Abstract
Background: Worldwide fracture rates are increasing as a result of the aging population, and prevention, both primary and secondary, is an important public health goal. Therefore, we systematically analyzed risk factors in subjects with a recent clinical fracture.
Methods: All men and women over fifty years of age who had been treated in the emergency department of, or hospitalized at, our institution because of a recent fracture during a one-year period were offered the opportunity to undergo an evidence-based bone and fall-related risk-factor assessment and bone densitometry. The women included in this study were also compared with a group of postmenopausal women without a fracture history who had been included in another cohort study.
Results: Of the 940 consecutive patients, 797 (85%) were eligible for this study and 568 (60%) agreed to participate. The prevalence of fall-related risk factors (75% [95% confidence interval = 71% to 78%]; n = 425) and the prevalence of bone-related risk factors (53% [95% confidence interval = 49% to 57%]; n = 299) at the time of fracture were higher than the prevalence of osteoporosis (35% [95% confidence interval = 31% to 39%]; n = 201) as defined by a dual x-ray absorptiometry T score of =-2.5 in the spine and/or hip. The fall and bone-related risk factors were present irrespective of the fracture location, patient age, or gender. An overlap between bone and fall-related risk factors was found in 50% of the patients. After adjusting for age, weight, and height, we found that women with a fracture more frequently had a diagnosis of osteoporosis (odds ratio = 2.9; 95% confidence interval = 2.0 to 4.1) and had a more extensive history of falls (odds ratio = 4.0; 95% confidence interval = 2.7 to 5.9) than did the postmenopausal women without a fracture history.
Conclusions: Men and women over fifty years of age who had recently sustained a clinical fracture had, at the time of that fracture, bone and fall-related risk factors that were greater than the risk predicted by the presence of osteoporosis. Risk factors were overlapping, heterogeneous, and found in multiple combinations. This was the case regardless of the patient's age, fracture location, or gender. These findings suggest that an integrated bone and fall-related risk-factor assessment is a preferable means for identifying elderly subjects at risk for fracture. Integrated bone and fall-related risk assessment and treatment studies are needed to document this proposal.
Worldwide fracture rates are increasing as a result of the aging population, and prevention, both primary and secondary, is an important public health goal. Unfortunately, the tools currently available to prevent fractures are not well applied. A better understanding of the numerous risk factors that contribute to fractures is needed in order to improve the implementation of preventive, diagnostic, and treatment modalities for patients with a recent fracture. For both men and women, the prevalence of osteoporosis and falls increases with age1, and between 1% and 5% of falls result in a fracture2.
In order to address this problem, numerous guidelines for evaluation of risk factors have been developed in various countries3. Although these guidelines have been available for many years, several reports indicate that case finding and patient treatment after a fracture are poorly implemented in daily practice4,5. Primary and secondary prevention is important for patients who are at high risk for fractures, even in the short term6,7. Currently, most secondary prevention programs concentrate on measures that correct causes of osteoporosis. These include correcting disturbed calcium homeostasis and increasing the resistance to fractures in patients with low bone mineral density and/or vertebral fractures. However, many patients with a clinical fracture do not have a low bone mineral density but rather are vulnerable to fracture because of other risk factors that are applicable in the clinical context8. Several investigators have conducted a baseline risk assessment in a population and then followed the patients to measure fracture rates8-11. To our knowledge, no one has previously conducted a baseline assessment of both bone and fall-related risks in patients with a recent fracture.
Using two evidence-based guidelines produced by the National Institute of Health Care in The Netherlands, we performed, over the course of one year, a systematic screening program for risk factors in all men and women over fifty years of age who were seen with a clinical fracture at the emergency unit at our hospital12,13. We analyzed the relative presence of risk factors in these patients, determined how many patients could have been identified with use of case finding prior to their current fracture, and explored the medical consequences in reference to the risk-factor profile.
This study was a preplanned systematic cross-sectional observational investigation and was approved by the medical ethical committee. Over the course of one year, subjects over fifty years of age who had attended the surgical emergency clinic of, or who had been admitted to, our hospital because of a clinical fracture were invited to participate in the study. Those who agreed to participate received a bone and fall-related risk-factor assessment and bone densitometry. These investigations were done in conjunction with the fracture treatment. Patients were excluded from this study if they did not provide informed consent, did not undergo bone densitometry, were receiving treatment for osteoporosis, resided in a different region, were unavailable for the next consultation, or had a pathologic fracture as confirmed on radiographs.
Fractures were classified, according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9), into skull; spine; thorax and/or clavicle; pelvis; humerus; radius and/or ulna; hand; hip and femur; tibia, fibula, and/or patella; and foot categories. For further analyses, these categories were clustered into four groups: upper limb, lower limb, other fractures, and multiple fractures (two or more fractures at the same time).
Three assessments of fracture risk were performed:
Type A: The bone mineral density of the spine and the left hip (or at the non-fracture site in the case of a unilateral hip fracture) were measured with dual x-ray absorptiometry with the Hologic QDR 4500 Elite densitometer (Waltham, Massachusetts) (coefficient of variation, 0.4%). Three patient groups were determined on the basis of the T scores: osteoporosis (T score of =-2.5), osteopenia (lower T score [in the hip or spine] in the range of -2.5 to -1), and normal (T score of =-1).
Type B: Clinical bone-related risk factors for fractures, including a previous fracture after the age of fifty, a mother with a fracture history, a body weight of <60 kg, severe immobility, and the use of glucocorticoids, were determined.
Type C: Fall-related risk factors for fractures, including more than one fall in the past year, the use of psychoactive drugs, a low level of activities of daily living before the current fracture, articular symptoms, impaired vision, urinary incontinence, and Parkinson disease, were determined.
The assessment of risk factors for fractures was based on the Dutch guidelines for the prevention of osteoporosis and falls12-14. These guidelines recommend case finding with the use of Type-B risk factors. Pharmaceutical treatment is recommended for individuals with a preexisting vertebral fracture or when other risk factors are present and the T-score is =-2.5 (Table I). According to the fall-prevention guideline, Type-C risk factors are the most important for assessment.
A specialist nurse trained in osteoporosis management and fall-risk assessment evaluated all of the patients included in this study. During the first consultation, the patient was provided with information about the study and an informed-consent form. If the patient agreed to participate, a dual x-ray absorptiometry measurement of the spine and hip and an investigation of bone and fall-related fracture risks were included in the second consultation. This was usually completed within two months following the fracture. The fall-risk assessment included an assessment of the ability to carry out activities of daily living with use of the Groningen Activity Restriction Scale (status before the fracture)15-18 and an assessment of the patient's vision with use of the Snellen eye chart18-21. In addition, the examination included documentation of any history of falls16,18,20,22-24, use of psychoactive drugs (benzodiazepines, antipsychotics, antidepressants, or neuroleptics)15,18,24-27, osteoarthritis19,20,23,25, urinary incontinence18,24, and Parkinson disease19,20.
Both the entire group and a group that had fallen from a standing height or less were analyzed.
A control group was included in the analysis as well. The control group was derived from a cohort of 759 postmenopausal women and comprised 492 women over the age of fifty years who had had no previous fracture. All control subjects were recruited from the practices of general practitioners. The only criterion for serving as a control subject was the absence of a fracture and an age above fifty years. The settings and methodology of this cohort have been described elsewhere28.
Statistical Analysis
The comparison of proportions was conducted with a chi-square test. To investigate differences between patients, univariate analyses were performed with use of binary logistic regression. Additionally, to determine the independent contributions of these risk factors, a stepwise logistic regression analysis was performed with sex, age, weight, height, and type of trauma.
The comparisons of the women in this cohort with those in the control group were also performed with use of univariate and multivariate binary logistic regression. Interaction was tested with use of multivariate analyses.
Odds ratios and 95% confidence intervals were calculated. Observations were considered significant when p was <0.05 (two-tailed).
Over the course of the year-long study period, 940 subjects over the age of fifty years presented to our emergency clinic with a fracture. Of these subjects, 229 were excluded on the basis of the previously mentioned criteria (failure to obtain a bone mineral density study, refusal to provide informed consent, etc.) and 143 were not eligible for inclusion for various other reasons (Fig. 1). As a result, 568 subjects participated in the study, giving an inclusion rate of 71% (568 of 797).
The 229 patients who chose not to participate tended to be older than those who did participate (seventy-six compared with sixty-seven years; p < 0.001). They also more frequently had a hip fracture (27% compared with 13%; p < 0.001); less frequently had a tibial, fibular, and/or patellar fracture (6% compared with 15%; p = 0.001); and less frequently had multiple fractures (1% compared with 5%; p = 0.02) than the participants in this study.
The group that received a risk assessment consisted of 406 women and 162 men and had a total of 600 recent clinical fractures. A fall from a standing height or less was the cause of the fracture in 455 (80%) of the subjects (Fig. 1). Other causes included falls from more than a standing height (6.5%), traffic injuries (8.5%), entrapment of the arm or leg (3.5%), and a small group of rare causes such as skating injuries (1.4%). Analyses of the total group are reported because the results found for the entire group were similar to those found when separate analyses were conducted for the group that had fallen from a standing height or less.
The mean age was sixty-eight years for the women compared with sixty-five years for the men (p = 0.001). An upper-limb fracture (humerus, radius and/or ulna, or hand) was sustained by 49% of the patients; a lower-limb fracture (hip and femur; tibia, fibula, and/or patella; or foot), by 37%; a clinical vertebral fracture, by 3%; and multiple simultaneous fractures, by 5% (Table II).
Osteoporosis of the hip and/or spine (a T score of =-2.5) was found in 201 subjects (35%; 95% confidence interval = 31% to 39%); osteopenia, in 250 (44%; 95% confidence interval = 40% to 48%); and normal bone mineral density, in 117 (21%; 95% confidence interval = 17% to 24%) (Table III).
At least one bone-related risk factor was found in 299 of the subjects (53%; 95% confidence interval = 49% to 57%) (Table III). Of these 299 subjects, 14% had two risk factors, 3% had three risk factors, and one patient had four risk factors. In total, 131 subjects (23%) had had a previous fracture after the age of fifty years.
Women and men had similar prevalences of bone-related risk factors, except for low body weight (20% compared with 12%, respectively; p < 0.05) and a previous fracture after the age of fifty (27% compared with 13%, respectively; p < 0.05), which were found more frequently in women.
At least one fall-related risk factor was found in 425 (75%) of the subjects (Table III): 33% had one risk factor, 22% had two risk factors, 10% had three risk factors, and 10% had four or more risk factors.
Fall-related risk factors were more frequently seen in women, with the exception of impaired vision, which was found in 25% of the women and 31% of the men. This difference was not significant.
When all risk factors were incorporated, it became apparent that the fracture population could be divided into eight groups (Fig. 2). Roughly one-quarter had only fall-related risk factors, one-fifth had both fall and bone-related risk factors, and one-fifth had fall and bone-related risk factors as well as osteoporosis.
Compared with patients without any risk factors, patients with bone and fall-related risk fractures as well as osteoporosis were more likely to be female (81% compared with 56%; p < 0.001), had a lower mean body weight (77 kg compared with 62 kg; p < 0.001), were shorter (155 cm compared with 170 cm; p = 0.001), and were more likely to have fallen from a standing height (93% compared with 60%; p < 0.001). The distribution of fracture locations was similar.
Multivariate analyses showed that lower weight (odds ratio = 1.1 per kg; p < 0.001; 95% confidence interval = 1.05 to 1.15), older age (odds ratio = 1.1 per year; p < 0.001; 95% confidence interval = 1.06 to 1.16), and type of trauma (in favor of a fall from standing height) (odds ratio = 3.6; p = 0.03; 95% confidence interval = 1.1 to 11.6) were significantly associated with the presence of all three types of fracture risk.
Regardless of the fracture location, fall-related risk factors were more frequent than bone-related risk factors, which in turn were more frequent than osteoporosis (Fig. 3). The prevalence of osteoporosis was highest in patients with clinical vertebral fractures (63%) and in those with multiple fractures (45%).
Compared with patients with osteoporosis, patients with osteopenia (lower T score [in the hip or spine] between -1 and -2.5) were younger (sixty-seven compared with seventy years; p < 0.01) and had a lower prevalence of clinical bone-related risk factors (48% compared with 67%; p < 0.01). The distribution of fracture locations was the same in patients with osteopenia and those with osteoporosis, with the exception of vertebral fractures, which were slightly more frequent in the osteoporosis group (6% compared with 2%; p = 0.05).
The 406 women in this cohort and a cohort of 492 women with no fracture history were compared with regard to age, height, weight, prevalence of osteoporosis of the spine and/or hip, maternal fracture history, steroid use, Parkinson disease, use of sedatives, and the occurrence of two or more falls in the previous twelve months. When compared with the control group, the patients with a recent fracture tended to be slightly older (sixty-eight compared with sixty-five years; p < 0.0001), weigh less (69 kg compared with 71 kg; p = 0.03), have a higher prevalence of osteoporosis in the spine and/or hip (38% compared with 19%; p < 0.0001), and have a higher prevalence of two or more falls in the previous twelve months (31% compared with 11%; p < 0.0001). Multivariate logistic regression analyses showed that, when adjusted for age, weight, and height, the above-mentioned differences were independent of the presence of osteoporosis (odds ratio = 2.9; 95% confidence interval = 2.0 to 4.1) and the history of falls (odds ratio = 4.0; 95% confidence interval = 2.7 to 5.9). Interaction was only significant for age and the presence of osteoporosis (p = 0.02).
Using the Dutch osteoporosis guideline12, we determined that 83% of the women with a clinical fracture would not have been identified as being at risk for a fracture before they had the recent fracture.
In a cohort of patients over fifty years of age who had been admitted to the emergency clinic of our hospital because of a recent clinical fracture, a heterogeneous mixture of bone and fall-related risks for fractures was found in both sexes, in association with all fracture locations, and irrespective of the patient's age, even when the analyses were limited to patients who had sustained the fracture in a simple fall. Osteoporosis (a bone mineral density T-score of =—2.5) was present in one-third of the patients, while half of the patients had at least one bone-related risk factor and three-quarters of the patients had at least one fall-related risk factor before the current fracture. The majority (71%) of this study population were women, and therefore the conclusions are predominantly based on results found in women.
These results highlight two important issues. First, most guidelines focus on identifying osteoporosis, as opposed to risk factors for fractures, and therefore they fail to prospectively identify most individuals at risk for fractures. Only a limited number of the patients in our study could have been identified, before their current clinical fracture, with use of the Dutch guideline. This indicates the need for additional approaches to identifying patients at risk for clinical, and usually nonvertebral, fractures. Such an initiative is under way with the World Health Organization (WHO) initiative to calculate the absolute fracture risk on the basis of bone mineral density and a group of clinical bone-related risk factors that is larger than that included in the Dutch guideline; the WHO list of bone-related risk factors includes use of multiple medications, cigarette smoking, excessive alcohol intake, rheumatoid arthritis, and self-rated poor health status29. WHO acknowledges that it chose to include only bone-related risks in this initiative. It identified the importance of fall-related risks but excluded them. In view of our results, the algorithms proposed by WHO could therefore underestimate fracture risk in patients with a higher risk of falls. To what extent such algorithms could overestimate the fracture risk in patients who have a lower risk of falls is also unclear and needs to be addressed in large-scale prospective population studies integrating both bone-related and fall-related risks. Indeed, Nguyen et al. reported that both bone and fall-related risk factors were predictive of hip fractures, the most important clinical fractures, over a period of fourteen years30. A recent review on osteoporosis by Sambrook and Cooper supported the view that case finding and therapeutic strategies will shift from an approach based primarily on bone mineral density measurements to an approach in which both fall and bone-related fracture risk factors are used to predict the absolute fracture risk31. Our data support this view and indicate that this approach may be particularly valuable in the context of patients entering the hospital for the treatment of a fracture.
The second important finding of our study is that most patients with a recent clinical fracture do not have osteoporosis. Thus, simply ordering a dual x-ray absorptiometry scan to select patients for treatment means that many patients with a high fracture risk will be discharged without further treatment. In these cases, the bone-related risk factors independent of bone mineral density and the fall-related risk factors will persist and will therefore need to be addressed and corrected whenever possible. Indeed, in our study, 53% of the patients had bone-related risk factors other than low bone mineral density, for which there are potentially several structural and material bone-related reasons, including structural features (micro-architecture and macro-architecture), high bone turnover, and material characteristics such as hypomineralization in the context of high bone turnover and osteomalacia, genetic polymorphisms (e.g., of collagen type I), and changes in collagen cross-linking32-34. As most patients in our study had had a fall, the high prevalence of fall-related risk factors was not unexpected. However, the frequent combination of fall and bone-related risk factors indicates that, in the context of case finding, those who fall need to be evaluated for bone-related risk factors and low bone mineral density (two of three patients who had fallen also had bone-related risk factors and/or low bone mineral density) and patients with bone-related risk factors and/or low bone mineral density need to be evaluated for fall-related risk factors (four of five also had fall-related risk factors). However, the clinical relevance of fall-related-risk evaluation and prevention for these patients remains unclear. Various studies have demonstrated a beneficial effect of focused or multifactorial fall prevention programs on the incidence of falls, but none have shown that this leads to fracture reduction2,35,36.
This study had several shortcomings. The number of patients included could be interpreted as small when compared with the numbers in prospective studies in which bone and fall-related risks were evaluated in several thousand subjects37,38. However, our study is by far the largest evaluating both bone and fall-related risk factors in patients with a recent clinical fracture. McLellan et al. conducted a study of 4600 patients with a recent fracture, but they only evaluated bone mineral density39. Becker et al. described 185 men and women with a recent fracture, but they focused mainly on causes of secondary osteoporosis and the influence of ethnicity40. They found a mean of 3.2 fall-related risk factors and a history of fracture in 40% of their patients. However, their study was based on a retrospective chart review.
A second shortcoming of our study is that blood sampling was not performed, as it was in the study by Streeten et al.41. Blood sampling may be important for diagnosing secondary causes of low bone mineral density.
Third, some bone-related risk factors (excessive alcohol intake, smoking, rheumatoid arthritis, and self-rated poor health status) were not included in our study because they are not included in the Dutch osteoporosis guideline. Miller et al. reported that an algorithm that included self-reported poor health for assessment of women with osteopenia correctly classified 74% of those who had sustained a fracture8. As self-reported poor health was not part of our evaluation, it remains to be determined if this additional information could have increased the proportion of patients who could have been identified as being at risk.
Fourth, 15% of the patients were not eligible for assessment and, of those who were eligible, 29% did not provide informed consent or failed to return for the bone mineral density study. Therefore, the conclusions drawn from these data are applicable only to those patients who are willing to cooperate with an assessment for fracture risk. The results show that older patients and patients with a hip fracture were less willing to participate in such a program.
Fifth, risk-factor assessment was conducted during the fracture treatment period in a study with a cross-sectional design. This may have affected recall regarding these risk factors. However, the evaluation was performed within two months after the fracture for most patients. As a result, recall bias was probably quite low.
Sixth, a control group was available only for the female subjects in this cohort.
Lastly, we must consider that not all clinical vertebral fractures are treated at the emergency department and that two of every three fractures do not have the clinical picture of an acute fracture. Therefore, no data on nonclinical morphometric vertebral fractures were obtained.
In summary, fracture prevention is essential to improve the quality of life of our growing elderly population. In order to be successful, we need to move beyond using bone-related or fall-related risk factors as the only, or as separate, risk factors for clinical fractures and we must develop screening tools that combine bone and fall-related risk factors in prospective population studies to better identify a greater proportion of the at-risk population. 
Note: The authors thank Gittie Willems for data aquisition as osteoporosis nurse practitioner; Evelien Pijpers, MD, for advice about fall risk-factor analysis; Geert Jan Dinant, MD, PhD, for advice about starting with the fracture and osteoporosis outpatient clinic; and Rene ten Broeke, MD, for recruiting patients from the orthopaedic trauma department.
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