Menopause Live (26 July, 2010) from IMS 

The publication of the data emerging from the Global Longitudinal Study of Osteoporosis in Women (GLOW) [1, 2] is a significant development. While other cohort studies have focused on identifying the risk factors associated with fracture incidence and the localization of low bone mineral density and its association with the risk of fractures, the GLOW study is trying to provide an international perspective on fracture in women, patient management practices, patient awareness, physical and emotional function after fracture, and assessment of the models for scoring fractures and outcomes after fracture. The design of the GLOW study involved 723 physician practices in 17 sites in ten countries (Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, the United Kingdom and the United States). The final number of participants was 60,393 women aged over 55 years; two-thirds of them were over 65 years (mean age of 69 years). The survey was conducted over a period of several years. The study questionnaire was self-administrated, covering different patient characteristics [1, 2].

The comparison of self-perceived risk was compared with the self-reported characteristics used by the FRAX algorithm. This was released by the World Health Organization for calculating 10-year absolute fracture risk in individual patients in primary-care settings for major osteoporotic fractures (clinical vertebral, hip, forearm and humerus fracture) and separately for hip fractures, with or without bone mineral density (BMD) measured by dual-energy X-ray absorptiometry. The data included in the FRAX algorithm are: age, history of fractures, parental risk of hip fracture, low body weight or body mass index (BMI), use of glucocorticosteroids, rheumatoid arthritis, current cigarette smoking, excessive alcohol intake (more then three units daily) and secondary osteoporosis [2, 3]. FRAX has been already implemented in the guidelines of the National Osteoporosis Foundation (in the US), the National Osteoporosis Society (in the UK) and the National Osteoporosis Guideline Group (in the UK). 

Self-perceived risk of fracture was assessed using a five-point scale ranging from ‘much lower’ to ‘much higher’ than that of other women of the same age. The overall results show that 35% of the women (20,345/58,434) perceived their risk as being much or a little lower than that of other women of the same age, 46% perceived their risk as being much the same, and 19% (10,951/58,434) perceived it as much or a little higher than the risk of other women.

Looking at the risks as perceived by women in the different regions chosen by the authors, only 14% of women from the North European countries reported themselves to be at higher risk for fractures compared with their peers, compared to 20% in Southern Europe, 19% in Canada, 17% in Australia and 20% in the US.

Even from the group of women with diagnosed osteoporosis, only 43% (5400/12,429) reported themselves as having an increased risk for fracture, and only 41% (4574/11,094) of the women who were currently under anti-osteoporotic therapy thought their risk of fracture was higher than that of other women of their age. 

Analysis of the risk factors for fracture, using a multivariable model, showed that only a few of the factors were statistically significant; those independently associated with the women’s perception of high risk were: previous fracture (odds ratio (OR) 3.3, 95% confidence interval (CI) 3.2–3.5), current use of cortisone (OR 2.6, 95% CI 2.3–2.9), lower weight (< 125 lb or < 56 kg) (OR 1.8, 95% CI 1.7–1.9), previous diagnosis of osteopenia (OR 4.4, 95% CI 4.1–4.7) or osteoporosis (OR 10, 95% CI 9.4–11).

Overview
The number of participants and the work involved in the GLOW study make it a reference study for further research in osteoporosis, for risk factors in fracture assessment and, not the least, a study that may influence health-care systems and health-care givers to consider its results when formulating their policies.

A study published by Mary Gerend and collaborators [4] about the perception of osteoporosis in a US community, in a sample of 358 women aged 40–86 years, also showed that 63% of the women perceived their risk as lower than that of women of their age, and only 16% perceived their risk as higher. Osteoporosis itself, as a concept, is more difficult to perceive than the fracture risk. Even if the fracture risk is more ‘real’ as a notion for people than osteoporosis, the ‘self-serving attribution bias’ may also appear in the GLOW study, which showed that people may try to attribute their own success to their own efforts and attribute their failures to external factors [5]. In this case, osteoporosis or fracture is something that ‘never happens to the person herself, but most probably to others’. In Gerend’s study, the results stratified by education and income showed better health and a more accurate perception in higher educated persons. It would be very useful to see the same analysis and possibly the analysis of more traditional personal factors in the GLOW study, since, according to its design [2], these data are available. From this analysis, one could identify the target population for interventions such as education, investigation, treatment or active medical screening. 

From the 60,393 women included in the GLOW study, 27,466 were from the US and 3882 from Canada, meaning that about half of the women were from the North American continent, while Europe was divided into North and South regions. The motivation for the distribution of the different regions was not provided by authors. The differences in self-perception of risk factors were not significant and showed the same lack of self-estimation of fracture risks, but further analysis of the data with the aim of developing specific interventions and awareness will be of less help for health authorities. For such attempts, it will be beneficial to discriminate between the impact of factors such as the education and medical care available to patients, the availability of diagnostic tools, and the level of health-care coverage; this may require the analysis of cases within the given country in Europe, for example, or in North and South United States if lifestyle and climate are considered.

Several risk factors for fractures have been identified and should be considered by physicians treating women aged 55 years and over: older age, low weight, parental hip fracture, personal history of fracture (clavicle, arm, wrist, spine, rib, hip, pelvis, upper leg, lower leg, ankle) since age 45, two or more falls in the past year, current use of cortisone or prednisone (steroids that are often prescribed for a number of medical conditions), rheumatoid arthritis, cigarette smoking, consumption of three or more alcoholic beverages daily. Other risk factors include a variety of medical conditions and medications [1, 2]. 

The results of the Dubbo Osteoporosis Epidemiology Study (DOES) [5], a population-based, longitudinal study on 952 women and 343 men with fracture who were followed for up to 18 years, showed an 40% increased mortality post fracture, compared with an age-matched population of women after 75 years old following a minor fracture (such as a wrist fracture); this risk increased almost two-fold for vertebral fractures and 2.5 times for hip fractures. The mortality varied with the severity of the fracture, age and sex, but did not seem to relate to any other illnesses that a person may have [6]. The premature mortality lasts for about 5 years post fracture, except for hip fracture when it lasts for around 10 years, and declines afterwards to the population level for age. The risk for new fractures also increases in the first 2 years and, if there is a subsequent fracture, the mortality risk will rise again for the next 5 years. Unfortunately, with the FRAX assessment tool, the subsequent fracture risk after an initial fracture is taken as a constant over time and the tool only calculates 10-year risks. 

These results, combined with the estimation in the GLOW study of the failure of self-perceived risk of fracture in women over 55 years, point to the importance of taking all fractures very seriously. The identification and awareness of the risk factors for fractures and osteoporosis should become educational targets, both for medical practitioners and women of any age, starting from the period of lactation, the first time when osteopenia and osteoporosis may be mentioned. The Garvan fracture risk calculator is based on the DOES results and also acts as a fracture risk prediction tool. It takes into account the history and the number of recent falls and the number of previous fractures and may better predict the type of fractures than the FRAX tool does; it also calculates the 5-year and 10-year risks of fracture. These data can also be used, if they are available, in the GLOW study, and will show which tool assessment is better for people with fractures or for people without fractures but with several other co-morbidities, with different lifestyles or from different regions of the world [7, 8].

FRAX is already a tool used world-wide, in different populations and countries. Until now, there has been no randomized, controlled trial, based on FRAX calculations of risk, for the prevention of fracture; further studies should be developed to evaluate the ability of treatment to reduce fracture risk in subjects at high risk for fractures, based on FRAX estimations. Also, FRAX cannot be used for patients who are under treatment for osteoporosis and the tool does not include the duration of medication – which may affect the bone characteristics for fractures (number, location, severity), for example corticosteroids, the level of vitamin D or other bone turnover markers [7, 8]. Some limitations of the FRAX assessment tool are due to the fall-related risk of fractures; these are independent of bone-related risks, especially for non-vertebral fractures and hip fractures, but can be prevented by education and recognition of the risks. 

A systematic review published by Elliot Gibson and colleagues in 2004 [9] identified the following as barriers against osteoporosis identification and treatment: cost of therapies, time and cost of resources for diagnosis, concern about medication and the lack of clarity regarding the responsibility to undertake this care. Nowadays, tools for diagnosis and risk assessment, including bone density testing and the World Health Organization FRAX fracture risk assessment tool, are widely available, but the connection between identified risk factors and serious fracture outcomes is not perceived by the majority of women who are at the highest risk. GLOW is the first large-scale international study to acknowledge this important observation. Since many fractures can be prevented by appropriate treatment, it is crucial that the elevated risk be recognized. 

In conclusion, the recent results of the GLOW study on the lack of self-perceived risk of fracture are just one set of a series of publications that will contribute to the enhancement of osteoporosis assessment and perception and will help to develop new and specific interventions for fracture prevention and ultimately decrease mortality secondary to fractures. The failure of women to appreciate their own risk of fracture is a barrier to receiving appropriate care and safe and effective treatments. The study demonstrates that increased efforts must be made to educate medical professionals and the public, including women of any age, about the risks of fracture. The importance of osteopenia, osteoporosis and their impact on fractures should be well defined and emphasized, the notion of risk of fracture and its main causes at any age should be explained, and protective factors and the lifestyle that may improve the overall health and reduce this risk for osteoporosis and fractures should be presented in an appropriate manner for each age and level of education.

Iuliana Ceausu
Senior Lecturer, Obstetrics and Gynecology, ‘Carol Davila’ University of Medicine and Pharmacy, and Senior Specialist in Obstetrics and Gynecology, Department of Obstetrics and Gynecology, ‘Dr. I. Cantacuzino’ Hospital, Bucharest, Romania 
e-mail: iceausu@hotmail.com

References
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http://www.ncbi.nlm.nih.gov/pubmed/20358360
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http://www.ncbi.nlm.nih.gov/pubmed/19190316
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