age of 75 years. We conclude that vertebral fractures have a major personal and societal impact that needs to be recognised in algorithms for assessment of risk and in health economic strategies for osteoporosis.