Trends of incidence and 1-year mortality of vertebral fractures in Korea using nationwide claims data.

Clinical Relevance of Vertebral Fractures in Men.

The present study evaluates the incidence and mortality of vertebral fractures in Korea, using data from the Health Insurance Review Assessment Service, which includes nationwide information entrusted by Korean government. A vertebral compression fracture is a serious complication associated with osteoporosis of the spine. We evaluated the incidence of vertebral fracture and subsequent mortality in South Korea, using nationwide data from the Health Insurance Review and Assessment Service (HIRA). All new visits or admissions to clinics or hospitals for fractures were recorded in nationwide cohort by the Korean HIRA using International Classification of Disease, tenth Revision (ICD-10) code. The incidence of vertebral fracture and excess mortality associated with vertebral fracture were evaluated, in men and women aged 50 years or more between 2005 and 2008. Standardized mortality ratio (SMR) was calculated to determine excess mortality associated with vertebral fracture. The crude overall incidence of vertebral fractures was 984 per 100,000 person years from 2005 to 2008. The overall mortality rate at 3 months, 6 months, 1 year, and 2 years after vertebral fracture in men (5.56%, 9.41%, 14.6%, and 20.61%, respectively) were higher than that in women (2.41%, 4.36%, 7.16%, and 10.48%, respectively). In both genders, the age-specific mortality rates were more than those of the general population. The SMR was highest during the first 3 months and gradually declined to 2.53 in men and 1.86 in women at the 2-year period. The incidence of vertebral fracture in South Korea was comparable with other countries such as Switzerland, and the mortality after vertebral fracture is higher than that of normal populations. The incidence of osteoporotic vertebral fracture and following high mortality are likely to become serious socioeconomic problems.

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.

Vertebral fractures are considered the most common fractures in osteoporosis. Nevertheless, little is known about the epidemiology of these fractures, especially in men. Therefore, the incidence of vertebral fractures was studied in 3469 men and women from the Rotterdam Study. Spinal radiographs were obtained at baseline and again after a mean follow-up of 6.3 years. The follow-up radiographs were scored for vertebral fractures using the McCloskey-Kanis assessment method. Whenever a vertebral fracture was detected, the radiograph was compared with the baseline radiograph. If this fracture was not already present at baseline, it was considered an incident fracture. The incidence increased strongly with age, ranging from 7.8/1,000 person years (PY) at ages 55-65 years to 19.6/1,000 PY at ages over 75 years for women, and 5.2-9.3/1,000 PY for men, respectively. Analyses repeated in strata of presence or absence of prevalent vertebral fractures showed that both in men and in women, the increase in incidence with age was almost exclusively observed in subjects with one or more prevalent fractures present at baseline. For both genders, the incidence of vertebral fractures doubled per SD decrease in lumbar spine or femoral neck bone mineral density (BMD). This study shows that overall, the incidence of vertebral fractures is higher in women-than in men. In both genders, the incidence increases with age. Furthermore, the presence of a prevalent vertebral fracture and a low BMD are strong independent predictors of incident vertebral fractures in men and women.

Bone mineral density (BMD) is an important predictor of future fracture risk in women; however, there are few prospective data in men. The aim of this analysis was to determine whether there are differences in the relationship between BMD and incident vertebral fracture in men and women. Men and women were recruited from population-based registers in 21 European centers. Those recruited were interviewed and had spinal radiographs performed. The radiographs were assessed morphometrically and prevalent vertebral deformity was defined using the McCloskey-Kanis method. Repeat spinal radiographs were performed at a mean of 3.8 years after the baseline radiographs. Incident fractures were defined using a combination of the point prevalence and 20% reduction in vertebral height (plus a 4-mm reduction in absolute height) criteria. BMD measurements were made in a subsample of those recruited. Poisson regression was used to explore the influence of gender, age, prevalent deformity, and BMD on the incidence of vertebral fracture. Thirty-four hundred sixty-one men and women had both paired spinal radiographs and bone density measurements performed. BMD at the spine and femoral neck was higher in men than in women. After adjusting for age, the risk of incident vertebral fracture was greater in women than in men (relative risk [RR] = 2.3; 95% CI, 1.5-3.6) and increased by a factor of 1.4 (95% CI, 1.2-1.8), 1.5 (95% CI, 1.2-1.8), and 1.6 (95% CI, 1.3-1.9) per decrease of 0.1 g/cm2 in BMD at the spine, femoral neck, and trochanter, respectively. After adjusting for BMD at the spine or trochanter, the gender difference in the predicted age-specific incidence of vertebral fracture was no longer significant (RR = 1.1 and 95% CI, 0.6-1.9 at the spine; RR = 1.5 and 95% CI, 0.8-2.7 at the trochanter), although it persisted after adjusting for femoral neck BMD (RR = 1.9; 95% CI, 1.1-3.3). The presence of a prevalent vertebral deformity was a strong risk factor for future vertebral fracture, although the strength of the association was reduced after adjustment for age, sex, and spine BMD. However, adjustment for the presence of a baseline vertebral deformity did not alter the main findings. In conclusion, at a given age and spine (although not femoral neck) bone density, the risk of incident vertebral fracture is similar in men and women. Incident vertebral fractures are more common in women than men because at any age their spine BMD is lower.

FRI0170 Incidence and Risk Factors for Osteoporotic Vertebral Fracture in Brazilian Community-Dwelling Elderly: A Population-Based Prospective Cohort Analysis from the SÃO Paulo Ageing & Health (SPAH) Study

Data on the relationship between disc degeneration (DD) and fragility fractures in men are limited. The aim of this study was to prospectively analyse the risk of vertebral and non-vertebral fractures in men with thoracolumbar DD according to the severity of its radiological signs: disc space narrowing (DSN), osteophytes and endplate sclerosis. Men >50 years of age (n = 765) had lateral spine radiographs and DXA and were monitored prospectively. We analysed the risk of incident vertebral (7.5 years) and non-vertebral fractures (10 years) in men according to the severity of DD. After adjustment for age and weight, BMD increased with increasing total DSN score, endplate sclerosis and osteophytosis. Over 7.5 years, 28 incident vertebral fractures occurred in 27 men. After adjustment for age, BMI, spine BMD, prior fractures and abdominal aortic calcifications, the vertebral fracture risk was 3-fold higher in the upper DSN quartile vs men without DSN. After adjustment for the same confounders, vertebral fracture risk was also nearly 3-fold higher in the upper DSN quartile vs the three lower quartiles combined. Over 10 years, 61 men sustained non-vertebral fragility fractures. After adjustment for age, BMI, hip BMD, abdominal aortic calcifications and prior falls and fractures, the non-vertebral fracture risk decreased with increasing DSN score. The risk of non-vertebral fracture was half as high in men above the median total DSN score vs men below the median. In older men, severe DD is associated with higher BMD. Multilevel severe DSN is associated with higher vertebral fracture risk and lower non-vertebral fracture risk.

This study assessed the effects of physical activity on a 10-year incidence of self-reported vertebral fractures in adult women of a large Japanese cohort. Medium levels of strenuous activity and long-duration sedentary activity were associated with a lower incidence of vertebral fractures; association patterns appear to be different from hip fractures. Physical activity helps prevent hip fracture, but little is known about the longitudinal association between physical activity and vertebral fractures. The purpose of this study was to evaluate the effects of physical activity on the 10-year incidence of symptomatic vertebral fractures using data from the Japan Public Health Center-based Prospective Study. Baseline studies were conducted in 1993-1994, and the follow-up study was conducted 10 years later. We analyzed 23,757 women aged 40-69 years. At baseline, physical activity was assessed as a predictor by using a questionnaire. Subjects were asked to report vertebral fractures that occurred during the 10-year follow-up period. Relative risks (RRs) adjusted for confounders were estimated by multiple logistic regression analysis. The 10-year cumulative incidence of vertebral fractures was 0.67%. Those who engaged in strenuous physical activity of <1 h/day had a significantly lower incidence of vertebral fractures than those who did not engage in such activity (RR = 0.52, 95% CI 0.28-0.97), while those engaged in such activity ≥1 h/day did not (RR = 0.82, 95% CI 0.58-1.14). Long-duration sedentary activity was associated with a low incidence of vertebral fractures (P for trend = 0.0002), but the frequencies of sports activities and metabolic equivalents were not (P for trend = 0.0729 and 0.4341, respectively). Strenuous activity and sedentary activity are associated with the incidence of vertebral fractures, although the association may not be linear. The pattern of association between physical activity and vertebral fractures appears to be different from that of hip fractures.

Low BMD and prevalent vertebral fractures are known risk factors for incident vertebral fractures. In 3001 men and women from the Rotterdam Study, prevalent nonvertebral fractures, early menopause, current smoking, and walking aid use were also strong risk factors for incident vertebral fractures. Thus far, age, low BMD, and prevalent vertebral fractures are the only well-known risk factors for incident vertebral fractures. Therefore, our aim was to investigate other potential risk factors for incident vertebral fractures in the elderly. This study was based on the Rotterdam Study, a large prospective population-based cohort study among men and women > or =55 years of age. For 3001 subjects, spinal radiographs were obtained at baseline and again approximately 6.3 years later. These follow-up radiographs were scored for vertebral fractures using the McCloskey-Kanis method. Whenever a vertebral fracture was detected, the radiograph was compared with the baseline radiograph. If this fracture was not already present at baseline, it was considered incident. At baseline, information on potential risk factors was obtained. Low BMD and prevalent vertebral fractures were strong risk factors for incident vertebral fractures in both men and women (RR 2.3 [1.6-3.3] and 2.2 [0.9-5.0] for men and RR 2.1 [1.6-2.6] and 4.1 [2.5-6.7] for women, respectively). For women, age, early menopause (< or =45 years of age; RR 1.0 [1.1-3.5]), current smoking (2.1 [1.2-3.5]), and walking aid use (2.5 [1.1-5.5]) were additional independent risk factors. For men, only a history of nonvertebral fractures was a significant independent risk factor (OR 2.4 [1.2-4.8]). Apart from low BMD and prevalent vertebral fractures, prevalent nonvertebral fractures are associated with an increased incident vertebral fracture risk in men. In women, early menopause, current smoking, and walking aid use are additional independent risk factors for incident vertebral fractures.

5056 Background: ADT increases bone resorption, reduces bone mineral density (BMD), and increases fracture risk. Previously, we reported that denosumab, a fully human monoclonal antibody against RANKL, increased BMD and reduced the incidence of vertebral fractures in men with PC on ADT. We now describe in further detail the effects of denosumab on fractures at other skeletal sites. Methods: Men receiving ADT for nonmetastatic PC were randomized to receive subcutaneous denosumab 60 mg every 6 months (n = 734) or placebo (n = 734), with daily calcium and vitamin D supplements for 3 years. Men &lt; 70 years old were required to have low BMD or a history of osteoporotic fracture. The primary endpoint was percentage change in lumbar spine BMD at 24 months. Key secondary endpoints were subject incidence of new vertebral fractures and fractures at any site (excluding fractures from severe trauma or pathologic fractures) over 3 years. Here, we evaluate the frequency of all fractures and fractures at key osteoporotic sites. The planned sample size (N = 1226) provided power to differentiate effects of denosumab from placebo for the primary and key secondary endpoints. Results: As previously reported, denosumab reduced the incidence of new vertebral fractures by 62% (p = 0.006), fractures at any site by 28% (p = 0.10), and multiple fractures at any site by 72% (p = 0.006) over 3 years. In a post-hoc analysis, we found a consistent trend showing a positive effect of denosumab on nonvertebral fractures. The occurrence of any fractures (counting all fractures within a subject) over 3 years was lower with denosumab than placebo (43 vs 77, p &lt; 0.01). The subject incidence of fractures at 6 high-risk sites (wrist, humerus, hip, pelvis, leg [excluding patella], and clavicle) was numerically lower with denosumab (15 vs 24 placebo; p = 0.12). Also, fewer subjects in the denosumab arm than in the placebo arm reported fractures at key osteoporotic sites (e.g., 2 for denosumab vs 10 for placebo at the radius). Overall rates of adverse events were balanced between treatment arms. Conclusions: Denosumab significantly reduced the incidence of new vertebral fractures and in a post-hoc analysis, showed a trend toward a positive effect on nonvertebral fractures in men receiving ADT for nonmetastatic PC. [Table: see text]

We ascertained the incidence and predictors of radiographic vertebral fracture in a Brazilian elderly cohort, since no data in this field have been reported in low-income countries. This is the first population-based study to demonstrate the high frequency of vertebral fracture in elderly Latin Americans. Age, prior fracture, BMD, and bone turnover were predictors of fracture. Vertebral fractures are associated with increased future fracture risk and mortality. No data on incidence of osteoporotic vertebral fracture have been reported in low-income countries where the population's aging has been faster. Thus, we sought to describe the incidence and risk factors for radiographic vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. 707 older adults (449 women and 258 men) were evaluated with spinal radiographs obtained at baseline and after a mean follow-up of 4.3 ± 0.8 years. New vertebral fracture was defined as distinct alteration in the morphology of vertebrae resulting in higher grade of deformity on the second radiograph when compared to the baseline radiograph. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. Multivariate Poisson regression models were used to identify independent predictors of fracture. The age-standardized incidence of vertebral fracture was 40.3/1,000 person-years in women and 30.6/1,000 in men. In women, three models of risk factors for fracture were fitted: (1) age (relative risks (RR) 2.46, 95 % confidence interval (CI) 1.66-3.65), previous osteoporotic fracture (RR 1.65, 95 % CI 1.00-2.71), and lumbar spine BMD (RR 1.21, 95 % CI 1.03-1.41); (2) age (RR 2.25, 95 % CI 1.52-3.34) and femoral neck BMD (RR 1.42, 95 % CI 1.11-1.81); (3) age (RR 2.11, 95 % CI 1.41-3.15) and total hip BMD (RR 1.56, 95 % CI 1.21-2.0). In men, the highest quartile of cross-linked C-telopeptide (CTx) (RR 1.96, 95 % CI 0.98-3.91) and prior fracture (RR 2.10, 95 % CI 1.00-4.39) were predictors of new vertebral fracture. This is the first population-based study to ascertain the incidence of vertebral fracture in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, BMD, and bone turnover were predictors of the short-term incidence of vertebral fracture.

This prospective four-year study indicates that post-menopausal osteoporotic women with mild prevalent and incident vertebral fractures have an increased risk of incident fractures. Mild vertebral fractures are under diagnosed as there is disagreement about their clinical significance. Our aim was to assess the risk of subsequent fractures induced by both prevalent and incident mild vertebral fractures in osteoporotic post-menopausal women. Three thousand three hundred and fifty-eight patients, aged 74 +/- 6 years, with post-menopausal osteoporosis included in the placebo groups of two clinical trials of strontium ranelate were followed for 4 years. A Cox regression model adjusted on age, body mass index and bone mineral density was used to calculate the relative risk (RR) of fracture in subjects with only mild fractures as compared to patients without fracture, and to patients with at least one grade >or= 2 fracture. These calculations were made for prevalent and then incident fractures. The RR of vertebral fracture in 4 years was 1.8 (1.3-2.4) p < 0.001, and 2.7 (2.3-3.3) p < 0.001 for patients having only mild vertebral fractures and at least one grade >or= 2 fracture at baseline respectively. The RR of vertebral fracture in the 3rd and 4th years of follow-up was 1.7 (1.1-2.6) p = 0.01, and 1.9 (1.3-2.6) p < 0.001 for patients having during the first 2 years incident mild fractures only, and for patients having at least one grade >or= 2 incident fracture respectively. The RR of non-vertebral fracture in 4 years was 1.3 (0.9-1.9) p = 0.15 and 1.7 (1.4-2.1) p < 0.001 for patients having only mild or at least one grade >or= 2 vertebral fracture at baseline respectively. For patients aged more than 70 years, these RR were 1.45 (0.99-2.11) (p = 0.06), and 1.72 (1.36-2.18) p < 0.001 respectively. The RR of non-vertebral fracture in the 3rd and 4th years was 1.68 (1.36-2.09) p < 0.001 for patients having at least one grade >or= 2 incident fracture during the 2 first years of follow-up. Mild vertebral fractures are a risk factor for subsequent vertebral and non-vertebral fracture in postmenopausal women with osteoporosis; 1 out of 4 patients with an incident mild vertebral fracture in 2 years will fracture again within the 2 next years.

To the Editor We appreciate that Dr. E. Kanterewicz et al. have shown interest in our study, in which we investigated associations between grade 1 vertebral fracture (VF), verified by vertebral fracture assessment (VFA), and incident fractures.(1) In their Letter, the authors point out that prior to our study, they had reported that VFA-verified prevalent minor vertebral deformities (MVDs) were associated with an increased risk of incident VFA-verified VF.(2) They also refer to other publications about associations between prevalent VF and incident VF, diagnosed by VFA.(3-5) Indeed, all these reports and our recent study to some extent support the usefulness of VFA to detect VF, and the importance of prevalent VF, including grade 1 VF or MVD, in assessing fracture risk in postmenopausal women. Although there are similarities between previous studies and our study, there are important differences. Kanterewicz et al.(2) examined a considerably younger age group (59–70 years) than the population of older women (75–80 years) included in our study. This is reflected by the large difference in VF prevalence at study inclusion (24.2% compared to 4.1%). In the study by Kanterewicz et al.,(2) both a morphometric classification and the Genant methods were used to identify VF, in contrast to our study, which solely utilized the Genant method, making it difficult to compare the results. It is also a fair assumption, that in the age group 75 to 80 years, identifying mild VFs is more challenging because of commonly present osteoarthritis, scoliosis, and sometimes impaired image quality, due to positioning difficulties, compared to younger age groups. As pointed out, by Kanterewicz et al. in their Letter, the study from Kadowaki et al.(3) found that prevalent vertebral deformities in middle-aged Japanese women were associated with a threefold increased risk for subsequent VF, but the prevalent vertebral deformities were not graded. Thus, the impact of mild vertebral deformities was not addressed, disabling a meaningful comparison with the results obtained in our study.(3) Ferrar et al.(4) graded prevalent VFs but could not find a significant association between prevalent mild VF and incident VF after adjustment for age and total hip bone mineral density (BMD). They also concluded that among postmenopausal women without prevalent VF but with short vertebral height (SVH) there was no association between SVH and incident VF.(4) Interestingly, this result contradicts the findings by Kanterewicz et al.(2) that MVD (vertebral height ratios between –2 and –2.99 standard deviations [SDs] below the reference) confers an increased risk of subsequent VF. Greendale et al.(5) found that two-thirds of the prevalent vertebral deformities were grade 1. They investigated the incidence rate of vertebral deformities but failed to detect a predictive role of grade 1 vertebral deformity on incident fracture.(5) However, the investigated population was considerably younger, and both the prevalence and incidence of VF much lower than in our study, arguably reducing the relevance of the comparison. Kanterewicz et al. further commented that the associations between grade 1 VFs, incident any fracture and incident VF, were dependent on BMD in our study. In fact, the association with incident any fracture (adjusting for all risk factors and BMD) was borderline significant (hazard ratio [HR] of 1.51; 95% confidence interval [CI], 0.98–2.34) and for incident VF, the risk estimates highly similar, but with much wider 95% CI (HR 1.52; 95% CI, 0.71–3.25). Our interpretation is that these results do not support lack of independent association between grade 1 VF and fracture incidence, but rather of the opposite, with the nonsignificant result being due to the low number of fractures and the resulting insufficient statistical power in the analyses, especially regarding incident VFs. Kanterewicz et al. argue that the incidences of VF in our study and in theirs were very similar. We disagree. Kanterewicz et al.(2) used follow-up scans to identifying incident VFs in their cohort, in contrast to our study, in which we only used digital x-rays to verify clinical fractures, which have a much lower incidence than morphometric VFs. Thus, the incidence ratios for VFs cannot be compared between studies. Finally, we can agree with Kanterewicz et al., and as stated in the introduction of our publication, that the literature is inconclusive regarding the role of grade 1 VF in predicting future fragility fractures. We believe that our study and those discussed herein contribute to the understanding of the clinical importance of grade 1 VFs. The authors have no conflicts of interest or relationships to disclose. Lisa Johansson: Conceptualization; data curation; formal analysis; investigation; methodology; project administration; software; validation; writing-original draft; writing-review & editing. Mattias Lorentzon: Conceptualization; data curation; formal analysis; funding acquisition; investigation; methodology; project administration; resources; software; supervision; validation; writing-original draft; writing-review & editing.

THU0094 Incidence and Predictors of Morphometric Vertebral Fractures in Patients with Ankylosing Spondylitis

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.