Design, Setting, and Participants Two prospective US cohort studies in community-dwelling adults 65 years or older from geographically diverse sites. The Study of Osteoporotic Fractures followed up women for 9. The Osteoporotic Fractures in Men Study followed up men for 5.
Incident nonspine fractures were confirmed by radiographic report. Fractures were classified, without knowledge of BMD, as high trauma due to motor vehicle crashes and falls from greater than standing height or as low trauma due to falls from standing height and less severe trauma.
Results Overall, women and 94 men sustained an initial high-trauma fracture and women and men sustained an initial low-trauma fracture. For women, each 1-SD reduction in total hip BMD was similarly associated with an increased risk of high-trauma fracture multivariate relative hazard [RH], 1. Results were consistent in men high-trauma fracture RH, 1.
Risk of subsequent fracture was not modeled for men. Conclusions Similar to low-trauma nonspine fractures, high-trauma nonspine fractures are associated with low BMD and increased risk of subsequent fracture in older adults.
High-trauma nonspine fractures should be included as outcomes in osteoporosis trials and observational studies. Approximately 1. By the current definition, fractures are recognized as osteoporotic if they are associated with low bone mineral density BMD and if they increase the risk of subsequent fracture.
Most low-trauma fractures eg, those resulting from falls from standing height or less are considered osteoporotic because they are related to low BMD 5 , 6 and subsequent fracture risk.
This belief has several important consequences. First, there is a pervasive clinical opinion that an older adult who has a high-trauma fracture does not require evaluation for osteoporosis. Preliminary evidence challenges the assumption that high-trauma fractures are unrelated to low BMD.
Data from the Geelong Osteoporosis Study showed that women older than 50 years with high-trauma fractures had significantly lower levels of BMD than a random, community-based sample of older women. An important clinical outcome of a low-trauma fracture is increased risk for subsequent fracture. One retrospective cohort study has shown that individuals who sustained high-trauma ankle or tibial fractures early in life had an increased risk of low-trauma fractures later in life compared with individuals having no prior history of high-trauma fracture.
In the current study, conducted in 2 large prospective cohorts of older women and men, we tested the hypotheses that low BMD increases the risk of high-trauma fracture and that high-trauma fracture increases the risk of subsequent fracture. During the baseline examination from to , community-dwelling white women 65 years or older were enrolled from population-based listings in 4 areas of the United States: Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and Monongahela Valley near Pittsburgh, Pennsylvania.
Six hundred thirty-three For both studies, women and men were not eligible to participate if they reported bilateral hip replacement or required the assistance of another person in ambulation. Details of the cohorts have been published. All participants provided written informed consent. For both studies, all hip scans were performed on the right hip unless a participant reported a hip prosthesis or other metal object s on the right side of the leg, in which case the left hip was scanned.
Standardized procedures for participant positioning and scan analysis were used for all scans. All densitometry operators at the clinical centers were trained and certified centrally in scanning and analysis techniques. For quality assurance, densitometry technicians at the coordinating center University of California, San Francisco reviewed a random sample of all scans, scans with exceptionally high or low BMD, and problematic scans identified at the clinical centers.
Cross-calibration studies were completed in both cohorts. Intraclinic CVs for hip phantoms 0. In both SOF and MrOS, demographic, anthropometric, lifestyle, neuromuscular function, and medical history data were obtained.
Height was measured with a wall-mounted Harpenden stadiometer Holtain Ltd, DyFed, United Kingdom , and body weight was measured with a balance beam scale except for the MrOS Portland site, which used a digital scale. Body mass index was calculated as weight in kilograms divided by height in meters squared. Smoking history ever vs never , history of falling in the past year, and history of fractures since age 50 years were ascertained through a self-administered questionnaire.
We contacted participants in the SOF and MrOS cohorts every 4 months by mailed questionnaires to determine whether they had sustained a fracture in the prior 4-month period. All fractures were validated by physician review of radiology reports or radiographs. When a fracture was reported, clinic staff interviewed participants about the fracture and how it occurred. Main analyses included all nonspine, nonpathological fractures that occurred after the second visit and before February in SOF and after the baseline visit and before February in MrOS.
In subanalyses, fractures not typically associated with BMD ie, those of the face, skull, finger, toe, and heel were excluded in SOF, 29 high-trauma and low-trauma fractures; in MrOS, 11 high-trauma and 38 low-trauma fractures. Clinic staff coded all fractures according to degree of trauma without knowledge of BMD.
High-trauma fractures included all fractures due either to severe trauma eg, motor vehicle crashes, being struck by a vehicle or other fast-moving projectile, or assault or to falls from greater than standing height eg, falls off a ladder, chair, porch, table, or other raised surface, not including stairs. Low-trauma fractures included all fractures due to 1 falls from standing height or less; 2 falls on stairs, steps, or curbs; 3 moderate trauma other than a fall eg, collisions with objects during normal activities ; and 4 minimal trauma other than a fall eg, turning over in bed.
We assumed that if the fracture had involved high trauma, the participant would have recalled it; therefore, if the source of trauma was unknown, we classified the fracture as low trauma. All analyses were stratified by sex. We censored on low-trauma fracture a competing risk.
These variables are known to be associated with nonspine osteoporotic fractures. We also examined risk of first incident high- and low-trauma fracture by clinical categories of BMD based on T scores, defined as the number of SDs below the mean BMD of young adults of the same sex and race, using the National Health and Nutrition Examination Survey database for total hip and femoral neck for adults aged 20 to 29 years.
For women in SOF, we had sufficient data to examine risk of subsequent fracture. In the first model, we used high-trauma fracture status, age, and total hip BMD as predictors of subsequent fracture, of which high-trauma fracture status was treated as time-varying. In the second model, we used low-trauma fracture status, age, and total hip BMD as predictors of subsequent fracture, of which low-trauma fracture status was treated as time-varying.
Since very few men experienced subsequent fractures, we did not have adequate power to accurately model risk of subsequent fracture for men in MrOS; therefore, we reported only the number of subsequent fractures for men. All analyses were conducted using SAS version 9.
Over a mean of 9. Of the high-trauma fractures, During the same period, women Nineteen pathological fractures were excluded. Compared with women who did not have a fracture, women who had a high-trauma fracture had lower body weight and body mass index and were more likely to report a fracture since age 50 years and a fall in the past year Table 1. Women who had a low-trauma fracture were older, had a lower body weight and body mass index, were less likely to report current use of hormone therapy, and were more likely to report a fracture since age 50 years and a fall in the past year than women who did not have a fracture.
Over a mean of 5. Of the 94 high-trauma fractures, 46 During the same period, men 5. Compared with men who did not have a fracture, men who had a high-trauma fracture were less likely to walk for exercise and were more likely to report a fracture since age 50 years and a fall in the past year Table 1. Men who had a low-trauma fracture were older; were more likely to report a fracture since age 50 years, a fall in the past year, and 1 or more medical conditions; and also were more likely to be unable to rise from a chair 5 times without using their arms than men without a fracture.
The distribution of fracture locations differed by level of trauma Table 2. In SOF women, rib and wrist fractures were the most common high-trauma fractures, and hip and wrist fractures were the most common low-trauma fractures.
In MrOS men, rib and wrist fractures were also the most common high-trauma fractures, and hip and rib fractures were the most common low-trauma fractures. Age per 5-year increase was associated with an increased risk of low-trauma fracture in women RH, 1. However, age per 5-year increase was not associated with risk of high-trauma fracture in women RH, 1.
Low BMD was associated with increased risk of high- and low-trauma fracture. However, a decomposition analysis reveals that the majority of this attributable fraction was ascribed to advancing age. A similar trend was observed in men. Again, a majority of this fracture was ascribed to advancing age in the presence or absence of low BMD. For vertebral fracture, about one-third of cases in women and men were attributable to advancing age or low BMD.
There was a substantial difference in the age or low-BMD—attributable fraction for wrist fracture between genders. As in the case of hip and vertebral fractures, advancing age contributed to most of the attributable fraction in women. However, the differences were not statistically significant. As mentioned earlier, fracture is associated with increased risk of mortality, and we sought to delineate the proportion of mortality attributable to fracture, low BMD, and advancing age.
In the absence of advancing age and low BMD, fracture alone accounted for 5. Although the strong association between low BMD or osteoporosis and fracture has long been recognized, the proportion of fractures attributable to osteoporosis has not been systematically investigated.
When low BMD was combined with advancing age, the two factors accounted for approximately one-third of all fractures. An immediate question arises as to what other factors account for the majority of fracture cases. A history of fall was associated with a fourfold increase in fracture risk Apart from fall, other factors such as lack of physical activity, poor grip strength, a history of hyperthyroidism, and low body mass index were also risk factors for fracture in nonosteoporotic women, but the magnitude of association for these risk factors was modest 6.
Taken together, our knowledge of risk factors that account for all fragility fractures is still limited. Although low BMD has been recognized as the most robust risk factor for fragility fracture, it has recently been shown that a majority of fractures actually occur in those without osteoporotic BMD.
In this study we confirmed that observation. These observations underline the fact that the relationship between BMD and fracture risk is continuous and that there is not really a clear cutoff value that defines high risk vs low risk. This finding also underscores the idea that fracture risk assessment for a patient should consider BMD as a continuous variable rather than being based on arbitrary classification.
We also observed that the magnitude of association between BMD and fracture risk declined with time from the baseline BMD measurement. In fact, for vertebral fracture in men and wrist fracture the association between baseline BMD and fracture risk after 20 years was not statistically significant. Our results are consistent with the findings of Black et al.
Taken together, these results indicate that BMD has a good predictive value of fracture when it is measured close to the event.
It has increasingly been recognized that fragility fracture is an important risk factor for mortality. Indeed, patients with a fragility have a twofold to threefold increase in mortality 30 , In this study, we demonstrated that the proportion of postfracture deaths was attributable mainly to advancing age.
Taken together, our data point out that fracture is indeed a risk factor for postfracture mortality, but the majority of this attributable fracture is due to advancing age. Age can be considered an index of cumulative exposure to environmental factors and stress. Advancing age is also associated with more comorbidities 32 , some of which may affect the risk of mortality. However, in a recent analysis 33 we found that comorbidities e. The present findings should be interpreted in the context of strengths and weaknesses.
A strength of this study is that the results were derived from a well-characterized cohort and a long-term follow-up. Moreover, we could ascertain fracture by X-ray report to avoid misclassification.
However, the number of wrist fractures is small, which could result in unstable estimate of attributable fraction. It could be argued that the dichotomization of age and BMD is arbitrary because there is no clear cutoff value to define advancing age.
However, the dichotomization is technically necessary for estimating the attributable risk fraction. In conclusion, these data suggest that a substantial health care burden of fragility fractures is on people under the age of 70 or those with nonosteoporotic BMD, suggesting that treatment of men and women with osteoporotic BMD is unlikely to reduce a large number of fractures in the general population. Population-based prevention targeting those at highest absolute risk is likely to be more effective in reducing health care burden of fracture than treating people with single risk factors e.
The authors gratefully acknowledge the expert assistance of Janet Watters, Donna Reeves, Shaye Field, and Jodie Rattey in the interviews, data collection, and measurement of bone densitometry and the invaluable help of the Dubbo Base Hospital radiology staff, Dr R. Slack-Smith, and Orana radiology. Disclosure Summary: The authors have nothing to disclose. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures.
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Sick individuals and sick populations. Int J Epidemiol. Prediction of osteoporotic fractures by postural instability and bone density. It is therefore difficult to compare the present sex-related vertebral fracture risk.
There has been some controversy in the literature about whether there is a higher risk of vertebral fractures in women than in men.
Our finding of non-significant difference in vertebral fracture risk between men and women before adjustment of age and BMD is not consistent with a previous review which suggested that the incidence of vertebral fractures in men is about one third to one half of that in women [ 34 ], but of course, our estimates are based on prevalent vertebral fractures. However, our results are in line with findings from the Dubbo Osteoporosis Epidemiological Study [ 35 ] where the prevalence of vertebral deformities was higher in men than in women.
In that study the higher prevalence in men was observed regardless of diagnostic criteria, suggesting, as in our study, that vertebral fractures may be overlooked in men. Several other studies report, similar to the present study, that low BMD measured at the femoral sites are associated with prevalent radiographic vertebral fractures [ 21 , 22 , 28 ]. The higher prevalence of vertebral deformities at these BMD levels in men indicate, as also suggested by others [ 16 ], that these deformities could be of other origin than osteoporosis, possibly mechanic or due to childhood diseases [ 34 ] and should be explored in follow up studies.
Studies defining the proportion of fractures attributable to trauma in childhood and young adulthood are lacking [ 34 ]. As Seeman et al. The finding from our study indicating that at a given age and given BMD level the OR for having a vertebral fracture is higher in men than in women, somehow corresponds to how the risk of hip fractures seems to be similar in men and women for any given BMD [ 16 , 32 , 36 , 37 ].
Although an unknown proportion of the vertebral fractures in men may be of mechanic origin, our study highlights the importance of osteoporosis and vertebral fracture risk in men, and that vertebral fractures should definitely not be considered a women health problem only. The present findings should be viewed within the context of strengths and potential limitations.
Because of its cross-sectional design, causal inference cannot be drawn from the findings and the results will need confirmation within a longitudinal design. For logistic reasons, we did not perform quality control using x-ray technology. The intra-class correlation coefficient for determination of average height of the vertebra was good. Ideally, we should have compared determination of fracture severity in the sample. This was, however, difficult to attain, since determination is done electronically by the software, based on identified vertebral heights.
Despite high rates of hip- and forearm fractures in Norway, the prevalence of vertebral fractures in this population was comparable to reports from others [ 38 — 40 ]. Although we should be careful drawing firm conclusions from our prevalence estimates, we still feel comfortable to compare between women and men, especially in age stratified analyses.
It is a major limitation to our study that we lack information of important risk factors included in FRAX [ 20 ], especially the history of vertebral fractures [ 21 , 33 ]. Although BMI [ 41 ] and smoking [ 42 ] are considered to be independent predictors of fracture risk, they did not contribute to the final model. The predictive value of physical activity, self-perceived health, and education to fracture risk is uncertain [ 43 ] and did not affect the results although the self-reported nature and our dichotomization of the variables may have precluded possible associations.
However, this study confirms that age and BMD are important predictors of vertebral fractures in women and men [ 21 , 22 ]. Advancing age and declining BMD are independent determinants of vertebral fracture risk in women and men, but accounting for less than half of the total risk. The predictive value of prevalent vertebral fractures on subsequent vertebral fractures and other types of fractures should be explored in longitudinal studies.
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