Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial

Prevalent vertebral fractures and baseline bone mineral density (BMD) predict subsequent fracture risk. The objective of this analysis is to examine whether baseline vertebral fracture severity can predict new vertebral and nonvertebral fracture risk. In the randomized, double-blind 3-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis (low BMD or prevalent vertebral fractures) were randomly assigned to placebo, raloxifene 60 mg/day, or raloxifene 120 mg/day. Post hoc analyses studied the association between baseline fracture severity and new fracture risk in the placebo group and the effects of placebo, raloxifene 60 mg/day, and raloxifene 120 mg/day on new fracture risk in women with the most severe prevalent vertebral fractures (n = 614). Vertebral fracture severity was visually assessed using semiquantitative analysis of radiographs and categorized by estimated decreases in vertebral heights. Reported new nonvertebral fractures were radiographically confirmed. Baseline vertebral fracture severity predicted vertebral and nonvertebral fracture risk at 3 years. In women without prevalent vertebral fractures, 4.3 and 5.5% had new vertebral and nonvertebral fractures, respectively. In women with mild, moderate, and severe prevalent vertebral fractures, 10.5, 23.6, and 38.1% respectively had new vertebral fractures, whereas 7.2, 7.7, and 13.8% respectively experienced new nonvertebral fractures. Number of prevalent vertebral fractures and baseline BMD also predicted vertebral fracture risk, but the severity of prevalent vertebral fractures was the only predictor of nonvertebral fracture risk and remained a significant predictor after adjustment for baseline characteristics, including baseline BMD. In patients with severe baseline vertebral fractures, raloxifene 60 mg/day decreased the risks of new vertebral [RR 0.74 (95% Cl 0.54, 0.99); P = 0.048] and nonvertebral (clavicle, humerus, wrist, pelvis, hip, and leg) fractures [RH 0.53 (95% CI 0.29, 0.99); P = 0.046] at 3 years. To prevent one new fracture at 3 years in women with severe baseline vertebral fractures with raloxifene 60 mg/day, the number needed to treat (NNT) was 10 for vertebral and 18 for nonvertebral fractures. Similar results were observed in women receiving raloxifene 120 mg/day. In summary, baseline vertebral fracture severity was the best independent predictor for new vertebral and nonvertebral fracture risk. Raloxifene decreased new vertebral and nonvertebral fracture risk in the subgroup of women with severe vertebral fractures at baseline. These fractures may reflect architectural deterioration, independent of BMD, leading to increased skeletal fragility.     

Mild morphometric vertebral fractures predict vertebral fractures but not non-vertebral fractures

Summary

In this meta-analysis of the control arms of four phase 3 trials, mild vertebral fractures were a significant risk factor for future vertebral fractures but not for non-vertebral fracture.

Introduction

A prior vertebral fracture is a risk factor for future fracture that is commonly used as an eligibility criterion for treatment and in the assessment of fracture probability. The aim of this study was to determine the prognostic significance of a morphometric fracture according to the severity of fracture.

Methods

We examined the control (placebo) treated arms of four phase 3 trials. Vertebral fracture status was graded at baseline in 7,623 women, and fracture outcomes were documented over the subsequent 20,000 patient-years. Fracture outcomes were characterised as a further vertebral fracture, a non-vertebral fracture or a clinical fracture (non-vertebral plus clinical vertebral fracture). The relative risk of fracture was computed from the merged β coefficients of each trial weighted according to the variance.

Results

Mild vertebral fractures were a significant risk factor for vertebral fractures [risk ratio (RR)?=?2.17; 95 % CI?=?1.70–2.76] but were not associated with an increased risk of non-vertebral fractures (RR?=?1.08; 95 % CI?=?0.86–1.36). Moderate/severe vertebral fractures were associated with a high risk of vertebral fractures (RR?=?4.23; 95 % CI?=?3.58–5.00) and a moderate though significant increase in non-vertebral fracture risk (RR?=?1.64; 95 % CI?=?1.38–1.94).

Conclusions

Prior moderate/severe morphometric vertebral fractures are a strong and significant risk factor for future fracture. The presence of a mild vertebral fracture is of no significant prognostic value for non-vertebral fractures. These findings should temper the use of morphometric fractures in the assessment of risk and the design of phase 3 studies.     

Prevalent vertebral fractures predict subsequent radiographic vertebral fractures in postmenopausal Korean women receiving antiresorptive agent

Summary  

The relationship between prevalent vertebral fractures and new vertebral fractures in Korean women has not been previously studied. We found that prevalent vertebral fracture is a strong risk factor for subsequent radiographic vertebral fracture, independent of age and spine bone mineral density (BMD) in postmenopausal Korean women receiving antiresorptive agents.     

Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of Osteoporotic Fractures Research Group.

Although vertebral deformities are known to predict future vertebral deformities, little is known about their ability to predict other osteoporotic fractures. We examined the association between prevalent vertebral deformities and incident osteoporotic fractures in the Study of Osteoporotic Fractures, a prospective study of 9704 women aged 65 years and older. Prevalent vertebral deformities were determined morphometrically from spinal radiographs at baseline and incident deformities from repeat spinal radiographs after a mean of 3.7 years. Appendicular fractures were collected by postcard every 4 months for a mean of 8.3 years. During follow-up, 389 women with new vertebral deformities, 464 with hip fractures, and 574 with wrist fractures were identified. Prevalent vertebral deformities were associated with a 5-fold increased risk (relative risk 5.4, 95% confidence interval [CI] 4.4, 6.6) of sustaining a further vertebral deformity; the risk increased dramatically with both the number and severity of the prevalent deformities. Similarly, the risks of hip and any nonvertebral fractures were increased with baseline prevalent deformity, with relative risks of 2.8 (95% CI 2.3, 3.4) and 1.9 (95% CI 1.7, 2.1), respectively. Risk increased with number and severity of deformities. These associations remained significant after adjustment for age and calcaneal bone mineral density (BMD). Although there was a small increased risk of wrist fracture, this was not significant after adjusting for age and BMD. In conclusion, the presence of prevalent morphometrically defined vertebral deformities predicts future vertebral and nonvertebral fractures, including hip but not wrist fractures. Spinal radiographs identifying prevalent vertebral deformities may be a useful additional measurement to classify further a woman's risk of future fracture.     

Risk factors for incident vertebral fractures in men and women: the Rotterdam Study.

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. INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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]). CONCLUSION: 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.     

Association between self-reported prior wrist fractures and risk of subsequent hip and radiographic vertebral fractures in older women: a prospective study.

In this large prospective cohort study of elderly women, the relationships between prior wrist fracture and incident hip and radiographic vertebral fractures were significantly attenuated when adjusted for BMD. This study suggests that BMD thresholds for drug therapy to prevent osteoporotic fracture should be only modestly adjusted in those with prior wrist fracture compared with those without prior wrist fracture. Validation of such an approach would require intervention trials in patients with prior wrist fracture. INTRODUCTION: Prior wrist fracture has been identified as a risk factor for incident hip and vertebral fractures and proposed as a criterion for determining who should be offered drug therapy to prevent osteoporotic fracture, even if their hip BMD T score is > -2.5. Previously published studies of the relationships between prior wrist fracture and incident hip and vertebral fractures did not adjust for BMD. MATERIALS AND METHODS: We ascertained prior history of wrist fracture since age 50, measured calcaneal and hip BMD, and performed lateral spine films in a cohort of 9704 elderly community-dwelling women, and then followed them prospectively for incident vertebral and hip fractures. Incident vertebral fractures were defined by morphometry using lateral spine radiography at the first examination and an average of 3.7 years later. Incident hip fractures were confirmed with radiographic reports over a mean follow-up period of 10.1 years. RESULTS: Prior wrist fracture was associated with an age-adjusted 72% increased odds of incident radiographic vertebral fracture (odds ratio [OR], 1.72; 95% CI, 1.31-2.25). After adjustment for calcaneal BMD, the association of prior wrist fracture with incident radiographic vertebral fracture was attenuated (OR, 1.39; 95% CI, 1.05-1.83). Prior wrist fracture was also associated with an age-adjusted 43% excess rate of incident hip fracture (hazards ratio [HR], 1.43; 95% CI, 1.17-1.74). After adjustment for hip BMD, the association of prior wrist fracture with rate of incident hip fracture was no longer statistically significant (HR, 1.12; 95% CI, 0.92-1.38). CONCLUSION: In elderly women, prior wrist fracture is a risk factor for radiographic vertebral fracture independent of BMD. The association between prior wrist fracture and incident hip fracture is largely explained by hip BMD. Modest adjustment of BMD drug treatment thresholds for prevention of osteoporotic fractures in those with prior wrist fracture compared with those without prior wrist fracture may be reasonable, but validation of such an approach would require intervention trials in patients with prior wrist fracture.     

Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial.

We used data from the Fracture Intervention Trial to assess the relationship change in bone turnover after 1 year of alendronate or placebo treatment and subsequent hip, non-spine, and spine fracture risk among 6186 postmenopausal women. In the alendronate group (n = 3105), greater reductions in one or more biochemical marker were associated with a lower risk of fracture. INTRODUCTION: There are few data on the relationship between short-term change in biochemical markers of bone turnover and non-spine fracture risk among bisphosphonate-treated women, and the clinical use of such measurements is unknown. MATERIALS AND METHODS: We measured biochemical markers of bone turnover (bone-specific alkaline phosphatase [bone ALP], intact N-terminal propeptide of type I collagen, and C-terminal crosslinked telopeptide of type 1 collagen) and BMD of the spine and hip at baseline and after 1 year of alendronate or placebo. During a mean follow-up of 3.6 years, 72 hip, 786 non-spine, and 336 vertebral fractures were documented. RESULTS AND CONCLUSIONS: Each 1 SD reduction in 1-year change in bone ALP was associated with fewer spine (odds ratio = 0.74; CI: 0.63, 0.87), non-spine (relative hazard [RH] = 0.89; CI: 0.78, 1.00; p < 0.050), and hip fractures (RH = 0.61; CI: 0.46, 0.78). Alendronate-treated women with at least a 30% reduction in bone ALP had a lower risk of non-spine (RH = 0.72; CI: 0.55, 0.92) and hip fractures (RH = 0.26; CI: 0.08, 0.83) relative to those with reductions <30%. We conclude that greater reductions in bone turnover with alendronate therapy are associated with fewer hip, non-spine, and vertebral fractures, and the effect is at least as strong as that observed with 1-year change in BMD.     

Risk factors for prevalent vertebral fractures in black and white female densitometry patients.

This cross-sectional study compared risk factors for prevalent vertebral fractures (diagnosed using densitometric spine image Vertebral Fracture Assessment [VFA]) in 176 black and 345 white women recruited during their clinical bone mineral density (BMD) testing at the University of Chicago Hospitals. We used logistic regression to assess the association of prevalent vertebral fractures and risk factors (age, height loss, history of nonvertebral fractures, BMD, and use of corticosteroids). The prevalence of vertebral fractures was 21% for both races. All risk factors of interest were significantly associated with vertebral fractures in white women. Among black women, only age and corticosteroid use were found to be significant predictors of presence of vertebral fracture(s). In women without history of corticosteroid use, the probability of having vertebral fracture(s) given age was lower (p=0.02) in black subjects. In 77 patients with a history of corticosteroid use, the probability of having vertebral fracture(s) was higher in black than in white women after adjustment for age (p=0.045), BMD (p=0.045), or cumulative corticosteroid dose (p=0.08). Fewer black women were prescribed pharmacologic therapy for osteoporosis, regardless of their BMD level and corticosteroid use. We conclude that use of corticosteroids may be associated with relatively greater vertebral fracture risk in blacks than in whites.     

Enhanced prediction of fracture risk combining vertebral fracture status and BMD

Summary 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. Background 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. Methods 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. Results 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. Conclusions 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. This study was supported by Eli Lilly and Company.     

Fracture prediction from bone mineral density in Japanese men and women.

In a cohort of 2356 Japanese elderly, after adjusting for age and prevalent vertebral fracture, baseline BMD predicted the risk of spine and hip fracture with similar RR to that obtained from previous reports in whites. The RR per SD decrease in BMD for fracture declined with age. INTRODUCTION: Low bone mineral density (BMD) is one of the most important predictors of a future fracture. However, we are not aware of any reports among Japanese in Japan. MATERIALS AND METHODS: We examined the association of BMD with risk of fracture of the spine or hip among a cohort of 2356 men and women aged 47-95 years, who were followed up by biennial health examinations. Follow-up averaged 4 years after baseline measurements of BMD that were taken with the use of DXA. Vertebral fracture was assessed using semiquantitative methods, and the diagnosis of hip fracture was based on medical records. Poisson and Cox regression analysis were used. RESULTS: The incidence was twice as high in women as in men, after adjusting for age. After adjusting for baseline BMD and prevalent vertebral fracture, however, the gender difference was no longer significant. Age, baseline BMD of spine and femoral neck, and prior vertebral fracture predicted vertebral fracture and hip fracture. Loss of absolute BMD of the femoral neck predicted spine fracture, after adjusting for baseline BMD; rates of change in percent BMD, weight, height, body mass index, and age at menopause did not. The predictive value of baseline BMD for vertebral fracture risk was similar in men and women. The relative risk (RR) for vertebral fracture and hip fracture per SD decrease in BMD declined with age, after adjustment for prevalent vertebral fractures. CONCLUSIONS: Baseline BMD, loss of femoral neck BMD, and prior vertebral fracture predict the risk of spine and hip fracture in Japanese with similar RR to that obtained from previous reports in whites. The RR per SD decrease in BMD for fracture declined with age, suggesting that factors other than BMD might play a greater role in the elderly.     

Thoracic kyphosis and rate of incident vertebral fractures: the Fracture Intervention Trial

Summary

Biomechanical analyses support the theory that thoracic spine hyperkyphosis may increase risk of new vertebral fractures. While greater kyphosis was associated with an increased rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture.

Introduction

Biomechanical analyses suggest hyperkyphosis may increase risk of incident vertebral fracture by increasing the load on vertebral bodies during daily activities. We propose to assess the association of kyphosis with incident radiographic vertebral fracture.

Methods

We used data from the Fracture Intervention Trial among 3038 women 55–81 years of age with low bone mineral density (BMD). Baseline kyphosis angle was measured using a Debrunner kyphometer. Vertebral fractures were assessed at baseline and follow-up from lateral radiographs of the thoracic and lumbar spine. We used Poisson models to estimate the independent association of kyphosis with incident fracture, controlling for age and femoral neck BMD.

Results

Mean baseline kyphosis was 48° (SD?=?12) (range 7–83). At baseline, 962 (32 %) participants had a prevalent fracture. There were 221 incident fractures over a median of 4 years. At baseline, prevalent fracture was associated with 3.7° greater average kyphosis (95 % CI 2.8–4.6, p?<?0.0005), adjusting for age and femoral neck BMD. Before adjusting for prevalent fracture, each 10° greater kyphosis was associated with 22 % increase (95 % CI 8–38 %, p?=?0.001) in annualized rate of new radiographic vertebral fracture, adjusting for age and femoral neck BMD. After additional adjustment for prevalent fracture, estimated increased annualized rate was attenuated and no longer significant, 8 % per 10° kyphosis (95 % CI ?4 to 22 %, p?=?0.18).

Conclusions

While greater kyphosis increased the rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture.

     

The associations between QCT-based vertebral bone measurements and prevalent vertebral fractures depend on the spinal locations of both bone measurement and fracture

Summary

We examined how spinal location affects the relationships between quantitative computed tomography (QCT)-based bone measurements and prevalent vertebral fractures. Upper spine (T4–T10) fractures appear to be more strongly related to bone measures than lower spine (T11–L4) fractures, while lower spine measurements are at least as strongly related to fractures as upper spine measurements.

Introduction

Vertebral fracture (VF), a common injury in older adults, is most prevalent in the mid-thoracic (T7–T8) and thoracolumbar (T12–L1) areas of the spine. However, measurements of bone mineral density (BMD) are typically made in the lumbar spine. It is not clear how the associations between bone measurements and VFs are affected by the spinal locations of both bone measurements and VF.

Methods

A community-based case–control study includes 40 cases with moderate or severe prevalent VF and 80 age- and sex-matched controls. Measures of vertebral BMD, strength (estimated by finite element analysis), and factor of risk (load:strength ratio) were determined based on QCT scans at the L3 and T10 vertebrae. Associations were determined between bone measures and prevalent VF occurring at any location, in the upper spine (T4–T10), or in the lower spine (T11–L4).

Results

Prevalent VF at any location was significantly associated with bone measures, with odds ratios (ORs) generally higher for measurements made at L3 (ORs?=?1.9–3.9) than at T10 (ORs?=?1.5–2.4). Upper spine fracture was associated with these measures at both T10 and L3 (ORs?=?1.9–8.2), while lower spine fracture was less strongly associated (ORs?=?1.0–2.4) and only reached significance for volumetric BMD measures at L3.

Conclusions

Closer proximity between the locations of bone measures and prevalent VF does not strengthen associations between bone measures and fracture. Furthermore, VF etiology may vary by region, with VFs in the upper spine more strongly related to skeletal fragility.     

The population burden of fractures originates in women with osteopenia, not osteoporosis

Introduction Osteoporosis is associated with increased risk for fracture. However, most postmenopausal women have bone mineral density (BMD) within the normal or osteopenic range. The aim of this study was to determine the proportion of the population burden of fragility fractures arising from women at modest risk for fracture.Methods We measured baseline BMD in a population-based random sample of 616 postmenopausal women aged 60–94 years and followed these individuals for a median of 5.6 years (IQR 3.9–6.5) to determine the incidence of fractures according to age, BMD and the presence of a prior fracture.Results Based on WHO criteria, 37.6% of the women had normal total hip BMD, 48.0% had osteopenia and 14.5% had osteoporosis. The incidence of fracture during follow-up was highest in women with osteoporosis, but only 26.9% of all fractures arose from this group; 73.1% occurred in women without osteoporosis (56.5% in women with osteopenia, 16.6% in women with normal BMD). Decreasing BMD, increasing age and prior fracture contributed independently to increased fracture risk; in a multivariate model, the relative risk for fracture increased 65% for each SD decrease in BMD (RR=1.65, 95%CI 1.32–2.05), increased 3% for every year of age (RR=1.03, 95%CI 1.01–1.06) and doubled with prevalent fracture (RR=2.01, 95% CI 1.40–2.88). A prevalent fracture increased the risk for fractures such that women with osteopenia and prevalent fracture had the same, if not greater, risk as women with osteoporosis alone.Conclusions Reducing the population burden of fractures requires attention to women with osteopenia, as well as osteoporosis, because over half of the fragility fractures in the population arise in these individuals, and women with osteopenia plus a prevalent fracture have the same fracture risk as women with osteoporosis.     

Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study

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.This work was presented in part at the 30th European Symposium on Calcified Tissues, 8–12 May 2003, Rome, Italy.A.J. Silman and J. Reeve are the EU Grant holders and Project Leaders.     

Association between prior non-spine non-hip fractures or prevalent radiographic vertebral deformities known to be at least 10 years old and incident hip fracture.

In this large cohort of elderly women, prior non-spine non-hip fractures and radiographic vertebral deformities >10 years old were modestly associated with incident hip fracture, but the excess risks of hip fracture attributable to those prior fractures and deformities seem to wane over time. INTRODUCTION: Whereas prior clinical fractures and prevalent radiographic vertebral deformities are well-documented predictors of incident hip fracture, the excess risks of incident fractures attributable to those prior fractures and deformities may decrease over time. Current guidelines regarding the assessment of fracture risk do not consider elapsed time since prior fracture or ascertainment of radiographic vertebral deformity. MATERIALS AND METHODS: We ascertained self-reported history of prior clinical fractures and calcaneal and total hip bone BMD and performed lateral spine radiographs in a cohort of 9516 community-dwelling elderly women who had not had a prior hip fracture. We prospectively followed them to assess incident hip fracture. Prevalent radiographic vertebral deformities were identified at baseline using morphometry, and incident hip fractures were confirmed by review of radiographic reports during three follow-up periods (0-5, >5-10, and >10 years after baseline exam). RESULTS: Among women who survived for 10 or more years after the baseline exam without having had a hip fracture, a history of non-spine non-hip fracture since age 50 reported at the baseline study examination was associated with a 21% age- and calcaneal BMD-adjusted excess risk (hazard ratio [HR], 1.21; 95% CI, 1.01-1.45) for subsequent incident hip fracture. Baseline radiographic vertebral deformity was associated with a 41% age- and BMD-adjusted excess risk (HR, 1.41; 95% CI, 1.15-1.73) of hip fracture after 10 years of follow-up. In comparison, the age- and BMD-adjusted HRs of incident hip fracture during the first 5 years of follow-up associated with prior non-spine non-hip fractures reported at the baseline study exam and prevalent radiographic vertebral deformities were 1.70 (95% CI, 1.30-2.22) and 2.10 (95% CI, 1.58-2.78), respectively. CONCLUSIONS: Self-reported prior non-spine non-hip fractures and prevalent radiographic vertebral deformities known to be at least 10 years old are modestly associated with incident hip fracture. The association between these predictor fractures and subsequent hip fractures seems to wane with increased time after ascertainment of the predictor fracture. Hip fracture risk assessment strategies incorporating prior fracture history should also consider elapsed time since those prior fractures.     

The prevalence and risk factors of vertebral fractures in Korea

We investigated the prevalence and risk factors of vertebral fractures in Korea. In a community-based prospective epidemiology study, 1,155 men and 1,529 women (mean age 59?years, range 43-74) were recruited from Ansung, a rural Korean community. Prevalent vertebral fractures were identified on the lateral spinal radiographs at T11 to L4 using vertebral morphometry. Bone mineral density (BMD) was measured at the lumbar spine, femur neck and total hip. Of the 2,684 subjects, 137 (11.9%) men and 227 (14.8%) women had vertebral fractures and the standardized prevalence for vertebral fractures using the age distribution of Korean population was 8.8% in men and 12.6% in women. In univariate analysis, older age, low hip circumference, low BMD, low income and education levels in both sexes, previous history of fracture in men, high waist-to-hip circumference ratio, postmenopausal status, longer duration since menopause, and higher number of pregnancies and deliveries in women were associated with an increased risk of vertebral fractures. However, after adjusting for age, only low BMD in both sexes and a previous history of fracture in men were significantly associated with an increased risk of vertebral fractures. Vertebral fractures are prevalent in Korea as in other countries. Older age, low BMD and a previous history of fracture are significant risk factors for vertebral fractures.     

Hyperkyphosis,Kyphosis Progression,and Risk of Non‐Spine Fractures in Older Community Dwelling Women: The Study of Osteoporotic Fractures (SOF)

While accentuated kyphosis is associated with osteoporosis, it is unknown whether it increases risk of future fractures, independent of bone mineral density (BMD) and vertebral fractures. We examined the associations of baseline Cobb angle kyphosis and 15 year change in kyphosis with incident non‐spine fractures using data from the Study of Osteoporotic Fractures. A total of 994 predominantly white women, aged 65 or older, were randomly sampled from 9704 original participants to have repeated Cobb angle measurements of kyphosis measured from lateral spine radiographs at baseline and an average of 15 years later. Non‐spine fractures, confirmed by radiographic report, were assessed every 4 months for up to 21.3 years. Compared with women in the lower three quartiles of kyphosis, women with kyphosis greater than 53° (top quartile) had a 50% increased risk of non‐spine fracture (95% CI, 1.10–2.06 after adjusting for BMD, prevalent vertebral fractures, prior history of fractures, and other fracture risk factors. Cobb angle kyphosis progressed an average of 7° (SD = 6.8) over 15 years. Per 1 SD increase in kyphosis change, there was a multivariable adjusted 28% increased risk of fracture (95% CI, 1.06–1.55) that was attenuated by further adjustment for baseline BMD (HR per SD increase in kyphosis change, 1.19; 95% CI 0.99–1.44). Greater kyphosis is associated with an elevated non‐spine fracture risk independent of traditional fracture risk factors in older women. Furthermore, worsening kyphosis is also associated with increased fracture risk that is partially mediated by low baseline BMD that itself is a risk factor for kyphosis progression. These results suggest that randomized controlled fracture intervention trials should consider implementing kyphosis measures to the following: (1) further study kyphosis and kyphosis change as an additional fracture risk factor; and (2) test whether therapies may improve or delay its progression. © 2014 American Society for Bone and Mineral Research.     

Smoking predicts incident fractures in elderly men: Mr OS Sweden

The aim of this study was to investigate the association between smoking and bone mineral density (BMD) and radiographically verified prevalent vertebral fractures and incident fractures in elderly men. At baseline 3003 men aged 69 to 80 years of age from the Swedish Mr Os Study completed a standard questionnaire concerning smoking habits and had BMD of the hip and spine measured using dual‐energy X‐ray absorptiometry (DXA); 1412 men had an X‐ray of the thoracic‐ and lumbar spine. Radiologic registers were used to confirm reported new fractures after the baseline visit. At baseline, 8.4% were current smokers. Current smokers had a 6.2% lower BMD at the total hip and a 5.4% lower BMD at the lumbar spine (p < .001). Current smoking remained independently inversely associated with BMD at the hip and lumbar spine after adjusting for age, height, weight, calcium intake, physical activity, and centers as covariates. Prevalent vertebral fractures among current smokers were increased in unadjusted analyses [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.26–2.87] and after adjustment for lumbar BMD (OR = 1.67, 95% CI 1.09–2.55). Smokers had a high risk for two or more prevalent vertebral fractures (OR = 3.18, 95% CI 1.88–5.36). During the average follow‐up of 3.3 years, 209 men sustained an X‐ray‐verified fracture. Incident fracture risk among smokers was calculated with Cox proportional hazard models. Current smokers had an increased risk of all new fractures [hazard ratio (HR) = 1.76, 95% CI 1.19–2.61]; nonvertebral osteoporotic fractures, defined as humerus, radius, pelvis, and hip fractures (HR = 2.14, 95% CI 1.18–3.88); clinical and X‐ray‐verified vertebral fractures (HR = 2.53, 95% CI 1.37–4.65); and hip fractures (HR = 3.16, 95% CI 1.44–6.95). After adjustment for BMD, including other covariates, no significant association between smoking and incident fractures was found. Current tobacco smoking in elderly men is associated with low BMD, prevalent vertebral fractures, and incident fractures, especially vertebral and hip fractures. © 2010 American Society for Bone and Mineral Research     

Bone mineral density and prevalent vertebral fractures in men and women

To test the hypothesis that the association between bone mineral density (BMD) and estimated volumetric BMD and prevalent vertebral fractures differs in men and women, we studied 317 Caucasian men and 2,067 Caucasian women (average age 73 years). A total of 43 (14%) men and 386 (19%) women had a vertebral fracture identified on lateral spine radiographs using vertebral morphometry. Hip and spine areal BMD was about 1/3 standard deviation lower among men and women with a vertebral fracture. A 0.10 g/cm² decrease in areal BMD was associated with 30–40% increased odds of having a fracture in men and 60–70% increased likelihood in women. Low bone mineral apparent density (BMAD) was also associated with 40–50% increased odds of a vertebral fracture in both genders. The probability of a man having a fracture was observed at higher absolute areal BMD values than observed for women (P=values for interaction of BMD × gender: trochanter, P=0.05; femoral neck, P=0.10; total hip, P=0.09). In contrast, the probability of fracture was similar in men and women across the range of estimated volumetric BMD (BMAD). In conclusion, low BMD and low BMAD are associated with increased odds of vertebral fracture in both men and women. Measures of bone mass that partially correct for gender differences in bone size may yield universal estimates of fracture risk. Prospective studies are needed to confirm this observation.     

Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis.

Numerous studies have reported increased risks of hip, spine, and other fractures among people who had previous clinically diagnosed fractures, or who have radiographic evidence of vertebral fractures. However, there is some variability in the magnitudes of associations among studies. We summarized the literature and performed a statistical synthesis of the risk of future fracture, given a history of prior fracture. The strongest associations were observed between prior and subsequent vertebral fractures; women with preexisting vertebral fractures (identified at baseline by vertebral morphometry) had approximately 4 times greater risk of subsequent vertebral fractures than those without prior fractures. This risk increases with the number of prior vertebral fractures. Most studies reported relative risks of approximately 2 for other combinations of prior and future fracture sites (hip, spine, wrist, or any site). The confidence profile method was used to derive a single pooled estimate from the studies that provided sufficient data for other combinations of prior and subsequent fracture sites. Studies of peri- and postmenopausal women with prior fractures had 2.0 (95 % CI = 1.8, 2.1) times the risk of subsequent fracture compared with women without prior fractures. For other studies (including men and women of all ages), the risk was increased by 2.2 (1.9, 2.6) times. We conclude that history of prior fracture at any site is an important risk factor for future fractures. Patients with a history of prior fracture, therefore, should receive further evaluation for osteoporosis and fracture risk.