Severity Of Prevalent Vertebral Fractures Research Articles

Prevalent Morphometrically Assessed Vertebral Fractures in Individuals With Type 2 Diabetes, Prediabetes and Normal Glucose Metabolism: The Maastricht Study.

BackgroundType 2 diabetes (T2D) is frequently reported to be associated with an increased fracture risk. Epidemiological data on prevalent morphometric vertebral fractures (VFs) in T2D are sparse and even less is known in the prediabetic state.PurposeTo determine the association between prevalence and severity of morphometric VFs and glucose metabolism state: normal glucose metabolism (NGM), impaired glucose metabolism (prediabetes) or T2D.MethodsThis study included cross-sectional data from 3625 participants of the Maastricht Study who had a vertebral fracture assessment on lateral Dual Energy X-Ray Absorptiometry images. VFs were classified based on morphometric assessment into mild, moderate and severe VFs (respectively 20–24%, 25–39% or ≥40% reduction in expected vertebral body height). Logistic regression models were used to investigate the association between glucose metabolism status and the prevalence and severity of VFs. Analyses were adjusted for subject characteristics and life-style factors.ResultsT2D individuals were older (62.8 ± 7.5 years old) and less often female (30.5%) compared to the NGM group (57.7 ± 8.5 years old, and 58.8% female, respectively). At least one mild, moderate or severe prevalent VF was found in 8.6% of the men and 2.2% of the women in the T2D group, in 9.4% and 8.4% in the prediabetes group and in 9.1% and 4.8% in the NGM group, respectively. After adjustment T2D in women was associated with a lower probability of having a prevalent VF compared to NGM [adjusted OR 0.25 (95% CI 0.09-0.65)], while this was not the case for prediabetes. Furthermore, women with T2D had a significantly lower probability of a prevalent moderate or severe VF [adjusted OR 0.32 (95% CI 0.11-0.96)]. In men there was no significant association between T2D or prediabetes and prevalent VFs.ConclusionWomen with T2D had a lower probability of prevalent VFs compared to women with a normal glucose metabolism, while this was not the case for men with T2D and participants with prediabetes.

The association between prevalent vertebral fractures and bone quality of the distal radius and distal tibia as measured with HR-pQCT in postmenopausal women with a recent non-vertebral fracture at the Fracture Liaison Service

SummaryWe evaluated the association between prevalent vertebral fractures and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women with a recent non-vertebral fracture visiting the Fracture Liaison Service. The presence and severity of prevalent vertebral fracture reflect generalized bone deterioration.IntroductionWe evaluated the association between prevalent vertebral fractures (VFs) and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women visiting the Fracture Liaison Service.MethodsIn this cross-sectional study in women aged 50–90 with a recent non-vertebral fracture (NVF), VFs were identified on lateral spine images by dual-energy X-ray absorptiometry. Bone micro-architecture and strength were measured at the non-dominant distal radius and distal tibia using HR-pQCT. Linear regression analyses were used to estimate the association between prevalent VFs and HR-pQCT parameters.ResultsWe included 338 women of whom 74 (21.9%) women had at least one prevalent VF. After adjustment for femoral neck aBMD (FN aBMD) and other parameters, women with at least one prevalent vertebral fracture had significantly lower total and trabecular vBMD and trabecular number (β − 16.7, − 11.8, and − 7.8 in the radius and − 21.4, − 16.6, and − 7.2 in the tibia, respectively), higher trabecular separation at the radius and tibia (β 9.0 and 9.3, respectively), and lower cortical thickness and calculated ultimate failure load and compressive bone strength at the tibia (β − 5.9, − 0.6, and − 10.9, respectively) as compared with those without prevalent VFs. Furthermore, more severe prevalent VFs were associated with even lower total and trabecular vBMD and lower ultimate failure load and compressive stiffness at the radius and tibia, and lower trabecular number and higher trabecular separation at the radius.ConclusionThis study indicates that the presence and severity of prevalent VFs reflect generalized bone deterioration in women with a recent NVF, independently of FN aBMD.

High Imminent Vertebral Fracture Risk in Subjects With COPD With a Prevalent or Incident Vertebral Fracture.

Subjects with chronic obstructive pulmonary disease (COPD) have an increased risk of vertebral fractures (VFs); however, VF incidence is largely unknown. Therefore, the aim of our study was to determine the incidence of new and/or worsening VF in subjects with COPD. Smokers and subjects with COPD (GOLD II-IV) from the ECLIPSE study with complete set of chest CT scans (baseline and 1- and 3-year follow-up) to evaluate vertebrae T1 down to L1 were included. If a VF was diagnosed on the last scan, detailed VF assessment of the previous scans was performed. VFs were scored according to the method of Genant as mild, moderate, or severe. Main outcome measure was the cumulative incidence of new and/or worsening VF at subject level, within 1 and 3 years. Of 1239 subjects (mean age 61 years, 757 males [61%], 999 subjects with COPD), 253 (20.5%) had ≥1 prevalent VF. The cumulative incidence of VFs was 10.1% within 1 year and 24.0% within 3 years. After adjustment for age, sex, body mass index (BMI), pack-years, and smoking status, prevalence and incidence were similar between smokers and COPD GOLD stages. Within 1 year, 29.2% of the subjects with a prevalent VF had an incident VF, compared with 5.1% in absence of prevalent VF (hazard ratio [HR] = 5.1; 95% confidence interval [CI] 3.6-7.4) and 58.5% versus 15.0% within 3 years (HR = 3.6; 95% CI 2.9-4.6). The incidence of VF was higher with increasing number and severity of prevalent VFs. Among subjects having an incident VF within the first year, 57.3% had a subsequent VF within the next 2 years. In this study, more than half of the smokers and subjects with COPD with a prevalent VF or an incident VF within the first year sustained a subsequent VF within 3 years. The 3-year risk was even higher in the presence of multiple or severe prevalent VFs. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

SAT0343 Severe prevalent vertebral fractures predict subsequent vertebral and non-vertebral fractures: A 3-year prospective study

ObjectivesTo examine whether a prevalent severe vertebral fracture predicts subsequent fracture and to assess the effect of strontium ranelate to reduce fracture in patients with such prevalent severe vertebral fracture.MethodsAnalysis...

Number and severity of prevalent vertebral fractures and the risk of subsequent vertebral fractures in Japanese women with osteoporosis: results from the minodronate trial

The aim was to evaluate the risk of new vertebral fractures with the increasing number and severity of prevalent vertebral fractures in women who received placebo or minodronate in a post hoc analysis of a 2-year randomized, double-blind, placebo-controlled study. The subjects were women aged 55-80years old with 1-5 fragility fractures between the T4 and L4 vertebrae and bone mineral density <80% of the young adult mean. A total of 704 subjects were randomized to take minodronate 1mg (n=359) or placebo (n=345) once a day for 24months. In the placebo group, the risk of incident vertebral fractures during the 2-year observational period was significantly related to the number and severity of prevalent vertebral fractures at baseline. The number of prevalent vertebral fractures was an independent risk factor for incident vertebral fracture in multivariate analysis. The relative risk reductions of vertebral fractures by minodronate treatment were 45.2, 61.1, and 64.2% for patients with 1, 2, and ≥3 prevalent vertebral fractures, respectively, and 87.8, 64.6, and 50.1% for patients with mild, moderate, and severe prevalent vertebral fractures, respectively. In conclusion, the number of prevalent vertebral fractures is an independent risk factor for incident vertebral fracture and minodronate reduces the fracture risk even in patients at a higher risk for fracture.

Treatment with Denosumab Reduces the Incidence of New Vertebral and Hip Fractures in Postmenopausal Women at High Risk

The FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial showed denosumab significantly reduced the risk of fractures in postmenopausal women with osteoporosis. We evaluated the effect of denosumab on the incidence of new vertebral and hip fractures in subgroups of women at higher risk for these fractures. FREEDOM was a 3-yr, randomized, double-blind, placebo-controlled, phase 3 trial. Postmenopausal women (N = 7808) with osteoporosis were enrolled at 213 study sites worldwide. Subjects received s.c. denosumab (60 mg) or placebo every 6 months and daily supplements of calcium (≥1000 mg) and vitamin D (≥400 IU). This post hoc analysis evaluated fracture incidence in women with known risk factors for fractures including multiple and/or moderate or severe prevalent vertebral fractures, aged 75 yr or older, and/or femoral neck bone mineral density T-score of -2.5 or less. Compared with placebo, denosumab significantly reduced the risk of new vertebral fractures in women with multiple and/or severe prevalent vertebral fractures (16.6% placebo vs. 7.5% denosumab; P < 0.001). Similarly, denosumab significantly reduced the risk of hip fractures in subjects aged 75 yr or older (2.3% placebo vs. 0.9% denosumab; P < 0.01) or with a baseline femoral neck bone mineral density T-score of -2.5 or less (2.8% placebo vs. 1.4% denosumab; P = 0.02). These risk reductions in higher-risk individuals were consistent with those seen in patients at lower risk of fracture. Denosumab reduced the incidence of new vertebral and hip fractures in postmenopausal women with osteoporosis at higher risk for fracture. These results highlight the consistent antifracture efficacy of denosumab in patients with varying degrees of fracture risk.

Teriparatide and Raloxifene Reduce the Risk of New Adjacent Vertebral Fractures in Postmenopausal Women with Osteoporosis

Vertebral fractures increase the risk of new vertebral fractures; however, we are not aware of any study addressing the risk of new vertebral fractures adjacent to existing vertebral fractures. Therefore, we sought to determine the influence of the number and severity of prevalent (preexisting) vertebral fractures on the risk of new adjacent vertebral fractures and to determine whether teriparatide (rhPTH [recombinant human parathyroid hormone] [1-34]) or raloxifene treatment reduces the incidence of adjacent vertebral fractures in postmenopausal women with osteoporosis. Data from the Fracture Prevention Trial and the Multiple Outcomes of Raloxifene Evaluation trial were analyzed to determine the incidences of new adjacent and new nonadjacent vertebral fractures in the placebo groups and the effect of treatment with raloxifene and teriparatide on the incidence of new adjacent vertebral fractures as compared with that of new nonadjacent vertebral fractures. Of 1226 untreated postmenopausal women with one or more prevalent vertebral fractures at baseline, 196 (16.0%) had a total of 292 new vertebral fractures during the two-year follow-up period, with 108 (8.8%) of the 1226 women having at least one new fracture adjacent to a prevalent fracture. Of the 292 new vertebral fractures, 136 (47%) were adjacent to a previously existing vertebral fracture. The risk of a new adjacent vertebral fracture was 2.5-fold higher than the risk of a new nonadjacent vertebral fracture (4.03% compared with 1.59%). The incidence of new adjacent vertebral fractures increased with both the number and the severity of prevalent vertebral fractures. Teriparatide reduced the risk of any new, new adjacent, and new nonadjacent vertebral fractures by 72%, 75%, and 70%, respectively, compared with the rates in the placebo group. Similarly, compared with the placebo, raloxifene treatment reduced the risk of any new vertebral fracture, new adjacent vertebral fracture, and new nonadjacent vertebral fracture by 54%, 54%, and 53%, respectively. In untreated postmenopausal women with osteoporosis, nearly half of the incident vertebral fractures occur adjacent to an existing vertebral fracture. Both teriparatide and raloxifene can significantly reduce the occurrence of new adjacent and nonadjacent vertebral fractures.

Hyperkyphosis Predicts Mortality Independent of Vertebral Osteoporosis in Older Women

Excessive kyphosis may be associated with earlier mortality, but previous studies have not controlled for clinically silent vertebral fractures, which are a known mortality risk factor. To determine whether hyperkyphosis predicts increased mortality independent of vertebral fractures. Prospective cohort study. Four clinical centers in Baltimore County, Maryland; Portland, Oregon; Minneapolis, Minnesota; and the Monongahela Valley, Pennsylvania. 610 women, age 67 to 93 years, from a cohort of 9704 women recruited from community-based listings between 1986 and 1988. Kyphosis was measured by using a flexicurve. Prevalent radiographic vertebral fractures at baseline were defined by morphometry, and mortality was assessed during an average follow-up of 13.5 years. In age-adjusted models, each SD increase in kyphosis carried a 1.14-fold increased risk for death (95% CI, 1.02 to 1.27; P = 0.023). After adjustment for age and other predictors of mortality, including such osteoporosis-related factors as low bone density, moderate and severe prevalent vertebral fractures, and number of prevalent vertebral fractures, women with greater kyphosis were at increased risk for earlier death (relative hazard per SD increase, 1.15 [CI, 1.01 to 1.30]; P = 0.029). On stratification by prevalent vertebral fracture status, only women with prevalent fractures were at increased mortality risk from hyperkyphosis, independent of age, self-reported health, smoking, spine bone mineral density, number of vertebral fractures, and severe vertebral fractures (relative hazard per SD increase, 1.58 [CI, 1.06 to 2.35]; P = 0.024). The study population included only white women. In older women with vertebral fractures, hyperkyphosis predicts an increased risk for death, independent of underlying spinal osteoporosis and the extent and severity of vertebral fractures. National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging.

Spinal deformity index (SDI) is a good predictor of incident vertebral fractures

The spinal deformity index is a convenient tool to quantify the number and the severity of prevalent vertebral fractures. It is a predictor of the risk of sustaining incident vertebral fracture. This quantification must be taken into account to improve management of patients. Prevalent fractures are strong risk factors for subsequent fractures. The study subjects were women from the placebo groups of two studies of strontium ranelate in postmenopausal osteoporosis (N = 723 and 637 patients, respectively). Three lateral radiographs of the spine were obtained at baseline and annually over 3 years, according to standardized procedures. The semiquantitative visual assessment of each vertebra from T4 to L4 was performed by the same reader throughout the study. A spinal deformity index (SDI) was calculated by summing for each patient the grade of each vertebra from T4 to L4. There was a linear relationship between baseline SDI and the 3-year incidence of vertebral fracture (adjusted R(2) = 0.76). The 3-year incidence of vertebral fractures was different among the tertiles of baseline SDI: 17.3 +/- 3.6%, 25.4 +/- 2.6%, and 47.6 +/- 3.1% from the lowest to the highest, respectively. There was no relationship between SDI and non-vertebral fractures incidence. SDI is a good predictor of incident vertebral fractures. Patients with highest SDI should receive highest priority to treatment.

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.

Prognostic utility of a semiquantitative spinal deformity index

The semiquantitative spinal deformity index (SDI) is a summary measure of the vertebral fracture status of the spine incorporating both the number and severity of vertebral fractures. For each vertebra, a visual semiquantitative grade of 0, 1, 2, or 3 is assigned for no fracture or mild, moderate, or severe fracture, respectively, and the SDI is calculated by summing the fracture grades of all vertebrae (T4 to L4). We investigated the effect of prevalent vertebral fracture number and severity, as integrated by the SDI, on 3-year vertebral fracture risk by performing logistic regression modeling with data from the MORE trial. There was a striking linear relationship between baseline SDI and the model-based vertebral fracture risk estimates, with a near-perfect correlation ( r = 0.98, P < 0.001). However, the SDI may be overly simplistic, as a given SDI value can be attained through differing vertebral fracture scenarios (i.e., an SDI of 3 can be realized three ways), each corresponding to potentially different vertebral fracture risk. To address this issue, a second, more complex model was constructed that included individual predictor variables for number of mild, number of moderate, and number of severe prevalent vertebral fractures. The model-based risk estimates for vertebral fracture using the SDI and the more complex model were highly correlated ( r = 0.91, P < 0.001), giving almost identical values up to an SDI of 5. Thus, for most clinical scenarios, it is not necessary to consider the particular fracture configuration that led to a given SDI score for predicting a patient's future vertebral fracture risk. These results validate the SDI as an accurate tool for assessing future vertebral fracture risk; patients with greater baseline SDI had greater future risk for vertebral fractures.

Treatment of Postmenopausal Osteoporosis

Osteoporosis is a major public health burden. The most devastating outcome of osteoporosis is fracture, which results in increased morbidity and mortality. These fractures most often occur in the vertebrae and indicate an increased risk of future vertebral and hip fractures. Consequently, it is important to identify patients at risk for fracture and to intervene with pharmacologic therapies, lifestyle changes, or both to reduce the frequency of the first or subsequent fracture. Moreover, because osteoporosis is a chronic condition requiring long-term therapy, factors that increase compliance and improve safety and efficacy outcomes should be considered when treatment is selected. The bisphosphonates alendronate and risedronate can substantially reduce the risk of both hip and vertebral fractures. Furthermore, these agents are available in once-weekly formulations that provide patients with a convenient alternative to a daily dosage regimen. Alendronate and the selective estrogen-receptor modulator raloxifene provide considerable vertebral fracture protection after 1 year of treatment, and risedronate markedly reduces the rate of vertebral and nonvertebral fractures after 6 months of treatment. Data suggest that calcitonin-salmon nasal spray also reduces the risk of vertebral, but not nonvertebral, fractures. Raloxifene decreases the risk of nonvertebral fracture, but only in women with severe prevalent vertebral fractures. Although evidence supports the efficacy of hormone therapy, the risks should be carefully considered before treatment is begun. In addition to the antiresorptive therapies, teriparatide is a daily injectable anabolic treatment that is effective in reducing the risk of vertebral and nonvertebral fractures. Therefore, clinicians and patients have several options for reducing the risk of fracture and achieving optimal dosing convenience.

Teriparatide Reduces the Fracture Risk Associated with Increasing Number and Severity of Osteoporotic Fractures

The relationship between prior fractures and risk of new fractures was evaluated in 931 postmenopausal women with prevalent vertebral fractures randomized to daily placebo or teriparatide (20 mug) in the Fracture Prevention Trial. The median observation time was 21 months. Among placebo patients with one, two, or three or more prevalent vertebral fractures, 7%, 16%, and 23%, respectively, developed vertebral fractures (by Cochran-Armitage trend test, P < 0.001), and 3%, 9%, and 17% developed moderate or severe vertebral fractures (P < 0.001). Among placebo patients with mild, moderate, or severe prevalent vertebral fractures, 10%, 13%, and 28%, respectively, developed vertebral fractures (P < 0.001), and 4%, 8%, and 23% developed moderate or severe vertebral fractures (P < 0.001). Among placebo patients with zero, one, or two or more prior nonvertebral fragility fractures, 4%, 8%, and 18%, respectively, developed nonvertebral fragility fractures (P < 0.001). In the teriparatide-treated group, there was no significant increase in vertebral or nonvertebral fracture risk in these subgroups. In summary, the number and severity of prevalent vertebral fractures independently predicted the risk for new vertebral fractures, and the number of prior nonvertebral fractures predicted the risk for new nonvertebral fractures in placebo patients. However, in teriparatide-treated patients, the increased fracture risk associated with prior number and severity of fracture was not observed.

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.