Original Full Length ArticleEffect of co-morbidities on fracture risk: Findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW)
Highlights
► We investigated the effect of co-morbidities on fracture risk. ► 3224 of 52,960 women (6.1%) sustained an incident fracture over 2 years. ► Parkinson's disease and multiple sclerosis had the greatest effect on fracture risk.
Introduction
Since its launch, the fracture-prediction algorithm, FRAX, has been in constant evolution to improve its predictive capacity internationally [1]. It has been suggested that further collection of information regarding co-morbidities may be helpful in this process. At present, the investigator is asked to provide information on the presence of rheumatoid arthritis, and to consider whether a number of conditions associated with “secondary osteoporosis” are present. Examples given are inflammatory bowel disease, insulin-dependent diabetes, and diseases associated with reduced mobility, such as stroke and Parkinson's disease. However, a number of other co-morbidities have been shown to be associated with fracture. For example, some papers have reported an excess risk of cardiovascular disease among patients with low bone density [2], [3]. The cause of this association is likely to be multifactorial, representing a combination of the disease process itself (ongoing inflammatory process and sex hormone deficiency) and lifestyle factors (poor mobility and tobacco use). Other studies suggest that there is an increased risk of fracture among patients with respiratory disease that cannot be explained by steroid use alone [4], [5]; while other co-morbidities, such as Parkinson's disease, may be associated with a significantly increased risk of falling.
We used a large, multinational cohort study to investigate the size of the effect of single co-morbidities on fracture risk, and specifically to investigate whether the number of co-morbidities present might also be an important determinant of fracture risk. Finally, we also considered whether incorporation of further information on medical history by means of generation of a ‘co-morbidity index’ might improve fracture prediction by the FRAX algorithm.
Section snippets
Setting
GLOW is an observational cohort study that is being conducted in physician practices at 17 sites in 10 countries (Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, U.K., and U.S.). These sites are located in major population centers. Clinical investigators at each of the 17 sites constitute the GLOW Scientific Advisory Board and are responsible for the management of the study. Details of the study design and methods have been previously described [6]. In brief, practices
Results
A total of 60,393 patients from the practices of 723 physicians were enrolled in the study between October 2006 and February 2008. Approximately 25,000 women were recruited from 274 physician practices in Europe; 28,000 from 255 practices in the U.S.; and almost 7000 from 86 practices in Canada and Australia. Of the 52,960 women with follow-up data, 3224 (6.1%) sustained an incident fracture over 2 years of follow-up. Co-morbidities were common: 26,215 women (49.5%) reported hypertension and
Discussion
In this study, all recorded co-morbidities were significantly associated with fracture, except for high cholesterol, hypertension, celiac disease, and cancer. The strongest association was seen with Parkinson's disease. Further analyses suggested that addition of information on co-morbidities to the conventional FRAX risk factors was a valuable addition, although one comparison (the c index) suggested that this was not the case. Other studies, however, have suggested that this statistic may not
Role of the funding source
Financial support for the GLOW study is provided by Warner Chilcott Company, LLC and sanofi-aventis to the Center for Outcomes Research, University of Massachusetts Medical School. The sponsors had no involvement in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to submit the article for publication. The design, conduct, and interpretation of the GLOW data are undertaken by an independent steering committee.
Acknowledgments
We thank the physicians and project coordinators participating in GLOW.
References (41)
- et al.
FRAX and its applications to clinical practice
Bone
(2009) - et al.
Epidemiology of Parkinson's disease
Lancet Neurol
(2006) - et al.
Cytokines, bone turnover markers and weight change in candidates for lung transplantation
Pulm Pharmacol Ther
(2008) - et al.
Severity of osteoporosis: what is the impact of co-morbidities?
Joint Bone Spine
(2010) - et al.
Fracture risk in people with celiac disease: a population-based cohort study
Gastroenterology
(2003) - et al.
Systematic review and meta-analysis of observational studies on the prevalence of fractures in celiac disease
Dig Liver Dis
(2008) - et al.
Development and use of FRAX in osteoporosis
Osteoporos Int
(2010) - et al.
Women with cardiovascular disease have increased risk of osteoporotic fracture
Calcif Tissue Int
(2011) - et al.
Low bone mineral density is associated with increased risk for myocardial infarction in men and women
Osteoporos Int
(2012) - et al.
An association between respiratory function and hip bone mineral density in older men: a cross-sectional study
Osteoporos Int
(2005)