EditorialObesity and fractures
Introduction
Obesity is defined as a body mass index (BMI) of ≥ 30 kg/m2. Worldwide, obesity has more than doubled since 1980 and in 2008 it was estimated that more than one in ten of the world's population was obese. In the US, 34% of women and 37% of men are obese, with corresponding figures of 23% and 20% in Europe and 24% and 26% in Australia.
Low BMI is associated with increased fracture risk, mostly as a result of low bone mineral density (BMD); after adjustment for BMD, the relationship between BMI and non-hip fractures is no longer significant. Conversely, the association between low BMI and hip fracture is partly independent of BMD, possibly as a result of increased frailty and falls risk. Overall, the relationship between BMI and fracture risk is non-linear, the steepest gradient of risk being observed at BMI values below 20 kg/m2 [1].
Until recently, obesity was widely believed to be protective against fractures as a result of higher BMD in obese subjects and the protective effect of soft tissue during falls. However, studies in postmenopausal women and older men have demonstrated that fractures in the obese population make a significant contribution to the overall burden of fractures. Premaor et al. reported that 28% of postmenopausal women aged ≤ 75 years attending a Fracture Liaison Clinic with a low trauma clinical fracture were obese [2]. In a large multinational, population-based, prospective, observational study of over 60,000 postmenopausal women aged 55 years or older, (GLobal study of Osteoporosis in Women [GLOW]), the fracture prevalence at baseline and incidence at 2 years were similar in obese and non-obese women; fractures in obese women accounted for 23% of all prevalent and 22% of all incident fractures [3]. In postmenopausal women participating in the Study of Osteoporotic Fractures (SOF) and followed for a mean period of 11 yrs, the incidence of non-vertebral fractures was 37.5% and 44% in obese and non-obese women respectively [4]. In the MrOS study in which men aged 65 years or older were followed up for a mean of 7 years, 19% of all non-vertebral fractures and 13% of hip fractures occurred in men who were obese [5]. A recent analysis of the National Health and Nutrition Examination Survey (NHANES) demonstrated that 14% of women and 11% of men who had suffered a hip fracture were obese [6].
Section snippets
Site of fracture
Obesity is associated with a predilection for fractures at some sites, whilst the risk at other sites is lower than that in non-obese individuals. In the GLOW study, increased risk of ankle, lower leg and upper leg (excluding hip) fractures was reported in postmenopausal women, with a reduced risk of hip, pelvis and wrist fractures [3]. Significantly higher risk of lower limb and lower risk of hip fractures was also reported in the Women's’ Health Initiative Observational Cohort study [7]. Data
Risk factors for fracture
Risk factors for fracture in obese and non-obese individuals show some similarities but also some differences. There is an age-related increase in incidence in both, [8] and a similar frequency of previous fracture history, glucocorticoid use and maternal hip fracture history [4]. A higher frequency of falls has been reported in obese women with fracture than their non-obese counterparts, together with a higher prevalence of some self-reported co-morbidities; obese women with fracture were also
Pathophysiology
The pathophysiology of bone fragility associated with obesity is currently the focus of intensive research. Increased production by visceral fat of the pro-inflammatory cytokines interleukin-1, interleukin-6 and tumour necrosis factors may increase bone resorption and inhibit bone formation, both directly and indirectly via up-regulation of receptor activator of NF-kappaB ligand (RANKL), sclerostin and Dickkopf (DKK) proteins. Increased production of adiponectin and reduced production of leptin
Fracture risk assessment
Because of higher BMI and BMD in obese women, fracture probabilities estimated by algorithms such as FRAX might be expected to underestimate fracture risk in obese individuals. The performance of FRAX to predict fractures in obese women has recently been investigated in postmenopausal women participating in the SOF study [16]. Predicted 10-year fracture probabilities in women with incident hip or major osteoporotic fractures were significantly lower in obese than in non-obese women (FRAX
Management considerations
The strong evidence base supporting the use of pharmacological interventions for prevention of fracture in postmenopausal women and, to a lesser extent, older men cannot necessarily be extrapolated to obese individuals since the pivotal clinical trials have included relatively few obese individuals and those participating have generally had low BMD. In a study of clodronate in postmenopausal women not selected on the basis of low BMD, the reduction in major osteoporotic fractures was less in
Conclusions
Fractures in obese postmenopausal women and men make a significant contribution to the overall fracture burden in the older population. Differences in the frequency of fracture at different sites between obese and non-obese individuals may reflect different patterns of falling, absence or presence of soft tissue padding and differences in cortical bone architecture. Fractures in obese subjects share some of the characteristics of fragility fractures in the non-obese including a similar
Disclosure of interest
The author declares that she has no conflicts of interest concerning this article.
Acknowledgements
JEC acknowledges support from the NIHR Cambridge Biomedical Research Centre.
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